L. Henry Goodnough, MD, PhD

All Publications

• Supplemental medial small fragment fixation adds stability to distal femur fixation: A biomechanical study. Injury Henry Goodnough, L., Salazar, B. P., Chen, M. J., Storaci, H., Guzman, R., Heffner, M., Tam, K., DeBaun, M. R., Gardner, M. J. 2021

  Abstract

  INTRODUCTION: Bridge plating of distal femur fractures with lateral locking plates is susceptible to varus collapse, fixation failure, and nonunion. While medial and lateral dual plating has been described in clinical series, the biomechanical effects of dual plating of distal femur fractures have yet to be clearly defined. The purpose of this study was to compare dual plating to lateral locked bridge plating alone in a cadaveric distal femur gap osteotomy model.MATERIALS AND METHODS: Gap osteotomies were created in eight matched pairs of cadaveric female distal femurs (average age: 64 yrs (standard deviation ± 4.4 yrs); age range: 57-68 yrs;) to simulate comminuted extraarticular distal femur fractures (AO/OTA 33A). Eight femurs underwent fixation with lateral locked plates alone and were matched with eight femurs treated with dual plating: lateral locked plates with supplemental medial small fragment non-locking fixation. Mechanical testing was performed on an ElectroPuls E10000 materials testing system using a 10kN/100 Nm biaxial load cell. Specimens were subject to 25,000 cycles of cyclic loading from 100-1000N at 2Hz.RESULTS: Two (2/8) specimens in the lateral only group failed catastrophically prior to completion of testing. All dual plated specimens survived the testing regimen. Dual plated specimens demonstrated significantly less coronal plane displacement (median 0.2 degrees, interquartile range [IQR], 0.0-0.5 degrees) compared to 2.0 degrees (IQR 1.9-3.3, p=0.02) in the lateral plate only group. Dual plated specimens demonstrated greater bending stiffness compared to the lateral plated group (median 29.0kN/degree, IQR 1.5-68.2kN/degree vs median 0.50kN/degree, IQR 0.23-2.28kN/degree, p=0.03).CONCLUSION: Contemporary fixation methods with a distal femur fractures are susceptible to mechanical failure and nonunion with lateral plates alone. Dual plate fixation in a cadaveric model of distal femur fractures underwent significantly less displacement under simulated weight bearing conditions and demonstrated greater stiffness than lateral plating alone. Given the significant clinical failure rates of lateral bridge plating in distal femur fractures, supplemental fixation should be considered, and dual plating of distal femurs augments mechanical stability in a clinically relevant magnitude.

  View details for DOI 10.1016/j.injury.2021.04.056

  View details for PubMedID 33985754

• Indications for cement augmentation in fixation of geriatric intertrochanteric femur fractures: a systematic review of evidence. Archives of orthopaedic and trauma surgery Goodnough, L. H., Wadhwa, H., Tigchelaar, S. S., DeBaun, M. R., Chen, M. J., Graves, M. L., Gardner, M. J. 2021

  Abstract

  INTRODUCTION: Achieving durable mechanical stability in geriatric intertrochanteric proximal femur fractures remains a challenge. Concomitant poor bone quality, unstable fracture patterns, and suboptimal reduction are additional risk factors for early mechanical failure. Cement augmentation of the proximal locking screw or blade is one proposed method to augment implant anchorage. The purpose of this review is to describe the biomechanical and clinical evidence for cement augmentation of geriatric intertrochanteric fractures, and to elaborate indications for cement augmentation.METHODS: The PubMed database was searched for English language studies up to January 2021. Studies that assessed effect of calcium phosphate or methylmethacrylate cement augmentation during open reduction and internal fixation of intertrochanteric fractures were included. Studies with sample size<5, nontraumatic or periprosthetic fractures, and nonunion or revision surgery were excluded. Study selection adhered to PRISMA criteria.RESULTS: 801 studies were identified, of which 40 met study criteria. 9 studies assessed effect of cement augmentation on fracture displacement. All but one found that cement decreased fracture displacement. 10 studies assessed effect of cement augmentation on total load or cycles to failure. All but one demonstrated that augmented implants increased this variable. Complication rates of cement augmentation during ORIF of intertrochanteric fractures ranged from 0 to 47%, while non-augmented implants ranged from 0 to 51%. Reoperation rates ranged from 0 to 11% in the cement-augmented group and 0 to 11% in the non-augmented group. Fixation failure ranged from 0 to 11% in the cement-augmented group and 0 to 20% in the non-augmented group. Nonunion ranged from 0 to 3.6% in the cement-augmented group and 0 to 34% in the non-augmented group.CONCLUSIONS: Calcium phosphate or PMMA-augmented CMN fixation of IT fractures increased construct stability and improved outcomes in biomechanical and early clinical studies. The findings of these studies suggest an important role for cement augmentation in patient populations at high risk of mechanical failure.

  View details for DOI 10.1007/s00402-021-03872-6

  View details for PubMedID 33829301

• White-Light Body Scanning Captures Three-Dimensional Shoulder Deformity After Displaced Diaphyseal Clavicle Fracture. Journal of orthopaedic trauma DeBaun, M. R., Lai, C., Schultz, B. J., Oquendo, Y. A., Campbell, S. T., Goodnough, L. H., Bishop, J. A., Gardner, M. J. 2021; 35 (4): e142–e147

  Abstract

  OBJECTIVE: We sought to determine if white-light three-dimensional (3D) body scanning can identify clinically relevant shoulder girdle deformity after displaced diaphyseal clavicle fracture (DCF).METHODS: Adult patients with DCF (OTA/AO 15A) were prospectively enrolled. Four subcutaneous osseous landmarks were used to measure shoulder girdle morphology of the injured and uninjured shoulder. Measurements were made both manually with a tape measure and digitally with a white-light 3D scanner. Bilateral radiographs were obtained, and clavicle length was recorded. Quick-Disabilities of the Arm, Shoulder, and Hand surveys were administered at injury and at 6 and 12 weeks.RESULTS: Twenty-two patients were included in the study. At the initial visit, all patients had significant differences in deformity measurements between injured and uninjured shoulders as measured by 3D scanning. There was no difference between shoulders measured using manual measurements. At 6 and 12 weeks, shoulder asymmetry was significantly less in patients treated with surgery compared with nonoperative patients as measured by the 3D scanner alone. Clavicle shortening measured on 3D scanning had weak and moderate positive correlations to radiographs (R = 0.27) and manual measurements (R = 0.53), respectively. Patients treated with surgery had significant functional improvements by 6 weeks, and a similar improvement was not seen until 12 weeks in nonsurgical patients.CONCLUSION: White-light 3D scanning was able to identify and monitor clinically relevant shoulder girdle deformity after DCF. This tool may become a useful adjunct to clinical examination and radiographic assessment, when determining clinically relevant deformity thresholds. In the future, quantifying and understanding shoulder deformity may inform clinical decision making in these patients.LEVEL OF EVIDENCE: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

  View details for DOI 10.1097/BOT.0000000000001957

  View details for PubMedID 32910627

• Medial Column Support in Pilon Fractures Using Percutaneous Intramedullary Large Fragment Fixation. Journal of orthopaedic trauma Goodnough, L. H., Tigchelaar, S. S., Van Rysselberghe, N. L., DeBaun, M. R., Gardner, M. J., Hecht, G. G., Lucas, J. F. 2021

  View details for DOI 10.1097/BOT.0000000000002073

  View details for PubMedID 33675625

• Cephalomedullary helical blade is independently associated with less collapse in intertrochanteric femur fractures than lag screws. European journal of orthopaedic surgery & traumatology : orthopedie traumatologie Goodnough, L. H., Wadhwa, H., Tigchelaar, S. S., Pfaff, K., Heffner, M., Van Rysselberghe, N., DeBaun, M. R., Bishop, J. A., Gardner, M. J. 2021

  Abstract

  OBJECTIVES: Excessive fracture site collapse and shortening in intertrochanteric femur fractures alter hip biomechanics and patient outcomes. The purpose of the study was to compare extent of collapse in cephalomedullary nails with blades or lag screws. We hypothesized that there would be no difference in collapse between helical blades and lag screws.DESIGN: Retrospective cohort study.SETTING: Single U.S. Level I Trauma Center.PATIENTS: 171 consecutive patients treated with cephalomedullary nails with either lag screw or blade for AO/OTA 31A1-3 proximal femur fractures and minimum 3-month follow-up.INTERVENTION: Lag screw or helical blade in a cephalomedullary nail.OUTCOME MEASURES: The primary outcome was fracture site collapse at 3months.RESULTS: There was a significantly higher proportion of reverse-oblique and transverse intertrochanteric femur fractures (31-A3) in the lag screw group (15/42 vs 25/129). A3 patterns were associated with more collapse. There was significantly less collapse in the blade group (median 4.7mm, inter-quartile range 2.5-7.8mm) than the screw group (median 8.4 mmm, inter-quartile range 3.7-11.2mm, p 0.006). Median collapse was no different between blades and screws when comparing stable and unstable patterns. However, blades were independently associated with 2.5mm less collapse (95%CI -4.2, -0.72mm, p 0.006) and lower likelihood of excessive collapse (>10mm at 3months, OR 0.3, 95% CI 0.13-0.74, p 0.007), regardless of fracture pattern.CONCLUSIONS: Helical blades are independently associated with significantly less collapse than lag screws in intertrochanteric proximal femur fractures, after adjusting for unstable fracture patterns. In fracture patterns at risk for collapse, surgeons can consider use of a helical blade due to its favorable sliding properties compared to screws.

  View details for DOI 10.1007/s00590-021-02875-8

  View details for PubMedID 33587180

• Short versus long cephalomedullary nailing of intertrochanteric fractures: a meta-analysis of 3208 patients. Archives of orthopaedic and trauma surgery Cinque, M. E., Goodnough, L. H., Md, B. J., Fithian, A. T., DeBaun, M. n., Lucas, J. F., Md, M. J., Bishop, J. A. 2021

  Abstract

  The purpose of the study was to compare treatment outcomes after short or long cephalomedullary nailing for intertrochanteric femur fractures.A systematic review of perioperative outcomes after short or long cephalomedullary nailing for intertrochanteric femur fractures was performed. The following databases were used: using the Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials, PubMed (1980-2019), and MEDLINE (1980-2019). The queries were performed in June 2019.The following search term query was used: "Intramedullary Nail AND Intertrochanteric Fracture OR "Long OR Short Nail AND intertrochanteric Fracture." Studies were excluded if they were "single-arm" studies (i.e., reporting on either long or short CMN but not both), or did not report at least one of the outcomes being meta-analyzed. Furthermore, cadaveric studies, animal studies, basic science articles, editorial articles, surveys and studies were excluded.Two investigators independently reviewed abstracts from all identified articles. Full-text articles were obtained for review if necessary, to allow further assessment of inclusion and exclusion criteria. Additionally, all references from the included studies were reviewed and reconciled to verify that no relevant articles were missing from the systematic review.Short nails were associated with statistically significantly less estimated blood loss and operative time compared to long nails. There were no significant differences in transfusion rates, implant failures or overall re-operation rates between implant lengths. Similarly, there was no significant difference in peri-implant fracture between implant lengths.Overall, the available clinical evidence supports the use of short cephalomedullary nails for the majority of intertrochanteric femur fractures.Meta-analysis; Level III, therapeutic.

  View details for DOI 10.1007/s00402-021-03752-z

  View details for PubMedID 33484311

• Incidence and Management of Articular Impaction in Geriatric Olecranon Fractures. The Journal of the American Academy of Orthopaedic Surgeons Wadhwa, H. n., Goodnough, L. H., Finlay, A. K., DeBaun, M. R., Campbell, S. T., Hecht, G. n., Lucas, J. F., Bishop, J. A., Gardner, M. J. 2021

  Abstract

  Olecranon fractures are common in the elderly. Articular impaction is encountered occasionally, but the incidence and outcomes after treatment of this injury pattern have not been well characterized.We evaluated a cohort of geriatric olecranon fractures to determine the incidence of articular impaction and describe a technique for open reduction and internal fixation.Of the 63 patients in our series, 31 had associated intraarticular impaction (49.2%). Patients with articular impaction did not have significantly different rates of postoperative complications (11/31, 35.5% versus 10/31, 32.3%; P = 1.00) or revision surgery (10/31, 32.3% versus 8/31, 25.8%; P = 0.780) compared with those without articular impaction.Articular impaction is a common feature of geriatric olecranon fractures. Surgeons must maintain a high index of suspicion and have a surgical plan in place for managing this component of the injury.

  View details for DOI 10.5435/JAAOS-D-20-01293

  View details for PubMedID 33999874

• Distal Femur Replacement versus Open Reduction and Internal Fixation for Treatment of Periprosthetic Distal Femur Fractures: Systematic Review and Meta-Analysis. Journal of orthopaedic trauma Wadhwa, H. n., Salazar, B. P., Goodnough, L. H., Van Rysselberghe, N. L., DeBaun, M. R., Wong, H. N., Gardner, M. J., Bishop, J. A. 2021

  Abstract

  To compare complications and functional outcomes of treatment with primary distal femoral replacement (DFR) versus open reduction and internal fixation (ORIF).PubMed, Embase, and Cochrane databases were searched for English language studies up to May 19, 2020, identifying 913 studies.Studies that assessed complications of periprosthetic distal femur fractures with primary DFR or ORIF were included. Studies with sample size ≤5, mean age <55, nontraumatic indications for DFR, ORIF with non-locking plates, native distal femoral fractures, or revision surgeries were excluded. Selection adhered to PRISMA criteria.Study quality was assessed using previously reported criteria. There were 40 Level IV studies, 17 Level III studies, and 1 Level II study.Fifty-eight studies with 1,484 patients were included in the meta-analysis. Complications assessed (Incidence Rate Ratio (IRR) (95%CI): 0.78 (0.59-1.03)) and reoperation or revision (IRR (95%CI): 0.71 (0.49-1.04)) were similar between the DFR and ORIF cohorts. Mean knee range of motion (ROM) was greater in the ORIF cohort (DFR: 90.47 vs. ORIF: 100.36, p < 0.05). Mean Knee Society Score (KSS) (DFR: 79.41 vs. ORIF: 82.07, p = 0.35) and return to preoperative ambulatory status were similar (IRR (95%CI): 0.82 (0.48-1.41)).In comparing complications among patients treated for periprosthetic distal femur fracture with DFR or ORIF, there was no difference between the groups. There were also no differences in functional outcomes, although knee ROM was greater in the ORIF group. This systematic review and meta-analysis highlights the need for future prospective trials evaluating the outcomes of these divergent treatment strategies.Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.

  View details for DOI 10.1097/BOT.0000000000002141

  View details for PubMedID 34001801

• Lateral Distractor Use During Internal Fixation of Tibial Plateau Fractures Has Minimal Risk of Iatrogenic Peroneal Nerve Palsy. Journal of orthopaedic trauma Chen, M. J., Salazar, B. P., Tigchelaar, S. S., Frey, C. S., DeBaun, M. R., Goodnough, L. H., Bellino, M. J., Bishop, J. A., Gardner, M. J. 2020

  Abstract

  OBJECTIVES: To determine the incidence of iatrogenic peroneal nerve palsy after application of an intraoperative lateral distractor during open reduction and internal fixation (ORIF) of tibial plateau fractures (TPF).DESIGN: Retrospective review.SETTING: Single academic Level I trauma center.PATIENTS: One hundred and forty-seven patients met criteria and were included in the study.INTERVENTION: Patients with unicondylar and bicondylar TPFs underwent ORIF and received application of an intraoperative lateral distractor to aid in visualization and reduction of the impacted lateral plateau.MAIN OUTCOME MEASUREMENTS: Incidence of iatrogenic peroneal nerve palsy.RESULTS: There was a 2.0% incidence of iatrogenic peroneal nerve symptoms (three of 147 patients), the majority of which were incomplete sensory deficits. There was no association with staged external fixation, regional anesthesia, or tourniquet use.CONCLUSION: Use of an intraoperative lateral distractor is safe and has a low incidence of iatrogenic peroneal nerve palsy if applied carefully.LEVEL OF EVIDENCE: Prognostic level IV. See Instructions for Authors for a complete description of levels of evidence.

  View details for DOI 10.1097/BOT.0000000000001875

  View details for PubMedID 33165211

• Delayed Union of a Diaphyseal Forearm Fracture Associated With Impaired Osteogenic Differentiation of Prospectively Isolated Human Skeletal Stem Cells. JBMR plus Goodnough, L. H., Ambrosi, T. H., Steininger, H., DeBaun, M. R., Abrams, G. D., McAdams, T. R., Gardner, M. J., Chan, C. K., Bishop, J. A. 2020; 4 (10): e10398

  Abstract

  Delayed union or nonunion are relatively rare complications after fracture surgery, but when they do occur, they can result in substantial morbidity for the patient. In many cases, the etiology of impaired fracture healing is uncertain and attempts to determine the molecular basis for delayed union and nonunion formation have been limited. Prospectively isolating skeletal stem cells (SSCs) from fracture tissue samples at the time of surgical intervention represent a feasible methodology to determine a patient's biologic risk for compromised fracture healing. This report details a case in which functional in vitro readouts of SSCs derived from human fracture tissue at time of injury predicted a poor fracture healing outcome. This case suggests that it may be feasible to stratify a patient's fracture healing capacity and predict compromised fracture healing by prospectively isolating and analyzing SSCs during the index fracture surgery. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

  View details for DOI 10.1002/jbm4.10398

  View details for PubMedID 33103027

• Human skeletal stem cell aging. Aging Ambrosi, T. H., Goodnough, L. H., Chan, C. K. 2020

  View details for DOI 10.18632/aging.104034

  View details for PubMedID 32929053

• Distal Femur Replacement versus Surgical Fixation for the Treatment of Geriatric Distal Femur Fractures: A Systematic Review. Journal of orthopaedic trauma Salazar, B. P., Babian, A. R., DeBaun, M. R., Githens, M. F., Chavez, G. A., Goodnough, H., Gardner, M. J., Bishop, J. A. 2020

  Abstract

  OBJECTIVES: The management of geriatric distal femur fractures is controversial, and both primary distal femur replacement (DFR) or surgical fixation (SF) are viable treatment options. The purpose of this study was to compare patient outcomes after these treatment strategies.DATA SOURCES: PubMed, Embase, and Cochrane databases were searched for English language papers up to April 24, 2020, identifying 2,129 papers.STUDY SELECTION: Studies evaluating complications in elderly patients treated for distal femur fractures with either immediate DFR or surgical fixation were included. Studies with mean patient age <55 years, nontraumatic indications for DFR, or SF with non-locking plates were excluded.DATA EXTRACTION: Two studies provided Level II or III evidence while the remaining 28 studies provided Level IV evidence. Studies were formally evaluated for methodologic quality using established criteria. Treatment failure between groups was compared using an incidence rate ratio.DATA SYNTHESIS: Treatment failure was defined for both surgical fixation and arthroplasty as complications requiring a major reoperation for reasons such as mechanical failure, nonunion, deep infection, aseptic loosening, or extensor mechanism disruption. There were no significant differences in complication rates or knee range of motion between SF and DFR.CONCLUSION: SF and DFR for the treatment of geriatric distal femur fractures demonstrate similar overall complication rates. Given the available evidence, no strong conclusions on the comparative effectiveness between the two treatments can be definitively made. More rigorous prospective research comparing SF versus DFR to treat acute geriatric distal femur fractures is warranted.LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

  View details for DOI 10.1097/BOT.0000000000001867

  View details for PubMedID 32569072

• Geriatric fragility fractures are associated with a human skeletal stem cell defect. Aging cell Ambrosi, T. H., Goodnough, L. H., Steininger, H. M., Hoover, M. Y., Kim, E., Koepke, L. S., Marecic, O., Zhao, L., Seita, J., Bishop, J. A., Gardner, M. J., Chan, C. K. 2020: e13164

  Abstract

  Fragility fractures have a limited capacity to regenerate, and impaired fracture healing is a leading cause of morbidity in the elderly. The recent identification of a highly purified bona fide human skeletal stem cell (hSSC) and its committed downstream progenitor cell populations provides an opportunity for understanding the mechanism of age-related compromised fracture healing from the stem cell perspective. In this study, we tested whether hSSCs isolated from geriatric fractures demonstrate intrinsic functional defects that drive impaired healing. Using flow cytometry, we analyzed and isolated hSSCs from callus tissue of five different skeletal sites (n=61) of patients ranging from 13 to 94years of age for functional and molecular studies. We observed that fracture-activated amplification of hSSC populations was comparable at all ages. However, functional analysis of isolated stem cells revealed that advanced age significantly correlated with reduced osteochondrogenic potential but was not associated with decreased in vitro clonogenicity. hSSCs derived from women displayed an exacerbated functional decline with age relative to those of aged men. Transcriptomic comparisons revealed downregulation of skeletogenic pathways such as WNT and upregulation of senescence-related pathways in young versus older hSSCs. Strikingly, loss of Sirtuin1 expression played a major role in hSSC dysfunction but re-activation by trans-resveratrol or a small molecule compound restored in vitro differentiation potential. These are the first findings that characterize age-related defects in purified hSSCs from geriatric fractures. Our results provide a foundation for future investigations into the mechanism and reversibility of skeletal stem cell aging in humans.

  View details for DOI 10.1111/acel.13164

  View details for PubMedID 32537886

• Complication Rates after Lateral Plate Fixation of Periprosthetic Distal Femur Fractures: A Multicenter Study. Injury Campbell, S. T., Lim, P. K., Kantor, A. H., Gausden, E. B., Goodnough, L. H., Park, A. Y., Bishop, J. A., Achor, T. S., Scolaro, J. A., Gardner, M. J. 2020

  Abstract

  OBJECTIVE: Periprosthetic fractures of the distal femur can be challenging injuries to treat; nonunion rates of up to 22% have been reported. The purpose of this study was to determine the rate of complications and nonunion in a multicenter series, and to identify patient or surgical factors that were associated with nonunion.DESIGN: Retrospective comparative study SETTING: Three Level 1 trauma centers PATIENTS: Fifty-five patients with a periprosthetic distal femur fracture proximal to a total knee arthroplasty. Minimum follow up for inclusion was six months or until union or failure.INTERVENTION: Surgical fixation using a precontoured lateral locking plate MAIN OUTCOME MEASUREMENT: Fracture union was the primary outcome. Patient demographic and injury variables (age, comorbidities, fracture classification and characteristics) and surgical technique factors (mode of plate fixation, plate material, working length, screw density, and proximal screw type) were identified and compared between patients who developed a nonunion and those who did not. Regression analysis was performed to identify independent risk factors for nonunion.RESULTS: The overall rate of nonunion was 18% and the total complication rate was 24%. After additional surgery, 49 of 55 patients went on to heal (89%). There were no statistical differences in patient demographic or injury variables between the union and nonunion groups, and none of the variables studied were independent risk factors for nonunion in the regression analysis.CONCLUSIONS: In this series of 55 patients with periprosthetic distal femur fractures treated with precontoured lateral locking plates, 18% developed nonunion and the overall complication rate was 24%. No patient or surgical variables were identified as risk factors. Future research should seek to identify patients at high risk for complication and nonunion who could benefit from alternative fixation strategies or distal femoral replacement.

  View details for DOI 10.1016/j.injury.2020.05.009

  View details for PubMedID 32482424

• How do pilon fractures heal? An analysis of dual plating and bridging callus formation. Injury Campbell, S. T., Goodnough, L. H., Salazar, B., Lucas, J. F., Bishop, J. A., Gardner, M. J. 2020

  Abstract

  OBJECTIVES: 1) To determine the effect of single versus dual plate metaphyseal fixation for pilon fractures on callus formation and reoperation rates, 2) to determine the effect of biomechanically matched versus unmatched fixation, and 3) to determine whether patient or surgical factors were independent predictors of bridging callus formation or need for reoperation.DESIGN: Retrospective comparative study.SETTING: Single level one trauma center.PATIENTS: Fifty patients with AO/OTA type C2 or C3 pilon fractures treated with plate fixation.INTERVENTION: Internal fixation with a plate and screw construct, with comparisons made between patients with single versus dual plate fixation, and patients treated with biomechanically matched or unmatched fixation.MAIN OUTCOME MEASUREMENTS: Modified RUST (mRUST) scores at three and six months and reoperation rate.RESULTS: At six months, mean mRUST scores were significantly lower in patients treated with dual metaphyseal plates compared to a single plate (8.7 vs 10.4, p=0.046) There were 15 open fractures; eight were treated with supplemental fixation, while seven were treated with single-column fixation. Open fracture (OR 51.05, p=0.008) was a risk factor for reoperation. Screw density between 0.4 and 0.5 was a protective factor against reoperation (OR 0.03, p=0.026). Biomechanically unmatched fixation did not affect mRUST scores or reoperation rates.CONCLUSIONS: Pilon fractures treated with a single plate had more callus formation six months after surgery compared to those treated with dual plate fixation, and there was no difference in reoperation rates. Screw density between 0.4-0.5 was protective against reoperation. These data may serve as the basis of future work to determine the ideal fixation construct for the frequently comminuted metaphysis in pilon fractures. Further work is necessary to determine whether callus formation in these injuries is desirable.LEVEL OF EVIDENCE: Three.

  View details for DOI 10.1016/j.injury.2020.04.023

  View details for PubMedID 32434713

• Selective screw fixation is associated with early failure of primary acetabular components for aseptic loosening. Journal of orthopaedic research : official publication of the Orthopaedic Research Society Henry Goodnough, L., Bonano, J. C., Finlay, A. K., Aggarwal, V., Huddleston, J. I., Maloney, W. J., Goodman, S. B., Amanatullah, D. F. 2020

  Abstract

  Selective augmentation of the acetabular component with screws during primary total hip arthroplasty (THA) assumes that the surgeon can detect when an acetabular component needs added stability. In contrast, non-selective screw users do not alter their practice based on their interpretation of stability and either use screws all or none of the time. We aimed to determine the effect of selective screw use on aseptic acetabular component loosening. We retrospectively reviewed aseptic failures of THA acetabular components. We compared the survivorship of selective to non-selective supplementation of acetabular fixation with screws, and compared time to revision, obesity and selective screw use. Selective screw use (n=16) was associated with earlier acetabular component aseptic loosening (median 1.9 years; interquartile range (IQR) 1.1-5.0) compared to non-selective screw use (n=22; median 5.6 years; IQR 2.0- 15.3, p = 0.010). Selective screw use was independently associated with earlier revision after adjusting for patient obesity. Obesity was associated with selective screw use in 50% of the cases versus 14% of non-selective cases (OR 6.3 CI 1.2-25.2, p = 0.028), possibly reflecting the increased difficulty in achieving acetabular component stability in this and other settings with compromised bone. Surgeons should carefully assess component stability at time of primary THA. If the acetabulum is not stable, the addition of screws alone may not be sufficient for acetabular component stability. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1002/jor.24649

  View details for PubMedID 32157712

• Is percutaneous screw fixation really superior to non-operative management after valgus-impacted femoral neck fracture: a retrospective cohort study. European journal of orthopaedic surgery & traumatology : orthopedie traumatologie Goodnough, L. H., Wadhwa, H. n., Fithian, A. T., DeBaun, M. R., Campbell, S. T., Gardner, M. J., Bishop, J. A. 2020

  Abstract

  The optimal management of valgus-impacted femoral neck fractures remains controversial. Internal fixation is associated with significant rates of re-operation, while historical non-operative management strategies consisting of prolonged bed rest also resulted in patient morbidity. Our hypothesis was that screw fixation would have comparable failure rates to non-operative treatment and immediate mobilization for valgus-impacted femoral neck fractures.Retrospective cohort at a single academic Level I trauma center of patients with valgus-impacted femoral neck fractures (AO/OTA 31-B1) treated with percutaneous screw fixation (n = 97) or non-operatively (n = 28). Operative treatment consisted of percutaneous screw fixation. Non-operative treatment consisted of early mobilization. The primary outcome was a salvage operation. Patient demographics were assessed between groups.More non-operatively treated patients were permitted unrestricted weight-bearing (WBAT; p = 0.002). There was no increase in complication rates or mortality, and return to previous ambulatory status was comparable between operatively and non-operatively treated patients. 35.7% (10/28) of non-operatively treated patients underwent a subsequent operation, compared to 15.5% (15/97) of patients with screw fixation (p = 0.03). Only WBAT was independently associated with treatment failure (OR 3.1, 95%CI 1.2-8.3, p =0.02). WBAT was predictive of treatment failure only in the non-operatively treated group (64.3%, 9/14 WBAT vs 8.3%, 1/12 partial, p =0.005).After controlling for weight-bearing restrictions, we found no difference in failure rates between non-operative treatment and screw fixation. Non-operative treatment with partial weight-bearing had low failure rates, comparable complication and mortality rates, and equivalent functional outcomes to operative treatment and is reasonable if a patient would like to avoid surgery and accepts the risk of subsequent arthroplasty. Overall, there were relatively high failure rates in all groups.

  View details for DOI 10.1007/s00590-020-02742-y

  View details for PubMedID 32710126

• Trochanteric fixation nail advanced with helical blade and cement augmentation: early experience with a retrospective cohort. European journal of orthopaedic surgery & traumatology : orthopedie traumatologie Goodnough, L. H., Wadhwa, H. n., Tigchelaar, S. S., DeBaun, M. R., Chen, M. J., Bishop, J. A., Gardner, M. J. 2020

  Abstract

  Intra-articular screw cut-out is a potential complication of intertrochanteric femur fracture fixation with a cephalomedullary nail. Cement augmentation of fixation in the proximal segment offers the prospect of increased stability and fewer complications, but clinical experience with non-resorbable cement is limited. To determine the handling properties and efficacy of this new technique, we performed a retrospective propensity-matched cohort of forty-four geriatric intertrochanteric femur fractures treated with a cephalomedullary nail with (n = 11) or without (n = 33) augmentation with non-resorbable cement injected into the proximal segment. In the patients treated with cement augmentation, at minimum 3-month follow-up, there were no instances of intra-articular cut-out, and no increase in re-operation compared to conventional fixation. Cement augmentation appears to be safe and effective in geriatric intertrochanteric femur fractures to mitigate risk of cut-out.

  View details for DOI 10.1007/s00590-020-02762-8

  View details for PubMedID 32804288

• How are peri-implant fractures below short versus long cephalomedullary nails different? European journal of orthopaedic surgery & traumatology : orthopedie traumatologie Goodnough, L. H., Salazar, B. P., Furness, J. n., Feng, J. E., DeBaun, M. R., Campbell, S. T., Lucas, J. F., Cross, W. W., Leucht, P. n., Grant, K. D., Gardner, M. J., Bishop, J. A. 2020

  Abstract

  Cephalomedullary nails are a commonly used implant for the treatment of many pertrochanteric femur fractures and are available in short and long configurations. There is no consensus on ideal nail length. Relative advantages can be ascribed to short and long intramedullary nails, yet both implant styles share the potentially devastating complication of peri-implant fracture. Determining the clinical sequelae after fractures below nails of different lengths would provide valuable information for surgeons choosing between short or long nails. Thus, the purpose of the study was to compare injury patterns and treatment outcomes following peri-implant fractures below short or long cephalomedullary nails.This was a multicenter retrospective cohort study that identified 33 patients referred for treatment of peri-implant fractures below short and long cephalomedullary nails (n = 19 short, n = 14 long). We compared fracture pattern, treatment strategy, complications, and outcomes between these two groups.Short nails were associated with more diaphyseal fractures (odds ratio [OR] 13.75, CI 2.2-57.9, p 0.002), which were treated more commonly with revision intramedullary nailing (OR, infinity; p 0.01), while long nails were associated with distal metaphyseal fractures (OR 13.75, CI 2.2-57.9, p 0.002), which were treated with plate and screw fixation (p 0.002). After peri-implant fracture, there were no differences in blood loss, operative time, weight bearing status, or complication rates based on the length of the initial nail. In patients treated with revision nailing, there was greater estimated blood loss (EBL, median 300 cc, interquartile range [IQR] 250-1200 vs median 200 cc, IQR 100-300, p 0.03), blood product utilization and complication rates (OR 11.1, CI 1.1-135.7, p 0.03), but a trend toward unrestricted post-operative weight-bearing compared to patients treated with plate and screw constructs.Understanding fracture patterns and patient outcomes after fractures below nails of different lengths will help surgeons make more informed implant choices when treating intertrochanteric hip fractures. Revision to a long nail for the treatment of fractures at the tip of a short nail may be associated with increased patient morbidity.

  View details for DOI 10.1007/s00590-020-02785-1

  View details for PubMedID 32909108

• Metaphyseal callus formation in pilon fractures is associated with loss of alignment: Is stiffer better? Injury Van Rysselberghe, N. L., Campbell, S. T., Goodnough, L. H., Salazar, B. P., Bishop, J. A., Bellino, M. J., Lucas, J. F., Gardner, M. J. 2020

  Abstract

  To assess the relationship between metaphyseal callus formation and preservation of distal tibial alignment in pilon fractures treated with internal plate fixation.Retrospective Review SETTING: Academic Level I Trauma Center PATIENTS: Forty-two patients with AO/OTA type C2 or C3 pilon fractures treated with plate fixation.Internal fixation with anterolateral plating, medial plating, or both. Modified Radiographic Union Score in Tibial fracture (mRUST) scores were determined from six-month radiographs.Change in lateral and anterior distal tibial angles (LDTA and ADTA) at six months post-operatively.High callus formation (mRUST ≥ 11 at six months) was associated with a greater loss of coronal reduction as measured by LDTA compared to low callus formation (mRUST < 11): 3.8 vs 2.1° (p = .019), with no difference in ADTA change between groups. In a multivariable logistic regression controlling for age, smoking, obesity, and open fracture, higher mRUST scores were a predictor of coronal reduction loss of five or more degrees (OR 1.71, p=.039). Dual column plating did not independently predict maintenance of alignment.Recent literature has popularized dual column fixation for pilon fractures, but it remains unknown whether increased metaphyseal stiffness enhances or impairs healing. In this series, decreased metaphyseal callus formation was associated with maintained coronal alignment, suggesting that a stiffer mechanical environment may be preferable to prevent short term reduction loss in these complex injuries.III.

  View details for DOI 10.1016/j.injury.2020.10.080

  View details for PubMedID 33097204

• Dual Mini-Fragment Plating is Comparable to Precontoured Small Fragment Plating for Operative Diaphyseal Clavicle Fractures: A Retrospective Cohort Study. Journal of orthopaedic trauma DeBaun, M. R., Chen, M. J., Campbell, S. T., Goodnough, L. H., Lai, C., Salazar, B. P., Bishop, J. A., Gardner, M. J. 2019

  Abstract

  OBJECTIVES: To compare precontoured (Pc) small fragment plating to dual mini-fragment plating (DmF) for open reduction and internal fixation (ORIF) of diaphyseal clavicle fractures.DESIGN: Retrospective Cohort SETTING:: Level 1 Trauma CenterPatients/Participants: A total of 133 patients with displaced fractures of the diaphyseal clavicle (OTA/AO 15-B1, -2, and -3) treated with ORIF with a minimum of 1 year follow up or until radiographic and clinical union.INTERVENTION: Two patient cohorts were identified: 1) patients treated with orthogonal DmF plate constructs and 2) patients treated with Pc clavicle-specific plates.OUTCOME MEASUREMENTS: Union rate and implant removal were assessed using standard descriptive statistics. Odds ratios (OR), 95% confidence intervals (CI), and p-values (p) were calculated.RESULTS: There were 60 DmF and 74 Pc patients. There were no significant differences between groups with respect to age, gender, surgeon, body mass index, or mode of fixation. There was no significant difference in union (98.3% DmF; 100% Pc, p=0.45) or maintenance of reduction (98.3% DmF; 100% Pc, p=0.45). A total of 8% of DmF patients had symptomatic implant removal compared to 20% of Pc patients (OR 0.36, CI 0.12-1.05, p=0.061).CONCLUSIONS: This retrospective comparative study found no difference in union or maintenance of reduction for diaphyseal clavicle fractures fixed with DmF compared to Pc plating. Patients treated with DmF plates may have lower rates of symptomatic implant removal.LEVEL OF EVIDENCE: Therapeutic Level III.

  View details for DOI 10.1097/BOT.0000000000001727

  View details for PubMedID 31868765

• Rates of Perioperative Complications Among Patients Undergoing Orthopedic Trauma Surgery Despite Having Positive Results for Methamphetamine ORTHOPEDICS Githens, T., DeBaun, M. R., Campbell, S. T., Wu, E. J., Goodnough, L., Lichstein, P., Painter, C., Krygier, J. E., Bishop, J., Gardner, M. J. 2019; 42 (4): 192–96

  Abstract

  The burden of psychosocial problems, including substance abuse, is high among trauma patients. Use of illicit substances is often noted during urine toxicology screening on admission and can delay surgery because of concerns for an interaction with anesthesia. Methamphetamine theoretically has potential to increase perioperative anesthetic risks. However, the authors are unaware of any studies documenting increased rates of cardiovascular complications in the perioperative period among orthopedic trauma patients. This study sought to determine the rate of cardiovascular complications in these patients. The authors reviewed the medical records of all patients between 2013 and 2018 who underwent orthopedic trauma surgery at two level I trauma centers in the setting of a methamphetamine-positive urine toxicology screening prior to surgery. Information on demographics, injury, type of surgical intervention, and incidence of perioperative cardiovascular and overall medical complications prior to discharge was recorded. Ninety-four patients were included in the study (mean age, 44 years; range, 16-78 years). Twenty-six (28%) patients had multiple injuries. Thirteen (14%) patients had debridement and/or provisional stabilization of an open or unstable fracture, 18 (19%) had treatment for an infection, and 63 (67%) had definitive fracture surgery. The overall rates of perioperative cardiovascular complications and perioperative medical complications were 2.1% and 3.2%, respectively. This study provides both a baseline understanding of the complication rate for methamphetamine-positive orthopedic trauma patients during general anesthesia and justification for larger multicenter studies to further investigate this topic. [Orthopedics. 2019; 42(4):192-196.].

  View details for DOI 10.3928/01477447-20190523-01

  View details for Web of Science ID 000476648200015

  View details for PubMedID 31136677

• Changing practice patterns: flexed versus semi-extended positioning for tibial nailing CURRENT ORTHOPAEDIC PRACTICE Goodnough, L., Campbell, S. T., Githens, M. F., Gardner, M. J., Bishop, J. A. 2019; 30 (4): 356–60

  View details for DOI 10.1097/BCO.0000000000000763

  View details for Web of Science ID 000474108600014

• Geriatric olecranon fractures treated with plate fixation have low complication rates CURRENT ORTHOPAEDIC PRACTICE Campbell, S. T., DeBaun, M. R., Goodnough, L., Bishop, J. A., Gardner, M. J. 2019; 30 (4): 353–55

  View details for DOI 10.1097/BCO.0000000000000765

  View details for Web of Science ID 000474108600013

• Decreased estimated blood loss in lateral trans-psoas versus anterior approach to lumbar interbody fusion for degenerative spondylolisthesis. Journal of spine surgery (Hong Kong) Goodnough, L. H., Koltsov, J., Wang, T., Xiong, G., Nathan, K., Cheng, I. 2019; 5 (2): 185–93

  Abstract

  Background: The goal of the current study was to compare the perioperative and post-operative outcomes of eXtreme lateral trans-psoas approach (XLIF) versus anterior lumbar interbody fusion (ALIF) for single level degenerative spondylolisthesis. The ideal approach for degenerative spondylolisthesis remains controversial.Methods: Consecutive patients undergoing single level XLIF (n=21) or ALIF (n=54) for L4-5 degenerative spondylolisthesis between 2008-2012 from a single academic center were retrospectively reviewed. Groups were compared for peri-operative data (estimated blood loss, operative time, adjunct procedures or additional implants), radiographic measurements (L1-S1 cobb angle, disc height, fusion grade, subsidence), 30-day complications (infection, DVT/PE, weakness/paresthesia, etc.), and patient reported outcomes (leg and back Numerical Rating Scale, and Oswestry Disability Index).Results: Estimated blood loss was significantly lower for XLIF [median 100; interquartile range (IQR), 50-100 mL] than for ALIF (median 250; IQR, 150-400 mL; P<0.001), including after adjusting for significantly higher rates of posterior decompression in the ALIF group. There were no significant differences in rates of complications within 30 days, radiographic outcomes, or in re-operation rates. Both groups experienced significant pain relief post-operatively.Conclusions: The lateral trans-psoas approach is associated with diminished blood loss compared to the anterior approach in the treatment of degenerative spondylolisthesis. We were unable to detect differences in radiographic outcomes, complication rates, or patient reported outcomes. Continued efforts to directly compare approaches for specific indications will minimize complications and improve outcomes. Further studies will continue to define indications for lateral versus anterior approach to lumbar spine for degenerative spondylolisthesis.

  View details for DOI 10.21037/jss.2019.05.08

  View details for PubMedID 31380471

• Identification of the Human Skeletal Stem Cell CELL Chan, C. F., Gulati, G. S., Sinha, R., Tompkins, J., Lopez, M., Carter, A. C., Ransom, R. C., Reinisch, A., Wearda, T., Murphy, M., Brewer, R. E., Koepke, L. S., Marecic, O., Manjunath, A., Seo, E., Leavitt, T., Lu, W., Allison Nguyen, Conley, S. D., Salhotra, A., Ambrosi, T. H., Borrelli, M. R., Siebel, T., Chan, K., Schallmoser, K., Seita, J., Sahoo, D., Goodnough, H., Bishop, J., Gardner, M., Majeti, R., Wan, D. C., Goodman, S., Weissman, I. L., Chang, H. Y., Longaker, M. T. 2018; 175 (1): 43-+

  View details for DOI 10.1016/j.cell.2018.07.029

  View details for Web of Science ID 000445120000013

• Obesity Is Independently Associated With Early Aseptic Loosening in Primary Total Hip Arthroplasty JOURNAL OF ARTHROPLASTY Goodnough, L. H., Finlay, A. K., Huddleston, J. I., Goodman, S. B., Maloney, W. J., Amanatullah, D. F. 2018; 33 (3): 882–86

  Abstract

  Obesity affects millions of patients in the United States and is associated with several complications after total hip arthroplasty (THA). The effect of obesity on the rate and mode of primary THA failure remains poorly understood, especially given other potentially confounding patient characteristics. We hypothesized that, among patients with a failed primary THA, obesity is independently associated with aseptic loosening and a higher rate of early revision.Six hundred eighty-four consecutive cases with failed THA referred to a single academic center for revision during a 10-year period were retrospectively reviewed. Multivariate logistic regression analysis was used to test the independent association between obesity and the timing as well as cause of THA failure.The rate of primary THA failure before 5 years was 48.8% in obese and 37.1% in nonobese patients (odds ratio [OR] = 1.57, P = .010). Primary THA failure before 5 years was more likely with increasing body mass index (BMI) (BMI: 35-40 kg/m2, OR = 2.31, P = .008; BMI >40 kg/m2, OR = 2.51, P = .049). The rate of primary THA failure for aseptic loosening before 5 years was 30% in obese and 18% in nonobese patients (OR = 1.88, P = .023). Obesity was not a risk for revision for infection, whereas an American Society of Anesthesiologists class ≥3 was independently associated with primary THA failure for infection (OR = 2.33, P < .001).Among patients with a failed THA, comorbidities may account for the risk of revision due to infection in obese patients. Obesity is independently associated with early primary THA failure for aseptic loosening.

  View details for DOI 10.1016/j.arth.2017.09.069

  View details for Web of Science ID 000425893000046

  View details for PubMedID 29089226

• Antiseptics Commonly Used in Total Joint Arthroplasty Interact and May Form Toxic Products JOURNAL OF ARTHROPLASTY Campbell, S. T., Goodnough, L. H., Bennett, C. G., Giori, N. J. 2018; 33 (3): 844–46

  Abstract

  Multiple antiseptics have been described for use in total joint arthroplasty infection, and the use of multiple antiseptic solutions during a single operation has been described. Our clinical experience is that chlorhexidine (CHX) and Dakin's solution (NaOCl) interact and form a precipitate. The purpose of this study is to determine whether this reaction could be replicated in a laboratory setting, and to determine if other commonly used antiseptics also visibly react when mixed.Four percent chlorhexidine gluconate (CHX), 0.5% sodium hypochlorite (NaOCl), 3% hydrogen peroxide (H2O2), and 10% povidone-iodine (BTD) solutions were obtained and all possible combinations were mixed. Any visible reactions were noted and recorded, and a literature search was performed to characterize the reaction and products.CHX and NaOCl, CHX and H2O2, and CHX and BTD reacted instantly, forming a precipitate. NaOCl and H2O2 reacted to produce a gas. NaOCl and BTD reacted and produced a color change. The literature review revealed that at least 2 of the reactions tested (CHX + NaOCl and NaOCl + H2O2) could result in byproducts toxic to humans.Surgeons must be aware of these interactions when using antiseptic solutions during procedures. Caution should be used combining or mixing antiseptics, and we recommend against concomitant introduction in a surgical wound.

  View details for DOI 10.1016/j.arth.2017.10.028

  View details for Web of Science ID 000425893000039

  View details for PubMedID 29137898

• Blood Transfusion Therapy. Medical clinics of North America Goodnough, L. T., Panigrahi, A. K. 2017; 101 (2): 431-447

  Abstract

  Transfusion of red blood cells (RBCs) is a balance between providing benefit for patients while avoiding risks of transfusion. Randomized, controlled trials of restrictive RBC transfusion practices have shown equivalent patient outcomes compared with liberal transfusion practices, and meta-analyses have shown improved in-hospital mortality, reduced cardiac events, and reduced bacterial infections. This body of level 1 evidence has led to substantial, improved blood utilization and reduction of inappropriate blood transfusions with implementation of clinical decision support via electronic medical records, along with accompanying educational initiatives.

  View details for DOI 10.1016/j.mcna.2016.09.012

  View details for PubMedID 28189180

• Management of anemia in patients with congestive heart failure AMERICAN JOURNAL OF HEMATOLOGY Goodnough, L. T., Comin-Colet, J., Leal-Noval, S., Ozawa, S., Takere, J., Henry, D., Javidroozi, M., Hohmuth, B., Bisbe, E., Gross, I., Shander, A. 2017; 92 (1): 88-93

  Abstract

  Anemia is an independent risk factor for adverse patient outcomes. There are no guidelines for management of anemia in patients with congestive heart failure (CHF), despite its high incidence. Four objectives were defined by the International Anemia Management and Clinical Outcomes Expert Panel (AMCO), a multinational group of interdisciplinary experts identified by the Society for the Advancement of Blood Management (SABM) to: determine the prevalence of anemia in outpatients; to determine the prevalence of hospital-acquired anemia; to assess the impact of anemia management on clinical outcomes such as quality of life and functional status; and to provide recommendations for primary care physicians and specialists for the diagnosis, evaluation, and management of anemia in patients with CHF. Anemia and iron deficiency were confirmed to be highly prevalent in patients with CHF. Intravenous iron therapy improves anemia, cardiac function and exercise tolerance, leading to improvement in quality of life. Anemia management has been demonstrated to be cost-effective. Clinical care pathways to manage anemia in patients with CHF are recommended as best practices in order to improve patient outcomes. Am. J. Hematol. 92:88-93, 2017. © 2016 Wiley Periodicals, Inc.

  View details for DOI 10.1002/ajh.24595

  View details for Web of Science ID 000393425300024

• "Simplified International Recommendations for the Implementation of Patient Blood Management" (SIR4PBM). Perioperative medicine (London, England) Meybohm, P., Froessler, B., Goodnough, L. T., Klein, A. A., Muñoz, M., Murphy, M. F., Richards, T., Shander, A., Spahn, D. R., Zacharowski, K. 2017; 6: 5-?

  Abstract

  More than 30% of the world's population are anemic with serious medical and economic consequences. Red blood cell transfusion is the mainstay to correct anemia, but it is also one of the top five overused procedures and carries its own risk and cost burden. Patient blood management (PBM) is a patient-centered and multidisciplinary approach to manage anemia, minimize iatrogenic blood loss, and harness tolerance to anemia in an effort to improve patient outcome. Despite resolution 63.12 of the World Health Organization in 2010 endorsing PBM and current guidelines which include evidence-based recommendations on the use of diagnostic/therapeutic resources to provide better health care, many hospitals have yet to implement PBM in routine clinical practice.A number of experienced clinicians developed the following "Simplified International Recommendations for Patient Blood Management." We propose a series of simple, cost-effective, best-practice, feasible, and evidence-based measures that will enable any hospital to reduce both anemia prevalence on the day of intervention/surgery and anemia-related unnecessary transfusion in surgical and medical patients, including obstetrics and gynecology.

  View details for DOI 10.1186/s13741-017-0061-8

  View details for PubMedID 28331607

• Patient Blood Management Bundles to facilitate implementation ANASTHESIOLOGIE & INTENSIVMEDIZIN Meybohm, P., Richards, T., Isbister, J., Hofmann, A., Shander, A., GOODNOUGH, L. T., Munoz, M., Gombotz, H., Weber, C. F., Choorapoikayil, S., Spahn, D. R., Zacharowski, K. 2017; 58: 16-29

  View details for Web of Science ID 000393543400004

• Patient Blood Management Bundles to Facilitate Implementation TRANSFUSION MEDICINE REVIEWS Meybohm, P., Richards, T., Isbister, J., Hofmann, A., Shander, A., Goodnough, L. T., Munoz, M., Gombotz, H., Weber, C. F., Choorapoikayil, S., Spahn, D. R., Zacharowski, K. 2017; 31 (1): 62-71

  Abstract

  More than 30% of the world's population are anemic with serious economic consequences including reduced work capacity and other obstacles to national welfare and development. Red blood cell transfusion is the mainstay to correct anemia, but it is also 1 of the top 5 overused procedures. Patient blood management (PBM) is a proactive, patient-centered, and multidisciplinary approach to manage anemia, optimize hemostasis, minimize iatrogenic blood loss, and harness tolerance to anemia. Although the World Health Organization has endorsed PBM in 2010, many hospitals still seek guidance with the implementation of PBM in clinical routine. Given the use of proven change management principles, we propose simple, cost-effective measures enabling any hospital to reduce both anemia and red blood cell transfusions in surgical and medical patients. This article provides comprehensive bundles of PBM components encompassing 107 different PBM measures, divided into 6 bundle blocks acting as a working template to develop institutions' individual PBM practices for hospitals beginning a program or trying to improve an already existing program. A stepwise selection of the most feasible measures will facilitate the implementation of PBM. In this manner, PBM represents a new quality and safety standard.

  View details for DOI 10.1016/j.tmrv.2016.05.012

  View details for PubMedID 27317382

• National and International Guidelines for Patient Blood Management in Obstetrics: A Qualitative Review ANESTHESIA AND ANALGESIA Shaylor, R., Weiniger, C. F., Austin, N., Tzabazis, A., Shander, A., Goodnough, L. T., Butwick, A. J. 2017; 124 (1): 216-232

  Abstract

  In developed countries, rates of postpartum hemorrhage (PPH) requiring transfusion have been increasing. As a result, anesthesiologists are being increasingly called upon to assist with the management of patients with severe PPH. First responders, including anesthesiologists, may adopt Patient Blood Management (PBM) recommendations of national societies or other agencies. However, it is unclear whether national and international obstetric societies' PPH guidelines account for contemporary PBM practices. We performed a qualitative review of PBM recommendations published by the following national obstetric societies and international groups: the American College of Obstetricians and Gynecologists; The Royal College of Obstetricians and Gynecologists, United Kingdom; The Royal Australian and New Zealand College of Obstetricians and Gynecologists; The Society of Obstetricians and Gynecologists of Canada; an interdisciplinary group of experts from Austria, Germany, and Switzerland, an international multidisciplinary consensus group, and the French College of Gynaecologists and Obstetricians. We also reviewed a PPH bundle, published by The National Partnership for Maternal Safety. On the basis of our review, we identified important differences in national and international societies' recommendations for transfusion and PBM. In the light of PBM advances in the nonobstetric setting, obstetric societies should determine the applicability of these recommendations in the obstetric setting. Partnerships among medical, obstetric, and anesthetic societies may also help standardize transfusion and PBM guidelines in obstetrics.

  View details for DOI 10.1213/ANE.0000000000001473

  View details for Web of Science ID 000390613500025

• Zika Virus and Patient Blood Management ANESTHESIA AND ANALGESIA Goodnough, L. T., Marques, M. B. 2017; 124 (1): 282-289

  Abstract

  Sporadic Zika virus infections had only occurred in Africa and Asia until an outbreak in Micronesia (Oceania) in 2007. In 2013 to 2014, several outer Pacific Islands reported local outbreaks. Soon thereafter, the virus was likely introduced in Brazil from competing athletes from French Polynesia and other countries that participated in a competition there. Transmission is thought to have occurred through mosquito bites and spread to the immunologically naive population. Being also a flavivirus, the Zika virus is transmitted by the Aedes mosquito that is endemic in South and Central America that is also the vector of West Nile virus, dengue, and chikungunya. In less than a year, physicians in Brazil reported a many-fold increase in the number of babies born with microcephaly. Despite initial skepticism regarding the causal association of the Zika virus epidemic and birth defects, extensive basic and clinical research evidence has now confirmed this relationship. In the United States, more than 4000 travel-associated infections have been reported by the middle of 2016 to the Centers for Disease Control and Prevention. Furthermore, many local mosquito-borne infections have occurred in Puerto Rico and Florida. Considering that the virus causes a viremia in which 80% of infected individuals have no symptoms, the potential for transfusion transmission from an asymptomatic blood donor is high if utilizing donor screening alone without testing. Platelet units have been shown to infect 2 patients via transfusion in Brazil. Although there was an investigational nucleic acid test available for testing donors, not all blood centers were initially required to participate. Subsequently, the US Food and Drug Administration issued a guidance in August 2016 that recommended universal nucleic acid testing for the Zika virus on blood donors.In this report, we review the potentially devastating effects of Zika virus infection during pregnancy and its implication in cases of Guillain-Barre syndrome in adults. Furthermore, we urge hospital-based clinicians and transfusion medicine specialists to implement perisurgical patient blood management strategies to avoid blood component transfusions with their potential risks of emerging pathogens, illustrated here by the Zika virus. Ultimately, this current global threat, as described by the World Health Organization, will inevitably be followed by future outbreaks of other bloodborne pathogens; the principles and practices of perioperative patient blood management will reduce the risks from not only known, but also unknown risks of blood transfusion for our patients.

  View details for DOI 10.1213/ANE.0000000000001770

  View details for PubMedID 27902502

• How I train specialists in transfusion medicine TRANSFUSION Goodnough, L. T., Murphy, M. F. 2016; 56 (12): 2923-2933

  Abstract

  The changing focus of transfusion medicine (TM) toward the hospital rather than the blood center and the involvement of TM specialists in a wide range of patient blood management and other specialist activities in the hospital, rather than just blood bank activities, means that the training of the transfusion specialists of the future should be under constant review.We provide overviews of the current training programs of the Accreditation Council for Graduate Medical Education in the United States and the Joint Royal Colleges of Physicians Training Board in the United Kingdom, along with specific descriptions of our own training programs at Stanford and Oxford.The numbers of TM fellows in training annually in the United States and of those who attempt to attain board certification have increased substantially over the last 20 years, despite the profound reduction in blood utilization since 2009. These trends reflect increasing job and career opportunities in new activities, such as patient blood management at hospital-based transfusion services. This trend has been seen to a lesser extent in the United Kingdom, although the focus of TM is similarly switching to hospital-based transfusion services.Based on current trends, transfusion medicine is a growing and robust specialty in the United States but perhaps less so in the United Kingdom, increasingly with hospital-centered job opportunities for improving blood utilization and clinical outcomes. Establishing pediatric TM training programs and improving research training are further opportunities for training TM specialists.

  View details for DOI 10.1111/trf.13862

  View details for PubMedID 27859432

• Management of Anemia in Patients with Congestive Heart Failure. American journal of hematology Goodnough, L. T., Comin-Colet, J., Leal-Noval, S., Ozawa, S., Takere, J., Henry, D., Javidroozi, M., Hohmuth, B., Bisbe, E., Gross, I., Shander, A. 2016

  Abstract

  Anemia is an independent risk factor for adverse patient outcomes. There are no guidelines for management of anemia in patients with congestive heart failure (CHF), despite its high incidence. Four objectives were defined by the International Anemia Management and Clinical Outcomes Expert Panel (AMCO), a multinational group of interdisciplinary experts identified by the Society for the Advancement of Blood Management (SABM) to: determine the prevalence of anemia in outpatients; to determine the prevalence of hospital-acquired anemia; to assess the impact of anemia management on clinical outcomes such as quality of life and functional status; and to provide recommendations for primary care physicians and specialists for the diagnosis, evaluation, and management of anemia in patients with CHF. Anemia and iron deficiency were confirmed to be highly prevalent in patients with CHF. Intravenous iron therapy improves anemia, cardiac function and exercise tolerance, leading to improvement in quality of life. Anemia management has been demonstrated to be cost-effective. Clinical care pathways to manage anemia in patients with CHF are recommended as best practices in order to improve patient outcomes. Am. J. Hematol. 92:88-93, 2017. © 2016 Wiley Periodicals, Inc.

  View details for DOI 10.1002/ajh.24595

  View details for PubMedID 27779769

• How I use clinical decision support to improve red blood cell utilization. Transfusion Tim Goodnough, L., Andrew Baker, S., Shah, N. 2016; 56 (10): 2406-2411

  Abstract

  Despite 20 years of published medical society guidelines for blood transfusion and a pivotal clinical trial in 1999 providing Level 1 evidence that restrictive transfusion practices can be utilized safely, blood transfusions did not begin to decline in the United States until 2010. Widespread adoption of electronic medical records allowed implementation of computerized systems such as clinical decision support (CDS) with best practice alerts to improve blood utilization. We describe our own experience using well-designed and highly targeted CDS to promote restrictive transfusion practices and improve red blood cell utilization, with a 42% reduction in blood transfusions from 2009 through 2015, accompanied by improved clinical outcomes.

  View details for DOI 10.1111/trf.13767

  View details for PubMedID 27546388

• How I use clinical decision support to improve red blood cell utilization TRANSFUSION Goodnough, L. T., Baker, S. A., Shah, N. 2016; 56 (10): 2406-2411

  Abstract

  Despite 20 years of published medical society guidelines for blood transfusion and a pivotal clinical trial in 1999 providing Level 1 evidence that restrictive transfusion practices can be utilized safely, blood transfusions did not begin to decline in the United States until 2010. Widespread adoption of electronic medical records allowed implementation of computerized systems such as clinical decision support (CDS) with best practice alerts to improve blood utilization. We describe our own experience using well-designed and highly targeted CDS to promote restrictive transfusion practices and improve red blood cell utilization, with a 42% reduction in blood transfusions from 2009 through 2015, accompanied by improved clinical outcomes.

  View details for DOI 10.1111/trf.13767

  View details for Web of Science ID 000385834800004

• Knowledge of blood loss at delivery among postpartum patients PEERJ Farber, M. K., Miller, C. M., Ramachandran, B., Hegde, P., Akbar, K., Goodnough, L. T., Butwick, A. J. 2016; 4

  Abstract

  Postpartum hemorrhage (PPH) is a leading cause of obstetric morbidity. There is limited understanding of patients' knowledge about blood loss at delivery, PPH, and PPH-related morbidities, including transfusion and anemia.We surveyed 100 healthy postpartum patients who underwent vaginal or cesarean delivery about blood loss, and whether they received information about transfusion and peripartum hemoglobin (Hb) testing. Responses were compared between women undergoing vaginal delivery vs. cesarean delivery; P < 0.05 considered as statistically significant.In our cohort, 49 women underwent vaginal delivery and 51 women underwent cesarean delivery. Only 29 (29%) of women provided blood loss estimates for their delivery. Women who underwent cesarean delivery were more likely to receive clear information about transfusion therapy than those undergoing vaginal delivery (43.1% vs. 20.4% respectively; P = 0.04). Women who underwent vaginal delivery were more likely to receive results of postpartum Hb tests compared to those undergoing cesarean delivery (49% vs. 29.4%; P = 0.02).Our findings suggest that women are poorly informed about the magnitude of blood loss at delivery. Hematologic information given to patients varies according to mode of delivery. Further research is needed to better understand the clinical implications of patients' knowledge gaps about PPH, transfusion and postpartum anemia.

  View details for DOI 10.7717/peerj.2361

  View details for PubMedID 27635332

• National and International Guidelines for Patient Blood Management in Obstetrics: A Qualitative Review. Anesthesia and analgesia Shaylor, R., Weiniger, C. F., Austin, N., Tzabazis, A., Shander, A., Goodnough, L. T., Butwick, A. J. 2016: -?

  Abstract

  In developed countries, rates of postpartum hemorrhage (PPH) requiring transfusion have been increasing. As a result, anesthesiologists are being increasingly called upon to assist with the management of patients with severe PPH. First responders, including anesthesiologists, may adopt Patient Blood Management (PBM) recommendations of national societies or other agencies. However, it is unclear whether national and international obstetric societies' PPH guidelines account for contemporary PBM practices. We performed a qualitative review of PBM recommendations published by the following national obstetric societies and international groups: the American College of Obstetricians and Gynecologists; The Royal College of Obstetricians and Gynecologists, United Kingdom; The Royal Australian and New Zealand College of Obstetricians and Gynecologists; The Society of Obstetricians and Gynecologists of Canada; an interdisciplinary group of experts from Austria, Germany, and Switzerland, an international multidisciplinary consensus group, and the French College of Gynaecologists and Obstetricians. We also reviewed a PPH bundle, published by The National Partnership for Maternal Safety. On the basis of our review, we identified important differences in national and international societies' recommendations for transfusion and PBM. In the light of PBM advances in the nonobstetric setting, obstetric societies should determine the applicability of these recommendations in the obstetric setting. Partnerships among medical, obstetric, and anesthetic societies may also help standardize transfusion and PBM guidelines in obstetrics.

  View details for PubMedID 27557476

• Clinical Pattern in Hypotensive Transfusion Reactions. Anesthesia and analgesia Metcalf, R. A., Bakhtary, S., Goodnough, L. T., Andrews, J. 2016; 123 (2): 268-273

  Abstract

  Hypotensive transfusion reactions (HyTRs) may be underreported and have been associated with patients taking angiotensin-converting enzyme inhibitors (ACEIs) receiving poststorage leukoreduced blood products through negatively charged filters. Although bedside leukoreduction is no longer commonplace, HyTRs still occur and are insufficiently characterized in the prestorage leukoreduction era. We describe recently reported cases at our institution.We reviewed transfusion reaction records at Stanford Healthcare from January 2014 to April 2015. HyTRs were defined by National Health Safety Network Hemovigilance Module classification.Eleven HyTRs occurred in 10 patients. All were adults (mean age 71.7 years; range 45-92 years), 7 were male, and all underwent major surgery 0 to 2 days before the reaction. Nine patients underwent cardiac or vascular surgery, and all 10 were taking ACEIs with the last dose taken within 48 hours of the transfusion reaction in 9 patients. Nine patients were on extracorporeal circuits within 24 hours before the reaction (median duration 180 minutes; range 87-474 minutes). In 5 reactions, the implicated unit was restarted with resultant recurrent hypotension. Implicated units included 9 packed red blood cells, 1 apheresis platelet, and 1 plasma frozen within 24 hours.Contrary to what has been previously reported in the era of prestorage leukoreduction, HyTRs at our institution showed consistent patterns in patients at risk. Patients scheduled to undergo major surgery with cardiopulmonary bypass may benefit from earlier preoperative cessation of ACEIs or temporarily switching to an alternative drug class.

  View details for DOI 10.1213/ANE.0000000000001387

  View details for PubMedID 27284999

• Transportation Cooler Interventions Reduce Plasma and RBC Product Wastage. American journal of clinical pathology Metcalf, R. A., Baker, S. A., Goodnough, L. T., Shah, N. 2016; 146 (1): 18-24

  Abstract

  The rate of plasma product wastage for the United States in 2011 was approximately 1.8%. The plasma wastage rate at our institution was higher, mainly due to products returned out of temperature range from procedural areas. A process review and intervention to reduce plasma wastage was undertaken, which included modifications to our transport cooler.A new cooler system was designed, and this device was implemented alongside an updated protocol for delivering plasma while also enhancing the previous RBC cooler validation time. We audited plasma and RBC product wastage prior to these interventions, from January 2013 to February 2014, vs after the intervention from April 2014 to March 2015.After the intervention, the monthly plasma wastage rate declined 60% (12.6 units/100 units transfused preintervention vs 5.0 units/100 units transfused postintervention; P < .0001). The monthly RBC wastage rate also decreased 28% (3.2 units/100 units transfused preintervention vs 2.3 units/100 units transfused postintervention; P < .01).Our intervention resulted in significantly decreased plasma and RBC wastage and is broadly applicable, since out-of-temperature product wastage in procedural areas is likely a significant problem at many institutions.

  View details for DOI 10.1093/ajcp/aqw082

  View details for PubMedID 27357292

• The Judicious Use of Recombinant Factor VIIa. Seminars in thrombosis and hemostasis Goodnough, L. T., Levy, J. H. 2016; 42 (2): 125-132

  Abstract

  Recombinant activated factor VIIa (rFVIIa) is a prohemostatic agent initially approved for use in hemophilia patients with inhibitors and recently for Glanzmann thrombasthenia. Despite its approval indications, rFVIIa has also been used for a diverse range of off-label indications to treat bleeding related to traumatic injury, major hemorrhage following surgery, intracranial hemorrhage, and for uncontrolled bleeding as a prothrombotic hemostatic agent. Despite its off-label use, the benefit of rFVIIa in most nonhemophilia settings remains uncertain as the majority of clinical trials have not consistently demonstrated beneficial effects as determined by reduced bleeding, decreased blood product utilization, or have not demonstrated a mortality benefit. As with any prohemostatic agent, the risk of thromboembolic events is increased when rFVIIa is used off-label. Pooled data from randomized nonhemophilia studies report an increased risk in the elderly for arterial thromboses, although most individual trials have been underpowered to determine adverse thrombotic events. The causes of thrombotic adverse events associated with off-label use of rFVIIa may be due to an increased risk of adverse events due to critical illness or due to higher doses of rFVIIa used in off-label trials. Without clearly supportive data, physicians should consider risk versus benefit and exercise restraint using rFVIIa in off-label settings. Further, evidence-based guidelines should be developed by professional organizations, and additional randomized controlled clinical trials are needed to further assess the efficacy and safety of off-label rFVIIa use.

  View details for DOI 10.1055/s-0035-1569068

  View details for PubMedID 26838698

• Twist1 Contributes to Cranial Bone Initiation and Dermal Condensation by Maintaining Wnt Signaling Responsiveness DEVELOPMENTAL DYNAMICS Goodnough, L., Dinuoscio, G. J., Atit, R. P. 2016; 245 (2): 144-156

  Abstract

  Specification of cranial bone and dermal fibroblast progenitors in the supraorbital arch mesenchyme is Wnt/β-catenin signaling-dependent. The mechanism underlying how these cells interpret instructive signaling cues and differentiate into these two lineages is unclear. Twist1 is a target of the Wnt/β-catenin signaling pathway and is expressed in cranial bone and dermal lineages.Here, we show that onset of Twist1 expression in the mouse cranial mesenchyme is dependent on ectodermal Wnts and mesenchymal β-catenin activity. Conditional deletion of Twist1 in the supraorbital arch mesenchyme leads to cranial bone agenesis and hypoplastic dermis, as well as craniofacial malformation of eyes and palate. Twist1 is preferentially required for cranial bone lineage commitment by maintaining Wnt responsiveness. In the conditional absence of Twist1, the cranial dermis fails to condense and expand apically leading to extensive cranial dermal hypoplasia with few and undifferentiated hair follicles.Thus, Twist1, a target of canonical Wnt/β-catenin signaling, also functions to maintain Wnt responsiveness and is a key effector for cranial bone fate selection and dermal condensation.

  View details for DOI 10.1002/DVDY.24367

  View details for Web of Science ID 000368168100005

  View details for PubMedID 26677825

  View details for PubMedCentralID PMC4715624

• How do I implement an automated screen for high-titer ABO antibody as an inventory management tool for ABO plasma-incompatible platelets? TRANSFUSION Fontaine, M. J., Webster, J., Gomez, S., Pham, T. D., Goodnough, L. T., Galel, S. A. 2015; 55 (12): 2783-2789

  Abstract

  Plasma volume reduction (PVR) may reduce the risk of hemolysis associated with transfusion of plateletpheresis blood products (PLTs) containing ABO-incompatible plasma. But PVR may delay PLT issue. In collaboration with our blood donor center we evaluated an automated screen of PLT for high-titer ABO antibody and to apply PVR to high-titer PLTs.At the donor center, plasma from PLT donors was tested using an automated microplate system (PK7300, Beckman). PK settings were set for a detection cutoff equivalent to 1 in 256 using a manual tube method. The donors associated with high-titer PLTs were characterized by sex and age. In the transfusion service, the number of PVR procedures was evaluated before and after implementation of the high-titer screen.During validation, 157 of 1008 PLT units (15%) were positive by the automated method versus 121 (12%) by manual method. After implementation, 2112 of 15,240 PLT units were high-titer, with higher frequency in donations from females versus males (18% vs. 12%, p < 0.0001). The PLT PVR rate was reduced by 50%.Implementation of an automated method to screen PLTs for high-titer ABO antibody at the donor center improves the inventory management of PLTs containing ABO-incompatible plasma at the hospital transfusion service.

  View details for DOI 10.1111/trf.13374

  View details for Web of Science ID 000367950600004

• Is there a "magic" hemoglobin number? Clinical decision support promoting restrictive blood transfusion practices. American journal of hematology Goodnough, L. T., Shah, N. 2015; 90 (10): 927-933

  Abstract

  Blood transfusion has been identified as one of the most frequently performed therapeutic procedures, with a significant percentage of transfusions identified to be inappropriate. Recent key clinical trials in adults have provided Level 1 evidence to support restrictive red blood cell (RBC) transfusion practices. However, some advocates have attempted to identify a "correct" Hb threshold for RBC transfusion; whereas others assert that management of anemia, including transfusion decisions, must take into account clinical patient variables, rather than simply one diagnostic laboratory test. The heterogeneity of guidelines for blood transfusion by a number of medical societies reflects this controversy. Clinical decision support (CDS) uses a Hb threshold number in a smart Best Practices Alert (BPA) upon physician order, to trigger a concurrent utilization self-review for whether blood transfusion therapy is appropriate. This review summarizes Level 1 evidence in seven key clinical trials in adults that support restrictive transfusion practices, along strategies made possible by CDS that have demonstrated value in improving blood utilization by promoting restrictive transfusion practices. Am. J. Hematol. 90:927-933, 2015. © 2015 Wiley Periodicals, Inc.

  View details for DOI 10.1002/ajh.24101

  View details for PubMedID 26113442

• Transfusions for anemia in adult and pediatric patients with malignancies. Blood reviews Shah, N., Andrews, J., Goodnough, L. T. 2015; 29 (5): 291-299

  Abstract

  Anemia is present in over two-thirds of patients with malignant hematological disorders. The etiology of anemia predominates from ineffective erythropoiesis from marrow infiltration, cytokine related suppression, erythropoietin suppression, and vitamin deficiency; ineffective erythropoiesis is further exacerbated by accelerated clearance due to antibody mediated hemolysis and thrombotic microangiopathy. As the anemia is chronic in nature, symptoms are generally well tolerated and often non-specific. Transfusion of red blood cells (RBCs) is a balance between providing benefit for patients while avoiding risks of transfusion. Conservative/restrictive RBC transfusion practices have shown equivalent patient outcomes compared to liberal transfusion practices, and meta-analysis has shown improved in-hospital mortality, reduced cardiac events, re-bleeding, and bacterial infections. The implications for a lower threshold for transfusion in patients with malignancies are therefore increasingly being scrutinized. Alternative management strategies for anemia with IV iron and erythropoietin stimulating agents (ESAs) should be considered in the appropriate settings.

  View details for DOI 10.1016/j.blre.2015.02.001

  View details for PubMedID 25796130

• Transfusion and coagulation management in major obstetric hemorrhage CURRENT OPINION IN ANESTHESIOLOGY Butwick, A. J., Goodnough, L. T. 2015; 28 (3): 275-284

  Abstract

  Major obstetric hemorrhage is a leading cause of maternal morbidity and mortality. We will review transfusion strategies and the value of monitoring the maternal coagulation profile during severe obstetric hemorrhage.Epidemiologic studies indicate that rates of severe postpartum hemorrhage (PPH) in well resourced countries are increasing. Despite these increases, rates of transfusion in obstetrics are low (0.9-2.3%), and investigators have questioned whether a predelivery 'type and screen' is cost-effective for all obstetric patients. Instead, blood ordering protocols specific to obstetric patients can reduce unnecessary antibody testing. When severe PPH occurs, a massive transfusion protocol has attracted interest as a key therapeutic resource by ensuring sustained availability of blood products to the labor and delivery unit. During early postpartum bleeding, recent studies have shown that hypofibrinogenemia is an important predictor for the later development of severe PPH. Point-of-care technologies, such as thromboelastography and rotational thromboelastometry, can identify decreased fibrin clot quality during PPH, which correlate with low fibrinogen levels.A massive transfusion protocol provides a key resource in the management of severe PPH. However, future studies are needed to assess whether formula-driven vs. goal-directed transfusion therapy improves maternal outcomes in women with severe PPH.

  View details for DOI 10.1097/ACO.0000000000000180

  View details for PubMedID 25812005

• Iron Deficiency Anemia in Women: A Practical Guide to Detection, Diagnosis, and Treatment OBSTETRICAL & GYNECOLOGICAL SURVEY Friedman, A. J., Shander, A., Martin, S. R., Calabrese, R. K., Ashton, M. E., Lew, I., Seid, M. H., Goodnough, L. T. 2015; 70 (5): 342-353

  Abstract

  Iron deficiency anemia (IDA) remains a widely underdiagnosed and unappreciated women's health issue, affecting women of all ages. Despite the fact that IDA is easily diagnosed and treated, it continues to be a major public health issue. The World Health Organization estimates that 30% of nonpregnant and more than 42% of pregnant women have anemia.A multidisciplinary Group for the Research and Education on Anemia Therapy in Women (GREAT Women II) was formed, sponsored by the Society for the Advancement of Blood Management. The goal was to focus attention on the impact of IDA on women at various stages of life and evaluate and use published literature to provide a simple, evidence-based approach to diagnose and treat IDA.The group developed specific recommendations for evaluating and treating IDA in women. Initial diagnosis is defined as hemoglobin less than 12 g/dL in nonpregnant women. A trial of iron therapy (4 weeks) can be considered a first-line diagnostic tool. Alternatively, a low or normal mean corpuscular volume (<100 fL), low serum ferritin (<30 μg/L), and/or low transferrin saturation (transferrin saturation <20%) is sufficient to confirm IDA. If the patient does not fit the diagnosis of IDA or fails to respond to a trial of oral iron, or mean corpuscular volume is elevated, further diagnostic evaluation is needed, including iron studies, B12, folate levels, and renal function tests. If results are not definitive, and IDA persists, a hematology referral is recommended.Clinicians should routinely identify and treat IDA, thereby decreasing its negative impact on health and quality of life of women.

  View details for PubMedID 25974731

• Dentate Gyrus Development Requires ERK Activity to Maintain Progenitor Population and MAPK Pathway Feedback Regulation JOURNAL OF NEUROSCIENCE Vithayathil, J., Pucilowska, J., Goodnough, L., Atit, R. P., Landreth, G. E. 2015; 35 (17): 6836-6848

  Abstract

  The ERK/MAPK pathway is an important developmental signaling pathway. Mutations in upstream elements of this pathway result in neuro-cardio-facial cutaneous (NCFC) syndromes, which are typified by impaired neurocognitive abilities that are reliant upon hippocampal function. The role of ERK signaling during hippocampal development has not been examined and may provide critical insight into the cause of hippocampal dysfunction in NCFC syndromes. In this study, we have generated ERK1 and conditional ERK2 compound knock-out mice to determine the role of ERK signaling during development of the hippocampal dentate gyrus. We found that loss of both ERK1 and ERK2 resulted in 60% fewer granule cells and near complete absence of neural progenitor pools in the postnatal dentate gyrus. Loss of ERK1/2 impaired maintenance of neural progenitors as they migrate from the dentate ventricular zone to the dentate gyrus proper, resulting in premature depletion of neural progenitor cells beginning at E16.5, which prevented generation of granule cells later in development. Finally, loss of ERK2 alone does not impair development of the dentate gyrus as animals expressing only ERK1 developed a normal hippocampus. These findings establish that ERK signaling regulates maintenance of progenitor cells required for development of the dentate gyrus.

  View details for DOI 10.1523/JNEUROSCI.4196-14.2015

  View details for Web of Science ID 000353647600018

  View details for PubMedID 25926459

  View details for PubMedCentralID PMC4412899

• Infusion pump-mediated mechanical hemolysis in pediatric patients. Annals of clinical and laboratory science Hughes, J., McNaughton, J., Andrews, J., George, T., Bergero, C., Pyke-Grimm, K., Galel, S. A., Gonzalez, C., Goodnough, L. T., Fontaine, M. J. 2015; 45 (2): 140-147

  Abstract

  Hemoglobinuria was observed after packed red blood cell transfusion in a series of patients at our pediatric treatment center. Laboratory testing was suggestive of intravascular hemolysis with no support for an immunohematologic process.We investigated these adverse events to define a quality improvement plan and to prevent future hemolytic adverse events. Multiple factors were investigated, and the only change identified was the implementation of a new infusion pump (Pump A) that replaced a previous model (Pump B).In vitro pump analyses, a retrospective review of urinalyses, and prospective urinalysis and nursing surveillances were also performed.In in vitro analysis of the pumps, irradiated units with higher hematocrit at a low flow rate through Pump A had a greater than thirty-fold increase in free hemoglobin from baseline compared to minimal free hemoglobin changes seen with Pump B. Irradiated units with a lower hematocrit had a minimal change in free hemoglobin from baseline with both Pumps A and B at either low or high flow rate. Subsequently, only units with lower hematocrits were issued for transfusion of pediatric patients, and Pump A was replaced by Pump B in the outpatient unit. Retrospective and prospective surveillances found no additional unexplained cases of gross hemoglobinuria associated with transfusion.The investigation determined that infusion of higher hematocrit units using a specific commercial pump was associated with mechanical hemolysis. The change to units with lower hematocrit through an alternative pump has been an effective corrective action to date.

  View details for PubMedID 25887866

• How I use fibrinogen replacement therapy in acquired bleeding BLOOD Levy, J. H., Goodnough, L. T. 2015; 125 (9): 1387-1393

  Abstract

  Fibrinogen is a critical protein for hemostasis and clot formation. However, transfusion guidelines have variable recommendations for maintaining fibrinogen levels in bleeding patients. An increasing number of studies support the practice of fibrinogen replacement therapy for acquired coagulopathies, and additional studies are underway. Fibrinogen therapy can be administered with cryoprecipitate or fibrinogen concentrates, and clinical practice varies according to their availability and licensing status. Fibrinogen concentrate therapy has been studied in animal models and clinical trials and supports the critical role of fibrinogen repletion in bleeding patients. Point-of-care testing will have an important role in guiding fibrinogen replacement for hemostatic therapy in clinical settings such as cardiovascular surgery, postpartum hemorrhage, and trauma. Fibrinogen therapy is an important component of a multimodal strategy for the treatment of coagulopathic bleeding.

  View details for DOI 10.1182/blood-2014-08-552000

  View details for PubMedID 25519751

• Why Providers Transfuse Blood Products Outside Recommended Guidelines in Spite of Integrated Electronic Best Practice Alerts JOURNAL OF HOSPITAL MEDICINE Chen, J. H., Fang, D. Z., Goodnough, L. T., Evans, K. H., Porter, M. L., Shieh, L. 2015; 10 (1): 1-7

  Abstract

  Best practice alerts (BPAs) provide clinical decision support (CDS) at the point of care to reduce unnecessary blood product transfusions, yet substantial transfusions continue outside of recommended guidelines.To understand why providers order blood transfusions outside of recommended guidelines despite interruptive alerts.Retrospective review.Tertiary care hospital.Inpatient healthcare providers.Provider-BPA interaction data were collected from January 2011 to August 2012 from the hospital electronic medical record.Provider (free-text) responses to blood transfusion BPA prompts were independently reviewed and categorized by 2 licensed physicians, with agreement assessed by χ(2) analysis and kappa scoring.Rationale for overriding blood transfusion BPAs was highly diverse, acute bleeding being the most common (>34%), followed by protocolized behaviors on specialty services (up to 26%), to "symptomatic" anemia (11%-12%). Many providers transfused in anticipation of surgical or procedural intervention (10%-15%) or imminent hospital discharge (2%-5%). Resident physicians represented the majority (55%) of providers interacting with BPAs.Providers interacting with BPAs (primarily residents and midlevel providers) often do not have the negotiating power to change ordering behavior. Protocolized behaviors, unlikely to be influenced by BPAs, are among the most commonly cited reasons for transfusing outside of guidelines. Symptomatic anemia is a common, albeit subjective, indication cited for blood transfusion. With a wide swath of individually uncommon rationales for transfusion behavior, secondary use of electronic medical record databases and integrated CDS tools are important to efficiently analyze common practice behaviors. Journal of Hospital Medicine 2014. © 2014 The Authors Journal of Hospital Medicine published by Wiley Periodicals, Inc. on behalf of Society of Hospital Medicine.

  View details for DOI 10.1002/jhm.2236

  View details for Web of Science ID 000347516300001

• Intravenous Iron Therapy in Patients with Iron Deficiency Anemia: Dosing Considerations. Anemia Koch, T. A., Myers, J., Goodnough, L. T. 2015; 2015: 763576-?

  Abstract

  Objective. To provide clinicians with evidence-based guidance for iron therapy dosing in patients with iron deficiency anemia (IDA), we conducted a study examining the benefits of a higher cumulative dose of intravenous (IV) iron than what is typically administered. Methods. We first individually analyzed 5 clinical studies, averaging the total iron deficit across all patients utilizing a modified Ganzoni formula; we then similarly analyzed 2 larger clinical studies. For the second of the larger studies (Study 7), we also compared the efficacy and retreatment requirements of a cumulative dose of 1500 mg ferric carboxymaltose (FCM) to 1000 mg iron sucrose (IS). Results. The average iron deficit was calculated to be 1531 mg for patients in Studies 1-5 and 1392 mg for patients in Studies 6-7. The percentage of patients who were retreated with IV iron between Days 56 and 90 was significantly (p < 0.001) lower (5.6%) in the 1500 mg group, compared to the 1000 mg group (11.1%). Conclusions. Our data suggests that a total cumulative dose of 1000 mg of IV iron may be insufficient for iron repletion in a majority of patients with IDA and a dose of 1500 mg is closer to the actual iron deficit in these patients.

  View details for DOI 10.1155/2015/763576

  View details for PubMedID 26257955

  View details for PubMedCentralID PMC4518169

• Cryoprecipitate therapy BRITISH JOURNAL OF ANAESTHESIA Nascimento, B., GOODNOUGH, L. T., Levy, J. H. 2014; 113 (6): 922-934

  Abstract

  Cryoprecipitate, originally developed as a therapy for patients with antihaemophilic factor deficiency, or haemophilia A, has been in use for almost 50 yr. However, cryoprecipitate is no longer administered according to its original purpose, and is now most commonly used to replenish fibrinogen levels in patients with acquired coagulopathy, such as in clinical settings with haemorrhage including cardiac surgery, trauma, liver transplantation (LT), or obstetric haemorrhage. Cryoprecipitate is a pooled product that does not undergo pathogen inactivation, and its administration has been associated with a number of adverse events, particularly transmission of blood-borne pathogens and transfusion-related acute lung injury. As a result of these safety concerns, along with emerging availability of alternative fibrinogen preparations, cryoprecipitate has been withdrawn from use in a number of European countries. Compared with the plasma from which it is prepared, cryoprecipitate contains a high concentration of coagulation factor VIII, coagulation factor XIII, and fibrinogen. Cryoprecipitate is usually licensed by regulatory authorities for the treatment of hypofibrinogenaemia, and recommended for supplementation when plasma fibrinogen levels decrease below 1 g litre(-1); however, this threshold is empiric and is not based on solid clinical evidence. Consequently, there is uncertainty over the appropriate dosing and optimal administration of cryoprecipitate, with some guidelines from professional societies to guide clinical practice. Randomized, controlled trials are needed to determine the clinical efficacy of cryoprecipitate, compared with the efficacy of alternative preparations. These trials will allow the development of evidence-based guidelines in order to inform physicians and guide clinical practice.

  View details for DOI 10.1093/bja/aeu158

  View details for Web of Science ID 000345822000007

  View details for PubMedID 24972790

• The Next Chapter in Patient Blood Management Real-Time Clinical Decision Support AMERICAN JOURNAL OF CLINICAL PATHOLOGY Goodnough, L. T., Shah, N. 2014; 142 (6): 741-747

  Abstract

  Blood transfusion was identified by the American Medical Association as one of the top five most frequently overused therapies. Utilization review has been required by accreditation agencies, but retrospective review has been ineffective due to labor-intense resources applied to only a sampling of transfusion events. Electronic medical records have allowed clinical decision support (CDS) to occur via a best practices alert at the critical decision point concurrently with physician order entry.We review emerging strategies for improving blood utilization.Implementation of CDS at our institution decreased the percentage of transfusions in patients with a hemoglobin level of more than 8 g/dL from 60% to less than 30%. Annual RBC transfusions were reduced by 24%, despite concurrent increases in patient discharge volumes and case mix complexity. This resulted in acquisition costs savings (direct blood product purchase costs) of $6.4 million over 4 years.We have been able to significantly reduce inappropriate blood transfusions and related costs through an educational initiative coupled with real-time CDS. In deriving increased value out of health care, CDS can be applied to a number of overuse measures in laboratory testing, radiology, and therapy such as antibiotics, as outlined by the American Board of Internal Medicine's Choosing Wisely campaign.

  View details for DOI 10.1309/AJCP4W5CCFOZUJFU

  View details for Web of Science ID 000345053900004

• Lack of dystrophin results in abnormal cerebral diffusion and perfusion in vivo NEUROIMAGE Goodnough, C. L., Gao, Y., Li, X., Qutaish, M. Q., Goodnough, L., Molter, J., Wilson, D., Flask, C. A., Yu, X. 2014; 102: 809-816

  Abstract

  Dystrophin, the main component of the dystrophin-glycoprotein complex, plays an important role in maintaining the structural integrity of cells. It is also involved in the formation of the blood-brain barrier (BBB). To elucidate the impact of dystrophin disruption in vivo, we characterized changes in cerebral perfusion and diffusion in dystrophin-deficient mice (mdx) by magnetic resonance imaging (MRI). Arterial spin labeling (ASL) and diffusion-weighted MRI (DWI) studies were performed on 2-month-old and 10-month-old mdx mice and their age-matched wild-type controls (WT). The imaging results were correlated with Evan's blue extravasation and vascular density studies. The results show that dystrophin disruption significantly decreased the mean cerebral diffusivity in both 2-month-old (7.38 ± 0.30 × 10(-4)mm(2)/s) and 10-month-old (6.93 ± 0.53 × 10(-4)mm(2)/s) mdx mice as compared to WT (8.49 ± 0.24 × 10(-4), 8.24 ± 0.25 × 10(-4)mm(2)/s, respectively). There was also an 18% decrease in cerebral perfusion in 10-month-old mdx mice as compared to WT, which was associated with enhanced arteriogenesis. The reduction in water diffusivity in mdx mice is likely due to an increase in cerebral edema or the existence of large molecules in the extracellular space from a leaky BBB. The observation of decreased perfusion in the setting of enhanced arteriogenesis may be caused by an increase of intracranial pressure from cerebral edema. This study demonstrates the defects in water handling at the BBB and consequently, abnormal perfusion associated with the absence of dystrophin.

  View details for DOI 10.1016/j.neuroimage.2014.08.053

  View details for Web of Science ID 000345391700054

  View details for PubMedID 25213753

  View details for PubMedCentralID PMC4320943

• Restrictive blood transfusion practices are associated with improved patient outcomes TRANSFUSION Goodnough, L. T., Maggio, P., Hadhazy, E., Shieh, L., Hernandez-Boussard, T., Khari, P., Shah, N. 2014; 54 (10): 2753-2759

  Abstract

  Blood transfusion has been cited as one of the five most overutilized therapeutic procedures in the United States. We assessed the impact of clinical decision support at computerized physician order entry and education on red blood cell (RBC) transfusions and clinical patient outcomes at our institution.Clinical patient outcomes and RBC transfusions were assessed before and after implementation of a best practice alert triggered for transfusions when the hemoglobin level was higher than 7 g/dL for all inpatient discharges from January 2008 through December 2013. Retrospective clinical and laboratory data related to RBC transfusions were extracted: case-mix complexity, patient discharges and selected surgical volumes, and patient outcomes (mortality, 30-day readmissions, length of stay).There was a significant improvement in RBC utilization as assessed by RBC units transfused per 100 patient-days-at-risk. Concurrently, hospital-wide clinical patient outcomes showed improvement (mortality, p = 0.034; length of stay, p = 0.003) or remained stable (30-day readmission rates, p = 0.909). Outcome improvements were even more pronounced in patients who received blood transfusions, with decreased mortality rate (55.2 to 33.0, p < 0.001), length of stay (mean, 10.1 to 6.2 days, p < 0.001), and 30-day readmission rate (136.9 to 85.0, p < 0.001). The mean number of units transfused per patient also declined (3.6 to 2.7, p < 0.001). Acquisition costs of RBC units per 1000 patient discharges decreased from $283,130 in 2009 to $205,050 in 2013 with total estimated savings of $6.4 million and likely far greater impact on total transfusion-related costs.Improved blood utilization is associated with improved clinical patient outcomes.

  View details for DOI 10.1111/trf.12723

  View details for Web of Science ID 000343821100023

• Blood utilization and hemoglobin levels in cancer patients after label and coverage changes for erythropoiesis-stimulating agents EXPERT REVIEW OF HEMATOLOGY Xu, H., Kaye, J. A., Saltus, C. W., Crawford, J., Gasal, E., Goodnough, L. T. 2014; 7 (5): 617-633

  Abstract

  A comprehensive literature search was performed to examine the influence of changes in erythropoietin-stimulating agent (ESA) label and reimbursement policies on utilization of red blood cell transfusions and patient hemoglobin levels in US cancer patients receiving chemotherapy or anemia management. Studies conducted in ESA-treated patients showed an increase in transfusion rates when comparing the post-intervention period with pre-intervention period (range of relative change: 15-125%). Results from studies conducted in patients receiving chemotherapy irrespective of anemia treatment were variable; single-institution-based studies tended to show a decrease in transfusion rates (range of relative change: -3.2 to -24.1%), while multiple-institution-based studies suggested an increase in transfusion rates (range of relative change: 12-182%). Studies showed decreases in hemoglobin levels during chemotherapy or at ESA initiation, and decreased ESA utilization.

  View details for DOI 10.1586/17474086.2014.943730

  View details for Web of Science ID 000342203200010

  View details for PubMedID 25081548

• Case report of a transfusion-associated hepatitis A infection TRANSFUSION Hughes, J. A., Fontaine, M. J., Gonzalez, C. L., Layon, A. G., Goodnough, L. T., Galel, S. A. 2014; 54 (9): 2202-2206

  Abstract

  Documented transfusion-associated hepatitis A (TAHA) is rare, and blood donors in the United States are not routinely screened for this infection. We report a case of TAHA associated with a donation made 8 days after a donor returned from a trip to South America.This is a review of donor and recipient records and a review of the literature.A donor developed symptoms of hepatitis 20 days after donation (28 days after returning from South America). The donor reported the illness 56 days after donation when contacted to schedule another visit. By this time, the red blood cell and frozen plasma components had been transfused. The recipient of the plasma, a 15-month-old female, tested positive for immunoglobulin M antibody to hepatitis A virus 43 days after transfusion. The recipient had displayed mild, nonspecific symptoms approximately 2 weeks after transfusion. Hospital infection control investigated the potential for further spread within the hospital because the recipient had been an inpatient for most of the posttransfusion period. The risk of transmission to other patients was determined to be negligible because the patient had been in isolation for other reasons. Family members, who included a health care professional, were counseled and offered prophylaxis.TAHA may be underrecognized. This case was identified only because of a donor report at the time of recruitment. Asymptomatic donor viremia has been documented in plasma donors. Although TAHA rarely results in severe disease, the risk it creates of secondary transmission especially within the hospital setting is not inconsequential.

  View details for DOI 10.1111/trf.12648

  View details for Web of Science ID 000342141300011

• The scientific basis for patient blood management TRANSFUSION CLINIQUE ET BIOLOGIQUE Murphy, M. F., GOODNOUGH, L. T. 2014; 22 (3): 90-96

  View details for DOI 10.1016/j.tracli.2015.04.001

  View details for Web of Science ID 000361270700003

• Iron Deficiency Anemia-Bridging the Knowledge and Practice Gap TRANSFUSION MEDICINE REVIEWS Shander, A., Goodnough, L. T., Javidroozi, M., Auerbach, M., Carson, J., Ershler, W. B., Ghiglione, M., Glaspy, J., Lew, I. 2014; 28 (3): 156-166

  Abstract

  Despite its high prevalence, anemia often does not receive proper clinical attention, and detection, evaluation, and management of iron deficiency anemia and iron-restricted erythropoiesis can possibly be an unmet medical need. A multidisciplinary panel of clinicians with expertise in anemia management convened and reviewed recent published data on prevalence, etiology, and health implications of anemia as well as current therapeutic options and available guidelines on management of anemia across various patient populations and made recommendations on the detection, diagnostic approach, and management of anemia. The available evidence confirms that the prevalence of anemia is high across all populations, especially in hospitalized patients. Anemia is associated with worse clinical outcomes including longer length of hospital stay, diminished quality of life, and increased risk of morbidity and mortality, and it is a modifiable risk factor of allogeneic blood transfusion with its own inherent risks. Iron deficiency is usually present in anemic patients. An algorithm for detection and management of anemia was discussed, which incorporated iron study (with primary emphasis on transferrin saturation), serum creatinine and glomerular filtration rate, and vitamin B12 and folic acid measurements. Management strategies included iron therapy (oral or intravenous), erythropoiesis-stimulating agents, and referral as needed.

  View details for DOI 10.1016/j.tmrv.2014.05.001

  View details for PubMedID 24931617

• Perioperative and transfusion outcomes in women undergoing cesarean hysterectomy for abnormal placentation. Transfusion Brookfield, K. F., Goodnough, L. T., Lyell, D. J., Butwick, A. J. 2014; 54 (6): 1530-1536

  Abstract

  Women with placenta increta (PI) and placenta percreta (PP) are at high risk of obstetric hemorrhage; however, the severity of hemorrhage and perioperative morbidity may differ according to the degree of placental invasion. We sought to compare blood component usage and perioperative morbidity between women with PI versus PP undergoing cesarean hysterectomy (CH).We identified 77 women who underwent CH for PI or PP from the NICHD MFMU Network Cesarean Registry, which sourced data from 19 centers from 1999 to 2002. We examined demographic, obstetric, and surgical data and rates of transfusion and perioperative morbidity. We performed statistical tests for between-group analyses; p values less than 0.05 were significant.Rates of intraoperative or postoperative red blood cell (RBC) transfusion were similar between groups (PI 84% vs. PP 88%; p = 0.7). We observed no between-group differences in rates of fresh-frozen plasma (FFP) transfusion (intraoperative FFP-PI 30% vs. PP 41%; p = 0.3; postoperative FFP-PI 28% vs. PP 18%; p = 0.4) or platelet (PLT) transfusion (intraoperative PLTs-PI 14% vs. PP 29%; p = 0.2; postoperative PLTs-PI 9% vs. PP 9%; p = 1.0). Among the morbidities, a higher proportion of PP women underwent cystotomy (PI 14% vs. PP 38%; p = 0.02) and postoperative mechanical ventilation (PI 14% vs. PP 35%; p = 0.03).Rates of intraoperative RBC, FFP, and PLT transfusion are similar for PI and PP women, and perioperative outcomes are worse for PP women. We suggest the same mobilization transfusion medicine support for both groups, including blood ordering (type and cross-match for CH) and availability of emergency blood protocols including fibrinogen-containing preparations.

  View details for DOI 10.1111/trf.12483

  View details for PubMedID 24188691

• Improved blood utilization using real-time clinical decision support. Transfusion Goodnough, L. T., Shieh, L., Hadhazy, E., Cheng, N., Khari, P., Maggio, P. 2014; 54 (5): 1358-1365

  Abstract

  We analyzed blood utilization at Stanford Hospital and Clinics after implementing real-time clinical decision support (CDS) and best practice alerts (BPAs) into physician order entry (POE) for blood transfusions.A clinical effectiveness (CE) team developed consensus with a suggested transfusion threshold of a hemoglobin (Hb) level of 7 g/dL, or 8 g/dL for patients with acute coronary syndromes. The CDS was implemented in July 2010 and consisted of an interruptive BPA at POE, a link to relevant literature, and an "acknowledgment reason" for the blood order.The percentage of blood ordered for patients whose most recent Hb level exceeded 8 g/dL ranged at baseline from 57% to 66%; from the education intervention by the CE team August 2009 to July 2010, the percentage decreased to a range of 52% to 56% (p = 0.01); and after implementation of CDS and BPA, by end of December 2010 the percentage of patients transfused outside the guidelines decreased to 35% (p = 0.02) and has subsequently remained below 30%. For the most recent interval, only 27% (767 of 2890) of transfusions occurred in patients outside guidelines. Comparing 2009 to 2012, despite an increase in annual case mix index from 1.952 to 2.026, total red blood cell (RBC) transfusions decreased by 7186 units, or 24%. The estimated net savings for RBC units (at $225/unit) in purchase costs for 2012 compared to 2009 was $1,616,750.Real-time CDS has significantly improved blood utilization. This system of concurrent review can be used by health care institutions, quality departments, and transfusion services to reduce blood transfusions.

  View details for DOI 10.1111/trf.12445

  View details for PubMedID 24117533

• Fibrinogen as a therapeutic target for bleeding: a review of critical levels and replacement therapy TRANSFUSION Levy, J. H., Welsby, I., Goodnough, L. T. 2014; 54 (5): 1389-1405

  Abstract

  Fibrinogen plays a critical role in achieving and maintaining hemostasis and is fundamental to effective clot formation. There is increasing awareness of the important role of fibrinogen as a key target for the treatment and prevention of acquired bleeding. Fibrinogen is the first coagulation factor to fall to critically low levels (<1.0 g/L) during major hemorrhage (normal plasma fibrinogen levels range from 2.0 to 4.5 g/L), and current guidelines recommend maintaining the plasma fibrinogen level above 1.5 g/L. Fibrinogen supplementation can be achieved using plasma or cryoprecipitate; however, there are a number of safety concerns associated with these allogeneic blood products and there is a lack of high-quality evidence to support their use. Additionally, there is sometimes a long delay associated with the preparation of frozen products for infusion. Fibrinogen concentrate provides a promising alternative to allogeneic blood products and has a number of advantages: it allows a standardized dose of fibrinogen to be rapidly administered in a small volume, has a very good safety profile, and is virally inactivated as standard. Administration of fibrinogen concentrate, often guided by point-of-care viscoelastic testing to allow individualized dosing, has been successfully used as hemostatic therapy in a range of clinical settings, including cardiovascular surgery, postpartum hemorrhage, and trauma. Results show that fibrinogen concentrate is associated with a reduction or even total avoidance of allogeneic blood product transfusion. Fibrinogen concentrate represents an important option for the treatment of coagulopathic bleeding; further studies are needed to determine precise dosing strategies and thresholds for fibrinogen supplementation.

  View details for DOI 10.1111/trf.12431

  View details for Web of Science ID 000335634700028

  View details for PubMedID 24117955

• Ferric carboxymaltose in patients with iron-deficiency anemia and impaired renal function: the REPAIR-IDA trial NEPHROLOGY DIALYSIS TRANSPLANTATION Onken, J. E., Bregman, D. B., Harrington, R. A., Morris, D., Buerkert, J., Hamerski, D., Iftikhar, H., Mangoo-Karim, R., Martin, E. R., Martinez, C. O., Newman, G. E., Qunibi, W. Y., Ross, D. L., Singh, B., Smith, M. T., Butcher, A., Koch, T. A., Goodnough, L. T. 2014; 29 (4): 833-842

  Abstract

  Iron-deficiency anemia in non-dialysis-dependent chronic kidney disease (NDD-CKD) frequently requires parenteral iron replacement, but existing therapies often require multiple administrations. We evaluated the efficacy and cardiovascular safety of ferric carboxymaltose (FCM), a non-dextran parenteral iron permitting large single-dose infusions, versus iron sucrose in patients with iron-deficiency anemia and NDD-CKD.A total of 2584 participants were randomized to two doses of FCM 750 mg in one week, or iron sucrose 200 mg administered in up to five infusions in 14 days. The primary efficacy endpoint was the mean change to highest hemoglobin from baseline to Day 56. The primary composite safety endpoint included all-cause mortality, nonfatal myocardial infarction, nonfatal stroke, unstable angina, congestive heart failure, arrhythmias and hyper- and hypotensive events.The mean hemoglobin increase was 1.13 g/dL in the FCM group and 0.92 g/dL in the iron sucrose group (95% CI, 0.13-0.28). Similar results were observed across all subgroups, except Stage 2 CKD. More subjects in the FCM group achieved a hemoglobin increase of ≥ 1.0 g/dL between baseline and Day 56 (48.6 versus 41.0%; 95% CI, 3.6-11.6%). There was no significant difference between FCM and iron sucrose recipients with respect to the primary composite safety endpoint, including the major adverse cardiac events of death, myocardial infarction, or stroke. A significant difference in the number of protocol-defined, predominantly transient hypertensive episodes was observed in the FCM group.Two 750-mg infusions of FCM are a safe and effective alternative to multiple lower dose iron sucrose infusions in NDD-CKD patients with iron-deficiency anemia.

  View details for DOI 10.1093/ndt/gft251

  View details for Web of Science ID 000336093700020

  View details for PubMedID 23963731

• Experience with intravenous ferric carboxymaltose in patients with iron deficiency anemia. Therapeutic advances in hematology Bregman, D. B., Goodnough, L. T. 2014; 5 (2): 48-60

  Abstract

  Erythropoiesis may be limited by absolute or functional iron deficiency or when chronic inflammatory conditions lead to iron sequestration. Intravenous iron may be indicated when oral iron cannot address the deficiency. Ferric carboxymaltose (FCM) is a nondextran iron preparation recently approved in the United States for intravenous treatment of iron deficiency anemia (IDA) in adult patients with intolerance or unsatisfactory response to oral iron or with nondialysis-dependent chronic kidney disease. The full dose is two administrations of up to 750 mg separated by at least 7 days (up to 1500 mg total). FCM can be injected in 7-8 min or diluted in saline for slower infusion. The efficacy and safety of this dose was established in two prospective trials that randomized over 3500 subjects, 1775 of whom received FCM. One trial showed similar efficacy of FCM to an approved intravenous iron regimen (1000 mg of iron sucrose) in 2500 subjects with chronic kidney disease and additional cardiovascular risk factors. The other trial showed superior efficacy of FCM to oral iron in subjects with IDA due to various etiologies (e.g. gastrointestinal or uterine bleeding). In these trials, there was no significant difference between FCM and comparator with respect to an independently adjudicated composite safety endpoint, including death, myocardial infarction, or stroke. A database of 5799 subjects exposed to FCM provided a safety profile acceptable for regulatory approval. Mechanistic studies demonstrated that the transient, asymptomatic reduction in serum phosphate observed following FCM administration results from induction of fibroblast growth factor 23, which in turn induces renal phosphate excretion. An elevated hepcidin level may identify patients with IDA who will not respond to oral iron but will respond to FCM. The ability to administer FCM in two rapid injections or infusions will likely be viewed favorably by patients and healthcare providers.

  View details for DOI 10.1177/2040620714521127

  View details for PubMedID 24688754

• Open aortic valve replacement in a patient with Glanzmann's thrombasthenia: a multidisciplinary strategy to minimize perioperative bleeding. Transfusion Sheikh, A. Y., Hill, C. C., Goodnough, L. T., Leung, L. L., Fischbein, M. P. 2014; 54 (2): 300-305

  Abstract

  BACKGROUND: Glanzmann thrombasthenia (GT) is an autosomal recessive disorder in which the platelet (PLT) glycoprotein IIb/IIIa complex is either deficient or dysfunctional. In its most severe form, GT may result in spontaneous bleeding, although most cases are first detected in the setting of an invasive procedure. CASE REPORT: A 59-year-old male with Type I GT and a history of transfusion reactions to PLT infusions developed severe aortic stenosis secondary to bicuspid valve disease. He successfully underwent open aortic valve replacement with cardiopulmonary bypass without perioperative bleeding complications. RESULTS: A multidisciplinary team (anesthesia, hematology, cardiac surgery, and transfusion medicine) was established to optimize perioperative hematologic management. Bleeding risk was assessed given the patient's prior history and a dosing timeline for administration of blood products and recombinant clotting factors was established. Successful management was achieved during the operation by prophylactic administration of HLA-matched PLTs and Factor VIIa. Prophylactic PLT administration was continued through the immediate postoperative period and no bleeding complications occurred. Thromboelastograms (TEGs) were used in conjunction with traditional hematologic laboratory analysis to optimize clinical management. CONCLUSION: Patients with GT requiring cardiac surgical procedures are at high risk for perioperative bleeding complications. This case report illustrates the importance of multidisciplinary planning, TEG analysis, and the judicious use of recombinant factors to minimize operative bleeding risk.

  View details for DOI 10.1111/trf.12275

  View details for PubMedID 23710629

• Distinct Requirements for Cranial Ectoderm and Mesenchyme-Derived Wnts in Specification and Differentiation of Osteoblast and Dermal Progenitors PLOS GENETICS Goodnough, L., DiNuoscio, G. J., Ferguson, J. W., Williams, T., Lang, R. A., Atit, R. P. 2014; 10 (2): e1004152

  Abstract

  The cranial bones and dermis differentiate from mesenchyme beneath the surface ectoderm. Fate selection in cranial mesenchyme requires the canonical Wnt effector molecule β-catenin, but the relative contribution of Wnt ligand sources in this process remains unknown. Here we show Wnt ligands are expressed in cranial surface ectoderm and underlying supraorbital mesenchyme during dermal and osteoblast fate selection. Using conditional genetics, we eliminate secretion of all Wnt ligands from cranial surface ectoderm or undifferentiated mesenchyme, to uncover distinct roles for ectoderm- and mesenchyme-derived Wnts. Ectoderm Wnt ligands induce osteoblast and dermal fibroblast progenitor specification while initiating expression of a subset of mesenchymal Wnts. Mesenchyme Wnt ligands are subsequently essential during differentiation of dermal and osteoblast progenitors. Finally, ectoderm-derived Wnt ligands provide an inductive cue to the cranial mesenchyme for the fate selection of dermal fibroblast and osteoblast lineages. Thus two sources of Wnt ligands perform distinct functions during osteoblast and dermal fibroblast formation.

  View details for DOI 10.1371/journal.pgen.1004152

  View details for Web of Science ID 000332021500027

  View details for PubMedID 24586192

  View details for PubMedCentralID PMC3930509

• A multicenter, randomized, active-controlled study to investigate the efficacy and safety of intravenous ferric carboxymaltose in patients with iron deficiency anemia TRANSFUSION Onken, J. E., Bregman, D. B., Harrington, R. A., Morris, D., Acs, P., Akright, B., Barish, C., Bhaskar, B. S., Smith-Nguyen, G. N., Butcher, A., Koch, T. A., Goodnough, L. T. 2014; 54 (2): 306-315

  Abstract

  BACKGROUND: Many patients receiving oral iron for iron deficiency anemia (IDA) cannot tolerate or fail to respond to therapy, and existing intravenous (IV) iron formulations often require repeated administrations. Ferric carboxymaltose (FCM), a nondextran IV formulation, permits larger single doses. STUDY DESIGN AND METHODS: We evaluated FCM versus oral iron in IDA patients. After 14 days of oral iron, 507 participants responding inadequately to oral iron (hemoglobin [Hb] increase <1 g/dL; Cohort 1) were assigned to Group A (two doses of FCM, 750 mg, 1 week apart) or Group B (oral iron, 325 mg, 3 × day for 14 additional days). Also, 504 subjects not appropriate for oral iron (Cohort 2) were assigned to Group C (FCM as above) or Group D (standard-of-care IV iron). The primary efficacy endpoint was change to highest observed Hb from baseline to Day 35. The composite safety endpoint included all-cause mortality, nonfatal myocardial infarction, nonfatal stroke, unstable angina, heart failure, arrhythmias, and hyper- or hypotensive events. RESULTS: Mean (± standard deviation [SD]) Hb increase was significantly greater in Group A-FCM than Group B-oral iron: 1.57 (±1.19) g/dL versus 0.80 (±0.80) g/dL (p = 0.001). Post hoc comparison of Group C-FCM and Group D-IV standard of care also demonstrated significant mean (±SD) increase in Hb from baseline to highest value by Day 35 in Group C versus Group D: 2.90 (±1.64) g/dL versus 2.16 (±1.25) g/dL (p = 0.001). Safety endpoints occurred in 17 of 499 (3.4%) participants receiving FCM versus 16 of 498 (3.2%) in comparator groups. CONCLUSION: Two 750-mg FCM infusions are safe and superior to oral iron in increasing Hb levels in IDA patients with inadequate oral iron response.

  View details for DOI 10.1111/trf.12289

  View details for PubMedID 23772856

• Successful treatment of recurrent hyperhemolysis syndrome with immunosuppression and plasma-to-red blood cell exchange transfusion TRANSFUSION Uhlmann, E. J., Shenoy, S., Goodnough, L. T. 2014; 54 (2): 384-388

  Abstract

  BACKGROUND: Hyperhemolysis syndrome is a serious transfusion reaction mostly reported in association with sickle cell disease, characterized by destruction of both donor and host red blood cells (RBCs) by an unknown mechanism. CASE REPORT: A 21-year-old man with sickle cell disease and multiple prior transfusions received two phenotype-matched, compatible RBC units during a brief admission for pain crisis. He developed rapid-onset progressive anemia and hemoglobinuria. Methylprednisolone, erythropoietin, and rituximab were administered. Fifteen days posttransfusion the hemoglobin (Hb) concentration decreased to 3.1 g/dL, with evidence of severe congestive heart failure. No new antibodies were identified. It was felt that his heart failure would not improve without increasing oxygen-carrying capacity. A combination of volume overload, anemia, and hemolysis prompted a novel isovolemic procedure to increase Hb level without removing his own RBCs or causing fluid overload. A cell separator was used operating on the plasma-exchange program, with three cross-match-compatible, washed RBC units as the replacement fluid. After the procedure, there was no evidence of hemolysis. Over the following 6 days, the congestive heart failure resolved, the Hb concentration increased to 7.5 g/dL, and the patient fully recovered. He had a similar event 3 years previously. CONCLUSIONS: Plasma-to-RBC replacement may be beneficial for selected patients with life-threatening anemia. This intervention provides immediate improvement in oxygen-carrying capacity, conserving the patient's own RBCs, while avoiding fluid overload. Although blood transfusion may precipitate further hemolysis, this case report describes successful plasma-to-RBC exchange transfusion with concurrent supportive care to offset hemolysis, including corticosteroid, intravenous immunoglobulin, and rituximab.

  View details for DOI 10.1111/trf.12258

  View details for PubMedID 23692505

• Evaluation and management of anemia in the elderly AMERICAN JOURNAL OF HEMATOLOGY Goodnough, L. T., Schrier, S. L. 2014; 89 (1): 88-96

  Abstract

  Anemia is now recognized as a risk factor for a number of adverse outcomes in the elderly, including hospitalization, morbidity, and mortality. What constitutes appropriate evaluation and management for an elderly patient with anemia, and when to initiate a referral to a hematologist, are significant issues. Attempts to identify suggested hemoglobin levels for blood transfusion therapy have been confounded for elderly patients with their co-morbidities. Since no specific recommended hemoglobin threshold has stood the test of time, prudent transfusion practices to maintain hemoglobin thresholds of 9-10 g/dL in the elderly are indicated, unless or until evidence emerges to indicate otherwise. Am. J. Hematol. 89:88-96, 2014. © 2013 Wiley Periodicals, Inc.

  View details for DOI 10.1002/ajh.23598

  View details for PubMedID 24122955

• Alternatives to blood transfusion LANCET Spahn, D. R., Goodnough, L. T. 2013; 381 (9880): 1855-1865

  Abstract

  The use of alternatives to allogeneic blood continues to rest on the principles that blood transfusions have inherent risks, associated costs, and affect the blood inventory available for health-care delivery. Increasing evidence exists of a fall in the use of blood because of associated costs and adverse outcomes, and suggests that the challenge for the use of alternatives to blood components will similarly be driven by costs and patient outcomes. Additionally, the risk-benefit profiles of alternatives to blood transfusion such as autologous blood procurement, erythropoiesis-stimulating agents, and haemostatic agents are under investigation. Nevertheless, the inherent risks of blood, along with the continued rise in blood costs are likely to favour the continued development and use of alternatives to blood transfusion. We summarise the current roles of alternatives to blood in the management of medical and surgical anaemias.

  View details for Web of Science ID 000319443700032

  View details for PubMedID 23706802

• Concepts of blood transfusion in adults. Lancet Goodnough, L. T., Levy, J. H., Murphy, M. F. 2013; 381 (9880): 1845-1854

  Abstract

  Recent progress has been made in the identification and implementation of best transfusion practices on the basis of evidence-based clinical trials, published clinical practice guidelines, and process improvements for blood use and clinical patient outcomes. However, substantial variability persists in transfusion outcomes for patients in some clinical settings--eg, patients undergoing cardiothoracic surgery. This variability could be the result of insufficient understanding of published guidelines; different recommendations of medical societies, including the specification of a haemoglobin concentration threshold to use as a transfusion trigger; the value of haemoglobin as a surrogate indicator for transfusion benefit, even though only changes in concentration and not absolute red cell mass of haemoglobin can be identified; and disagreement about the validity of the level 1 evidence for clinical practice guidelines. Nevertheless, institutional experience and national databases suggest that a restrictive blood transfusion approach is being increasingly implemented as best practice.

  View details for DOI 10.1016/S0140-6736(13)60650-9

  View details for PubMedID 23706801

• Transfusion outcomes in patients undergoing coronary artery bypass grafting treated with prasugrel or clopidogrel: TRITON-TIMI 38 retrospective data analysis JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Goodnough, L. T., Smith, P. K., Levy, J. H., Poston, R. S., Short, M. A., Weerakkody, G. J., LeNarz, L. A. 2013; 145 (4): 1077-?

  Abstract

  Coronary artery bypass grafting-related bleeding and associated transfusion is a concern with dual antiplatelet therapy in patients with acute coronary syndromes. The objective of the present study was to characterize a potential risk-adjusted difference in transfusion requirements between prasugrel and clopidogrel cohorts.The data from 422 patients undergoing isolated coronary artery bypass grafting from the TRial to assess Improvement in Therapeutic Outcomes by optimizing platelet InhibitioN with prasugrel Thrombolysis In Myocardial Infarction 38 were analyzed retrospectively.We found no difference in baseline transfusion risk scores between cohorts. As predicted, the number of units of red blood cells transfused perioperatively correlated with the transfusion risk score (P < .0001). Overall, the 12-hour chest tube drainage volumes and platelet transfusion rates in the prasugrel cohort were significantly greater. However, no statistically significant differences were found in the number of red blood cell transfusions, total hemostatic components transfused, or total blood donor exposure. A significantly greater number of platelet units were transfused postoperatively in the prasugrel patients who underwent surgery within 5 days or less after withdrawal of drug. In an analysis adjusted for the predicted risk of mortality, total donor exposure was not associated with increased mortality.The use of prasugrel compared with clopidogrel was associated with greater 12-hour chest tube drainage volumes and platelet transfusion rates but without any significant differences in red blood cell transfusions, total hemostatic components transfused, or total blood donor exposure.

  View details for DOI 10.1016/j.jtcvs.2012.07.059

  View details for PubMedID 22995726

• Logistics of transfusion support for patients with massive hemorrhage CURRENT OPINION IN ANESTHESIOLOGY Goodnough, L. T., Spain, D. A., Maggio, P. 2013; 26 (2): 208-214

  Abstract

  Traditionally, trauma resuscitation protocols have advocated sequential administration of therapeutic components, beginning with crystalloid solutions infused to replace lost intravascular volume. However, rapid restoration of the components of blood is essential for ensuring adequate tissue perfusion and for preventing acidosis, coagulopathy, and hypothermia, referred to as the 'lethal triad' in trauma settings. The review summarizes practical approaches for transfusion support of patients with massive hemorrhage.Massive transfusion protocols for blood transfusion support are reviewed, including practical considerations from our own. We maintain an inventory of thawed, previously frozen plasma (four units each of blood group O and A), which can be issued immediately for patients in whom the blood type is known. As frozen plasma requires 45 min to thaw, liquid AB plasma (26 day outdate) functions as an excellent alternative, particularly for patients with unknown or blood group B or AB types.Close monitoring of bleeding and coagulation in trauma patients allows goal-directed transfusions to optimize patients' coagulation, reduce exposure to blood products, and to improve patient outcomes. Future studies are needed to understand and demonstrate improved patient outcomes.

  View details for DOI 10.1097/ACO.0b013e32835d6f8f

  View details for PubMedID 23446185

• Update on erythropoiesis-stimulating agents. Best practice & research. Clinical anaesthesiology Goodnough, L. T., Shander, A. 2013; 27 (1): 121-129

  Abstract

  Erythropoiesis-stimulating agents (ESAs) have long been approved for the management of anaemia in a variety of clinical settings. Subsequently, a number of clinical trials were undertaken in which the haemoglobin end points were targeted to be maintained at normal or high-normal ranges, in an attempt to demonstrate improvements in long-term survival. For patients undergoing spine surgery, patients with cancer chemotherapy-induced anaemia and those with chronic kidney disease, adverse outcomes in these clinical trials were found, including death, thrombosis and/or cardiovascular events. Informed choice by patients for risks of ESA therapy as well as for blood transfusion should be part of the consent process for management of anaemia. Despite current regulations restricting ESA use, these agents are an effective treatment of anaemia, particularly for those who would be transfusion dependent without ESA therapy.

  View details for DOI 10.1016/j.bpa.2012.11.006

  View details for PubMedID 23590921

• Hepcidin levels predict nonresponsiveness to oral iron therapy in patients with iron deficiency anemia AMERICAN JOURNAL OF HEMATOLOGY Bregman, D. B., Morris, D., Koch, T. A., He, A., Goodnough, L. T. 2013; 88 (2): 97-101

  Abstract

  Levels of hepcidin, a major regulator of iron homeostasis, may identify patients with iron deficiency anemia (IDA) who will not respond to oral iron therapy. In this study, IDA patients underwent a 14-day trial (run-in) course of ferrous sulfate therapy. Nonresponders (Hgb increase <1 g/dL with 67% compliance rate) were randomized to IV ferric carboxymaltose (FCM; two injections of 750 mg) or further oral iron for 14 days. Screening hepcidin levels were 38.4 versus 11.3 ng/mL, P = 0.0002 in nonresponders versus responders to a trial of oral iron. Hepcidin of > 20 ng/mL, showed sensitivity of 41.3%, specificity of 84.4%, and positive predictive value of 81.6% for predicting nonresponsiveness to oral iron. PPVs for ferritin> 30 ng/mL or transferrin saturation (TSAT)>15% were 59.2 and 55%, respectively. Negative predictive values for hepcidin, ferritin, and TSAT were 46.3, 22.7, and 19.7, respectively. FCM versus oral iron showed Hgb increases of ≥ 1 gm/dL in 65.3% versus 20.8% (P < 0.0001) and Hgb increases of 1.7 ± 1.3 versus 0.6 ± 0.9 g/dL (P = 0.0025), respectively. We conclude that hepcidin predicts nonresponsiveness to oral iron in patients with IDA and is superior to TSAT or ferritin for this purpose. Nonresponse to oral iron therapy does not rule out IDA, since two-thirds of patients subsequently responded to intravenous iron.

  View details for DOI 10.1002/ajh.23354

  View details for Web of Science ID 000314149700003

  View details for PubMedID 23335357

• Current Status of Pharmacologic Therapies in Patient Blood Management ANESTHESIA AND ANALGESIA Goodnough, L. T., Shander, A. 2013; 116 (1): 15-34

  Abstract

  Patient blood management(1,2) incorporates patient-centered, evidence-based medical and surgical approaches to improve patient outcomes by relying on the patient's own (autologous) blood rather than allogeneic blood. Particular attention is paid to preemptive measures such as anemia management. The emphasis on the approaches being "patient-centered" is to distinguish them from previous approaches in transfusion medicine, which have been "product-centered" and focused on blood risks, costs, and inventory concerns rather than on patient outcomes. Patient blood management(3) structures its goals by avoiding blood transfusion(4) with effective use of alternatives to allogeneic blood transfusion.(5) These alternatives include autologous blood procurement, preoperative autologous blood donation, acute normovolemic hemodilution, and intra/postoperative red blood cell (RBC) salvage and reinfusion. Reviewed here are the available pharmacologic tools for anemia and blood management: erythropoiesis-stimulating agents (ESAs), iron therapy, hemostatic agents, and potentially, artificial oxygen carriers.

  View details for DOI 10.1213/ANE.0b013e318273f4ae

  View details for PubMedID 23223098

• Blood ordering from the operating room: turnaround time as a quality indicator TRANSFUSION McClain, C. M., Hughes, J., Andrews, J. C., Blackburn, J., Sephel, S., France, D., Viele, M., Goodnough, L. T., Young, P. P. 2013; 53 (1): 41-48

  Abstract

  Quality indicators in transfusion medicine are necessary for patient safety and customer satisfaction. The turnaround time (TAT) of issuing red blood cells (RBCs) has emerged as a quality indicator but is not an established benchmark. We examined the TAT for issuing RBCs from the blood bank to the operating rooms (ORs) at Vanderbilt University Medical Center (VUMC) and Stanford University Medical Center (SUMC).TAT was defined from time of request to when RBCs exited the blood bank. Cases eligible for analysis had completed type-and-screen results with requests for four or fewer RBC units. Patients with a positive antibody screen had serologically crossmatched units prepared and reserved for intraoperative use. We also e-mailed surveys to academic institutions to establish the current state of TAT monitoring and to anesthesiologists at VUMC to gauge the TAT expectations of the OR.The mean TATs at the two institutions were comparable (VUMC, 10 ± 3.8 min; SUMC, 14 ± 7.2 min) for orders of RBCs. The most common reasons for delayed TAT were overlapping orders, medical technologists occupied by phone calls, and oversaturation of pneumatic tube stations. Only 3 of 24 surveyed institutions actively monitored RBC TAT. Surveyed anesthesiologists (n = 7) reported an expectation for RBC TAT of 5 to 15 minutes for urgent cases. Established internal TAT policies were 15 and 20 minutes at VUMC and SUMC, respectively, for crossmatched RBC requests for patients with complete diagnostic testing.Many of the surveyed institutions do not monitor stat RBC issue TAT as a quality indicator. This study serves as a starting point for establishing a benchmark for TAT for issuing RBCs from the blood bank to ORs.

  View details for DOI 10.1111/j.1537-2995.2012.03670.x

  View details for Web of Science ID 000313348900009

  View details for PubMedID 22536922

• Twist1 mediates repression of chondrogenesis by beta-catenin to promote cranial bone progenitor specification DEVELOPMENT Goodnough, L., Chang, A. T., Treloar, C., Yang, J., Scacheri, P. C., Atit, R. P. 2012; 139 (23): 4428-4438

  Abstract

  The bones of the mammalian skull vault form through intramembranous ossification. Skull bones ossify directly, in a process regulated by β-catenin, instead of passing through a cartilage intermediate. We tested whether β-catenin is necessary for fate selection of intramembranous bone progenitors in the skull. Here, we show in mice that removal of β-catenin from skull bone progenitors results in the near complete transformation of the skull bones to cartilage, whereas constitutive β-catenin activation inhibits skull bone fate selection. β-catenin directly activated Twist1 expression in skull progenitors, conditional Twist1 deletion partially phenocopied the absence of β-catenin, and Twist1 deletion partially restored bone formation in the presence of constitutive β-catenin activation. Finally, Twist1 bound robustly to the 3'UTR of Sox9, the central initiator of chondrogenesis, suggesting that Twist1 might directly repress cartilage formation through Sox9. These findings provide insight into how β-catenin signaling via Twist1 actively suppresses the formation of cartilage and promotes intramembranous ossification in the skull.

  View details for DOI 10.1242/dev.081679

  View details for Web of Science ID 000310780300015

  View details for PubMedID 23095887

  View details for PubMedCentralID PMC3509735

• Mortality Benefit With Prasugrel in the TRITON-TIMI 38 Coronary Artery Bypass Grafting Cohort Risk-Adjusted Retrospective Data Analysis JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Smith, P. K., Goodnough, L. T., Levy, J. H., Poston, R. S., Short, M. A., Weerakkody, G. J., LeNarz, L. A. 2012; 60 (5): 388-396

  Abstract

  The objective of this study was to characterize the bleeding, transfusion, and other outcomes of patients related to the timing of prasugrel or clopidogrel withdrawal before coronary artery bypass grafting (CABG).There is little evidence to guide clinical decision making regarding the use of prasugrel in patients who may need urgent or emergency CABG. Experience with performing CABG in the presence of clopidogrel has raised concern about perioperative bleeding complications that are unresolved.A subset of the TRITON-TIMI 38 study (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel-Thrombolysis In Myocardial Infarction 38), in which patients with acute coronary syndrome were randomized to treatment with aspirin and either clopidogrel or prasugrel, underwent isolated CABG (N = 346). A supplemental case report form was designed and administered, and the data combined with the existing TRITON-TIMI 38 database. Baseline imbalances were corrected for using elements of the European System for Cardiac Operative Risk Evaluation and The Society of Thoracic Surgeons predictive algorithm.A significantly higher mean 12-h chest tube blood loss (655 ± 580 ml vs. 503 ± 378 ml; p = 0.050) was observed with prasugrel compared with clopidogrel, without significant differences in red blood cell transfusion (2.1 U vs. 1.7 U; p = 0.442) or the total donor exposure (4.4 U vs. 3.0 U; p = 0.463). All-cause mortality was significantly reduced with prasugrel (2.31%) compared with 8.67% with clopidogrel (adjusted odds ratio: 0.26; p = 0.025).Despite an increase in observed bleeding, platelet transfusion, and surgical re-exploration for bleeding, prasugrel was associated with a lower rate of death after CABG compared with clopidogrel.

  View details for DOI 10.1016/j.jacc.2012.03.030

  View details for Web of Science ID 000306694300006

  View details for PubMedID 22633653

  View details for PubMedCentralID PMC3407327

• Iron deficiency syndromes and iron-restricted erythropoiesis (CME) TRANSFUSION Goodnough, L. T. 2012; 52 (7): 1584-1592

  Abstract

  The relationships between erythropoietin (EPO), iron, and erythropoiesis and the presence of iron-restricted erythropoiesis have important implications in anemia management. Iron-restricted erythropoiesis occurs in the presence of one or more iron deficiency syndromes: absolute iron deficiency, functional iron deficiency, and/or iron sequestration. Absolute iron deficiency is a common nutritional deficiency in women's health, pediatrics, and the elderly and is therefore an important public health problem. Functional iron deficiency occurs in patients with significant EPO-mediated erythropoiesis or therapy with erythropoiesis-stimulating agents, even when storage iron is present. Iron sequestration mediated by hepcidin is an underappreciated but common cause of iron-restricted erythropoiesis in patients with chronic inflammatory disease. The challenge for treating and laboratory-based physicians is to understand the contributory role(s) of each of these syndromes, so that the potential value of emerging and innovative pharmacologic strategies can be considered as options in patient blood management.

  View details for DOI 10.1111/j.1537-2995.2011.03495.x

  View details for PubMedID 22211566

• A Reappraisal of Plasma, Prothrombin Complex Concentrates, and Recombinant Factor VIIa in Patient Blood Management CRITICAL CARE CLINICS Goodnough, L. T. 2012; 28 (3): 413-?

  Abstract

  Plasma therapy and plasma products such as prothrombin complex concentrates (PCCs), and recombinant activated factor VII (rFVIIa) are used in the setting of massive or refractory hemorrhage. Their roles have evolved because of newly emerging options, variable availability, and heterogeneity in guidelines. These factors can be attributable to lack of evidence-based support for a defined role for plasma therapy, variability in coagulation factor content among PCCs, and uncertainty regarding safety and efficacy of rFVIIa in these settings. This review summarizes these issues and provides insight regarding use of these options in management of refractory or massive bleeding.

  View details for DOI 10.1016/j.ccc.2012.04.002

  View details for PubMedID 22713615

• Postpartum hemorrhage treated with a massive transfusion protocol at a tertiary obstetric center: a retrospective study INTERNATIONAL JOURNAL OF OBSTETRIC ANESTHESIA Gutierrez, M. C., GOODNOUGH, L. T., Druzin, M., Butwick, A. J. 2012; 21 (3): 230-235

  Abstract

  A massive transfusion protocol may offer major advantages for management of postpartum hemorrhage. The etiology of postpartum hemorrhage, transfusion outcomes and laboratory indices in obstetric cases requiring the massive transfusion protocol were retrospectively evaluated in a tertiary obstetric center.We reviewed medical records of obstetric patients requiring the massive transfusion protocol over a 31-month period. Demographic, obstetric, transfusion, laboratory data and adverse maternal outcomes were abstracted.Massive transfusion protocol activation occurred in 31 patients (0.26% of deliveries): 19 patients (61%) had cesarean delivery, 10 patients (32%) had vaginal delivery, and 2 patients (7%) had dilation and evacuation. Twenty-six patients (84%) were transfused with blood products from the massive transfusion protocol. The protocol was activated within 2h of delivery for 17 patients (58%). Median [IQR] total estimated blood loss value was 2842 [800-8000]mL. Median [IQR] number of units of red blood cells, plasma and platelets from the massive transfusion protocol were: 3 [1.75-7], 3 [1.5-5.5], and 1 [0-2.5] units, respectively. Mean (SD) post-resuscitation hematologic indices were: hemoglobin 10.3 (2.4)g/dL, platelet count 126 (44)×10(9)/L, and fibrinogen 325 (125)mg/dL. The incidence of intensive care admission and peripartum hysterectomy was 61% and 19%, respectively.Our massive transfusion protocol provides early access to red blood cells, plasma and platelets for patients experiencing unanticipated or severe postpartum hemorrhage. Favorable hematologic indices were observed post resuscitation. Future outcomes-based studies are needed to compare massive transfusion protocol and non-protocol based transfusion strategies for the management of hemorrhage.

  View details for DOI 10.1016/j.ijoa.2012.03.005

  View details for Web of Science ID 000307685000005

  View details for PubMedID 22647592

• Operational, Quality, and Risk Management in the Transfusion Service: Lessons Learned TRANSFUSION MEDICINE REVIEWS Goodnough, L. T. 2012; 26 (3): 252-261

  Abstract

  For general health care, the difference between quality and safety has been unclear for measurable patient outcomes. In contrast, in the transfusion service (TS), the relationship between quality and safety has been direct and demonstrable. Case studies are summarized to illustrate the relationship between operations, quality management, and risk management in the TS. In blood availability for elective surgery over 3 audited intervals, the incidence of patients undergoing elective surgery without available crossmatched blood that had been requested was 1:333, 1:328, and 1:225 for pre-quality improvement, post-quality improvement, and subsequent postintervention audit assessment, respectively. In event discovery reports (EDRs) over 2 years, incidence of biologic product deviation reports (Food and Drug Administration reportable) was successfully reduced from 60 biologic product deviation reports (12%) of 507 EDRs in 2009 to 42 (12%) of 336 EDRs in 2010. In wrong blood in tube, 102 specimens were identified (by a change in patient's ABO/Rh) from 176,711 type and screen/cross-match specimens received over a 5-year interval, detected either by previous patient record of ABO/Rh or by a second specimen for blood type confirmation implemented in our TS for the last 3 years. No known cases of "mismatched" red blood cell transfusion have occurred during this interval. There is an inverse relationship between resources/time expended on quality and risk management relative to volumes of operations in the TS. Laboratory-based initiatives that improve patient safety and clinical outcomes need to have resources aligned with the personnel and time required for quality management and risk management.

  View details for DOI 10.1016/j.tmrv.2011.10.002

  View details for PubMedID 22138578

• Use of point-of-care testing for plasma therapy TRANSFUSION Goodnough, L. T., Hill, C. C. 2012; 52: 56S-64S

  Abstract

  Use of point-of-care testing (POCT) has been driven by limitations of laboratory-based testing as a tool for decisions for transfusions of blood components. Clinical settings such as liver transplantation, cardiothoracic surgery, and trauma are particularly in need of such diagnostic tests because of the complex coagulopathies that can develop in these settings of substantial hemorrhage and need for blood component support. Successful implementation of POCT requires collaboration between surgery, anesthesia, critical care, and the laboratory to ensure proper quality control of equipment, operator training and competency, medical records test results, billing procedures, and consensus-derived transfusion algorithms for cost-effective, targeted blood component transfusion support. In this review we summarize clinical evidence for the effectiveness of POCT, along with some future directions for this strategy.

  View details for DOI 10.1111/j.1537-2995.2012.03624.x

  View details for PubMedID 22578372

• A novel allocation strategy for blood transfusions: investigating the tradeoff between the age and availability of transfused blood TRANSFUSION Atkinson, M. P., Fontaine, M. J., Goodnough, L. T., Wein, L. M. 2012; 52 (1): 108-117

  Abstract

  Recent studies show that transfusing older blood may lead to increased mortality. This raises the issue of whether transfusing fresher blood can be achieved without jeopardizing blood availability.We propose a simple family of policies that is defined by a single threshold: rather than transfusing the oldest available blood that is younger than 42 days, we transfuse the oldest blood that is younger than the threshold, and if there is no blood younger than the threshold then we transfuse the youngest blood that is older than the threshold. To assess this policy, we build a simulation model using data from Stanford University Medical Center. We focus on the tradeoff between the mean age of transfused blood and the fraction of transfused blood that is imported.For hospitals in which the local supply is greater than demand, our policy with a threshold of 14 days leads to a decrease of 10 to 20 days in the mean age of transfused blood while increasing the fraction of imported blood to less than 0.005 (i.e., 0.5%). If the health benefits from transfusing fresher blood can be confirmed by randomized clinical trials, then conservative assumptions suggest that this policy could reduce the annual number of transfused patients who die within 1 year by 20,000.The proposed allocation policy with a threshold of 14 days could allow many US hospitals to significantly reduce the age of transfused blood, thereby possibly reducing morbidity and mortality, while having a negligible impact on supply chain operations.

  View details for DOI 10.1111/j.1537-2995.2011.03239.x

  View details for Web of Science ID 000298736000016

  View details for PubMedID 21756261

• How we treat: transfusion medicine support of obstetric services TRANSFUSION Goodnough, L. T., Daniels, K., Wong, A. E., Viele, M., Fontaine, M. F., Butwick, A. J. 2011; 51 (12): 2540-2548

  Abstract

  Obstetric services depend on the transfusion service (TS) to provide diagnostic testing and blood component therapy for clinical care pathways.We describe three quality improvement (QI) initiatives implemented to improve TS support of obstetric services.We implemented a pathway for patients requiring an ABO/Rh order for every admission to obstetric services, along with reconciliation of the daily hospital birth manifest and TS umbilical cord log to identify every woman eligible for RhIG. After assessment over 6 months, 21 (1%) of 2041 women lacked an admission ABO/Rh; all subsequently had ABO/Rh determinations. Umbilical cords were missing for eight (0.4%) mothers; four were D- and received RhIG. We developed algorithms for diagnostic blood ordering for patients deemed at "low,"moderate," or "high" risk of blood transfusion. A 27% reduction in total diagnostic test volumes and 24% reduction in charges was documented after compared to before implementation. We analyzed the impact of our massive transfusion protocol (MTP) on blood inventory management for 31 (0.25%) women undergoing 12,945 deliveries, representing 11% of 286 MTPs for all clinical services over a 32-month interval. O- uncrossmatched red blood cells (RBCs) represented 103 (24%) of 421 RBC units issued. Wastage rates of RBCs, plasma, and platelets ordered and issued in the MTPs were 0.7, 16, and 3%, respectively.QI initiatives for RhIG prophylaxis, diagnostic blood test ordering, and MTP improve TS support of obstetric services.

  View details for DOI 10.1111/j.1537-2995.2011.03152.x

  View details for PubMedID 21542850

• Complement (C1q) fixing solid-phase screening for HLA antibodies increases the availability of compatible platelet components for refractory patients TRANSFUSION Fontaine, M. J., Kuo, J., Chen, G., Galel, S. A., Miller, E., Sequeira, F., Viele, M., Goodnough, L. T., Tyan, D. B. 2011; 51 (12): 2611-2618

  Abstract

  Immune refractoriness to platelet (PLT) transfusion is primarily due to HLA antibody. Patients at our institution are identified as refractory due to HLA by a Luminex-based immunoglobulin (Ig)G-single-antigen-bead (SAB) assay, but in highly sensitized patients, antigen-negative compatible donors cannot be found due to the high sensitivity of the IgG-SAB method. We developed an assay that detects only HLA antibodies binding the first complement component (C1q). We hypothesized that the C1q-SAB method might be more relevant than the IgG-SAB method because the antibodies identified may activate the complement cascade causing PLT destruction.Thirteen highly sensitized refractory patients received 177 PLT units incompatible by the IgG-SAB method. They were retrospectively retested by the C1q-SAB method. Calculated percent reactive antibody (CPRA) and HLA antibody specificities were compared between the two methods and corrected count increment (CCI) values were analyzed. Additionally the impact of ABO compatibility on CCI responses was evaluated.The mean CPRA value was significantly lower by C1q-SAB (60%) than by IgG-SAB (94%; p < 0.05). Patients showed significantly better CCI (10.6 × 10(9) ± 0.8 × 10(9) /L) with C1q-compatible (n = 134) than with C1q-incompatible PLTs (n = 43) (2.5 × 10(9) ± 0.9 × 10(9) /L/m(2) ; p < 0.0001). ABO compatibility did not significantly impact the CCI values (p < 0.0001). Our results show that 75% of PLT units previously considered incompatible were actually compatible.For highly refractory patients to PLT transfusion, the C1q-based SAB binding assay may be a better method for identifying clinically relevant HLA antibodies and selecting PLT units that will result in acceptable CCI.

  View details for DOI 10.1111/j.1537-2995.2011.03194.x

  View details for PubMedID 21615749

• Massive Transfusion Protocols for Patients With Substantial Hemorrhage TRANSFUSION MEDICINE REVIEWS Young, P. P., Cotton, B. A., Goodnough, L. T. 2011; 25 (4): 293-303

  Abstract

  Transfusion medicine for the resuscitation of patients with massive hemorrhage has recently advanced from reactive, supportive treatment with crystalloid and red blood cell therapy to use of standardized massive transfusion protocols (MTPs). Through MTPs, medical facilities are able to standardize the most effective posthemorrhage treatments and execute them rapidly while reducing potential waste of blood products. Damage control resuscitation is an example of an MTP, where patients are (1) allowed more permissive hypotension, (2) spared large volumes of crystalloid/colloid therapy (through low volume resuscitation), and (3) transfused with blood products preemptively using a balanced ratio of plasma and platelets to red blood cells. This focused approach improves the timely availability of blood components during resuscitation. However, the use of MTPs remains controversial. This review describes published experiences with MTPs and illustrates the potential value of several MTPs currently utilized by academic transfusion services.

  View details for DOI 10.1016/j.tmrv.2011.04.002

  View details for Web of Science ID 000295186700002

  View details for PubMedID 21664104

  View details for PubMedCentralID PMC3176940

• Appropriateness of Allogeneic Red Blood Cell Transfusion: The International Consensus Conference on Transfusion Outcomes TRANSFUSION MEDICINE REVIEWS Shander, A., Fink, A., Javidroozi, M., Erhard, J., Farmer, S. L., Corwin, H., Goodnough, L. T., Hofmann, A., Isbister, J., Ozawa, S., Spahn, D. R. 2011; 25 (3): 232-246

  Abstract

  An international multidisciplinary panel of 15 experts reviewed 494 published articles and used the RAND/UCLA Appropriateness Method to determine the appropriateness of allogeneic red blood cell (RBC) transfusion based on its expected impact on outcomes of stable nonbleeding patients in 450 typical inpatient medical, surgical, or trauma scenarios. Panelists rated allogeneic RBC transfusion as appropriate in 53 of the scenarios (11.8%), inappropriate in 267 (59.3%), and uncertain in 130 (28.9%). Red blood cell transfusion was most often rated appropriate (81%) in scenarios featuring patients with hemoglobin (Hb) level 7.9 g/dL or less, associated comorbidities, and age older than 65 years. Red blood cell transfusion was rated inappropriate in all scenarios featuring patients with Hb level 10 g/dL or more and in 71.3% of scenarios featuring patients with Hb level 8 to 9.9 g/dL. Conversely, no scenario with patient's Hb level of 8 g/dL or more was rated as appropriate. Nearly one third of all scenarios were rated uncertain, indicating the need for more research. The observation that allogeneic RBC transfusions were rated as either inappropriate or uncertain in most scenarios in this study supports a more judicious transfusion strategy. In addition, the large number of scenarios in which RBC transfusions were rated as uncertain can serve as a road map to identify areas in need of further investigation.

  View details for DOI 10.1016/j.tmrv.2011.02.001

  View details for Web of Science ID 000292485200006

  View details for PubMedID 21498040

• How I treat warfarin-associated coagulopathy in patients with intracerebral hemorrhage BLOOD Goodnough, L. T., Shander, A. 2011; 117 (23): 6091-6099

  Abstract

  Intracerebral hemorrhage in patients with warfarin-associated coagulopathy is an increasingly common life-threatening condition that requires emergent management. The evolution of therapeutic options in this setting, as well as recently published guidelines, has resulted in some heterogeneity in recommendations by professional societies. This heterogeneity can be attributed to lack of evidence-based support for plasma therapy; the variability in availability of prothrombin complex concentrates; the variability in the coagulation factor levels and contents of prothrombin complex concentrates; ambiguity about the optimal dose and route of administration of vitamin K; and the lack of standardized clinical care pathways, particularly in community hospitals, for the management of these critical care patients. In this review, we summarize the relevant literature about these controversies and present recommendations for management of patients with warfarin-associated coagulopathy and intracerebral hemorrhage.

  View details for DOI 10.1182/blood-2010-11-316075

  View details for PubMedID 21411756

• 2011 Update to The Society of Thoracic Surgeons and the Society of Cardiovascular Anesthesiologists Blood Conservation Clinical Practice Guidelines ANNALS OF THORACIC SURGERY Ferraris, V. A., Brown, J. R., Despotis, G. J., Hammon, J. W., Reece, T. B., Saha, S. P., Song, H. K., Clough, E. R., Shore-Lesserson, L. J., Goodnough, L. T., Mazer, C. D., Shander, A., Stafford-Smith, M., Waters, J., Baker, R. A., Dickinson, T. A., Fitzgerald, D. J., Likosky, D. S., Shann, K. G. 2011; 91 (3): 944-982

  Abstract

  Practice guidelines reflect published literature. Because of the ever changing literature base, it is necessary to update and revise guideline recommendations from time to time. The Society of Thoracic Surgeons recommends review and possible update of previously published guidelines at least every three years. This summary is an update of the blood conservation guideline published in 2007.The search methods used in the current version differ compared to the previously published guideline. Literature searches were conducted using standardized MeSH terms from the National Library of Medicine PUBMED database list of search terms. The following terms comprised the standard baseline search terms for all topics and were connected with the logical 'OR' connector--Extracorporeal circulation (MeSH number E04.292), cardiovascular surgical procedures (MeSH number E04.100), and vascular diseases (MeSH number C14.907). Use of these broad search terms allowed specific topics to be added to the search with the logical 'AND' connector.In this 2011 guideline update, areas of major revision include: 1) management of dual anti-platelet therapy before operation, 2) use of drugs that augment red blood cell volume or limit blood loss, 3) use of blood derivatives including fresh frozen plasma, Factor XIII, leukoreduced red blood cells, platelet plasmapheresis, recombinant Factor VII, antithrombin III, and Factor IX concentrates, 4) changes in management of blood salvage, 5) use of minimally invasive procedures to limit perioperative bleeding and blood transfusion, 6) recommendations for blood conservation related to extracorporeal membrane oxygenation and cardiopulmonary perfusion, 7) use of topical hemostatic agents, and 8) new insights into the value of team interventions in blood management.Much has changed since the previously published 2007 STS blood management guidelines and this document contains new and revised recommendations.

  View details for DOI 10.1016/j.athoracsur.2010.11.078

  View details for Web of Science ID 000287697700068

  View details for PubMedID 21353044

• Quality management in the transfusion service: case studies in process improvement TRANSFUSION Goodnough, L. T., Viele, M., Fontaine, M., Chua, L., Ferrer, Z., Jurado, C., Quach, P., Dunlap, M., Arber, D. A. 2011; 51 (3): 600-609

  Abstract

  Laboratory-based quality improvement (QI) initiatives can improve clinical outcomes and patient safety.We present three cases of QI that impact processes from the transfusion service (TS) laboratory to the patient's bedside.Case 1 was event discovery reporting (EDR). We were able to reduce our biologic product deviation reports from 41 (17%) of 238 EDRs to only 19 (7%) of 272 (p < 0.01) EDRs after implementation of a QI workflow process. Case 2 was antibody evaluation before elective surgery. We implemented process improvement strategies: 1) surgical safety checklist with confirmation of type-and-screen completion and antibody evaluation before patients can proceed to surgery; 2) specimen retention policy of 30 days to allow advance testing; and 3) daily review to identify specimens needed on day of surgery. After intervention, only 7 (0.3%) of 2298 patients required antibody evaluation on day of surgery, compared to 65 (0.75%) of 8656 patients (p < 0.01) before intervention. Case 3 was wrong blood in tube (WBIT). We have a two-specimen requirement for blood type verification before transfusion. To determine whether trauma patients should be exempted, we reviewed WBIT errors. Six WBIT errors were from the emergency department (an error rate of 1:400) and nine WBIT specimens were institution-wide. Three patients were transfused after correction of the WBIT error. Based on this analysis, our institution agreed that no clinical units shall be exempted from our policy.Successful QI in the TS improves processes that promote efficiency, effectiveness, and patient safety.

  View details for DOI 10.1111/j.1537-2995.2010.02857.x

  View details for PubMedID 20738826

• Detection, evaluation, and management of preoperative anaemia in the elective orthopaedic surgical patient: NATA guidelines BRITISH JOURNAL OF ANAESTHESIA Goodnough, L. T., Maniatis, A., Earnshaw, P., Benoni, G., Beris, P., Bisbe, E., Fergusson, D. A., Gombotz, H., Habler, O., Monk, T. G., Ozier, Y., Slappendel, R., Szpalski, M. 2011; 106 (1): 13-22

  Abstract

  Previously undiagnosed anaemia is common in elective orthopaedic surgical patients and is associated with increased likelihood of blood transfusion and increased perioperative morbidity and mortality. A standardized approach for the detection, evaluation, and management of anaemia in this setting has been identified as an unmet medical need. A multidisciplinary panel of physicians was convened by the Network for Advancement of Transfusion Alternatives (NATA) with the aim of developing practice guidelines for the detection, evaluation, and management of preoperative anaemia in elective orthopaedic surgery. A systematic literature review and critical evaluation of the evidence was performed, and recommendations were formulated according to the method proposed by the Grades of Recommendation Assessment, Development and Evaluation (GRADE) Working Group. We recommend that elective orthopaedic surgical patients have a haemoglobin (Hb) level determination 28 days before the scheduled surgical procedure if possible (Grade 1C). We suggest that the patient's target Hb before elective surgery be within the normal range, according to the World Health Organization criteria (Grade 2C). We recommend further laboratory testing to evaluate anaemia for nutritional deficiencies, chronic renal insufficiency, and/or chronic inflammatory disease (Grade 1C). We recommend that nutritional deficiencies be treated (Grade 1C). We suggest that erythropoiesis-stimulating agents be used for anaemic patients in whom nutritional deficiencies have been ruled out, corrected, or both (Grade 2A). Anaemia should be viewed as a serious and treatable medical condition, rather than simply an abnormal laboratory value. Implementation of anaemia management in the elective orthopaedic surgery setting will improve patient outcomes.

  View details for DOI 10.1093/bja/aeq361

  View details for Web of Science ID 000285192900004

  View details for PubMedID 21148637

  View details for PubMedCentralID PMC3000629

• Detection, evaluation, and management of anemia in elective surgery ANASTHESIOLOGIE & INTENSIVMEDIZIN GOODNOUGH, L. T. 2011; 52: 37-40

  View details for Web of Science ID 000286774400007

• Detection, evaluation, and management of iron-restricted erythropoiesis BLOOD Goodnough, L. T., Nemeth, E., Ganz, T. 2010; 116 (23): 4754-4761

  Abstract

  Progress in our understanding of iron-restricted erythropoiesis has been made possible by important advances in defining the molecular mechanisms of iron homeostasis. The detection and diagnostic classification of iron-restricted erythropoiesis can be a challenging process for the clinician. Newer assays for markers of inflammation may allow more targeted management of the anemia in these conditions. The availability of new intravenous iron preparations provides new options for the treatment of iron-restricted erythropoiesis. This review summarizes recent advances regarding the detection, evaluation, and management of iron-restricted erythropoiesis.

  View details for DOI 10.1182/blood-2010-05-286260

  View details for PubMedID 20826717

• Recombinant Factor VIIa: An Assessment of Evidence Regarding Its Efficacy and Safety in the Off-Label Setting HEMATOLOGY-AMERICAN SOCIETY OF HEMATOLOGY EDUCATION PROGRAM Logan, A. C., Goodnough, L. T. 2010: 153-159

  View details for DOI 10.1182/asheducation-2010.1.153

  View details for Web of Science ID 000208759600024

• Age of blood as a limitation for transfusion: potential impact on blood inventory and availability TRANSFUSION Fontaine, M. J., Chung, Y. T., Erhun, F., Goodnough, L. T. 2010; 50 (10): 2233-2239

  Abstract

  Evolving concerns about storage lesions for red blood cells (RBCs) have led to ongoing trials evaluating the benefits of transfusing fresher blood to acutely ill patients.We evaluated several RBC maximum shelf lives (MSLs) and their impact on RBC availability and outdate rate. First, we determined the mean age of the RBC units in our inventory by analyzing the data set of 18,987 nonirradiated RBC units transfused at our institution from April 2008 to March 2009. Second, we determined the feasibility of issuing RBC units of a designated age to patients using the same data set. We defined six scenarios where RBC units have different MSLs: Scenarios 1, 2, 3, 4, and 5 used a MSL of 7, 14, 21, 28, and 35 days, respectively. Scenario 6 used a combination of different MSLs depending on the category of patients.RBC units spent on average 8.6 days on the shelf with a mean age of 10.2 days at delivery and 18.8 days at issue for transfusion. Using the original 18,987 data points, we observed a shortfall in the availability of RBC units, decreased by 51, 20, 10, 4, 1, and 0% and an increase in the outdate rate to 3.2, 2.2, 1.0, 0.6, 0.4, and 4.5% for Scenarios 1, 2, 3, 4, 5, and 6, respectively, compared to baseline.Changing the MSL for RBC units would require novel approaches to RBC inventory management to meet hospital demands with acceptable outdate rates.

  View details for DOI 10.1111/j.1537-2995.2010.02690.x

  View details for PubMedID 20497519

• Impact of cytomegalovirus (CMV) antibody reflex testing in the transfusion service on management of CMV-seronegative blood inventory TRANSFUSION Fontaine, M. J., Jurado, C., Miller, E., Viele, M., Goodnough, L. T. 2010; 50 (8): 1685-1689

  Abstract

  Our goal is to minimize unnecessary cytomegalovirus (CMV)-seronegative blood transfusion to preserve the CMV-seronegative blood inventory for patients who are identified as CMV seronegative.We implemented a CMV antibody reflex testing protocol for patients who require CMV-compatible blood but in whom a CMV serostatus is unknown (coded as CMVT in our computer system). A solid-phase red blood cell (RBC) adherence antibody detection system was validated to detect CMV antibodies in plasma samples (received for ABO/Rh type and RBC antibody screen) with acceptable sensitivity and specificity. We evaluated the impact of this CMV antibody reflex testing on the management of RBC and platelet (PLT) inventory for patients requiring CMV-compatible blood.Over a 16-month period, implementation of CMV antibody reflex testing identified 361 (34%) of 1063 previously CMV-untested patients who required CMV-compatible blood and who were CMV seronegative. We observed a 75% decrease in the number of CMVT patients in our data base from 190 per month before implementation to 57 at 16 months postimplementation. Consequently we reevaluated the percentage in our blood inventory of CMV-seronegative units required while potentially saving 1234 CMV-seronegative blood products (835 RBCs and 399 PLTs) each month.A strategy of performing CMV antibody reflex testing in the transfusion service allows more effective blood inventory management and control in maintaining a CMV-seronegative blood inventory dedicated for patients who truly require it.

  View details for DOI 10.1111/j.1537-2995.2010.02643.x

  View details for PubMedID 20412530

• Randomized Evaluation of efficacy and safety of ferric carboxymaltose in Patients with iron deficiency Anaemia and Impaired Renal function (REPAIR-IDA): rationale and study design NEPHROLOGY DIALYSIS TRANSPLANTATION Szczech, L. A., Bregman, D. B., Harrington, R. A., Morris, D., Butcher, A., Koch, T. A., Goodnough, L. T., Wolf, M., Onken, J. E. 2010; 25 (7): 2368-2375

  Abstract

  Patients with iron deficiency anaemia (IDA) in the setting of non-dialysis-dependent chronic kidney disease (NDD-CKD) may benefit from treatment with intravenous (IV) iron. Ferric carboxymaltose (FCM) is a novel IV iron formulation designed to permit larger infusions compared to currently available IV standards such as Venofer(R) (iron sucrose).The primary objective of REPAIR-IDA is to estimate the cardiovascular safety and efficacy of FCM (two doses at 15 mg/kg to a maximum of 750 mg per dose) compared to Venofer(R) (1000 mg administered as five infusions of 200 mg) in subjects who have IDA and NDD-CKD. REPAIR-IDA is a multi-centre, randomized, active-controlled, open-label study. Eligible patients must have haemoglobin (Hgb) < or = 11.5 g/dL and CKD defined as (1) GFR < 60 mL/min/1.73 m(2) on two occasions or (2) GFR < 90 mL/min/1.73 m(2) and either evidence of renal injury by urinalysis or elevated Framingham cardiovascular risk score. Two thousand and five hundred patients will be randomized to FCM or Venofer(R) in a 1:1 ratio. The primary efficacy endpoint is mean change in Hgb from baseline to the highest observed Hgb between baseline and Day 56. The primary safety endpoint is the proportion of subjects experiencing at least one of the following events: death due to any cause, non-fatal myocardial infarction, non-fatal stroke, unstable angina requiring hospitalization, congestive heart failure requiring hospitalization or medical intervention, arrhythmias, hypertension or hypotension during the 120 days following randomization.REPAIR-IDA will assess the efficacy and safety of two 750-mg infusions of FCM compared to an FDA-approved IV iron regimen in patients with NDD-CKD at increased risk for cardiovascular disease.

  View details for DOI 10.1093/ndt/gfq218

  View details for Web of Science ID 000279189400051

  View details for PubMedID 20466657

• Comparative gene expression analysis of avian embryonic facial structures reveals new candidates for human craniofacial disorders HUMAN MOLECULAR GENETICS Brugmann, S. A., Powder, K. E., Young, N. M., Goodnough, L. H., Hahn, S. M., James, A. W., Helms, J. A., Lovett, M. 2010; 19 (5): 920-930

  Abstract

  Mammals and birds have common embryological facial structures, and appear to employ the same molecular genetic developmental toolkit. We utilized natural variation found in bird beaks to investigate what genes drive vertebrate facial morphogenesis. We employed cross-species microarrays to describe the molecular genetic signatures, developmental signaling pathways and the spectrum of transcription factor (TF) gene expression changes that differ between cranial neural crest cells in the developing beaks of ducks, quails and chickens. Surprisingly, we observed that the neural crest cells established a species-specific TF gene expression profile that predates morphological differences between the species. A total of 232 genes were differentially expressed between the three species. Twenty-two of these genes, including Fgfr2, Jagged2, Msx2, Satb2 and Tgfb3, have been previously implicated in a variety of mammalian craniofacial defects. Seventy-two of the differentially expressed genes overlap with un-cloned loci for human craniofacial disorders, suggesting that our data will provide a valuable candidate gene resource for human craniofacial genetics. The most dramatic changes between species were in the Wnt signaling pathway, including a 20-fold up-regulation of Dkk2, Fzd1 and Wnt1 in the duck compared with the other two species. We functionally validated these changes by demonstrating that spatial domains of Wnt activity differ in avian beaks, and that Wnt signals regulate Bmp pathway activity and promote regional growth in facial prominences. This study is the first of its kind, extending on previous work in Darwin's finches and provides the first large-scale insights into cross-species facial morphogenesis.

  View details for DOI 10.1093/hmg/ddp559

  View details for Web of Science ID 000274341400015

  View details for PubMedID 20015954

  View details for PubMedCentralID PMC2816616

• Recombinant factor VIIa: an assessment of evidence regarding its efficacy and safety in the off-label setting. Hematology / the Education Program of the American Society of Hematology. American Society of Hematology. Education Program Logan, A. C., Goodnough, L. T. 2010; 2010: 153-159

  Abstract

  Recombinant human factor VIIa (rFVIIa) is approved by the US Food and Drug Administration for use in the setting of hemorrhage associated with factor VIII or factor IX inhibitors in patients with congenital or acquired hemophilia. This indication represents only a small number of bleeding conditions. Since it became available, rFVIIa has been increasingly used in the management of off-label indications, ranging from emergent hemostasis in traumatic hemorrhage to prophylactic hemostasis in patients undergoing major surgery. Prominent off-label indications include the management of patients with coagulopathies, such as occurs in trauma patients experiencing massive and uncontrolled hemorrhage, and in patients undergoing cardiovascular surgery with cardiopulmonary bypass. Other occasions for use occur in patients with intact coagulation systems, with nontraumatic intracranial hemorrhage being the most common in this group. Uncertainties regarding the efficacy and safety associated with use of rFVIIa in these off-label scenarios have led to evidence-based assessments of patient outcomes, including mortality, the rate of thromboembolic adverse events, and posttreatment functional status. We review the evidence regarding the efficacy and safety of this important, but controversial, hemostatic agent in the off-label setting.

  View details for DOI 10.1182/asheducation-2010.1.153

  View details for PubMedID 21239786

• Management of preoperative anaemia in patients undergoing elective surgery 31st International Congress of the International-Society-of-Blood-Transfusion/43rd Congress of the DGTI Goodnough, L. T., Manaitis, A., Earnshaw, P. WILEY-BLACKWELL. 2010: 120–24

  View details for Web of Science ID 000284993800021

• Large-dose intravenous ferric carboxymaltose injection for iron deficiency anemia in heavy uterine bleeding: a randomized, controlled trial TRANSFUSION Van Wyck, D. B., Mangione, A., Morrison, J., Hadley, P. E., Jehle, J. A., Goodnough, L. T. 2009; 49 (12): 2719-2728

  Abstract

  The objective was to evaluate efficacy and safety of rapid, large-dose intravenous (IV) administration of ferric carboxymaltose compared to oral iron in correcting iron deficiency anemia due to heavy uterine bleeding.In a randomized, controlled trial, 477 women with anemia, iron deficiency, and heavy uterine bleeding were assigned to receive either IV ferric carboxymaltose (or= 12 g/dL) of anemia (73% vs. 50%, p < 0.001). Patients treated with ferric carboxymaltose compared to those prescribed ferrous sulfate reported greater gains in vitality and physical function and experienced greater improvement in symptoms of fatigue (p < 0.05). There were no serious adverse drug events.In patients with iron deficiency anemia due to heavy uterine bleeding, rapid IV administration of large doses of a new iron agent, ferric carboxymaltose, is more effective than oral iron therapy in correcting anemia, replenishing iron stores, and improving quality of life.

  View details for DOI 10.1111/j.1537-2995.2009.02327.x

  View details for Web of Science ID 000272344900024

  View details for PubMedID 19682342

• Improving platelet supply chains through collaborations between blood centers and transfusion services TRANSFUSION Fontaine, M. J., Chung, Y. T., Rogers, W. M., Sussmann, H. D., Quach, P., Galel, S. A., Goodnough, L. T., Erhun, F. 2009; 49 (10): 2040-2047

  Abstract

  Blood centers and hospital transfusion services are challenged with maintaining an adequate platelet (PLT) inventory to minimize the number of outdated units without risking a major shortage. A novel approach to inventory management was established at our institution through a collaboration between the Stanford University Medical Center (SUMC) Transfusion Service, the Stanford Blood Center (SBC), and the Department of Management Science and Engineering.An analysis of the supply chain performance between SBC and SUMC Transfusion Service was performed. First, the interaction between processes, such as blood collection, rotation, and inventory management, was studied. Second, changes were implemented based on the recommendations from the analysis team. Finally, a postanalysis was performed reflecting on the improvement of the operations between SUMC and SBC.A comprehensive data analysis of the PLT supply chain allowed the identification of three series of improvements to be implemented: 1) on SBC's PLT collection, 2) on SBC's rotation process, and 3) on the PLT inventory management policy at SUMC. A postimplementation analysis showed a reduction in the overall PLT outdate rate from 19% in the first quarter of 2006, down to 9% in the third quarter of 2008.A multidisciplinary effort among SUMC Transfusion Service, SBC, and experts in supply chain management resulted in a process improvement, which reduced the rate of PLT outdate at both SBC and SUMC Transfusion Service down to 9%, with a significant cost reduction of more than half a million dollars per year.

  View details for DOI 10.1111/j.1537-2995.2009.02236.x

  View details for PubMedID 19538430

• Retrospective analysis of transfusion outcomes in pregnant patients at a tertiary obstetric center INTERNATIONAL JOURNAL OF OBSTETRIC ANESTHESIA Butwick, A. J., Aleshi, P., Fontaine, M., Riley, E. T., GOODNOUGH, L. T. 2009; 18 (4): 302-308

  Abstract

  The decision to use red blood cell transfusion and/or blood products (fresh frozen plasma, platelets, cryoprecipitate) to manage obstetric hemorrhage or treat postpartum anemia is often made empirically by physicians. We performed a retrospective study to review transfusion outcomes in pregnant and postpartum patients at a large obstetric center.A retrospective, observational study was performed of obstetric in-patients who received red blood cell transfusion and/or blood products over a one-year period. Data abstracted included transfusion data, pre-transfusion hemoglobin (Hb) and lowest recorded (nadir) Hb, and maternal and neonatal outcomes.During the study period, 74 patients received transfusion therapy (1.4%). Pre-transfusion and nadir Hb values were 7.6 g/dL and 7.0 g/dL respectively. Median [IQR] total red blood cells transfused were 2 units [2-3], with 41 (55%) patients receiving 1-2 units. Based on chart review, no specific indications for transfusion were identified in 25 patients (34%), and 13 patients (18%) had undetected postpartum anemia (Hb values <8.2 g/dL) at least 24h after delivery.More formal assessment and documentation of the etiologic factors associated with transfusion management in pregnant patients is advised. In addition, the identification and management of undetected postpartum anemia is underappreciated.

  View details for DOI 10.1016/j.ijoa.2009.02.005

  View details for Web of Science ID 000271135300002

  View details for PubMedID 19628384

• Implementation of a two-specimen requirement for verification of ABO/Rh for blood transfusion TRANSFUSION Goodnough, L. T., Viele, M., Fontaine, M. J., Jurado, C., Stone, N., Quach, P., Chua, L., Chin, M., Scott, R., Tokareva, I., Tabb, K., Sharek, P. J. 2009; 49 (7): 1321-1328

  Abstract

  This study presents our implementation of a two-specimen requirement with no prior record of ABO/Rh to verify patients' blood type before transfusion.Blood type verification was introduced, discussed, approved, and implemented over a 12-month period (May 2007 to May 2008). Potential barriers and impact on benchmark indicators were identified and tracked.Inpatient identification and/or specimen labeling for nursing and laboratory phlebotomists baseline corrected error rates were 1:467 and 1:5555, respectively. This study therefore sought and obtained approval to initiate a new policy of blood type verification before blood transfusion. Compliance in turnaround time (TAT) before and after implementation for completion of STAT type and screen/crossmatch within 60 minutes worsened marginally, from 90% to 80%. The impact on use of O-, uncrossmatched blood was found to be manageable. Seven (of 25 total) recorded electronic complaints were received after implementation. The corrected error rate for nurse phlebotomy draws after implementation was 1:630.Despite the lack of an instigating event, verification of blood type before blood transfusion was successfully implemented. An impact on resources and benchmark indicators such as TAT can be anticipated and managed. Further process improvement efforts will be needed to ensure safety (e.g., at time of blood transfusion) for patients receiving blood transfusions. ABO/Rh verification may be necessary even after future implementation of bar coding and/or RFID chips, because human errors continue to occur even with systems improvements.

  View details for DOI 10.1111/j.1537-2995.2009.02157.x

  View details for PubMedID 19389026

• Why an Alternative to Blood Transfusion? CRITICAL CARE CLINICS Shander, A., Goodnough, L. T. 2009; 25 (2): 261-?

  Abstract

  Allogeneic blood transfusions have been associated with several risks and complications and with worse outcomes in a substantial number of patient populations and clinical scenarios. Allogeneic blood is costly and difficult to procure, transport, and store. Global and local shortages are imminent. Alternatives to transfusion provide many advantages, and their use is likely to improve outcomes as safer and more effective agents are developed.

  View details for DOI 10.1016/j.ccc.2008.12.012

  View details for Web of Science ID 000265560000002

  View details for PubMedID 19341908

• Iron overload and toxicity: the hidden risk of multiple blood transfusions VOX SANGUINIS Shander, A., Cappellini, M. D., GOODNOUGH, L. T. 2009; 97 (3): 185-197

  Abstract

  The quantity of iron in body is carefully regulated, primarily by control of iron absorption, and excess total body iron can be extremely toxic. Since humans have no mechanism for elimination of excess iron, multiple transfusions of red blood cells, which are required for the management of a number of disorders, inevitably result in iron overload. Cumulative iron overload, in turn, leads to iron toxicity with organ dysfunction and damage.This review examines the relationship between iron metabolism and hematologic disorders treated with multiple transfusions, with emphasis on the diagnosis and current methods of management of iron overload and toxicity in transfusion-dependent patients. Primarily using key words, we identified and reviewed more than 100 pertinent articles in English and other languages in the Medline database plus an additional number of abstracts of presentations at recent meetings of relevant scientific associations.Transfusion-dependent disorders include those characterized by decreased red blood cell production, increased red blood cell destruction, or chronic blood loss. Patients receiving chronic transfusion therapy should be screened and monitored for iron overload, yet in our opinion, this is not always done routinely. Once iron overload has been identified, it should be treated to reduce the risk of morbidity and mortality from iron toxicity, which particularly affects the liver and heart.Increased awareness of the risks of iron overload from chronic transfusion therapy should result in greater use of interventions such as iron chelation to reduce total body iron and the risk of long-term sequelae.

  View details for DOI 10.1111/j.1423-0410.2009.01207.x

  View details for Web of Science ID 000270182800001

  View details for PubMedID 19663936

• The role of intravenous iron in anemia management and transfusion avoidance TRANSFUSION Auerbach, M., Goodnough, L. T., Picard, D., Maniatis, A. 2008; 48 (5): 988-1000

  View details for DOI 10.1111/j.1537-2995.2007.01633.x

  View details for Web of Science ID 000255497600027

  View details for PubMedID 18346021

• Impact of clinical trial design and execution-related factors on incidence of thromboembolic events in cancer patients: a systematic review and metaanalysis CURRENT MEDICAL RESEARCH AND OPINION Reynolds, M. W., Shibata, A., Zhao, S., Jones, N., Fahrbach, K., Goodnough, L. T. 2008; 24 (2): 497-505

  Abstract

  The objective of this study was to quantify the incidence of thromboembolic events (specifically, deep vein thromboses [DVT] and pulmonary embolism [PE]) in patients with cancer, and to examine the effects of a major clinical trial design and execution factors on those incidence rates.The study included a systematic review of Medline, Current Contents, and accepted study bibliographies, as well as an analysis of studies. Studies included both longitudinal studies (prospective and retrospective) published in the English language between January 1990 and October 2005. Studies of patients with cancer that reported the incidence of thromboembolic events (DVT, PE, and total venous thromboembolic events [VTE]) were eligible for inclusion. Incidence of these events was calculated by study design, surveillance type (active or passive), length of follow-up, and other treatment risk factors. Incidence rates were estimated by random effects Poisson meta-regression modeling.One hundred and eighty-three studies met all inclusion criteria. Incidence rates of all outcomes (DVT, PE, and total VTE) were 3-55 times higher for active surveillance than for passive surveillance. Studies with a follow-up time 6 months. Additionally, the incidence rates for all outcome events when using passive surveillance were 3-12 times higher in non-randomized clinical trials (non-RCTs) than in RCTs.These results provide a benchmark for the incidence of thromboembolic events in patients with cancer. Factors such as study design, length of follow-up, and method of case ascertainment (type of surveillance - active or passive) must be considered when interpreting thromboembolic incidence rates. This review is comprehensive in its inclusion of all studies with a scientific objective of examining the risk of thromboembolic events in patients with cancer from 1990 to 2005. However, other studies published prior to 1990, more recently than 2005, or with other scientific objectives in their research may also provide supportive information to these risk estimates.

  View details for DOI 10.1185/0300799O8X261050

  View details for Web of Science ID 000253902900020

  View details for PubMedID 18194590

• Alloimmunization to red blood cell antigens affects clinical outcomes in liver transplant patients LIVER TRANSPLANTATION Boyd, S. D., Stenard, F., Lee, D. K., Goodnough, L. T., Esquivel, C. O., Fontaine, M. J. 2007; 13 (12): 1654-1661

  Abstract

  Transfusion therapy of liver transplant patients remains a challenge. High volumes of intraoperative blood transfusion have been shown to increase the risk of poor graft or patient survival. We conducted a retrospective study of 209 consecutive liver transplant cases at our institution. Only patients receiving their first liver transplant, with no other simultaneous organ transplants, were included. Cox proportional hazard modeling was used to identify clinical variables correlated with postoperative patient mortality. Statistically significant variables for poor patient survival were the number of red blood cell and plasma units transfused, a history of red blood cell alloantibodies, and the immunosuppressive regimen used. History of pregnancy also approached statistical significance but was less robust than the other 3 variables. Our findings suggest that blood transfusion and immune modulation greatly affect the survival of patients after liver transplantation.

  View details for DOI 10.1002/It.21241

  View details for PubMedID 18044783

• Transfusion triggers 2nd Thrombin Symposium on Challenges in Surgical Hemostasis Goodnough, L. T. MOSBY-ELSEVIER. 2007: S67–S70

  Abstract

  The decision to transfuse a patient is not always clear and straightforward, particularly because no single number, neither extraction ratio nor hemoglobin level, can serve as an absolute indicator of transfusion need. Clinical assessment of the patient in conjunction with physiologic values helps in determining the appropriateness of transfusion before the advent of hypoxia or ischemia. The benefit of transfusion in relation to mortality and morbidity is discussed here based on an assessment of the literature, and transfusion guidelines from several organizations are summarized.

  View details for DOI 10.1016/j.surg.2007.06.027

  View details for PubMedID 18019935

• Wnt signaling mediates regional specification in the vertebrate face DEVELOPMENT Brugmann, S. A., Goodnough, L. H., Gregorieff, A., Leucht, P., Ten Berge, D., Fuerer, C., Clevers, H., Nusse, R., Helms, J. A. 2007; 134 (18): 3283-3295

  Abstract

  At early stages of development, the faces of vertebrate embryos look remarkably similar, yet within a very short timeframe they adopt species-specific facial characteristics. What are the mechanisms underlying this regional specification of the vertebrate face? Using transgenic Wnt reporter embryos we found a highly conserved pattern of Wnt responsiveness in the developing mouse face that later corresponded to derivatives of the frontonasal and maxillary prominences. We explored the consequences of disrupting Wnt signaling, first using a genetic approach. Mice carrying compound null mutations in the nuclear mediators Lef1 and Tcf4 exhibited radically altered facial features that culminated in a hyperteloric appearance and a foreshortened midface. We also used a biochemical approach to perturb Wnt signaling and found that in utero delivery of a Wnt antagonist, Dkk1, produced similar midfacial malformations. We tested the hypothesis that Wnt signaling is an evolutionarily conserved mechanism controlling facial morphogenesis by determining the pattern of Wnt responsiveness in avian faces, and then by evaluating the consequences of Wnt inhibition in the chick face. Collectively, these data elucidate a new role for Wnt signaling in regional specification of the vertebrate face, and suggest possible mechanisms whereby species-specific facial features are generated.

  View details for DOI 10.1242/dev.005132

  View details for Web of Science ID 000249013700006

  View details for PubMedID 17699607

• Update on transfusion medicine PHARMACOTHERAPY Shander, A., Goodnough, L. T. 2007; 27 (9): 57S-68S

  Abstract

  Clinical pharmacists often participate on critical care teams that manage patients with bleeding emergencies. Although blood products are usually dispensed from the blood bank and not the pharmacy, pharmacists should be conversant in the language and trends of transfusion medicine, much like they are with other therapeutic agents. Toward that goal, this review provides a concise transfusion medicine tutorial, covering all commonly used blood products, including red blood cells, platelets, fresh frozen plasma, and plasma derivatives such as cryoprecipitate, prothrombin complex concentrates, and albumin. Usage patterns, the rationale for administering the various blood products, and studies that have attempted to determine appropriate criteria for ordering transfusions (transfusion triggers) are discussed. The benefits, risks, and several ongoing controversies that relate to the appropriateness and safety of blood product use are also summarized.

  View details for Web of Science ID 000249108800003

  View details for PubMedID 17723109

• How we treat: management of life-threatening primary postpartum hemorrhage with a standardized massive transfusion protocol TRANSFUSION Burtelow, M., Riley, E., Druzin, M., Fontaine, M., Viele, M., Goodnough, L. T. 2007; 47 (9): 1564-1572

  Abstract

  Management of massive, life-threatening primary postpartum hemorrhage in the labor and delivery service is a challenge for the clinical team and hospital transfusion service. Because severe postpartum obstetrical hemorrhage is uncommon, its occurrence can result in emergent but variable and nonstandard requests for blood products. The implementation of a standardized massive transfusion protocol for the labor and delivery department at our institution after a maternal death caused by amniotic fluid embolism is described. This guideline was modeled on a existing protocol used by the trauma service mandating emergency release of 6 units of group O D- red cells (RBCs), 4 units of fresh frozen or liquid plasma, and 1 apheresis unit of platelets (PLTs). The 6:4:1 fixed ratio of uncrossmatched RBCs, plasma, and PLTs allows the transfusion service to quickly provide blood products during the acute phase of resuscitation and allows the clinical team to anticipate and prevent dilutional coagulopathy. The successful management of three cases of massive primary postpartum hemorrhage after the implementation of our new massive transfusion protocol in the maternal and fetal medicine service is described.

  View details for DOI 10.1111/j.1537-2995.2007.01404.x

  View details for PubMedID 17725718

• Stage-dependent craniofacial defects resulting from Sprouty2 overexpression DEVELOPMENTAL DYNAMICS Goodnough, L. H., Brugmann, S. A., Hu, D., Helms, J. A. 2007; 236 (7): 1918-1928

  Abstract

  Sprouty genes encode intracellular regulators of receptor tyrosine kinases that function in a variety of developmental events. Although mice carrying null mutations in Sprouty genes exhibit craniofacial anomalies, the precise role of these regulatory proteins in facial development remains unclear. Here, we show that overexpression of spry2 at the initiation of craniofacial development results in a dramatic arrest in outgrowth of the facial prominences. Although endogenous spry2 and fibroblast growth factor 8 (fgf8) are coexpressed throughout much of craniofacial development, overexpression of spry2 did not alter the spatiotemporal patterns of fgf target gene expression. The morphological consequences of spry2 overexpression were specific: all of the facial prominences were truncated, but despite this gross malformation, the programs of osteogenesis and chondrogenesis were not impaired. Collectively, these data suggest that Sprouty2 plays a role in the outgrowth of facial prominences independent of canonical Fgf signaling.

  View details for DOI 10.1002/dvdy.21195

  View details for Web of Science ID 000248041000018

  View details for PubMedID 17576140

• Functional demarcation of active and silent chromatin domains in human HOX loci by Noncoding RNAs CELL Rinn, J. L., Kertesz, M., Wang, J. K., Squazzo, S. L., Xu, X., Brugmann, S. A., Goodnough, L. H., Helms, J. A., Farnham, P. J., Segal, E., Chang, H. Y. 2007; 129 (7): 1311-1323

  Abstract

  Noncoding RNAs (ncRNA) participate in epigenetic regulation but are poorly understood. Here we characterize the transcriptional landscape of the four human HOX loci at five base pair resolution in 11 anatomic sites and identify 231 HOX ncRNAs that extend known transcribed regions by more than 30 kilobases. HOX ncRNAs are spatially expressed along developmental axes and possess unique sequence motifs, and their expression demarcates broad chromosomal domains of differential histone methylation and RNA polymerase accessibility. We identified a 2.2 kilobase ncRNA residing in the HOXC locus, termed HOTAIR, which represses transcription in trans across 40 kilobases of the HOXD locus. HOTAIR interacts with Polycomb Repressive Complex 2 (PRC2) and is required for PRC2 occupancy and histone H3 lysine-27 trimethylation of HOXD locus. Thus, transcription of ncRNA may demarcate chromosomal domains of gene silencing at a distance; these results have broad implications for gene regulation in development and disease states.

  View details for DOI 10.1016/j.cell.2007.05.022

  View details for PubMedID 17604720

• Blood management ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE Goodnough, L. T., Shander, A. 2007; 131 (5): 695-701

  Abstract

  We provide an overview of the principles of blood management: the appropriate use of blood and blood components, with a goal of minimizing their use.To review the strategies that exploit combinations of surgical and medical techniques, technologic devices, and pharmaceuticals, along with an interdisciplinary team approach that combines specialists who are expert at minimizing allogeneic blood transfusion.A search on Medline and PubMed for the terms English and humans used in articles published within the last 20 years.Blood management is most successful when multidisciplinary, proactive programs are in place so that these strategies can be individualized to specific patients.

  View details for PubMedID 17488154

• Erythropoietin and iron-restricted erythropoiesis International Symposium on Recent Advances in Radiation Effects, Hematopoiesis and Malignancy in honor of Eugene P Cronkite Goodnough, L. T. ELSEVIER SCIENCE INC. 2007: 167–72

  Abstract

  Twenty five years ago, Finch summarized knowledge gained primarily from studies of normal individuals, patients with hereditary hemolytic anemias, and patients with hemochromatosis [1]. Under conditions of basal erythropoiesis in normal subjects, plasma iron turnover (as an index of marrow erythropoietic response) is little affected, whether transferrin saturation ranges from very low to very high levels. In contrast, the erythropoietic response in individuals with congenital hemolytic anemia, in whom erythropoiesis is chronically raised up to sixfold over basal levels [2], is affected (and limited) by serum iron levels and by transferrin saturation [3]. Patients with hemochromatosis who underwent serial phlebotomy were observed to mount erythropoietic responses of up to eightfold over basal rates, attributed to the maintenance of very high serum iron and transferrin saturation levels in these patients [4], whereas normal individuals were shown to have difficulty providing sufficient iron to support rates of erythropoiesis greater than three times basal rates [5]. These observations led Finch to identify a "relative iron deficiency" state, also known as "functional iron deficiency," which he defined as circumstances in which increased erythron iron requirements exceed the available supply of iron [6]. In another clinical setting, patients undergoing autologous blood donation represent a model for perisurgical blood loss and the erythropoietic response. Insights gained over the last 20 years regarding the relationship between erythropoietin, iron, and erythropoiesis, along with implications for clinical management, will be reviewed.

  View details for DOI 10.1016/j.exphem.2007.01.026

  View details for PubMedID 17379103

• Objectives and limitations of bloodless medical care CURRENT OPINION IN HEMATOLOGY Shander, A., Goodnough, L. T. 2006; 13 (6): 462-470

  Abstract

  To outline the rationale, limitations, and execution of bloodless medical and surgical programs, highlighting characteristics that contribute to successful outcomes.Clinical experiences with patients who refuse blood transfusions for religious reasons have provided valuable lessons and raise intriguing questions about the necessity of routine blood transfusions. Healthcare centers with bloodless medicine and surgery programs feature a novel concept of patient care aimed at improving outcomes. A one-tiered approach to minimize blood usage for all patients, regardless of religious beliefs, is being successfully adopted at an increasing number of institutions. Since most single blood-conservation techniques reduce blood usage by just 1-2 units, a series of integrated preoperative, intraoperative, and postoperative conservation approaches is required. These include preoperative autologous donation, erythropoietic support, acute normovolemic hemodilution, individualized assessment of anemia tolerance, implementation of conservative transfusion thresholds, meticulous surgical techniques, and judicious use of phlebotomy and pharmacologic agents for limiting blood loss.The objectives of bloodless medicine and surgery programs are straightforward but require staff with expertise in transfusion medicine, intensive teamwork, patient-specific customization, careful planning, and integrated use of multimodal strategies.

  View details for Web of Science ID 000241690600010

  View details for PubMedID 17053460

• The relevance of iron in erythropoietin-stimulated erythropoiesis SEMINARS IN HEMATOLOGY Goodnough, L. T. 2006; 43 (4): S3-S8

  View details for DOI 10.1053/j.seminhematol.2006.08.003

  View details for Web of Science ID 000241375400002

• Clinical benefits and risks associated with epoetin and darbepoetin in patients with chemotherapy-induced anemia: A systematic review of the literature CLINICAL THERAPEUTICS Ross, S. D., Allen, I. E., Henry, D. H., Seaman, C., Sercus, B., Goodnough, L. T. 2006; 28 (6): 801-831

  Abstract

  Erythropoiesis-stimulating proteins (ESPs) are indicated for the treatment of chemotherapy-induced anemia (CIA). Evidence-based guidelines and systematic reviews of the management of CIA do not yet include all currently approved ESPs or all of the clinically relevant benefits and risks of ESPs.The aims of this work were to provide up-to-date assessments of the clinical efficacy and effectiveness (ie, transfusions and quality-of-life [QoL] benefits) and safety (ie, risk of venous thromboembolism [VTE] and all-cause or treatment-associated death) of epoetin-alfa, epoetin-beta, and darbepoetin-alfa for the treatment of CIA in cancer patients with hemoglobin<11 g/dL. We also considered the impact of differences in study design, patients, and treatments on the results.A systematic review of the literature was performed to identify and analyze English-language studies (controlled trials and prospective uncontrolled studies with >or=300 patients) published between 1980 and July 2005. The databases searched were MEDLINE and the Cochrane Library. Relevant abstracts from the last 2 annual meetings of the American Society of Clinical Oncology, American Society of Hematology, and European Society for Medical Oncology were also included. Studies were selected, using predefined eligibility criteria. Two reviewers had to agree on all included and excluded studies, and on all data extracted from each accepted study before they were entered into a relational database. Meta-analyses were performed to quantify benefit and risk outcomes.In total, 40 studies including 21,378 patients were eligible for analysis. Each ESP was found to have efficacy relative to standard care or placebo. The odds ratio (OR) for transfusions in studies of epoetin versus controls was 0.44 (95% CI, 0.35-0.55) and of darbepoetin versus controls was 0.41 (95% CI, 0.31-0.55). Patients receiving ESPs experienced a significant improvement in QoL; the mean difference in Functional Assessment of Cancer Therapy-Fatigue score for ESPs versus controls was 0.23 (95% CI, 0.10-0.36; P=0.001). The frequency of VTE and death was not significantly different between ESPs and control (VTE OR, 1.41 [95% CI, 0.81-2.47]; all-cause mortality OR, 1.00 [95% CI, 0.69-1.44]).This analysis of key clinical benefits and risks of epoetin and darbepoetin in the treatment of CIA found no clinically relevant differences between these drugs.

  View details for DOI 10.1016/j.clinthera.2006.06.003

  View details for Web of Science ID 000239100300001

  View details for PubMedID 16860166

• Identification, diagnosis, and management of anemia in adult ambulatory patients treated by primary care physicians: evidence-based and consensus recommendations CURRENT MEDICAL RESEARCH AND OPINION Dubois, R. W., GOODNOUGH, L. T., Ershler, W. B., Van Winkle, L., Nissenson, A. R. 2006; 22 (2): 385-395

  Abstract

  Provide recommendations for the identification, diagnosis, and management of ambulatory patients with anemia.The RAND/UCLA Appropriateness Method was used to develop the recommendations. A literature review of anemia prevalence (based on a search of PubMed for the period 1990 to 2003), etiology, and treatment outcomes was reviewed by a panel comprised of nine physicians (six primary care, three specialists) who then rated 336 clinical scenarios and grouped them into three categories: 'appropriate', 'uncertain', or 'inappropriate'.Performing a complete blood count on a yearly basis was rated 'appropriate' for patients with an underlying chronic condition, for men > or = 50 years old, and for all women with no chronic condition on an every-5-years basis. Specific recommendations were made for five anemia management options (observation, referral, empiric trial of iron, transfusion, and erythropoietic growth factors). Recommendations for observation alone were based on age, gender, and hemoglobin level. Immediate referral to a gastroenterologist or hematologist for a work-up was rated 'inappropriate' in all cases. An empiric trial of iron was rated 'inappropriate' for women over age 40 and for all men. Recommendations on the use of erythropoietic growth factors were based on hemoglobin level and anemia symptoms ('appropriate' if Hb < 9.5 g/dL, or if Hb = 9.5-11.0 g/dL and anemia symptoms were present). Finally, recommendations about transfusion were based on the severity of anemia and the presence of cardiovascular disease ('appropriate' in patients > or = 70 years old and in those presenting with either symptoms of anemia or underlying cardiovascular disease). The recommendations did not address anemia related to nutritional deficiencies, cancer/chemotherapy, or chronic renal failure.Primary care physicians should obtain screening blood counts, perform diagnoses, and manage anemia in patient groups known to be at risk. These recommendations on the identification, diagnosis, and management of anemia represent an opportunity to improve outcomes in ambulatory patients with anemia.

  View details for DOI 10.1185/030079906X89720

  View details for Web of Science ID 000236302200017

  View details for PubMedID 16466611

• Detection, evaluation, and management of anemia in the elective surgical patient ANESTHESIA AND ANALGESIA Goodnough, L. T., Shander, A., Spivak, J. L., Waters, J. H., Friedman, A. J., Carson, J. L., Keating, E. M., Maddox, T., Spence, R. 2005; 101 (6): 1858-1861

  Abstract

  The prevalence of anemia in elective surgical patients may be as frequent as 75% in certain populations. A national audit demonstrated that 35% of patients scheduled for joint replacement therapy have a hemoglobin <13 g/dL on preadmission testing. Standard practice currently consists of preadmission testing 3 to 7 days before an elective operative procedure, precluding the opportunity to effectively evaluate and manage a patient with unexpected anemia. Therefore, a standardized approach for the detection, evaluation, and management of anemia in the preoperative surgical setting was identified as an unmet medical need. To address this knowledge gap, we convened a panel of physicians to develop a clinical care pathway for anemia management in this setting. Elective surgery patients should receive a hemoglobin (Hgb) determination a minimum of 30 days before the scheduled surgical procedure. Because the identification and evaluation of anemia in this setting will assist in expedited diagnosis and treatment of underlying comorbidities and will improve patient outcomes, unexplained anemia (Hgb <12 g/dL for females and <13 g/dL for males) should cause elective surgery to be deferred until an evaluation can be performed.

  View details for DOI 10.1213/01.ANE.0000184124.29397.EB

  View details for PubMedID 16301274

• Current issues in transfusion medicine. Clinical advances in hematology & oncology : H&O Goodnough, L. 2005; 3 (8): 614-616

  View details for PubMedID 16167045

• Risks of blood transfusion. Anesthesiology clinics of North America Goodnough, L. T. 2005; 23 (2): 241-?

  Abstract

  This article discusses advances in blood safety during the last 20 years, particularly for prevention of transfusion-transmitted viral infections. Although the most serious known risks from blood transfusion are administrative errors, transfusion-related acute lung injury, and bacterial contamination in platelet products, infection from emerging pathogens such as West Nile virus emphasizes the need for implementing proactive strategies. Pathogen inactivation technologies and reactive strategies such as nucleic acid testing ensure continued advances in blood safety.

  View details for PubMedID 15922896

• Autologous blood donation. Anesthesiology clinics of North America Goodnough, L. T. 2005; 23 (2): 263-?

  Abstract

  Preoperative autologous blood donation has become accepted as a standard practice in elective surgery. Subsequent improvements in blood safety and evolving surgical techniques resulting in less blood loss have caused a national decline in preoperative autologous blood donation by approximately 50%. Nevertheless, the continuing emergence of new pathogens and the potential for severe blood inventory shortages continue to give preoperative autologous blood donation an important role in blood conservation strategies.

  View details for PubMedID 15922898

• Medical progress: Anemia of chronic disease NEW ENGLAND JOURNAL OF MEDICINE Weiss, G., GOODNOUGH, L. T. 2005; 352 (10): 1011-1023

  View details for Web of Science ID 000227491200010

• Rationale for blood conservation. Surgical infections Goodnough, L. T. 2005; 6: S3-8

  Abstract

  Exposure of patients to allogeneic blood transfusion can be minimized or avoided by the systematic use of multiple blood conservation techniques. Current use of these technologies is variable.Review of pertinent English language literature.Enthusiasm for preoperative autologous blood donation (PAD) has declined considerably, perhaps due to increased cost and inconvenience to patients. Acute normovolemic hemodilution (ANH) has several practical advantages over PAD, but has not become generally accepted as a blood conservation strategy. Erythropoietin, iron, and artificial oxygen carriers are pharmacologic alternatives.Pharmacologic stimulation of erythropoiesis offers substantial potential to progress toward a goal of bloodless medicine. The potential of artificial blood substitutes is still being defined.

  View details for DOI 10.1089/sur.2005.6.s1-3

  View details for PubMedID 19284355

• Therapeutic efficacy and safety of platelets treated with a photochemical process for pathogen inactivation: the SPRINT Trial BLOOD McCullough, J., Vesole, D. H., Benjamin, R. J., Slichter, S. J., Pineda, A., Snyder, E., Stadtmauer, E. A., Lopez-Plaza, I., Coutre, S., Strauss, R. G., GOODNOUGH, L. T., Fridey, J. L., Raife, T., Cable, R., Murphy, S., Howard, F., Davis, K., Lin, J. S., Metzel, P., Corash, L., Koutsoukos, A., Lin, L., Buchholz, D. H., Conlan, M. G. 2004; 104 (5): 1534-1541

  Abstract

  We report a transfusion trial of platelets photochemically treated for pathogen inactivation using the synthetic psoralen amotosalen HCl. Patients with thrombocytopenia were randomly assigned to receive either photochemically treated (PCT) or conventional (control) platelets for up to 28 days. The primary end point was the proportion of patients with World Health Organization (WHO) grade 2 bleeding during the period of platelet support. A total of 645 patients (318 PCT and 327 control) were evaluated. The primary end point, the incidence of grade 2 bleeding (58.5% PCT versus 57.5% control), and the secondary end point, the incidence of grade 3 or 4 bleeding (4.1% PCT versus 6.1% control), were equivalent between the 2 groups (P =.001 by noninferiority). The mean 1-hour posttransfusion platelet corrected count increment (CCI) (11.1 x 10(3) PCT versus 16.0 x 10(3) control), average number of days to next platelet transfusion (1.9 PCT versus 2.4 control), and number of platelet transfusions (8.4 PCT versus 6.2 control) were different (P <.001). Transfusion reactions were fewer following PCT platelets (3.0% PCT versus 4.4% control; P =.02). The incidence of grade 2 bleeding was equivalent for PCT and conventional platelets, although posttransfusion platelet count increments and days to next transfusion were decreased for PCT compared with conventional platelets.

  View details for Web of Science ID 000223544000052

  View details for PubMedID 15138160

• Blood and blood conservation: A national perspective JOURNAL OF CARDIOTHORACIC AND VASCULAR ANESTHESIA Goodnough, L. T. 2004; 18 (4): 6S-11S

  View details for DOI 10.1053/j.jvca.2004.05.001

  View details for PubMedID 15368198

• A PHASE-III RANDOMIZED STUDY COMPARING CISPLATIN AND FLUOROURACIL AS SINGLE AGENTS AND IN COMBINATION FOR ADVANCED SQUAMOUS-CELL CARCINOMA OF THE HEAD AND NECK JOURNAL OF CLINICAL ONCOLOGY Jacobs, C., Lyman, G., VELEZGARCIA, E., Sridhar, K. S., Knight, W., Hochster, H., GOODNOUGH, L. T., Mortimer, J. E., Einhorn, L. H., Schacter, L., CHERNG, N., Dalton, T., Burroughs, J., Rozencweig, M. 1992; 10 (2): 257-263

  Abstract

  To determine whether combination chemotherapy is superior to single agents for recurrent/metastatic head and neck cancer, we compared the efficacy and toxicity of cisplatin (CP) and fluorouracil (5-FU), alone and in combination in a phase III trial.Two hundred forty-nine patients with recurrent head and neck cancer were randomized to one of three treatments: CP (100 mg/m2) and 5-FU (1 g/m2 x 4), CP, or 5-FU every 3 weeks.The overall response rate to the combination (32%) was superior to that of CP (17%) or 5-FU (13%) (P = .035). Response was associated with good performance status (PS) but not with primary site, site of recurrence, histology, prior irradiation, or relative dose intensity. Median time to progression was less than 2.5 months, and there was no significant difference in median survival (5.7 months) among the groups. By multivariate analysis, patients with better PS and poorly differentiated tumors had superior survival. Hematologic toxicity and alopecia were worse in the combination arm.Although the response rate to the combination of CP plus 5-FU was superior to that achieved with single agents, survival did not improve.

  View details for Web of Science ID A1992HB27000011

  View details for PubMedID 1732427