Kenneth Michael Lin, MD

All Publications

• No Difference in Chondrocyte Viability Using Manual Versus Custom-Cutting Technique for Matrix-Induced Autologous Chondrocyte Implantation. Orthopaedic journal of sports medicine Chang, W. T., Atzmon, R., Vel, M. S., Lin, K. M., Abrams, G. D., Sherman, S. L. 2025; 13 (2): 23259671241308855

  Abstract

  Matrix-induced autologous chondrocyte implantation (MACI) was developed for knee cartilage restoration involving seeding autologous chondrocytes onto a collagen membrane. Maintaining chondrocyte viability and achieving proper membrane size and contour are crucial for successful outcomes. Scissor cutting (Sc) has traditionally been used to shape the membrane, but recently, custom cutting (CC) have gained popularity for their enhanced preparation efficiency.To determine the difference in chondrocyte viability using the Sc versus CC methods.Controlled laboratory study.Using Sc and CC methods, 15 mm-diameter circular specimens were cut from 5 residual membranes. Membranes were stained, and confocal microscopy was used to visualize live/dead cells. Three zones were defined: the impact zone (the outermost zone at the cut edge), the central zone (the least manipulated zone), and the adjacent zone (the intermediate zone between the central and impact zones). For each circular specimen, the following measurements were recorded: the dimension of the impact zone, cell viability (percentage of live cells among total) for each zone, and the total number of cells within each zone (as cell density ×105/cm2).The width of the impact zone (mean ± standard error) was 355 ± 31 μm and 342 ± 24 μm for CC and Sc, respectively, and the impact zone occupied approximately 10% of the specimen. With both cutting techniques, cell viability was significantly lower in the impact zone (mean ± standard error: CC, 36.42% ± 3.85%; Sc, 40.94% ± 2.85%) compared with the adjacent zone (CC, 77.69% ± 2.97%; Sc, 74.17% ± 2.8%). The cell density from all zones varied from 5.84 ± 0.26 to 6.49 ± 0.34 × 105/cm2, with no significant difference in cell viability in the impact zones between the cutting methods.Both cutting techniques led to a significant reduction in cell viability in the impact zone compared with other zones of the MACI specimen. There was no significant difference in chondrocyte viability or cell density for membranes cut by Sc or CC.This evaluation of the newly introduced CC method on the chondrocyte viability of the MACI membrane will enable surgeons to make a more informed decision regarding cutting techniques.

  View details for DOI 10.1177/23259671241308855

  View details for PubMedID 39931633

  View details for PubMedCentralID PMC11808760

• An ultrastructure analysis of the developing human anterior cruciate ligament tibial enthesis. Journal of orthopaedic research : official publication of the Orthopaedic Research Society Hidalgo Perea, S., Uppstrom, T. J., Lin, K. M., Klinger, C. E., Bromage, T. G., Shea, K. G., Green, D. W., Rodeo, S. A. 2024

  Abstract

  This study aimed to investigate the ultrastructural anatomy of the developing ACL tibial enthesis. We hypothesized that enthesis architecture would progressively mature and remodel, eventually resembling that of the adult by the early postnatal stage. Five fresh-frozen human pediatric cadaveric knees aged 1-36 months underwent anatomical dissection to harvest the ACL insertion and underlying tibial chondroepiphysis. The samples were prepared for scanning electron microscopy (SEM) to examine the ultrastructural anatomy of the enthesis and underwent histological staining for circular polarized light (CPL) and light microscopy imaging. SEM analysis of the 1- and 8-month-old samples revealed a shallow interdigitation between the dense fibrous (ligamentous) tissue and unmineralized chondrogenic tissues, with a minimal transition zone. By 11-month, a more complex transition zone was present. By age 19- and 36-month-old, a progressively more complex and defined fibrocartilage zone was observed. CPL analysis revealed distinct collagen fiber continuity, alignment, and organization changes over time. By 19 and 36 months, the samples exhibited complex fiber arrangements and a progression toward uniform fiber orientation. Similarly, histological analysis demonstrated progressive remodeling of the enthesis with increasing age. Our results suggest that the ACL enthesis of the developing knee begins to mimic that of an adult as early as 19 months of age, as a more complex transition between ligamentous and chondro-epiphyseal tissue can be appreciated. We hypothesize that the observed changes are likely due to mechanical loading of the enthesis with the onset of weightbearing. Future investigations of ACL reconstruction and repair will benefit from improved understanding of the chondro-epiphyseal/ACL regions.

  View details for DOI 10.1002/jor.25999

  View details for PubMedID 39447005

• Assessment of trochanteric vascularity using quantitative magnetic resonance imaging in a cadaveric model. Journal of experimental orthopaedics Klinger, C. E., Altintas, B., Barth, K. A., Lin, K. M., Dewar, D. C., Lazaro, L. E., Dyke, J. P., Wellman, D. S., Helfet, D. L. 2024; 11 (4): e70092

  Abstract

  Purpose: Few studies have assessed trochanteric vascularity despite its implications for bone healing and surgical approaches. This study aimed to assess the regional arterial contributions of the medial femoral circumflex artery (MFCA) versus the lateral femoral circumflex artery (LFCA) to trochanteric vascularity.Methods: Ten adult human cadaveric pelvises to mid-femur specimens were obtained. One hip was randomly assigned experimental (either MFCA or LFCA MRI-contrast infusion) and contralateral as control (MFCA and LFCA magnetic resonance imaging [MRI]-contrast infusion). Vascular dissection was performed for MFCA and LFCA cannulation. Pre- and post-contrast 3T MRI was completed, and intra-osseous contributions were quantified by region: greater trochanter (GT), intertrochanteric (IT), lesser trochanter (LT) and subtrochanteric (ST). A polyurethane compound mixed with barium sulfate was injected into the LFCA cannula, and into the MFCA cannula for the contralateral hip. Computed tomography (CT) imaging was completed to assess terminal branch locations.Results: MFCA provided the majority of arterial contributions to the full trochanteric region (68.5% MFCA, 31.5% LFCA; standard deviation [SD]: 10.7%, p<0.001). Over 70% of arterial contributions to ST, LT and IT regions are derived from MFCA. GT contributions were more balanced (52.5% MFCA, 47.5% LFCA; SD: 33.7%; p=0.853). Significant differences were found between MFCA and LFCA contributions in all regions except for the GT. CT revealed multiple consistent MFCA and LFCA trochanteric terminal branches.Conclusions: MFCA provided the dominant trochanteric arterial supply, which highlights MFCA's importance to overall hip vascularity. LFCA's trochanteric contribution was smaller but still provided trochanteric contributions, especially the GT region. Knowledge of trochanteric arterial contributions can be beneficial for optimizing surgical approaches and fixation to protect terminal branches during trochanteric fracture, nonunion treatment and trochanteric osteotomies.Level of Evidence: Not applicable.

  View details for DOI 10.1002/jeo2.70092

  View details for PubMedID 39553420

• Augmented Ulnar Collateral Ligament Repair With Structural Bioinductive Scaffold: A Biomechanical Study. The American journal of sports medicine Lin, K. M., Brinson, K., Atzmon, R., Chan, C. K., Sherman, S. L., Safran, M. R., Freehill, M. T. 2024: 3635465241236465

  Abstract

  Elbow ulnar collateral ligament (UCL) repair with suture brace augmentation shows good time-zero biomechanical strength and a more rapid return to play compared with UCL reconstruction. However, there are concerns about overconstraint or stress shielding with nonabsorbable suture tape. Recently, a collagen-based bioinductive absorbable structural scaffold has been approved by the Food and Drug Administration for augmentation of soft tissue repair.This study aimed to assess the initial biomechanical performance of UCL repair augmented with this scaffold. We hypothesized that adding the bioinductive absorbable structural scaffold to primary UCL repair would impart additional time-zero restraint to the valgus opening.Controlled laboratory study.Eight cadaveric elbow specimens-from midforearm to midhumerus-were utilized. In the native state, elbows underwent valgus stress testing at 30o, 60o, and 90o of flexion, with a cyclical valgus rotational torque. Changes in valgus rotation from 2- to 5-N·m torque were recorded as valgus gapping. Testing was then performed in 4 states: (1) native intact UCL-with dissection through skin, fascia, and muscle down to an intact UCL complex; (2) UCL-transected-distal transection of the ligament off the sublime tubercle; (3) augmented repair with bioinductive absorbable scaffold; and (4) repair alone without scaffold. The order of testing of repair states was alternated to account for possible plastic deformation during testing.The UCL-transected state showed the greatest increase in valgus gapping of all states at all flexion angles. Repair alone showed similar valgus gapping to that of the UCL-transected state at 30° (P = .62) and 60° of flexion (P = .11). Bioinductive absorbable scaffold-augmented repair showed less valgus gapping compared with repair alone at all flexion angles (P = .021, P = .024, and P = .024 at 30°, 60°, and 90°, respectively). Scaffold-augmented repair showed greater gapping compared with the native state at 30° (P = .021) and 90° (P = .039) but not at 60° of flexion (P = .059). There was no difference when testing augmented repair or repair alone first.UCL repair augmented with a bioinductive, biocomposite absorbable structural scaffold imparts additional biomechanical strength to UCL repair alone, without overconstraint beyond the native state. Further comparative studies are warranted.As augmented primary UCL repair becomes more commonly performed, use of an absorbable bioinductive scaffold may allow for improved time-zero mechanical strength, and thus more rapid rehabilitation, while avoiding long-term overconstraint or stress shielding.

  View details for DOI 10.1177/03635465241236465

  View details for PubMedID 38650304

• Association of Quadriceps Tendon Harvest for ACL Reconstruction With Development of Osteochondritis Dissecans of the Patella in Pediatric Patients. Orthopaedic journal of sports medicine Hidalgo Perea, S., Chipman, D. E., Cordasco, F. A., Lin, K. M., Gorelick, D., Asaro, L. A., Green, D. W. 2024; 12 (2): 23259671231219712

  Abstract

  There are various reported complications after primary anterior cruciate ligament reconstruction (ACLR) necessitating additional surgery in skeletally immature patients, regardless of technique and autograft type.To analyze the rate and type of complications encountered with soft tissue quadriceps tendon autograft (QTA) for ACLR in patients ≤18 years as well as the overall rate of second surgery, unrelated to the use of the QTA.Case series; Level of evidence, 4.A total of 141 patients ≤18 years who underwent ACLR with a QTA and had minimum 6-month follow-up were included. All patients underwent ACLR by utilizing a full-thickness soft tissue QTA. Complications associated with the QTA harvest site and use of QTA were reported.The mean age of the included cohort (84 men, 57 women) was 14.8 ± 1.6 years. The average follow-up was of 2.0 ± 1.2 years. A total of 30 (21%) patients had a subsequent complication that required surgical intervention; in 11 (8%) patients, the complication was specifically associated with the use of a QTA, whereas in 19 (13%) patients, the complication was related to the ACLR. In addition, 13 (9%) patients underwent a contralateral ACLR procedure. Of the QTA-related complications, 2 patients developed osteochondritis dissecans (OCD)-like lesions in the superior aspect of the patella, 2 patients had injured their quadriceps extensor mechanism and required surgical repair, and 8 patients had a subsequent procedure to remove nonabsorbable sutures used for donor site quadriceps tendon closure. One of the patients who underwent the removal of nonabsorbable sutures also had an arthroscopic debridement of patellar chondral damage.We reported complications encountered with soft tissue QTA for ACLR. The complication rate for QTA harvest was 8%. However, given that the removal of nonabsorbable sutures from the donor site was caused by the surgical technique used, the revised nonsuture-related complication rate for QTA graft harvest was 2%. Although the use of a QTA has recently gained popularity due to its high return-to-sport and low graft-failure rates, surgeons should be aware of the complications associated with using this graft type.

  View details for DOI 10.1177/23259671231219712

  View details for PubMedID 38379578

  View details for PubMedCentralID PMC10878225

• Common Soft Tissue Injuries About the Knee in American Football. HSS journal : the musculoskeletal journal of Hospital for Special Surgery Lin, K. M., Atzmon, R., Pierre, K. J., Vel, M. S., Brinson, K., Sherman, S. L. 2023; 19 (3): 330-338

  View details for DOI 10.1177/15563316231165298

  View details for PubMedID 37435123

  View details for PubMedCentralID PMC10331270

• Orthobiologic Techniques for Surgical Augmentation. Physical medicine and rehabilitation clinics of North America Lin, K. M., Frey, C. S., Atzmon, R., Pierre, K., Vel, M. S., Sherman, S. L. 2023; 34 (1): 265-274

  Abstract

  General awareness and clinical utilization of orthobiologic therapy has increased sharply in the recent years. Orthobiologics can be defined as "biological materials and substrates that promote bone, ligament, muscle, and tendon healing." There are 3 major strategies by which orthobiologics are thought to augment tissue repair or native biologic potential: factor-based, cell-based, and biomechanical augmentation. The purpose of this review is to synthesize the recent literature on orthobiologic techniques for surgical augmentation, with focus on several key areas including meniscus repair, osteochondral grafting, and rotator cuff repair.

  View details for DOI 10.1016/j.pmr.2022.08.015

  View details for PubMedID 36410886

• Rehabilitation and Return to Sport Following Elbow Injuries. Arthroscopy, sports medicine, and rehabilitation Lin, K. M., Ellenbecker, T. S., Safran, M. R. 2022; 4 (3): e1245-e1251

  Abstract

  Elbow injuries are frequently seen in throwing and overhead athletes. This review provides a framework for diagnosis, treatment, and particularly rehabilitation of common elbow pathologies, including ulnar collateral ligament injury, valgus extension overload, and medial and lateral epicondylitis. Advanced rehabilitation facilitates complete return to functional sport-specific activity and is based on objective criteria. As diagnostic and therapeutic modalities improve our understanding of elbow pathologies in the athletic patient, continued research will further elucidate objective evidence-based rehabilitation techniques.

  View details for DOI 10.1016/j.asmr.2022.01.012

  View details for PubMedID 35747663

• Achilles Tendon Repairs: Identification of Risk Factors for and Economic Impact of Complications and Reoperation SPORTS HEALTH-A MULTIDISCIPLINARY APPROACH Trivedi, N. N., Varshneya, K., Calcei, J., Lin, K., Sochaki, K. R., Voos, J. E., Safran, M. R., Calcei, J. G. 2022: 19417381221087246

  Abstract

  Compared with nonoperative management, Achilles tendon repair is associated with increased rates of complications and increased initial healthcare cost. However, data are currently lacking on the risk factors for these complications and the added healthcare cost associated with common preoperative comorbidities.Identify the independent risk factors for complications and reoperation after acute Achilles tendon repair and calculate the added cost of care associated with having each preoperative risk factor.Retrospective cohort study.Level 3.A retrospective review of a large commercial claims database was performed to identify patients who underwent primary operative management for Achilles tendon rupture between 2007 and 2016. The primary outcome measures of the study were risk factors for (1) postoperative complications, (2) revision surgery, and (3) increased healthcare resource utilization.A total of 50,279 patients were included. The overall complication rate was 2.7%. The most common 30-day complication was venous thromboembolism (1.2%). The rate of revision surgery was 2.5% at 30 days and 4.3% at 2 years. Independent risk factors for 30-day complications in our cohort included increasing age, hyperlipidemia, hypertension, female sex, obesity, and diabetes. Independent risk factors for revision surgery within 2 years included female sex, tobacco use, hypertension, obesity, and the presence of any postoperative complication. The average 5-year cost of operative intervention was $17,307. The need for revision surgery had the largest effect on 5-year overall cost, increasing it by $6776.40. This was followed by the presence of a postoperative complication ($3780), female sex ($3207.70), and diabetes ($3105).Achilles tendon repair is a relatively low-risk operation. Factors associated with postoperative complications include increasing age, hyperlipidemia, hypertension, female sex, obesity, and diabetes. Factors associated with the need for revision surgery include female sex, hypertension, obesity, and the presence of any postoperative complication. Female sex, diabetes, the presence of any complication, and the need for revision surgery had the largest added costs associated with them.Surgeons can use this information for preoperative decision-making and during the informed consent process.

  View details for DOI 10.1177/19417381221087246

  View details for Web of Science ID 000806267500001

  View details for PubMedID 35635017

• Vascularity of the early post-natal human distal femoral chondroepiphysis: Quantitative MRI analysis JOURNAL OF CHILDRENS ORTHOPAEDICS Lin, K. M., Gadinsky, N. E., Klinger, C. E., Kleeblad, L. J., Shea, K. G., Dyke, J. P., Helfet, D. L., Rodeo, S. A., Green, D. W., Lazaro, L. E. 2022; 16 (2): 152-158

  View details for DOI 10.1177/18632521221084179

  View details for Web of Science ID 000789111500011

• Vascularity of the early post-natal human distal femoral chondroepiphysis: Quantitative MRI analysis. Journal of children's orthopaedics Lin, K. M., Gadinsky, N. E., Klinger, C. E., Kleeblad, L. J., Shea, K. G., Dyke, J. P., Helfet, D. L., Rodeo, S. A., Green, D. W., Lazaro, L. E. 2022; 16 (2): 152-158

  Abstract

  Injury to or abnormality of developing distal femoral chondroepiphysis blood supply has been implicated in osteochondritis dissecans development. Progressive decrease in epiphyseal cartilage blood supply occurs in normal development; however, based on animal studies, it is hypothesized that there is greater decrease in regions more prone to osteochondritis dissecans lesions. We aimed to quantify differential regional perfusion of the immature distal femoral chondroepiphysis. We hypothesized there is decreased perfusion in the lateral aspect of the medial femoral condyle, the classic osteochondritis dissecans lesion location.Five fresh-frozen human cadaveric knees (0-6 months old) were utilized. The superficial femoral artery was cannulated proximally and contrast-enhanced magnetic resonance imaging performed using a previously reported protocol for quantifying osseous and soft tissue perfusion. Regions of interest were defined, and signal enhancement changes between pre- and post-contrast images, normalized to background muscle, were compared.When comparing average normalized post-contrast signal enhancement of whole condyles, as well as distal, posterior, and inner (toward the notch) aspects of the medial and lateral condyles, no significant perfusion differences between condyles were found. In the medial condyle, no significant perfusion difference was found between the medial and lateral aspects.We quantified immature distal femoral chondroepiphysis regional vascularity in the early post-natal knee. In specimens aged 0-6 months, no distinct watershed region was detected. Despite possible limitations, given small sample size, as well as resolution of magnetic resonance imaging and analysis, our results suggest the hypothesized vascular abnormality predisposing osteochondritis dissecans either does not occur universally or occurs after this developmental age.

  View details for DOI 10.1177/18632521221084179

  View details for PubMedID 35620125

  View details for PubMedCentralID PMC9127880

• Quantitative assessment of the vascularity of the skeletally immature patella: a cadaveric study using MRI JOURNAL OF CHILDRENS ORTHOPAEDICS Gadinsky, N. E., Lin, K. M., Klinger, C. E., Dyke, J. P., Kleeblad, L. J., Shea, K. G., Helfet, D. L., Rodeo, S. A., Green, D. W., Lazaro, L. E. 2021; 15 (2): 157-165

  Abstract

  While predominant blood supply to the adult patella enters inferomedially, little is known about skeletally immature patellar perfusion. Improved knowledge of immature patella vascularity can further understanding of osteochondritis dissecans, dorsal defects of the patella and bipartite patella, and help ensure safe surgical approaches. We hypothesized that the immature patella would exhibit more uniform blood flow. The study purpose was to quantify immature patella regional perfusion in comparison with adults.Ten cadaveric knees were utilized (five immature, five mature). The superficial femoral artery was cannulated proximally. Signal enhancement increases were compared from pre- to post-contrast MRI to assess relative arterial contributions to patella regions (quadrants, anterior/posterior, superior/inferior, medial/lateral, and outer/inner).Quantitative-MRI analysis revealed similar distribution of enhancement between the immature and mature patella. The inferior pole exhibited significantly higher arterial contribution versus superior pole in both immature and mature groups (p = 0.009; both groups), while the inferomedial quadrant had the highest arterial contribution of all quadrants in both groups. The superolateral quadrant demonstrated the lowest arterial contribution in the immature group and second lowest in the adult group. The patella outer periphery had significantly greater arterial contribution than the inner central region in both immature (p = 0.009) and mature (p = 0.009) groups.Distribution of arterial contributions between the immature and mature patella was similar. Our results highlight the importance of inferior and inferomedial blood supply in both immature and mature patellas. These findings have implications for paediatric and adult patients; surgical damage to inferior patellar vessels should be avoided to prevent associated complications.

  View details for DOI 10.1302/1863-2548.15.200261

  View details for Web of Science ID 000642209000009

  View details for PubMedID 34040662

  View details for PubMedCentralID PMC8138784

• Increased Vascularity in the Neonatal versus Adult Meniscus: Evaluation with Magnetic Resonance Imaging. Cartilage Lin, K. M., Gadinsky, N. E., Klinger, C. E., Dyke, J. P., Rodeo, S. A., Green, D. W., Fabricant, P. D., Helfet, D. L., Shea, K. G., Lazaro, L. E. 2020: 1947603520923143

  Abstract

  Objective. Quantification of meniscus vascularity has been limited with previous techniques, and minimal data exist describing differential vascular zones in the skeletally immature meniscus. The objective of this study is to use quantitative contrast-enhanced magnetic resonance imaging (MRI) to compare meniscal vascularity in neonatal specimens with adults. We hypothesized that the developing meniscus has greater and more uniform vascularity throughout all zones. Design. Ten fresh-frozen human cadaveric knees (5 neonatal, age 0-6 months; 5 adult, 34-67 years) underwent gadolinium-enhanced MRI using an established vascularity quantification protocol. Regions of interest corresponding to peripheral and central zones of the meniscus were identified on pre-contrast coronal images, and signal enhancement within the same regions (normalized against background tissue) was compared between pre- and post-contrast images. Results. The medial and lateral menisci had similar distribution of perfusion (45.8% ± 8.1% medial vs. 54.2% ± 8.1% lateral in neonatal knees; 50.6% ± 11.3% medial vs. 49.4% ± 11.3% lateral in adult knees, P = 0.47). Increased perfusion was demonstrated in the periphery compared with the central zone (2.3:1 in neonatal knees and 3.25:1 in adult knees, P = 0.31). Neonatal specimens demonstrated 6.0-fold greater overall post-contrast meniscal signal enhancement compared with adults (P < 0.0001), with the 0-month specimen demonstrating the greatest proportional signal enhancement. Conclusions. While blood flow to the periphery is greater than to central zones in all menisci, younger menisci receive proportionally greater overall blood flow compared to adults, including to the central zone, suggesting that the immature meniscus is a more biologically active tissue than its adult counterpart.

  View details for DOI 10.1177/1947603520923143

  View details for PubMedID 32447965

• Clinical Practice Guideline: Nosebleed (Epistaxis) Executive Summary. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery Tunkel, D. E., Anne, S. n., Payne, S. C., Ishman, S. L., Rosenfeld, R. M., Abramson, P. J., Alikhaani, J. D., Benoit, M. M., Bercovitz, R. S., Brown, M. D., Chernobilsky, B. n., Feldstein, D. A., Hackell, J. M., Holbrook, E. H., Holdsworth, S. M., Lin, K. W., Lind, M. M., Poetker, D. M., Riley, C. A., Schneider, J. S., Seidman, M. D., Vadlamudi, V. n., Valdez, T. A., Nnacheta, L. C., Monjur, T. M. 2020; 162 (1): 8–25

  Abstract

  Nosebleed, also known as epistaxis, is a common problem that occurs at some point in at least 60% of people in the United States. While the great majority of nosebleeds are limited in severity and duration, about 6% of people who experience nosebleeds will seek medical attention. For the purposes of this guideline, we define the target patient with a nosebleed as a patient with bleeding from the nostril, nasal cavity, or nasopharynx that is sufficient to warrant medical advice or care. This includes bleeding that is severe, persistent, and/or recurrent, as well as bleeding that impacts a patient's quality of life. Interventions for nosebleeds range from self-treatment and home remedies to more intensive procedural interventions in medical offices, emergency departments, hospitals, and operating rooms. Epistaxis has been estimated to account for 0.5% of all emergency department visits and up to one-third of all otolaryngology-related emergency department encounters. Inpatient hospitalization for aggressive treatment of severe nosebleeds has been reported in 0.2% of patients with nosebleeds.The primary purpose of this multidisciplinary guideline is to identify quality improvement opportunities in the management of nosebleeds and to create clear and actionable recommendations to implement these opportunities in clinical practice. Specific goals of this guideline are to promote best practices, reduce unjustified variations in care of patients with nosebleeds, improve health outcomes, and minimize the potential harms of nosebleeds or interventions to treat nosebleeds. The target patient for the guideline is any individual aged ≥3 years with a nosebleed or history of nosebleed who needs medical treatment or seeks medical advice. The target audience of this guideline is clinicians who evaluate and treat patients with nosebleed. This includes primary care providers such as family medicine physicians, internists, pediatricians, physician assistants, and nurse practitioners. It also includes specialists such as emergency medicine providers, otolaryngologists, interventional radiologists/neuroradiologists and neurointerventionalists, hematologists, and cardiologists. The setting for this guideline includes any site of evaluation and treatment for a patient with nosebleed, including ambulatory medical sites, the emergency department, the inpatient hospital, and even remote outpatient encounters with phone calls and telemedicine. Outcomes to be considered for patients with nosebleed include control of acute bleeding, prevention of recurrent episodes of nasal bleeding, complications of treatment modalities, and accuracy of diagnostic measures. This guideline addresses the diagnosis, treatment, and prevention of nosebleed. It will focus on nosebleeds that commonly present to clinicians with phone calls, office visits, and emergency room encounters. This guideline discusses first-line treatments such as nasal compression, application of vasoconstrictors, nasal packing, and nasal cautery. It also addresses more complex epistaxis management, which includes the use of endoscopic arterial ligation and interventional radiology procedures. Management options for 2 special groups of patients, patients with hemorrhagic telangiectasia syndrome (HHT) and patients taking medications that inhibit coagulation and/or platelet function, are included in this guideline. This guideline is intended to focus on evidence-based quality improvement opportunities judged most important by the working group. It is not intended to be a comprehensive, general guide for managing patients with nosebleed. In this context, the purpose is to define useful actions for clinicians, generalists, and specialists from a variety of disciplines to improve quality of care. Conversely, the statements in this guideline are not intended to limit or restrict care provided by clinicians based upon their experience and assessment of individual patients.The guideline development group made recommendations for the following key action statements: (1) At the time of initial contact, the clinician should distinguish the nosebleed patient who requires prompt management from the patient who does not. (2) The clinician should treat active bleeding for patients in need of prompt management with firm sustained compression to the lower third of the nose, with or without the assistance of the patient or caregiver, for 5 minutes or longer. (3a) For patients in whom bleeding precludes identification of a bleeding site despite nasal compression, the clinician should treat ongoing active bleeding with nasal packing. (3b) The clinician should use resorbable packing for patients with a suspected bleeding disorder or for patients who are using anticoagulation or antiplatelet medications. (4) The clinician should educate the patient who undergoes nasal packing about the type of packing placed, timing of and plan for removal of packing (if not resorbable), postprocedure care, and any signs or symptoms that would warrant prompt reassessment. (5) The clinician should document factors that increase the frequency or severity of bleeding for any patient with a nosebleed, including personal or family history of bleeding disorders, use of anticoagulant or antiplatelet medications, or intranasal drug use. (6) The clinician should perform anterior rhinoscopy to identify a source of bleeding after removal of any blood clot (if present) for patients with nosebleeds. (7a) The clinician should perform, or should refer to a clinician who can perform, nasal endoscopy to identify the site of bleeding and guide further management in patients with recurrent nasal bleeding, despite prior treatment with packing or cautery, or with recurrent unilateral nasal bleeding. (8) The clinician should treat patients with an identified site of bleeding with an appropriate intervention, which may include 1 or more of the following: topical vasoconstrictors, nasal cautery, and moisturizing or lubricating agents. (9) When nasal cautery is chosen for treatment, the clinician should anesthetize the bleeding site and restrict application of cautery only to the active or suspected site(s) of bleeding. (10) The clinician should evaluate, or refer to a clinician who can evaluate, candidacy for surgical arterial ligation or endovascular embolization for patients with persistent or recurrent bleeding not controlled by packing or nasal cauterization. (11) In the absence of life-threatening bleeding, the clinician should initiate first-line treatments prior to transfusion, reversal of anticoagulation, or withdrawal of anticoagulation/antiplatelet medications for patients using these medications. (12) The clinician should assess, or refer to a specialist who can assess, the presence of nasal telangiectasias and/or oral mucosal telangiectasias in patients who have a history of recurrent bilateral nosebleeds or a family history of recurrent nosebleeds to diagnose hereditary hemorrhagic telangiectasia syndrome (HHT). (13) The clinician should educate patients with nosebleeds and their caregivers about preventive measures for nosebleeds, home treatment for nosebleeds, and indications to seek additional medical care. (14) The clinician or designee should document the outcome of intervention within 30 days or document transition of care in patients who had a nosebleed treated with nonresorbable packing, surgery, or arterial ligation/embolization. The policy level for the following recommendation about examination of the nasal cavity and nasopharynx using nasal endoscopy was an option: (7b) The clinician may perform, or may refer to a clinician who can perform, nasal endoscopy to examine the nasal cavity and nasopharynx in patients with epistaxis that is difficult to control or when there is concern for unrecognized pathology contributing to epistaxis.

  View details for DOI 10.1177/0194599819889955

  View details for PubMedID 31910122

• Clinical Practice Guideline: Nosebleed (Epistaxis). Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery Tunkel, D. E., Anne, S. n., Payne, S. C., Ishman, S. L., Rosenfeld, R. M., Abramson, P. J., Alikhaani, J. D., Benoit, M. M., Bercovitz, R. S., Brown, M. D., Chernobilsky, B. n., Feldstein, D. A., Hackell, J. M., Holbrook, E. H., Holdsworth, S. M., Lin, K. W., Lind, M. M., Poetker, D. M., Riley, C. A., Schneider, J. S., Seidman, M. D., Vadlamudi, V. n., Valdez, T. A., Nnacheta, L. C., Monjur, T. M. 2020; 162 (1_suppl): S1–S38

  Abstract

  Nosebleed, also known as epistaxis, is a common problem that occurs at some point in at least 60% of people in the United States. While the majority of nosebleeds are limited in severity and duration, about 6% of people who experience nosebleeds will seek medical attention. For the purposes of this guideline, we define the target patient with a nosebleed as a patient with bleeding from the nostril, nasal cavity, or nasopharynx that is sufficient to warrant medical advice or care. This includes bleeding that is severe, persistent, and/or recurrent, as well as bleeding that impacts a patient's quality of life. Interventions for nosebleeds range from self-treatment and home remedies to more intensive procedural interventions in medical offices, emergency departments, hospitals, and operating rooms. Epistaxis has been estimated to account for 0.5% of all emergency department visits and up to one-third of all otolaryngology-related emergency department encounters. Inpatient hospitalization for aggressive treatment of severe nosebleeds has been reported in 0.2% of patients with nosebleeds.The primary purpose of this multidisciplinary guideline is to identify quality improvement opportunities in the management of nosebleeds and to create clear and actionable recommendations to implement these opportunities in clinical practice. Specific goals of this guideline are to promote best practices, reduce unjustified variations in care of patients with nosebleeds, improve health outcomes, and minimize the potential harms of nosebleeds or interventions to treat nosebleeds. The target patient for the guideline is any individual aged ≥3 years with a nosebleed or history of nosebleed who needs medical treatment or seeks medical advice. The target audience of this guideline is clinicians who evaluate and treat patients with nosebleed. This includes primary care providers such as family medicine physicians, internists, pediatricians, physician assistants, and nurse practitioners. It also includes specialists such as emergency medicine providers, otolaryngologists, interventional radiologists/neuroradiologists and neurointerventionalists, hematologists, and cardiologists. The setting for this guideline includes any site of evaluation and treatment for a patient with nosebleed, including ambulatory medical sites, the emergency department, the inpatient hospital, and even remote outpatient encounters with phone calls and telemedicine. Outcomes to be considered for patients with nosebleed include control of acute bleeding, prevention of recurrent episodes of nasal bleeding, complications of treatment modalities, and accuracy of diagnostic measures. This guideline addresses the diagnosis, treatment, and prevention of nosebleed. It focuses on nosebleeds that commonly present to clinicians via phone calls, office visits, and emergency room encounters. This guideline discusses first-line treatments such as nasal compression, application of vasoconstrictors, nasal packing, and nasal cautery. It also addresses more complex epistaxis management, which includes the use of endoscopic arterial ligation and interventional radiology procedures. Management options for 2 special groups of patients-patients with hereditary hemorrhagic telangiectasia syndrome and patients taking medications that inhibit coagulation and/or platelet function-are included in this guideline. This guideline is intended to focus on evidence-based quality improvement opportunities judged most important by the guideline development group. It is not intended to be a comprehensive, general guide for managing patients with nosebleed. In this context, the purpose is to define useful actions for clinicians, generalists, and specialists from a variety of disciplines to improve quality of care. Conversely, the statements in this guideline are not intended to limit or restrict care provided by clinicians based on their experience and assessment of individual patients.The guideline development group made recommendations for the following key action statements: (1) At the time of initial contact, the clinician should distinguish the nosebleed patient who requires prompt management from the patient who does not. (2) The clinician should treat active bleeding for patients in need of prompt management with firm sustained compression to the lower third of the nose, with or without the assistance of the patient or caregiver, for 5 minutes or longer. (3a) For patients in whom bleeding precludes identification of a bleeding site despite nasal compression, the clinician should treat ongoing active bleeding with nasal packing. (3b) The clinician should use resorbable packing for patients with a suspected bleeding disorder or for patients who are using anticoagulation or antiplatelet medications. (4) The clinician should educate the patient who undergoes nasal packing about the type of packing placed, timing of and plan for removal of packing (if not resorbable), postprocedure care, and any signs or symptoms that would warrant prompt reassessment. (5) The clinician should document factors that increase the frequency or severity of bleeding for any patient with a nosebleed, including personal or family history of bleeding disorders, use of anticoagulant or antiplatelet medications, or intranasal drug use. (6) The clinician should perform anterior rhinoscopy to identify a source of bleeding after removal of any blood clot (if present) for patients with nosebleeds. (7a) The clinician should perform, or should refer to a clinician who can perform, nasal endoscopy to identify the site of bleeding and guide further management in patients with recurrent nasal bleeding, despite prior treatment with packing or cautery, or with recurrent unilateral nasal bleeding. (8) The clinician should treat patients with an identified site of bleeding with an appropriate intervention, which may include one or more of the following: topical vasoconstrictors, nasal cautery, and moisturizing or lubricating agents. (9) When nasal cautery is chosen for treatment, the clinician should anesthetize the bleeding site and restrict application of cautery only to the active or suspected site(s) of bleeding. (10) The clinician should evaluate, or refer to a clinician who can evaluate, candidacy for surgical arterial ligation or endovascular embolization for patients with persistent or recurrent bleeding not controlled by packing or nasal cauterization. (11) In the absence of life-threatening bleeding, the clinician should initiate first-line treatments prior to transfusion, reversal of anticoagulation, or withdrawal of anticoagulation/antiplatelet medications for patients using these medications. (12) The clinician should assess, or refer to a specialist who can assess, the presence of nasal telangiectasias and/or oral mucosal telangiectasias in patients who have a history of recurrent bilateral nosebleeds or a family history of recurrent nosebleeds to diagnose hereditary hemorrhagic telangiectasia syndrome. (13) The clinician should educate patients with nosebleeds and their caregivers about preventive measures for nosebleeds, home treatment for nosebleeds, and indications to seek additional medical care. (14) The clinician or designee should document the outcome of intervention within 30 days or document transition of care in patients who had a nosebleed treated with nonresorbable packing, surgery, or arterial ligation/embolization. The policy level for the following recommendation, about examination of the nasal cavity and nasopharynx using nasal endoscopy, was an option: (7b) The clinician may perform, or may refer to a clinician who can perform, nasal endoscopy to examine the nasal cavity and nasopharynx in patients with epistaxis that is difficult to control or when there is concern for unrecognized pathology contributing to epistaxis.

  View details for DOI 10.1177/0194599819890327

  View details for PubMedID 31910111

• Bone marrow aspirate concentrate with cancellous allograft versus iliac crest bone graft in the treatment of long bone nonunions. OTA international : the open access journal of orthopaedic trauma Lin, K. n., VandenBerg, J. n., Putnam, S. M., Parks, C. D., Spraggs-Hughes, A. n., McAndrew, C. M., Ricci, W. M., Gardner, M. J. 2019; 2 (1): e012

  Abstract

  The purpose of this study was to compare bone marrow aspirate concentrate (BMAC) with cancellous allograft to iliac crest bone graft (ICBG) in the treatment of long bone nonunions.Retrospective cohort study.A single level I trauma center.26 patients with long bone diaphyseal or metaphyseal nonunions with defects >2 mm and treated with open repair and BMAC, compared to 25 patients with long bone diaphyseal or metaphyseal nonunions with defects >2 mm and treated with open repair and ICBG.Open repair of long bone nonunion using either autologous ICBG or BMAC with cancellous allograft.Nonunion healing, radiographically measured by the modified Radiographic Union Score for Tibia (mRUST) score. Secondary outcomes included risk factors associated with failed repair.The union rates for the BMAC and ICBG cohorts were 75% and 78%, respectively (P = .8). Infection was the only risk factor of statistical significance for failure.In this study, we found no significant difference in union rate for long bone nonunions treated with ICBG or BMAC with allograft. BMAC and allograft led to 75% successful healing in this series. Given the heterogeneity of the control group and loss to follow-up, further prospective investigation should be conducted to more rigorously compare BMAC to ICBG for nonunion treatment.III, retrospective cohort.

  View details for DOI 10.1097/OI9.0000000000000012

  View details for PubMedID 33937649

  View details for PubMedCentralID PMC7953544

• Authors' reply to Selvapatt and colleagues, Matthews and colleagues, Badrinath, and Ward and Lee. BMJ (Clinical research ed.) Koretz, R. L., Lin, K. W., Ioannidis, J. P., Lenzer, J. 2015; 350: h674-?

  View details for DOI 10.1136/bmj.h674

  View details for PubMedID 25711896

• Is widespread screening for hepatitis C justified? BMJ (Clinical research ed.) Koretz, R. L., Lin, K. W., Ioannidis, J. P., Lenzer, J. 2015; 350: g7809-?

  View details for DOI 10.1136/bmj.g7809

  View details for PubMedID 25587052

• Authors' reply to Foster and colleagues. BMJ (Clinical research ed.) Koretz, R. L., Lin, K. W., Ioannidis, J. P., Lenzer, J. 2015; 350: h1000-?

  View details for DOI 10.1136/bmj.h1000

  View details for PubMedID 25711887

• Homocysteine-induced vascular dysregulation is mediated by the NMDA receptor VASCULAR MEDICINE Qureshi, I., Chen, H. J., Brown, A. T., Fitzgerald, R., Zhang, X. J., Breckenridge, J., Kazi, R., Crocker, A. J., Stuhlinger, M. C., Lin, K., Cooke, J. P., Eidt, J. F., Moursi, M. M. 2005; 10 (3): 215-223

  Abstract

  Elevated plasma homocysteine accelerates myointimal hyperplasia and luminal narrowing after carotid endarterectomy. N-methyl D aspartate receptors (NMDAr) in rat cerebrovascular cells are involved in homocysteine uptake and receptor-mediated stimulation. In the vasculature, NMDAr subunits (NR1, 2A-2D) have been identified by sequence homology in rat aortic endothelial cells. Exposure of these cells to homocysteine increased expression of receptor subunits, an effect that was attenuated by dizocilpine (MK801), a noncompetitive NMDA inhibitor. The objective of this study was to investigate the existence of an NMDAr in rat vascular smooth muscle (A7r5) cells, and also the effect of homocysteine on vascular dysregulation as mediated by this receptor. Subunits of the NMDAr (NR1, 2A-2D) were detected in the A7r5 cells by using the reverse transcriptase polymerase chain reaction and Western blotting. Homocysteine induced an increase in A7r5 cell proliferation, which was blocked by MK801. Homocysteine, in a dose and time dependent manner, increased expression of matrix metallinoproteinase-9 and interleukin-1beta, which have been implicated in vascular smooth muscle cell migration and/or proliferation. Homocysteine reduced the vascular elaboration of nitric oxide and increased the elaboration of the nitric oxide synthase inhibitor, asymmetric dimethylarginine. All of these homocysteine mediated effects were inhibited by MK801. NMDAr exist in vascular smooth muscle cells and appear to mediate, at least in part, homocysteine-induced dysregulation of vascular smooth muscle cell functions.

  View details for DOI 10.1191/1358863x05vm626oa

  View details for Web of Science ID 000232556600006

  View details for PubMedID 16235775