All Publications

  • Musculoskeletal Educational Resources for the Aspiring Orthopaedic Surgeon. JB & JS open access Wadhwa, H., Van Rysselberghe, N. L., Campbell, S. T., Bishop, J. A. 2022; 7 (1)


    Musculoskeletal (MSK) education is underemphasized in medical school curricula, which can lead to decreased confidence in treating MSK conditions and suboptimal performance on orthopaedic surgery elective rotations or subinternships. Given the low amount of formalized education in MSK medicine, students aiming to learn about orthopaedic surgery must gain much of their foundational knowledge from other resources. However, there are currently no centralized introductory educational resources to fill this need. We provide a framework for navigating the different types of resources available for trainees and highlight the unaddressed needs in this area.

    View details for DOI 10.2106/JBJS.OA.21.00113

    View details for PubMedID 35651664

  • Role of c-Met/β1 integrin complex in the metastatic cascadein breast cancer. JCI insight Lau, D., Wadhwa, H., Sudhir, S., Chang, A. C., Jain, S., Chandra, A., Nguyen, A. T., Spatz, J. M., Pappu, A., Shah, S. S., Cheng, J., Safaee, M. M., Yagnik, G., Jahangiri, A., Aghi, M. K. 2021


    Metastases cause 90% of human cancer deaths. The metastatic cascade involves local invasion, intravasation, extravasation, metastatic site colonization, and proliferation. While individual mediators of these processes have been investigated, interactions between these mediators remain less well defined. We previously identified a complex between receptor tyrosine kinase c-Met and β1 integrin in metastases. Using novel cell culture and in vivo assays, we found that c-Met/β1 complex induction promotes intravasation and vessel wall adhesion in triple-negative breast cancer cells, but does not increase extravasation. These effects may be driven by the ability of the c-Met/β1 complex to increase mesenchymal and stem cell characteristics. Multiplex transcriptomic analysis revealed upregulated Wnt and hedgehog pathways after c-Met/β1 complex induction. A β1 integrin point mutation that prevented binding to c-Met reduced intravasation. OS2966, a therapeutic antibody disrupting c-Met/β1 binding, decreased breast cancer cell invasion and mesenchymal gene expression. Bone-seeking breast cancer cells exhibited higher c-Met/β1 complex levels than parental controls and preferentially adhered to tissue-specific matrix. Patient bone metastases demonstrated higher c-Met/β1 complex than brain metastases. Thus, the c-Met/β1 complex drives intravasation of triple-negative breast cancer cells and preferential affinity for bone-specific matrix. Pharmacological targeting of the complex may prevent metastases, particularly osseous metastases.

    View details for DOI 10.1172/jci.insight.138928

    View details for PubMedID 34003803

  • Hypotensive Anesthesia does not reduce Transfusion Rates during and after Acetabular Fracture Surgery. Injury Wadhwa, H., Chen, M. J., Tigchelaar, S. S., Bellino, M. J., Bishop, J. A., Gardner, M. J. 2021


    BACKGROUND: Acetabular fracture open reduction and internal fixation (ORIF) is generally associated with high intraoperative blood loss. Hypotensive anesthesia has been shown to decrease blood loss and intraoperative transfusion in total joint arthroplasty and posterior spinal fusion. In this study, we assessed the effect of reduction in intraoperative mean arterial pressures (MAPs) during acetabular fracture surgery on intraoperative blood loss and need for transfusion.METHODS: Three hundred and one patients with acetabular fractures who underwent ORIF at an academic Level 1 trauma center were retrospectively reviewed. Patients were separated based on mean intraoperative MAPs (<60 mmHg, 60-70 mmHg, >70 mmHg). Thirteen patients had mean intraoperative MAP <60 mmHg, 95 had MAP 60-70 mmHg, and 193 had MAP >70 mmHg. Rates of intraoperative and postoperative allogeneic blood transfusion were compared.RESULTS: Mean intraoperative MAPs were significantly different between groups (p < 0.0001). Time from injury to surgery, estimated blood loss, operative time and intraoperative IV fluids were comparable. The proportion of patients who received blood transfusion and mean units transfused intraoperatively and postoperatively were similar between groups. Mean differences in preoperative and postoperative hemoglobin and hematocrit were also similar. There was no difference in hospital length of stay or perioperative complications between the groups. Multivariate logistic regression analysis demonstrated that body mass index > 30 (p < 0.05) and anterior surgical approach (p < 0.01) were independently associated with intraoperative transfusion and an anterior surgical approach (p < 0.001) was independently associated with postoperative transfusion.CONCLUSION: Decreased intraoperative MAP during acetabular fracture surgery does not reduce blood loss or need for transfusion. On the other hand, no increased end-organ ischemia was seen with hypotensive anesthesia.LEVEL OF EVIDENCE: Therapeutic Level III.

    View details for DOI 10.1016/j.injury.2021.03.059

    View details for PubMedID 33832703

  • 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


    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

  • Trends, Payments, and Costs Associated with BMP Use in Medicare Beneficiaries Undergoing Spinal Fusion. The spine journal : official journal of the North American Spine Society Wadhwa, H., Wu, J. Y., Malacon, K., Ames, C., Ratliff, J., Zygourakis, C. 2023


    Bone morphogenic protein (BMP) promotes bony fusion but increases costs. Recent trends in BMP use among Medicare patients have not been well-characterized.To assess utilization trends, complication, payments, and costs associated with BMP use in spinal fusion in a Medicare-insured population.Retrospective cohort study PATIENT SAMPLE: : 316,070 patients who underwent spinal fusion in a 20% sample of Medicare-insured patients, 2006-2015 OUTCOME MEASURES: : Utilization trends across time and geography, complications, payments, and costs.Patients were stratified by fusion type and diagnosis. Multivariable logistic and linear regression were used to adjust for the effect of baseline characteristics on complications and total payments or cost, respectively.BMP was used in 60,249 cases (19.1%). BMP utilization rates decreased from 23.1% in 2006 to 12.0% in 2015, most significantly in anterior cervical (7.5% to 3.1%), posterior cervical (17.0% to 8.3%), and posterior lumbar fusions (31.5% to 15.8%). There are significant state- and region-level geographic differences in BMP utilization. Across all years, states with the highest BMP use were Indiana (28.5%), Colorado (26.6%), and Nevada (25.7%). States with the lowest BMP use were Maine (2.3%), Vermont (8.2%), and Mississippi (10.4%). After multivariate risk adjustment, BMP use was associated with decreased overall complications in thoracic (OR (95% CI): 0.89 (0.81-0.99) and anterior lumbar fusions (OR (95% CI): 0.89 (0.84-0.95)), as well as increased reoperation rates in anterior cervical (OR (95% CI): 1.11 (1.04-1.19)), posterior cervical (OR (95% CI): 1.14 (1.04-1.25)), thoracic (OR (95% CI): 1.32 (1.23-1.41)), and posterior lumbar fusions (OR (95% CI): 1.11 (1.06-1.16)). BMP use was also associated with greater total costs, independent of fusion type, after multivariate risk adjustment (p < 0.0001). Payments, however, were comparable between groups in anterior and posterior cervical fusion with or without BMP. BMP use was associated with greater total payments in thoracic, anterior lumbar, and posterior lumbar fusions. Notably, the difference in payments was smaller than the associated cost increase in all fusion types.BMP use has declined across all fusion types over the last decade, after a peak in 2007. While BMP is associated with greater costs, reimbursement does not increase proportionally with BMP cost.

    View details for DOI 10.1016/j.spinee.2023.01.012

    View details for PubMedID 36709918

  • Utilization Trends, Cost, and Payments for Adult Spinal Deformity Surgery in Commercial and Medicare-Insured Populations. Neurosurgery Wadhwa, H., Leung, C., Sklar, M., Ames, C. P., Veeravagu, A., Desai, A., Ratliff, J., Zygourakis, C. C. 2022


    BACKGROUND: Previous studies have characterized utilization rates and cost of adult spinal deformity (ASD) surgery, but the differences between these factors in commercially insured and Medicare populations are not well studied.OBJECTIVE: To identify predictors of increased payments for ASD surgery in commercially insured and Medicare populations.METHODS: We identified adult patients who underwent fusion for ASD, 2007 to 2015, in 20% Medicare inpatient file (n = 21614) and MarketScan commercial insurance database (n = 38789). Patient age, sex, race, insurance type, geographical region, Charlson Comorbidity Index, and length of stay were collected. Outcomes included predictors of increased payments, surgical utilization rates, total cost (calculated using Medicare charges and hospital-specific charge-to-cost ratios), and total Medicare and commercial payments for ASD.RESULTS: Rates of fusion increased from 9.0 to 8.4 per 10000 in 2007 to 20.7 and 18.2 per 10000 in 2015 in commercial and Medicare populations, respectively. The Medicare median total charges increased from $88106 to $144367 (compound annual growth rate, CAGR: 5.6%), and the median total cost increased from $31846 to $39852 (CAGR: 2.5%). Commercial median total payments increased from $58164 in 2007 to $64634 in 2015 (CAGR: 1.2%) while Medicare median total payments decreased from $31415 in 2007 to $25959 in 2015 (CAGR: -2.1%). The Northeast and Western regions were associated with higher payments in both populations, but there is substantial state-level variation.CONCLUSION: Rate of ASD surgery increased from 2007 to 2015 among commercial and Medicare beneficiaries. Despite increasing costs, Medicare payments decreased. Age, length of stay, and BMP usage were associated with increased payments for ASD surgery in both populations.

    View details for DOI 10.1227/neu.0000000000002140

    View details for PubMedID 36136402

  • Operative Versus Nonoperative Management of Unstable Spine Fractures in the Elderly: Outcomes and Mortality. Spine Malacon, K., Rangwalla, T., Wadhwa, H., Zygourakis, C. 2022


    STUDY DESIGN: Retrospective cohort study.OBJECTIVE: To assess outcomes and mortality in elderly patients following unstable spine fractures depending on treatment modality.SUMMARY OF BACKGROUND DATA: Operative management of unstable spine fractures in the elderly remains controversial due to increased risk of perioperative complications. Mortality rates after operative versus nonoperative treatment of these injuries have not been well-characterized.METHODS: Patients age >65 with unstable spine fractures without neurologic injury from 2015-2021 were identified from the Clinformatics Data Mart (CDM) Database. Demographics, complications, and mortality were collected. Multivariable logistic regression was used to adjust for the effect of baseline characteristics on mortality following unstable fracture diagnosis.RESULTS: Of 3,688 patients included, 1,330 (36.1%) underwent operative management and 2,358 (63.9%) nonoperative. At baseline, nonoperative patients were older, female, had higher Elixhauser comorbidity scores, and were more likely to have a cervical fracture. Operative patients had a longer length of stay in the hospital compared to nonoperative patients (9.7 vs. 7.7d; P<0.001). Although patients in the operative group had higher rates of readmission at 30-, 60-, 90-, and 120-days after diagnosis (P<0.01), they had lower mortality rates up to 5 years after injury. After adjusting for covariates, nonoperative patients had a 60% greater risk of mortality compared to operative patients (HR: 1.60 [1.40-1.78], P<0.001). After propensity score matching, operative patients age 65-85 had greater survivorship compared to their nonoperative counterparts.CONCLUSION: Elderly patients with an unstable spine fracture who undergo surgery experience lower mortality rates up to five years post diagnosis compared to patients who received nonoperative management, despite higher hospital readmission rates and an overall perioperative complication rate of 37.3%. Operating on elderly patients with unstable spine fractures may outweigh the risks and should be considered as a viable treatment option in appropriately selected patients.

    View details for DOI 10.1097/BRS.0000000000004466

    View details for PubMedID 36083602

  • The Role of the Flexor Carpi Radialis Groove in Trapeziometacarpal Osteoarthritis. Hand (New York, N.Y.) Mitchell, A. R., Kerkhof, F. D., Wadhwa, H., Ladd, A. L. 2022: 15589447221120844


    BACKGROUND: Thumb carpometacarpal (CMC) osteoarthritis (OA) is a common condition. The contribution of surrounding ligaments and tendons to the stability of the CMC joint is likely altered in OA. The flexor carpi radialis (FCR) tendon runs in the trapezial FCR groove and is often noted to be frayed during CMC arthroplasty. We hypothesized that decreased integrity of the FCR tendon is related to FCR groove morphology and is associated with increased severity of CMC OA.METHODS: We examined 3-dimensional surface models based on computed tomography (CT) scans of explanted trapezia from patients who underwent thumb CMC arthroplasty. Fraying of the FCR tendon was rated intraoperatively. Measurements were taken of the FCR groove to evaluate its morphology. Preoperative thumb CMC radiographs for each patient were scored using the modified Eaton classification system and the Thumb Osteoarthritis Index. Differences in the tendon groups were examined, and multivariable linear regression models were used to test the association between tendon group and FCR groove measurement.RESULTS: There were 136 patients who were categorized into 4 tendon groups: intact, minor fraying, fraying, and ruptured. There were no differences between the tendon groups on any measures.CONCLUSIONS: Our findings do not demonstrate a significant influence of FCR groove morphology on FCR tendon fraying in CMC arthroplasty patients. We also did not find a significant association between the FCR tendon state and degree of radiographic CMC OA. Further studies should investigate the in vivo FCR tendon to evaluate its tearing and inflammation in relation to basilar thumb pain.

    View details for DOI 10.1177/15589447221120844

    View details for PubMedID 36050929

  • Drilling the cement mantle in well-fixed periprosthetic femur fractures is not associated with arthroplasty-related complications. European journal of orthopaedic surgery & traumatology : orthopedie traumatologie Van Rysselberghe, N. L., DeBaun, M. R., Sanchez, M., Wadhwa, H., Pfaff, K. E., Bellino, M. J., Gardner, M. J., Bishop, J. A. 2022


    OBJECTIVE: To determine if screw fixation across a cement mantle is safe and effective during plate fixation of well-fixed periprosthetic femur fractures.DESIGN: Retrospective cohort study.SETTING: Academic Level I Trauma Center.PATIENTS: Twenty-eight patients with AO/OTA 32A[B1] or 32A[C] periprosthetic femur fractures treated with open reduction and internal plate and screw fixation after cemented or uncemented hip arthroplasty.INTERVENTION: Screw placement into the cement mantle during internal fixation.OUTCOME MEASUREMENTS: Primary outcome was revision arthroplasty for aseptic loosening. Secondary outcomes included radiographic evidence of aseptic loosening, infection, nonunion, implant failure, and overall reoperation rate.RESULTS: There were 28 patients who met inclusion criteria. A total of 9 patients had screws placed in the cement mantle while the remaining 19 patients had screws placed around an uncemented stem. At a mean of 3.7-year follow-up, there were no cases of revision arthroplasty or aseptic loosening in either group. There were no significant differences in rates of infection, nonunion, implant failure, or reoperation rate between patients who had screw placement into a cement mantle vs around an uncemented stem.CONCLUSION: Drilling into the cement mantle during fixation of a periprosthetic femur fracture around a well-fixed cemented hip stem appears safe and effective. When possible, surgeons can consider bicortical screws around a cemented stem, given the biomechanical advantages over unicortical screw or cerclage fixation. Larger prospective trials confirming the safety of this technique are warranted prior to routine implementation.LEVEL OF EVIDENCE: III.

    View details for DOI 10.1007/s00590-022-03308-w

    View details for PubMedID 35788424

  • Site of service of irrigation and debridement of open finger and hand fractures: a retrospective review of trends and outcomes CURRENT ORTHOPAEDIC PRACTICE Wadhwa, H., Zhuang, T., Shapiro, L. M., Welch, J. M., Richard, M. J., Kamal, R. N. 2022; 33 (4): 358-362
  • Site of service of irrigation and debridement of open finger and hand fractures: a retrospective review of trends and outcomes. Current orthopaedic practice Wadhwa, H., Zhuang, T., Shapiro, L. M., Welch, J. M., Richard, M. J., Kamal, R. N. 2022; 33 (4): 358-362


    Irrigation and debridement (I&D) of open finger and hand fractures can be performed in the emergency department as opposed to the operating room (OR), though reports of postoperative infection rates vary greatly. The authors hypothesized that I&D of open finger and hand fractures in the OR would decrease over time. They also describe rates of postoperative infection, reoperation, readmission, and costs.A large nationwide administrative claims dataset was retrospectively reviewed to identify patients who underwent I&D after open finger and hand fractures from 2007 to 2016. The incidence of I&D procedures performed outside the OR was reported and trends over the study period were assessed.The proportion of open finger and hand fractures that underwent I&D outside the OR did not change significantly over time. Rates of postoperative surgical site infection, readmission, and reoperation were higher in the OR cohort at 90 days after the index stay. The OR cohort had greater total costs and out-of-pocket costs for the index stay. At 90 days, the OR cohort had greater total cost, but out-of-pocket costs were similar.Site of service for treatment of open finger and hand fractures has not significantly changed from 2007 to 2016. Given that total costs are significantly greater among patients undergoing I&D in the OR, prospective trials are needed to assess the safety of treating open finger and hand fractures outside of the OR to optimize management of these injuries.III.

    View details for DOI 10.1097/bco.0000000000001123

    View details for PubMedID 36188628

    View details for PubMedCentralID PMC9524536

  • How do orthopaedic surgery residency program websites feature diversity? An analysis of 187 orthopaedic surgery programs in the United States. Current orthopaedic practice Cohen, S. A., Xiao, M., Zhuang, T., Michaud, J., Wadhwa, H., Shapiro, L., Kamal, R. N. 2022; 33 (3): 258-263


    Background: The orthopaedic surgery residency program website represents a recruitment tool that can be used to demonstrate a program's commitment to diversity and inclusion to prospective applicants. The authors assessed how orthopaedic surgery residency programs demonstrated diversity and inclusion on their program websites and whether this varied based on National Institutes of Health (NIH) funding, top-40 medical school affiliation, university affiliation, program size, or geographic region.Methods: The authors evaluated 187 orthopaedic surgery residency program websites for the presence of 12 elements that represented program commitment to diversity and inclusion values, based on prior work and ACGME recommendations. Mann-Whitney U and Kruskal-Wallis tests were used to assess whether NIH funding and other program characteristics were associated with commitment to diversity and inclusion on affiliated residency websites.Results: Orthopaedic surgery residency websites included a mean of 4.9 ± 2.1 diversity and inclusion elements, with 21% (40/187) featuring a majority (7+) of elements. Top 40 NIH funded programs (5.4 ± 2.0) did not have significantly higher website diversity scores when compared with nontop-40 programs (4.8 ± 2.1) (P = 0.250). University-based or affiliated programs (5.2 ± 2.0) had higher diversity scores when compared with community-based programs (3.6 ± 2.2) (P = 0.003).Conclusions: Most orthopaedic surgery residency websites contained fewer than half of the diversity and inclusion elements studied, suggesting opportunities for further commitment to diversity and inclusion. Inclusion of diversity initiatives on program websites may attract more diverse applicants and help address gender and racial or ethnic disparities in orthopaedic surgery.Level of Evidence: Level V.

    View details for DOI 10.1097/bco.0000000000001101

    View details for PubMedID 35685001

  • Mini-fragment plating of olecranon fractures is comparable to precontoured small-fragment plating. Journal of orthopaedics Wadhwa, H., Oquendo, Y. A., Goodnough, L. H., DeBaun, M. R., Bishop, J. A., Gardner, M. J. 2022; 30: 41-45


    Introduction: Though long-term functional outcomes of olecranon fracture plate fixation are favorable, postoperative implant irritation commonly leads to elective removal. We hypothesized that mini-fragment plates will decrease implant removal compared to precontoured plates.Methods: Patients with isolated olecranon fracture (AO/OTA 2U1-B1) treated with plate fixation were retrospectively reviewed. Patients were stratified into groups based on whether they underwent open reduction and internal fixation with a (1) surgeon contoured mini-fragment or (2) precontoured olecranon-specific plate. Rates of symptomatic implants and implant removal were compared.Results: 98 and 32 patients were treated with precontoured and mini-fragment plates, respectively. Baseline demographics and comorbidities were similar. Mean follow-up was 20.6 months. There were no differences in rates of postoperative complication (22/98, 22.4% vs. 5/32, 15.6%; p=0.41) or reoperation (37/98, 37.8% vs. 8/32, 25%; p=0.19). Symptomatic implants were common in the precontoured cohort (44/98, 44.9% vs. 7/32, 21.9%; p<0.05). Implant removal rates were 36.7% and 18.8%, respectively (p=0.06).Discussion/conclusion: Olecranon fracture stabilization with mini-fragment plate is associated with lower rates of symptomatic implants, with no difference in postoperative complications or reoperations. Mini-fragment plating is a safe and promising alternative to precontoured plating.

    View details for DOI 10.1016/j.jor.2022.02.009

    View details for PubMedID 35241886

  • A bioactive synthetic membrane improves bone healing in a preclinical nonunion model. Injury DeBaun, M. R., Salazar, B. P., Bai, Y., Gardner, M. J., Yang, Y. P., Stanford iTEAM group, Pan, C., Stahl, A. M., Moeinzadeh, S., Kim, S., Lui, E., Kim, C., Lin, S., Goodnough, L. H., Wadhwa, H. 1800


    OBJECTIVES: High energy long bone fractures with critical bone loss are at risk for nonunion without strategic intervention. We hypothesize that a synthetic membrane implanted at a single stage improves bone healing in a preclinical nonunion model.METHODS: Using standard laboratory techniques, microspheres encapsulating bone morphogenic protein-2 (BMP2) or platelet derived growth factor (PDGF) were designed and coupled to a type 1 collagen sheet. Critical femoral defects were created in rats and stabilized by locked retrograde intramedullary nailing. The negative control group had an empty defect. The induced membrane group (positive control) had a polymethylmethacrylate spacer inserted into the defect for four weeks and replaced with a bare polycaprolactone/beta-tricalcium phosphate (PCL/beta-TCP) scaffold at a second stage. For the experimental groups, a bioactive synthetic membrane embedded with BMP2, PDGF or both enveloped a PCL/beta-TCP scaffold was implanted in a single stage. Serial radiographs were taken at 1, 4, 8, and 12 weeks postoperatively from the definitive procedure and evaluated by two blinded observers using a previously described scoring system to judge union as primary outcome.RESULTS: All experimental groups demonstrated better union than the negative control (p=0.01). The groups with BMP2 incorporated into the membrane demonstrated higher average union scores than the other groups (p=0.01). The induced membrane group performed similarly to the PDGF group. Complete union was only demonstrated in groups with BMP2-eluting membranes.CONCLUSIONS: A synthetic membrane comprised of type 1 collagen embedded with controlled release BMP2 improved union of critical bone defects in a preclinical nonunion model.

    View details for DOI 10.1016/j.injury.2022.01.015

    View details for PubMedID 35078617

  • Countersinking the Lag Screw or Blade During Cephalomedullary Nailing of Geriatric Intertrochanteric Femur Fractures: Less Collapse and Implant Prominence Without Increased Cutout Rates. The Journal of the American Academy of Orthopaedic Surgeons Henry Goodnough, L., Wadhwa, H., Tigchelaar, S. S., Pfaff, K., Heffner, M., van Rysselberghe, N., DeBaun, M. R., Gardner, M. J., Bishop, J. A. 1800; 30 (1): e83-e90


    INTRODUCTION: The lag screw or helical blade of a cephalomedullary nail facilitates controlled collapse of intertrochanteric proximal femur fractures. However, excessive collapse results in decreased hip offset and symptomatic lateral implants. Countersinking the screw or helical blade past the lateral cortex may minimize subsequent prominence, but some surgeons are concerned that this will prevent collapse and result in failure through cutout. We hypothesized that patients with countersunk lag screws or helical blades do not experience higher rates of screw or blade cutout and have less implant prominence after fracture healing.METHODS: A retrospective review of 175 consecutive patients treated with cephalomedullary nails for AO/OTA 31A1-3 proximal femur fractures and a minimum 3-month follow-up and 254 patients with a 6-week follow-up at a single US level I trauma center. Patients were stratified based on countersunk versus noncountersunk lag screw or helical blade in a cephalomedullary nail. The primary outcome was the cutout rate at minimum 3 months, and the secondary outcome was radiographic collapse at minimum 6 weeks.RESULTS: Cutout rates were no different in patients with countersunk and noncountersunk screws and blades, and countersinking was associated with less collapse and less implant prominence at 6 weeks.DISCUSSION: Surgeons can countersink the lag screw or blade when treating intertrochanteric proximal femur fractures with a cephalomedullary nail without increasing failure rates and with the potential benefits of less prominent lateral implants and decreased collapse.

    View details for DOI 10.5435/JAAOS-D-20-01029

    View details for PubMedID 34932507

  • CHARACTERIZATION OF CANCER-ASSOCIATED FIBROBLASTS IN GBM AND DEFINING THEIR PRO-TUMORAL EFFECTS Jain, S., Rick, J., Joshi, R., Beniwal, A., Spatz, J., Chang, A., Nguyen, A., Shudir, S., Chandra, A., Haddad, A., Wadhwa, H., Shah, S., Choi, S., Yagnik, G., Costello, J., Diaz, A., Aghi, M. K. OXFORD UNIV PRESS INC. 2021: 200
  • Do Epidural Steroid Injections Affect Outcomes and Costs in Cervical Degenerative Disease? A Retrospective MarketScan Database Analysis. Global spine journal Wadhwa, H., Varshneya, K., Stienen, M. N., Veeravagu, A. 2021: 21925682211050320


    STUDY DESIGN: Retrospective cohort study.OBJECTIVE: To investigate the effect of preoperative epidural steroid injection (ESI) on quality outcomes and costs in patients undergoing surgery for cervical degenerative disease.METHODS: We queried the MarketScan database, a national administrative claims dataset, to identify patients who underwent cervical degenerative surgery from 2007 to 2016. Patients under 18 and patients with history of tumor or trauma were excluded. Patients were stratified by ESI use at 3, 6, 12, 18, and 24 or more months preoperative. Propensity score matched controls for these groups were obtained. Baseline demographics, postoperative complications, reoperations, readmissions, and costs were compared via univariate and multivariate analysis.RESULTS: 97117 patients underwent cervical degenerative surgery, of which 29963 (30.7%) had ESI use at any time preoperatively. Overall, 90-day complication rate was not significantly different between groups. The ESI cohorts had shorter length of stay, but higher 90-day readmission and reoperation rates. ESI use was associated with higher total payments through the 2-year follow-up period. Among patients who received preoperative ESI, male sex, history of cancer, obesity, PVD, rheumatoid arthritis, nonsmokers, cervical myelopathy, BMP use, anterior approach, 90-day complication, 90-day reoperation, and 90-day readmission were independently associated with increased 90-day total cost.CONCLUSION: ESI can offer pain relief in some patients refractory to other conservative management techniques, but those who eventually undergo surgery have greater healthcare resource utilization. Certain characteristics can predispose patients who receive preoperative ESI to incur higher healthcare costs.

    View details for DOI 10.1177/21925682211050320

    View details for PubMedID 34686085

  • First case report using optical topographic-guided navigation in revision spinal fusion for calcified thoracic disk. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia Sklar, M., Fatemi, P., Wadhwa, H., Leung, C., Zygourakis, C. 2021; 91: 80-83


    Computer assisted navigation systems are frequently used in spine surgery to improve the accuracy of pedicle screw placement. The 7D Surgical System utilizes optical topographic imaging (OTI) with a camera positioned directly above the surgical field to perform rapid registration from a pre-operative CT scan onto anatomical landmarks with zero intra-operative radiation exposure. This current technology requires an open approach with well-exposed bony anatomy, raising concerns about using the 7D Surgical System in revision surgery, where typical anatomical landmarks may be altered, missing, or obscured by prior hardware. To overcome this, the 7D Surgical System is capable of registering off prior hardware. Here, we present the first published report of 7D Surgical System's registration off prior hardware in a revision spinal fusion. The registration was accurate, and the workflow was easy and efficient with one registration required for 3 levels of instrumentation and discectomy/corpectomy. This demonstrates that the 7D Surgical System can be used in revision cases with altered, missing, or obscured anatomy.

    View details for DOI 10.1016/j.jocn.2021.06.031

    View details for PubMedID 34373063

  • Geographic landscape of foreign medical graduates in US neurosurgery training programs from 2007 to 2017. Clinical neurology and neurosurgery Chandra, A., Brandel, M. G., Wadhwa, H., Pereira, M. P., Lewis, C. T., Haddad, Y. W., Lu, V. M., Almeida, N. D., Nuru, M. O., Esquenazi, Y., Aghi, M. K. 2021; 209: 106891


    OBJECTIVE: Although foreign medical graduates (FMGs) have been essential to the US physician workforce, the increasing competitiveness has made it progressively challenging for FMGs to match in US neurosurgery programs. We describe geographic origins and characteristics associated with successful match into US neurosurgery training programs.METHODS: Retrospective review of AANS membership data (2007-2017). Scopus was used to collect bibliometrics.RESULTS: From 2009 neurosurgical residents, 165 (8.2%) were FMGs. Most were male (n=148; 89.6%) with a median age of 34.0 years. Top six feeder countries (TFC) included India (13.9%; n=23), Lebanon and Pakistan (9.1%; n=15), Caribbean Region (7.2%; n=12), Mexico (6.67%; n=11), and Greece (3.6%; n=6). Compared to FMGs from non-top feeder countries (NTFC), TFC FMGs had higher H-indices (2 vs 4, p=0.049), greater number of publications (2 vs 5, p=0.04), were more likely to have an MBBS/MBBCh (n=38 vs n=17, p=0.03), and had twice as many candidates from major feeder medical schools that successfully matched into a US neurosurgery program (n=43 vs NTFC=20, p<0.001). NTFC FMGs were almost 3-times more likely to match at an affiliated neurosurgery program (8 vs TFC=3, p=0.03), while TFC FMGs were 1.5-times more likely to match at an NIH Top-40 program (33 vs NTFC=21, p=0.03).CONCLUSIONS: TFC graduates have higher bibliometrics, frequently come from major feeder schools, and have greater match success at a broader selection of programs and NIH top-40 programs. Future studies characterizing FMG country and medical school origins may enable foreign students to geographically target institutions of interest and could allow US programs to better evaluate foreign training environments.

    View details for DOI 10.1016/j.clineuro.2021.106891

    View details for PubMedID 34492549

  • Comparison of the Distribution of Standardized Cosmesis and Health Nasal Outcomes Survey Scores Between Symptomatic and Asymptomatic Patients. Facial plastic surgery & aesthetic medicine Patel, P. N., Wadhwa, H., Okland, T., Kandathil, C. K., Most, S. P. 2021


    Background: The Standardized Cosmesis and Health Nasal Outcomes Survey (SCHNOS) is a validated patient-reported outcome measure that evaluates subjective cosmetic and functional complaints. The goal of this study was to compare scores between patients with and without nasal complaints. Methods: This is a retrospective review of SCHNOS-O (obstructive) and SCHNOS-C (cosmetic) scores in patients presenting for functional or cosmetic concerns between 2019 and 2020. Receiver operating characteristic curve analysis was used to determine the score that best separated symptomatic from asymptomatic patients. SCHNOS scores were also subdivided to define severity of presenting complaints. Results: In total, 414 patients were included. A SCHNOS-O score of 40 differentiated patients with and without nasal obstruction. Patients may be categorized as having mild (<40), moderate (45-70), and severe (75-100) nasal obstruction based on the SCHNOS-O score. A score of 30 on the SCHNOS-C differentiated patients with and without aesthetic concerns. Patients may be categorized as having mild (<33.3), moderate (33.3-66.6), and severe (>66.6) aesthetic distress based on the SCHNOS-C. Conclusion: An understanding of SCHNOS scores that differentiate symptomatic for asymptomatic patients can aid in the preoperative evaluation of rhinoplasty patients.

    View details for DOI 10.1089/fpsam.2021.0054

    View details for PubMedID 34185595

  • Surgical Outcomes of Human Immunodeficiency Virus-positive Patients Undergoing Lumbar Degenerative Surgery. Clinical spine surgery Varshneya, K., Wadhwa, H., Ho, A. L., Medress, Z. A., Stienen, M. N., Desai, A., Ratliff, J. K., Veeravagu, A. 2021


    STUDY DESIGN: This was a retrospective cohort studying using a national administrative database.OBJECTIVE: The objective of this study was to determine the postoperative complications and quality outcomes of the human immunodeficiency virus (HIV)-positive patients undergoing surgical management for lumbar degenerative disease (LDD).METHODS: This study identified patients with who underwent surgery for LDD between 2007 and 2016. Patients were stratified based on whether they were HIV positive at the time of surgery. Multivariate regression was utilized to reduce the confounding of baseline covariates. Patients who underwent 3 or more levels of surgical correction were under the age of 18 years, or those with any prior history of trauma or tumor were excluded from this study. Baseline comorbidities, postoperative complication rates, and reoperation rates were determined.RESULTS: A total of 120,167 patients underwent primary lumbar degenerative surgery, of which 309 (0.26%) were HIV positive. In multivariate regression analysis, the HIV-positive cohort was more likely to be readmitted at 30 days [odds ratio (OR)=1.9, 95% confidence interval (CI): 1.2-2.8], 60 days (OR=1.7, 95% CI: 1.2-2.5), and 90 days (OR=1.5, 95% CI: 1.0-2.2). The HIV-positive cohort was also more likely to experience any postoperative complication (OR=1.7, 95% CI: 1.2-2.3). Of the major drivers identified, HIV-positive patients had significantly greater odds of cerebrovascular disease and postoperative neurological complications (OR=3.8, 95% CI: 1.8-6.9) and acute kidney injury (OR=3.4, 95% CI: 1.3-7.1). Costs of index hospitalization were not significantly different between the 2 cohorts ($30,056 vs. $29,720, P=0.6853). The total costs were also similar throughout the 2-year follow-up period.CONCLUSION: Patients who are HIV positive at the time of LDD surgery are at a higher risk for postoperative central nervous system and renal complications and unplanned readmissions.

    View details for DOI 10.1097/BSD.0000000000001221

    View details for PubMedID 34183544

  • One surgeon's learning curve with single position lateral lumbar interbody fusion: perioperative outcomes and complications. Journal of spine surgery (Hong Kong) Warren, S. I., Wadhwa, H., Koltsov, J. C., Michaud, J. B., Cheng, I. 2021; 7 (2): 162-169


    Background: Single position (SP) lateral transpsoas lumbar interbody fusion (LLIF) with posterior pedicle screw fixation (PPSF) reduces operative time compared to dual positioning. However, the learning curve has not yet been described. The purpose of this study was to define the learning curve SP LLIF with PPSF.Methods: This retrospective case series included the first 161 consecutive patients who underwent SP LLIF and PPSF with the senior author. Primary analysis of operative time versus case number included single level cases without adjacent level procedures. Secondary analyses included 1-3 level cases without adjacent level procedures. Operative time for 2 and 3 level procedures was normalized to single-level cases. The learning curve was assessed with linear regression, which was found to fit the data better than logarithmic regression as judged by R2 values and data visualization. Perioperative outcomes as a function of case number were analyzed by least squares linear regression and Mann Whitney U-tests.Results: For single level surgeries without adjacent procedures (n=87), operative time decreased by a total of 28.7 (95% CI, 9.6, 47.9) minutes over the series (P<0.001). For 1-3 level cases with no adjacent procedures (n=131), normalized operative time decreased by 23.1 (7.6, 38.6) minutes (P<0.001). Post-operative change in hematocrit, length of hospital stay, post-operative change in lordosis, 90-day complications, suboptimal screw placement, and 6-week post-operative Oswestry Disability Index (ODI) score did not correlate with case number. Intraoperative fluids decreased 3.7 mL (95% CI, 0.7, 6.7) per case (P=0.015).Conclusions: In SP LLIF with PPSF, case number correlated with decreased operative time, but not complications. The surgeon's prior experience with dual position (DP) LLIF likely contributed to the minimal learning curve observed. Surgeons adopting SP LLIF with minimal prior DP LLIF experience may experience a steeper curve.

    View details for DOI 10.21037/jss-21-13

    View details for PubMedID 34296028

  • First reported use of real-time intraoperative computed tomography angiography image registration using the Machine-vision Image Guided Surgery system: illustrative case. Journal of neurosurgery. Case lessons Wadhwa, H., Malacon, K., Medress, Z. A., Leung, C., Sklar, M., Zygourakis, C. C. 2021; 1 (18): CASE2125


    Vertebral artery injury is a devastating potential complication of C1-2 posterior fusion. Intraoperative navigation can reduce the risk of neurovascular complications and improve screw placement accuracy. However, the use of intraoperative computed tomography (CT) increases radiation exposure and operative time, and it is unable to image vascular structures. The Machine-vision Image Guided Surgery (MvIGS) system uses optical topographic imaging and machine vision software to rapidly register using preoperative imaging. The authors presented the first report of intraoperative navigation with MvIGS registered using a preoperative CT angiogram (CTA) during C1-2 posterior fusion.MvIGS can register in seconds, minimizing operative time with no additional radiation exposure. Furthermore, surgeons can better adjust for abnormal vertebral artery anatomy and increase procedure safety.CTA-guided navigation generated a three-dimensional reconstruction of cervical spine anatomy that assisted surgeons during the procedure. Although further study is needed, the use of intraoperative MvIGS may reduce the risk of vertebral artery injury during C1-2 posterior fusion.

    View details for DOI 10.3171/CASE2125

    View details for PubMedID 35855470

    View details for PubMedCentralID PMC9245760

  • Tranexamic acid does not affect intraoperative blood loss or in-hospital outcomes after acetabular fracture surgery. European journal of orthopaedic surgery & traumatology : orthopedie traumatologie Wadhwa, H., Tigchelaar, S. S., Chen, M. J., Koltsov, J. C., Bellino, M. J., Bishop, J. A., Gardner, M. J. 2021


    PURPOSE: Tranexamic acid (TXA) reduces need for transfusion in total joint arthroplasty, though findings in acetabular surgery are conflicting. We compared outcomes after acetabular fracture surgery with or without perioperative intravenous (IV) TXA administration.METHODS: We performed a retrospective review of 305 patients with acetabular fractures that underwent open reduction and internal fixation (ORIF). Eighty-nine patients received TXA, and 216 did not. The primary outcome was rates of intraoperative and postoperative allogeneic blood transfusion.RESULTS: Baseline demographics and characteristics were similar. Time from injury to surgery and estimated blood loss were comparable. Operative time (p<0.01) and intraoperative IV fluids (p<0.01) were greater in the non-TXA group. The proportion of patients who received blood transfusion and mean units transfused intraoperatively and postoperatively did not differ. Mean differences in preoperative and postoperative hemoglobin and hematocrit, hospital length of stay, and perioperative complications also did not differ. In a multivariable regression model, age 60-70years, Charlson Comorbidity Index, Injury Severity Score, and fracture patterns likely to bleed were independently associated with intraoperative transfusion. Anterior surgical approaches and intraoperative transfusion requirement were independently associated with postoperative transfusion.CONCLUSION: In this study, perioperative IV TXA did not decrease blood loss, need for transfusion, or improve in-hospital outcomes of acetabular fracture surgery. Age 60-70, CCI, ISS, and fracture patterns likely to bleed were independently associated with intraoperative transfusion. Anterior surgical approach and need for intraoperative transfusion were independently associated with postoperative transfusion. Further prospective trials are warranted to confirm these findings.

    View details for DOI 10.1007/s00590-021-02985-3

    View details for PubMedID 33891154

  • 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


    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

  • Telehealth Adoption Across Neurosurgical Subspecialties at a Single Academic Institution During the COVID-19 Pandemic. World neurosurgery Leung, C., Wadhwa, H., Sklar, M., Sheth, K., Loo, S., Ratliff, J., Zygourakis, C. C. 2021


    OBJECTIVE: The COVID-19 pandemic has dramatically changed healthcare, forcing providers to adopt and implement telehealth technology to provide continuous care for their patients. Amid this rapid transition from in-person to remote visits, differences in telehealth utilization have arisen among neurosurgical subspecialties. In this study, we analyze the impact of telehealth on neurosurgical healthcare delivery during the COVID-19 pandemic at our institution and highlight differences in telehealth utilization across different neurosurgical subspecialties.METHODS: To quantify differences in telehealth utilization, we analyzed all outpatient neurosurgery visits at a single academic institution. Internal surveys were administered to neurosurgeons and to patients to determine both physician and patient satisfaction with telehealth visits. Patient Likelihood-to-Recommend Press Ganey scores were also evaluated.RESULTS: There was a decrease in outpatient visits during the COVID-19 pandemic in all neurosurgical subspecialties. Telehealth adoption was higher in spine, tumor, and interventional pain than in functional, peripheral nerve, or vascular neurosurgery. Neurosurgeons agreed that telehealth was an efficient (92%) and effective (85%) methodology; however, they noted it was more difficult to evaluate and bond with patients. The majority of patients were satisfied with their video visits and would recommend video visits over in-person visits.CONCLUSIONS: During the COVID-19 pandemic, neurosurgical subspecialties varied in adoption of telehealth, which may be due to the specific nature of each subspecialty and their necessity to perform in-person evaluations. Telehealth visits will likely continue after the pandemic as they can improve clinical efficiency; overall both patients and physicians are satisfied with healthcare delivery over video.

    View details for DOI 10.1016/j.wneu.2021.03.062

    View details for PubMedID 33746106

  • 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


    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

  • Effect of Lateral Crural Procedures on Nasal Wall Stability and Tip Aesthetics in Rhinoplasty. The Laryngoscope Abdelwahab, M., Patel, P., Kandathil, C. K., Wadhwa, H., Most, S. P. 2021


    OBJECTIVES/HYPOTHESIS: To evaluate the lateral nasal wall stability, nasal function, and cosmesis when creating an aesthetically pleasing nasal tip subunit utilizing lateral crus (LC) altering procedures.STUDY DESIGN: Retrospective cohort.METHODS: In this retrospective cohort study, cosmetic rhinoplasty patients undergoing LC procedures with available lateral wall insufficiency (LWI) scores were included. An LWI grading system was used to evaluate internal (zone 1) and external (zone 2) nasal valves objectively. Secondarily, Nasal Obstruction Symptom Evaluation (NOSE) Score, Visual Analog Scale (VAS) and Standardized Cosmesis and Health Nasal Outcomes Survey (SCHNOS) results were evaluated. Based on the LC intervention, the cohort was divided into six groups: lateral cural strut graft (LCSG), mini-LCSG, lateral crural overlay (LCO) with and without additional support, cephalic trimming, and cephalic turn-in flaps.RESULTS: Subjects undergoing LCO with and without support, LCSG, and mini-LCSG showed significant improvement in zone 1 LWI (P =.042, P =.041, P <.001, and P <.001, respectively), while cephalic trimming and turn-in/hinged flaps had no effect. Subjects undergoing LCO with support and LCSG showed significant improvement in zone 2 LWI (P =.022, P =.004), while LCO without support, mini-LCSG, cephalic trimming, and turn-in flaps showed no effect on LWI. The SCHNOS-C and VAS-C showed significant improvement in all subgroups (P <.05) when comparing pre- to postoperative values. Alar-spanning sutures did not significantly change zone 1 scores but did conceal zone 2 improvements in LCSG and LCO with support groups.CONCLUSIONS: Selected LC procedures are robust techniques for improving tip cosmesis independently without compromising nasal lateral wall stability. Some LC procedures can improve nasal valves patency in tip surgery. Laryngoscope, 2021.

    View details for DOI 10.1002/lary.29389

    View details for PubMedID 33459395

  • Functional neurological disorders in patients undergoing spinal surgery: illustrative case. Journal of neurosurgery. Case lessons Yerneni, K., Wadhwa, H., Fatemi, P., Zygourakis, C. C. 2021; 1 (2): CASE2068


    "Conversion disorder" refers to bodily dysfunction characterized by either sensory or motor neurological symptoms that are unexplainable by a medical condition. Given their somatosensory context, such disorders often require extensive medical evaluation, and the diagnosis can only be made after structural disease is excluded or fails to account for the severity and/or spectrum of the patient's deficits.The authors briefly review functional psychiatric disorders and discuss the comprehensive workup of a patient with a functional postoperative neurological deficit, drawing from their recent experience with a patient who presented with conversion disorder immediately after undergoing anterior cervical discectomy and fusion.Conversion disorder has been found to be associated with bodily stress, requiring surgeons to be aware of this condition in the postoperative setting. This is especially true in neurosurgery, given the overlap of true neurological pathology, postoperative complications, and manifestations of conversion disorder. Although accurately diagnosing and managing patients with conversion disorder remains challenging, an understanding of the multifactorial nature of its etiology can help clinicians develop a methodical approach to this condition.

    View details for DOI 10.3171/CASE2068

    View details for PubMedID 35854933

    View details for PubMedCentralID PMC9241316

  • Gluteus Minimus Debridement During Acetabular Fracture Surgery Does Not Prevent Heterotopic Ossification - A Comparative Study. Journal of orthopaedic trauma Chen, M. J., Tigchelaar, S. S., Wadhwa, H. n., Frey, C. S., Bishop, J. A., Gardner, M. J., Bellino, M. J. 2021


    To compare rates of heterotopic ossification (HO) after acetabular fracture surgery, through a posterior approach, with and without gluteus minimus muscle (GMM) debridement.Retrospective comparative study.Single academic Level I trauma center.Ninety-four patients in the GMM preserved group and 42 patients in the GMM debrided group met inclusion criteria.GMM preservation or debridement during acetabular fracture surgery through a single-posterior approach.Primary outcomes were incidence and severity of HO. Reoperation for HO excision was assessed. Other risk factors for severe HO (Brooker class III-IV) were secondarily assessed using multivariable logistic regression analyses. Odds ratios (OR) with 95% confidence intervals (CI) were calculated. Significance was set at p-value ≤ 0.05.There was no difference in the incidence or severity of HO between the debrided and preserved groups. Rates of reoperation for HO excision were comparable. American Society of Anesthesiologists (ASA) physical status class (OR = 3.3), head injury (OR = 4.6), and abdominal injury (OR = 4.5) were associated with severe HO.GMM debridement was not associated with a decreased incidence of HO after acetabular fracture surgery. ASA class is a novel risk factor associated with severe HO formation.Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

    View details for DOI 10.1097/BOT.0000000000002061

    View details for PubMedID 33480642

  • First reported use of real-time intraoperative computed tomography angiography image registration using the Machine-vision Image Guided Surgery system: illustrative case Journal of Neurosurgery: Case Lessons Wadhwa, H., Malacon, K., Medress, Z. A., Leung, C., Sklar, M., Zygourakis, C. C. 2021

    View details for DOI 10.3171/CASE2125

  • 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


    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

  • Obesity in Patients Undergoing Lumbar Degenerative Surgery-A Retrospective Cohort Study of Postoperative Outcomes. Spine Varshneya, K., Wadhwa, H., Stienen, M. N., Ho, A. L., Medress, Z. A., Aikin, J., Li, G., Desai, A., Ratliff, J. K., Veeravagu, A. 2021; 46 (17): 1191-1196


    Retrospective cohort studying using a national, administrative database.The aim of this study was to determine the postoperative complications and quality outcomes of patients with and without obesity undergoing surgical management for lumbar degenerative disease (LDD).Obesity is a global epidemic that negatively impacts health outcomes. Characterizing the effect of obesity on LDD surgery is important given the growing elderly obese population.This study identified patients with who underwent surgery for LDD between 2007 and 2016. Patients were stratified based on whether the patient had a concurrent diagnosis of obesity at time of surgery. Propensity score matching (PSM) was then utilized to mitigate intergroup differences between patients with and without obesity. Patients who underwent three or more levels surgical correction, were under the age of 18 years, or those with any previous history of trauma or tumor were excluded from this study. Baseline comorbidities, postoperative complication rates, and reoperation rates were determined.A total of 67,215 patients underwent primary lumbar degenerative surgery, of which 22,405 (33%) were obese. After propensity score matching, baseline covariates of the two cohorts were similar. The complication rate was 8.3% in the nonobese cohort and 10.4% in the obese cohort (P < 0.0001). Patients with obesity also had longer lengths of stay (2.7 days vs. 2.4 days, P < 0.05), and higher rates of reoperation and readmission at all time-points through the study follow-up period to their nonobese counterparts (P < 0.05). Including payments after discharge, lumbar degenerative surgery in patients with obesity was associated with higher payments throughout the 2-year follow-up period ($68,061 vs. $59,068 P < 0.05).Patients with a diagnosis of obesity at time of LDD surgery are at a higher risk for postoperative complications, reoperation, and readmission.Level of Evidence: 4.

    View details for DOI 10.1097/BRS.0000000000004001

    View details for PubMedID 34384097

  • Single vs Multistage Surgical Management of Single and Two-Level Lumbar Degenerative Disease. World neurosurgery Varshneya, K., Wadhwa, H., Stienen, M. N., Ho, A. L., Medress, Z. A., Herrick, D. B., Desai, A., Ratliff, J. K., Veeravagu, A. 2021


    Retrospective cohort studying using a national, administrative database.To determine the postoperative complications and quality outcomes of single and multi-stage surgical management for lumbar degenerative disease (LDD).This study identified patients with who underwent surgery for LDD between 2007 - 2016. Patients were stratified based on whether their surgeon choose to correct their LDD in a single or multistage manner, and these cohorts were mutually exclusive. Propensity score matching (PSM) was then utilized to mitigate intergroup differences between single and multi-stage patients. Patients who underwent three or more levels surgical correction, were under the age of 18 years, or those with any prior history of trauma or tumor were excluded from this study. Baseline comorbidities, postoperative complication rates, and reoperation rates were determined.A total of 47,190 patients underwent primary surgery for LDD, of which 9,438 (20%) underwent multi-stage surgery. After propensity score matching, baseline covariates of the two cohorts were similar. The complication rate was 6.1% in the single stage cohort and 11.0% in the multistage cohort. Rates of post-hemorrhagic anemia, infection, wound complication, DVT, and hematoma were all higher in the multistage cohort. Lengths of stay, revision, and readmission rates were also significantly higher in the multi-stage cohort. Through 2-years of follow up, multi-stage surgery was associated with higher payments throughout the 2-year follow-up period ($57,036 vs $39,318, p < 0.05).Single stage surgery for lumbar degenerative disc disease demonstrates improved outcomes and lower healthcare utilization. Spine surgeons should carefully consider single-stage surgery when treating patients with less than three-level LDD.

    View details for DOI 10.1016/j.wneu.2021.05.115

    View details for PubMedID 34087456

  • Anterior Cervical Discectomy and Fusion vs. Laminoplasty for Multilevel Cervical Spondylotic Myelopathy: A National Administrative Database Analysis. World neurosurgery Wadhwa, H., Sharma, J., Varshneya, K., Fatemi, P., Nathan, J., Medress, Z. A., Stienen, M. N., Ratliff, J. K., Veeravagu, A. 2021


    Anterior cervical discectomy and fusion (ACDF) is effective for treatment of single level cervical spondylotic myelopathy (CSM), but data surrounding multilevel CSM remains controversial. One alternative is laminoplasty, though evidence comparing these strategies remains sparce. In this paper, we retrospectively review readmission and reoperation rates among patients undergoing ACDF or laminoplasty for multilevel CSM from a national longitudinal administrative claims database.We queried the MarketScan Commercial Claims and Encounters database to identify patients who underwent ACDF or laminoplasty for multilevel CSM from 2007-2016. Patients were stratified by operation type. Patients younger than 18 years of age, with a history of tumor or trauma, or underwent an anterior-posterior approach were excluded from this study.A total of 5,445 patients were included, of which 1,521 underwent laminoplasty. A matched cohort who underwent ACDF was identified. The overall 90-day postoperative complication rate was higher in the laminoplasty cohort (OR 1.48 (95% CI 1.18 - 1.86); p < 0.0001). Mean length of stay and 90-day rates of readmission were higher in the laminoplasty cohort. Hospital and total costs of the index hospitalization were higher in the ACDF cohort, as were total payments up to 2 years after the index hospitalization.In this administrative claims database study, there was no difference in reoperation rate between ACDF and laminoplasty. ACDF had fewer complications and readmissions than laminoplasty but was associated with higher costs. Further, prospective research should investigate the factors driving the higher cost of ACDF in this population, and long-term clinical outcomes.

    View details for DOI 10.1016/j.wneu.2021.06.064

    View details for PubMedID 34153482

  • Functional neurological disorders in patients undergoing spinal surgery: illustrative case Journal of Neurosurgery: Case Lessons Yerneni, K., Wadhwa, H., Fatemi, P., Zygourakis, C. C. 2021; 1 (2)

    View details for DOI 10.3171/CASE2068

  • Risk of Venous Thromboembolism Following Rhinoplasty. Aesthetic surgery journal Okland, T. S., Wadhwa, H. n., Patel, P. N., Most, S. P. 2021


    Although prior studies have identified a low risk of venous thromboembolism (VTE) in rhinoplasty, these studies are limited by small samples, and associated risk factors remain unknown.We sought to discern the incidence of VTE following rhinoplasty in a large patient population using a nationwide insurance claims database.Population-based retrospective analysis of insurance claims of patients who underwent rhinoplasty between 2007 and 2016. Established risk factors for VTE, demographic data, procedural details, and absolute incidence of VTE were collected.We identified a total of 55,287 patients who underwent rhinoplasty from 2007 to 2016. Mean age (SEM) was 38.74 ± 0.06 (range 18-74), and 54% were female. The overall incidence of VTE was 111, of which 70 were DVT, 41 were PE. On multivariate regression analysis, previous VTE (OR, 52.8, 95% CI, 35.2-78.6, p < 0.0001), PICC/central line placement (OR, 19.6, 95% CI, 9.8-153, p < 0.05), rib graft (OR, 4.6, 95% CI, 2.3-8.5, p < 0.0001), age 41-60 (OR, 2.65, 95% CI, 1.7-4.3 p < 0.01), IBD (OR 2.6, 95% CI, 1.0-5.5, p < 0.05), and age 61-74 (OR, 2.4, 95% CI, 1.2-4.8, p < 0.05) were associated with an increased risk of VTE.We demonstrate a low overall incidence of VTE in rhinoplasty patients. Previous VTE, PICC/central line, advancing age, IBD and intraoperative rib graft harvest were most strongly associated with VTE in this population cohort.

    View details for DOI 10.1093/asj/sjaa427

    View details for PubMedID 33388763

  • Advanced Age Does Not Impact Outcomes After 1-level or 2-level Lateral Lumbar Interbody Fusion. Clinical spine surgery Wadhwa, H., Oquendo, Y. A., Tigchelaar, S. S., Warren, S. I., Koltsov, J. C., Desai, A., Veeravagu, A., Alamin, T. F., Ratliff, J. K., Hu, S. S., Cheng, I. 2021


    This was a retrospective comparative study.The objective of this study was to assess the effect of increased age on perioperative and postoperative complication rates, reoperation rates, and patient-reported pain and disability scores after lateral lumbar interbody fusion (LLIF).LLIF was developed to minimize soft tissue trauma and reduce the risk of vascular injury; however, there is little evidence regarding the effect of advanced age on outcomes of LLIF.Patients who underwent LLIF from 2009 to 2019 at one institution with a minimum 6-month follow-up were retrospectively reviewed. Patients less than 18 years old with musculoskeletal tumor or trauma were excluded. The primary outcome was the preoperative to postoperative change in the Numeric Pain Rating Scale (NPRS) for back pain. Operative time, estimated blood loss, length of stay, perioperative and 90-day complications, unplanned readmissions, reoperations, and change in Oswestry Disability Index were also evaluated. Relationships with age were assessed both with age as a continuous variable and segmenting by age below 70 versus 70+.In total, 279 patients were included. The median age was 65±13 years and 159 (57%) were female. Age was not related to improvements in back NPRS and Oswestry Disability Index. Operative time, estimated blood loss, length of stay, perioperative and 90-day complications, unplanned readmissions, reoperations, and radiographic fusion rate also were not related to age. After multivariable risk adjustment, increasing age was associated with greater improvements in back NPRS. The decrease in back NPRS was 0.68 (95% confidence interval: 0.14, 1.22; P=0.014) points greater for every 10-year increase in age. Age was not associated with rates of complication, readmission, or reoperation.LLIF is a safe and effective procedure in the elderly population. Advanced age is associated with larger improvements in preoperative back pain. Surgeons should consider the benefits of LLIF and other minimally invasive techniques when evaluating elderly candidates for lumbar fusion.Level III.

    View details for DOI 10.1097/BSD.0000000000001270

    View details for PubMedID 34724454

  • Management of the posterior wall fracture in associated both column fractures of the acetabulum. European journal of orthopaedic surgery & traumatology : orthopedie traumatologie Chen, M. J., Hollyer, I. n., Wadhwa, H. n., Tigchelaar, S. S., Van Rysselberghe, N. L., Bishop, J. A., Bellino, M. J., Gardner, M. J. 2021


    The primary aim of this study was to compare clinical outcomes in patients with associated both column (ABC) acetabular fractures with fracture of the posterior wall (PW), in which the PW underwent reduction and fragment-specific fixation versus those that were treated with column fixation alone. Secondary aims were to assess PW fracture incidence and morphology, as well as to compare radiographic outcomes including fracture healing and interval displacement of the PW in those that did and did not undergo fragment-specific fixation of the PW.This was a retrospective series of ABC acetabular fractures treated at a single Level I trauma center. Separate fractures of the PW were identified, and associated features were assessed. Associated both column fractures that underwent reduction and fragment-specific fixation of the PW where then compared to ABC fractures with PW involvement that underwent column reconstruction alone. Radiographic and clinical outcomes were compared.Fractures of the PW occurred in 55.7% of ABC fractures and were associated with central displacement of the femoral head. The majority of PW fractures were large and involved the acetabular roof. All PW fractures healed without displacement by 3 months, regardless of whether or not reduction and stabilization was performed. Mid-term outcomes at 1-year were similar regardless of whether or not the PW was reduced and stabilized, with regards to Tönnis grade, Merle d'Aubigné-Postel score, and conversion to total hip arthroplasty.Reduction and fragment-specific fixation of the PW component of ABC acetabular fractures did not improve outcomes in this small comparative study. Posterior wall fractures associated with ABC patterns are frequently large-sized fragments that involve the acetabular roof and are rendered stable after reconstruction of the columns.

    View details for DOI 10.1007/s00590-020-02850-9

    View details for PubMedID 33386470

  • Evaluating the clinical utility and cost of imaging strategies in adults with newly diagnosed primary intradural spinal tumors. World neurosurgery Safaee, M. M., Burke, J. F., Dalle Ore, C. L., Lau, D., Choy, W., Osorio, J. A., Wadhwa, H., Shah, S. S., Pereira, M. P., Ames, C. P. 2020


    OBJECTIVE: In patients with new primary intradural spinal tumors, the best screening strategy for additional central nervous system (CNS) lesions is unclear. The goal of this study was to document the rate of additional CNS tumors in these patients.METHODS: Adults with primary intradural spinal tumors at an academic center were retrospectively reviewed. Imaging strategy at diagnosis was classified as focused-spine (cervical, thoracic, or lumbar), total-spine, or complete-neuraxis (brain and total-spine). Tumor pathology, genetic syndromes, and presence of additional CNS lesions at diagnosis or follow-up were collected.RESULTS: 319 patients with mean age of 51 years and mean follow-up of 41 months were identified. In 151 patients with focused-spine imaging, three (2.0%) were found to have new lesions with two (1.4%) requiring treatment. In 35 patients with total-spine imaging, there were no additional lesions. In 133 patients with complete-neuraxis imaging, four (3.0%) were found to have new lesions with two (1.5%) required treatment. There was no difference in the identification of new lesions (p=0.542) or new lesions requiring treatment (p=0.772) across imaging strategies. Among patients without genetic syndromes, rates of new lesions requiring treatment were 1.4% for focused-spine, 0% for total-spine, and 2.2% for complete-neuraxis (p=0.683). There were no cases of delayed identification causing risk to life or neurologic function. Complete-neuraxis imaging carried an increased charge of $4,420 per patient.CONCLUSIONS: Among patients without an underlying genetic syndrome, the likelihood of identifying additional CNS lesions requiring treatment is low. In appropriate cases, focused-spine imaging may be a more cost-effective strategy.

    View details for DOI 10.1016/j.wneu.2020.12.027

    View details for PubMedID 33316483

  • Implementation of outpatient minimally invasive lumbar decompression at an academic medical center without ambulatory surgery centers: A cost analysis and systematic review. World neurosurgery Safaee, M. M., Chang, D., Hillman, J. M., Shah, S. S., Garcia, J., Wadhwa, H., Ames, C. P., Clark, A. J. 2020


    BACKGROUND: Lumbar decompressions are increasingly performed at ambulatory surgery centers (ASCs). We sought to compare costs of open and minimally invasive (MIS) lumbar decompressions performed at a university without dedicated ASC.METHODS: Lumbar decompressions performed at a tertiary academic hospital or satellite university hospital dedicated to outpatient surgery were retrospectively reviewed. Care pathways were same-day, overnight-observation, or inpatient admission. Patient demographics, American Society of Anesthesiology (ASA) classification, Charlson comorbidity index (CCI), surgical characteristics, 30-day readmission, and costs were collected. A systematic review of lumbar decompression cost literature was performed.RESULTS: A total of 354 patients, mean age 55 years with 128 women (36.2%), were reviewed. There was no significant difference in age, gender, BMI, ASA; classification, or CCI between open and MIS cases. Open decompression was associated with higher total cost ($21,280 vs. $14,407, p<0.001), however this was driven by care pathway and length of stay. When stratifying by care pathway, there was no difference in total cost between open vs. MIS among same-day ($10,609 vs. $11,074, p=0.556), overnight-observation ($14,097 vs. $13,992, p=0.918), or inpatient admissions ($24,507 vs. $27,929, p=0.311).CONCLUSION: When accounting for care pathway, the cost of open and MIS decompression were no different. Transition from a tertiary academic hospital to a university hospital specializing in outpatient surgery was not associated with lower costs. Academic departments may consider transitioning lumbar decompressions to a dedicated ASC to maximize cost savings, however additional studies are needed.

    View details for DOI 10.1016/j.wneu.2020.11.044

    View details for PubMedID 33248311

  • Cost analysis of outpatient anterior cervical discectomy and fusion at an academic medical center without dedicated ambulatory surgery centers. World neurosurgery Safaee, M. M., Chang, D., Hillman, J. M., Shah, S. S., Wadhwa, H., Ames, C. P., Clark, A. J. 2020


    BACKGROUND: Anterior cervical discectomy and fusion (ACDF) are increasingly performed at ambulatory surgical centers (ASCs). Academic centers lacking dedicated ASCs must perform these at large university hospitals, which pose unique challenges to cost savings and efficiency.OBJECTIVE: Describe the safety and cost of outpatient ACDF at a major academic medical center without a dedicated ASC.METHODS: ACDFs performed from 2015-2018 were retrospectively reviewed. Cases were performed at the major tertiary university hospital or a satellite university hospital dedicated to outpatient surgery. Patient demographics, surgical characteristics, perioperative complications, fusion at 12-months, and cost were collected.RESULTS: A total of 470 patients were included. Mean age was 56 years with 255 women (54.3%). When comparing same-day discharge, overnight observation, or inpatient admission, there were no differences in age, gender, or number of levels fused. Same-day and overnight observation cases were associated with shorter procedure duration and estimated blood loss. There were no differences in perioperative complications, 30-day readmissions, or fusion at 12-months. Direct and total costs were lowest for same-day cases, followed by overnight observation and inpatient admissions (p<0.001).CONCLUSION: Academic centers without dedicated ASCs can safely perform ACDF as a same-day or overnight observation procedure with significant reductions in cost. The lack of a dedicated ASC should not preclude academic centers from allocating appropriately selected patients into same-day or overnight observation care pathways. This strategy can improve resource utilization and preserve precious hospital resources for the most critically ill patients, while also allowing these centers to build viable outpatient spine practices.

    View details for DOI 10.1016/j.wneu.2020.11.049

    View details for PubMedID 33217594

  • Sequential ilioinguinal or anterior intrapelvic approach with anterior approach to the hip during combined internal fixation and total hip arthroplasty for acetabular fractures. European journal of orthopaedic surgery & traumatology : orthopedie traumatologie Chen, M. J., Wadhwa, H., Bellino, M. J. 2020


    PURPOSE: This study examined the complications and outcomes of geriatric acetabular fractures treated with open reduction internal fixation (ORIF) and total hip arthroplasty (THA) performed via combined ilioinguinal or anterior intrapelvic (AIP) approach to acetabulum and anterior approach to the hip.METHODS: Eight patients with a fracture of the acetabulum were treated at a Level I trauma center between 2010 and 2019 with combined ORIF/THA using an ilioinguinal or AIP approach for the acetabulum and a separate anterior approach to the hip. Wound dehiscence, peri-incisional skin necrosis, surgical site infection, dislocation, fracture union, acetabular component stability, and heterotopic ossification (HO) were utilized as outcome measures. Merle d'Aubigne-Postel scores were collected for the six patients that had one-year minimum follow-up.RESULTS: The mean patient age was 77years. Four patients had anterior wall fractures, two had associated both column fractures, and two had anterior column-posterior hemitransverse fractures. All fractures healed with stable fixation of the acetabular component by 6 months. There were no instances of skin necrosis, dislocation, infection, or re-operation. One patient had a superficial wound dehiscence that resolved with local wound care. One patient developed radiographic HO but was clinically asymptomatic. The mean Merle d'Aubigne-Postel score was 15.8 (range=14-16).CONCLUSIONS: Our small series of geriatric patients with fracture of the acetabulum treated with combined ORIF/THA, via the ilioinguinal or AIP approach with a separate anterior approach to the hip, demonstrates satisfactory outcomes with low complications after one-year of follow-up. Further research of these challenging injuries with more patients is warranted in order to determine the subset of fracture types best treated with this method and THA survivorship.

    View details for DOI 10.1007/s00590-020-02810-3

    View details for PubMedID 33099680

  • Clonal ZEB1-driven mesenchymal transition promotes targetable oncologic anti-angiogenic therapy resistance. Cancer research Chandra, A. n., Jahangiri, A. n., Chen, W. n., Nguyen, A. T., Yagnik, G. n., Pereira, M. P., Jain, S. n., Garcia, J. H., Shah, S. S., Wadhwa, H. n., Joshi, R. S., Weiss, J. n., Wolf, K. J., Lin, J. G., Müller, S. n., Rick, J. W., Diaz, A. A., Gilbert, L. A., Kumar, S. n., Aghi, M. K. 2020


    Glioblastoma responses to bevacizumab are invariably transient with acquired resistance. We profiled paired patient specimens and bevacizumab-resistant xenograft models pre- and post-resistance towards the primary goal of identifying regulators whose targeting could prolong the therapeutic window, and the secondary goal of identifying biomarkers of therapeutic window closure. Bevacizumab-resistant patient specimens and xenografts exhibited decreased vessel density and increased hypoxia versus pre-resistance, suggesting that resistance occurs despite effective therapeutic devascularization. Microarray analysis revealed upregulated mesenchymal genes in resistant tumors correlating with bevacizumab treatment duration and causing three changes enabling resistant tumor growth in hypoxia. First, perivascular invasiveness along remaining blood vessels, which co-opts vessels in a VEGF-independent and neo-angiogenesis-independent manner, was upregulated in novel biomimetic 3D bioengineered platforms modeling the bevacizumab-resistant microenvironment. Second, tumor-initiating stem cells housed in the perivascular niche close to remaining blood vessels were enriched. Third, metabolic reprogramming assessed through real-time bioenergetic measurement and metabolomics upregulated glycolysis and suppressed oxidative phosphorylation. Single-cell sequencing of bevacizumab-resistant patient glioblastomas confirmed upregulated mesenchymal genes, particularly glycoprotein YKL-40 and transcription factor ZEB1, in later clones, implicating these changes as treatment-induced. Serum YKL-40 was elevated in bevacizumab-resistant vs. bevacizumab-naïve patients. CRISPR and pharmacologic targeting of ZEB1 with honokiol reversed the mesenchymal gene expression and associated stem cell, invasion, and metabolic changes defining resistance. Honokiol caused greater cell death in bevacizumab-resistant than bevacizumab-responsive tumor cells, with surviving cells losing mesenchymal morphology. Employing YKL-40 as a resistance biomarker and ZEB1 as a target to prevent resistance could fulfill the promise of anti-angiogenic therapy.

    View details for DOI 10.1158/0008-5472.CAN-19-1305

    View details for PubMedID 32041837

  • Functional Outcomes of Septal Extension Grafting in Aesthetic Rhinoplasty: A Cohort Analysis. Facial plastic surgery & aesthetic medicine Patel, P. N., Abdelwahab, M. n., Shukla, N. D., Wadwha, H. n., Grimm, D. R., Kandathil, C. K., Most, S. P. 2020


    Background: Septal extension grafts (SEGs) are used widely in rhinoplasty as a means of controlling tip position. Grafts positioned in a side-to-side configuration may cause nasal airway obstruction. Methods: Retrospective cohort analysis of patients undergoing cosmetic rhinoplasty. Patients undergoing SEG placement were grouped according to completion of the Nasal Obstruction Symptom Evaluation (NOSE) or Standardized Cosmesis and Health Nasal Outcomes Survey (SCHNOS). The latter has a cosmetic (C) and functional (O) domain. Each group was matched to a cohort that did not undergo SEG placement using criteria: preoperative NOSE or SCHNOS-O score, age, and gender. Patient demographics and outcomes, including NOSE, SCHNOS, and visual analog scale (VAS) scores, were compared between SEG and no-SEG groups using univariate and multivariate analyses. If patients underwent placement of an SEG and complained of obstruction, the laterality of the graft in relation to the complaint was examined. Results: SEGs were placed in 79 patients, of whom 77 completed the NOSE survey and 37 completed the SCHNOS-O both pre- and postoperatively. These patients were matched to patients without SEGs. For both the SCHNOS and NOSE-matched cohorts, functional outcomes (NOSE, SCHNOS-O, and VAS-F) did not significantly differ between SEG and no-SEG groups. These findings were also observed when patients were stratified by cosmetic surgery alone versus combined functional and cosmetic surgery. On multivariate linear regression analysis, when accounting for intraoperative techniques, there was no difference in postoperative NOSE or SCHNOS-O outcomes between the SEG and no-SEG cohorts. Side of postoperative nasal obstruction did not correlate with side of SEG placement. Conclusion: SEGs, when used in a unilateral side-to-side configuration, yield excellent aesthetic results without compromising functional outcomes.

    View details for DOI 10.1089/fpsam.2020.0304

    View details for PubMedID 32716730

  • 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


    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

  • Complications, Costs, and Quality Outcomes of Patients Undergoing Cervical Deformity Surgery with Intraoperative BMP Use. Spine Varshneya, K. n., Wadhwa, H. n., Pendharkar, A. V., Medress, Z. A., Stienen, M. N., Ratliff, J. K., Veeravagu, A. n. 2020


    An epidemiological study using national administrative data from the MarketScan database.To identify the impact of bone morphogenetic protein (BMP) on postoperative outcomes in patients undergoing adult cervical deformity (ACD) surgery.BMP has been shown to stimulate bone growth and improve fusion rates in spine surgery. However, the impact of BMP on reoperation rates and postoperative complication rate is controversial.We queried the MarketScan database to identify patients who underwent ACD surgery from 2007-2015. Patients were stratified by BMP use in the index operation. Patients under 18 and those with any history of tumor or trauma were excluded. Baseline demographics and comorbidities, postoperative complication rates and reoperation rates were analyzed.A total of 13,549 patients underwent primary ACD surgery, of which 1155 (8.5%) had intraoperative BMP use. The overall 90-day complication rate was 27.6% in the non-BMP cohort and 31.1% in the BMP cohort (p < 0.05). Patients in the BMP cohort had longer average length of stay (4.0 days vs 3.7 days, p < 0.05) but lower revision surgery rates at 90-days (14.5% vs 28.3%, p < 0.05), 6 months (14.9% vs 28.6%, p < 0.05), 1 year (15.7% vs 29.2%, p < 0.05), and 2 years (16.5% vs 29.9%, p < 0.05) postoperatively. BMP use was associated with higher payments throughout the 2-year follow-up period ($107,975 vs $97,620, p < 0.05). When controlling for baseline group differences, BMP use independently increased the odds of postoperative complication (OR 1.22, 95% CI 1.1 - 1.4) and reduced the odds of reoperation throughout 2-years of follow-up (OR 0.49, 95% CI 0.4 - 0.6).Intraoperative BMP use has benefits for fusion integrity in ACD surgery but is associated with increased postoperative complication rate. Spine surgeons should weigh these benefits and drawbacks to identify optimal candidates for BMP use in ACD surgery.3.

    View details for DOI 10.1097/BRS.0000000000003629

    View details for PubMedID 32756275

  • Does double-blind peer review impact gender authorship trends? An evaluation of two leading neurosurgical journals from 2010 to 2019. Journal of neurosurgery Mahajan, U. V., Wadhwa, H. n., Fatemi, P. n., Xu, S. n., Shan, J. n., Benzil, D. L., Zygourakis, C. C. 2020: 1–9


    Publications are key for advancement within academia. Although women are underrepresented in academic neurosurgery, the rates of women entering residency, achieving board certification, and publishing papers are increasing. The goal of this study was to assess the current status of women in academic neurosurgery publications. Specifically, this study sought to 1) survey female authorship rates in the Journal of Neurosurgery (JNS [not including JNS: Spine or JNS: Pediatrics]) and Neurosurgery from 2010 to 2019; 2) analyze whether double-blind peer review (started in Neurosurgery in 2011) altered female authorship rates relative to single-blind review (JNS); and 3) evaluate how female authorship rates compared with the number of women entering neurosurgery residency and obtaining neurosurgery board certification.Genders of the first and last authors for JNS and Neurosurgery articles from 2010 to 2019 were obtained. Data were also gathered on the number and percentage of women entering neurosurgery residency and women obtaining American Board of Neurological Surgeons (ABNS) certification between 2010 and 2019.Women accounted for 13.4% (n = 570) of first authors and 6.8% (n = 240) of last authors in JNS and Neurosurgery publications. No difference in rates of women publishing existed between the two journals (first authors: 13.0% JNS vs 13.9% Neurosurgery, p = 0.29; last authors: 7.3% JNS vs 6.0% Neurosurgery, p = 0.25). No difference existed between women first or last authors in Neurosurgery before and after initiation of double-blind review (p = 0.066). Significant concordance existed between the gender of first and last authors: in publications with a woman last author, the odds of the first author being a woman was increased by twofold (OR 2.14 [95% CI 1.43-3.13], p = 0.0001). Women represented a lower proportion of authors of invited papers (8.6% of first authors and 3.1% of last authors were women) compared with noninvited papers (14.1% of first authors and 7.4% of last authors were women) (first authors: OR 0.576 [95% CI 0.410-0.794], p = 0.0004; last authors: OR 0.407 [95% CI 0.198-0.751], p = 0.001). The proportion of women US last authors (7.4%) mirrors the percentage of board-certified women neurosurgeons (5.4% in 2010 and 6.8% in 2019), while the percentage of women US first authors (14.3%) is less than that for women entering neurosurgical residency (11.2% in 2009 and 23.6% in 2018).This is the first report of female authorship in the neurosurgical literature. The authors found that single- versus double-blind peer review did not impact female authorship rates at two top neurosurgical journals.

    View details for DOI 10.3171/2020.6.JNS20902

    View details for PubMedID 33186905

  • Systematic Review of Cost-Effectiveness Analyses in US Spine Surgery. World neurosurgery Chang, D. n., Zygourakis, C. C., Wadhwa, H. n., Kahn, J. G. 2020

    View details for DOI 10.1016/j.wneu.2020.05.123

    View details for PubMedID 32446983

  • 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


    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

  • Prospectively Assigned AAST Grade versus Modified Hinchey Class and Acute Diverticulitis Outcomes. The Journal of surgical research Choi, J. n., Bessoff, K. n., Bromley-Dulfano, R. n., Li, Z. n., Gupta, A. n., Taylor, K. n., Wadhwa, H. n., Seltzer, R. n., Spain, D. A., Knowlton, L. M. 2020


    The American Association for the Surgery of Trauma (AAST) recently developed a classification system to standardize outcomes analyses for several emergency general surgery conditions. To highlight this system's full potential, we conducted a study integrating prospective AAST grade assignment within the electronic medical record.Our institution integrated AAST grade assignment into our clinical workflow in July 2018. Patients with acute diverticulitis were prospectively assigned AAST grades and modified Hinchey classes at the time of surgical consultation. Support vector machine-a machine learning algorithm attuned for small sample sizes-was used to compare the associations between the two classification systems and decision to operate and incidence of complications.67 patients were included (median age of 62 y, 40% male) for analysis. The decision for operative management, hospital length of stay, intensive care unit admission, and intensive care unit length of stay were associated with both increasing AAST grade and increasing modified Hinchey class (all P < 0.001). AAST grade additionally showed a correlation with complication severity (P = 0.02). Compared with modified Hinchey class, AAST grade better predicted decision to operate (88.2% versus 82.4%).This study showed the feasibility of electronic medical record integration to support the full potential of AAST classification system's utility as a clinical decision-making tool. Prospectively assigned AAST grade may be an accurate and pragmatic method to find associations with outcomes, yet validation requires further study.

    View details for DOI 10.1016/j.jss.2020.10.016

    View details for PubMedID 33248670

  • Trochanteric osteotomy for acetabular fracture fixation: a case series and literature review. European journal of orthopaedic surgery & traumatology : orthopedie traumatologie Chen, M. J., Wadhwa, H. n., Tigchelaar, S. S., Frey, C. S., Gardner, M. J., Bellino, M. J. 2020


    This study examined osteotomy union and heterotopic ossification (HO) after performing digastric trochanteric osteotomies during open reduction and internal fixation (ORIF) of acetabular and combined femoral head fractures. Femoral head osteonecrosis and trochanteric screw removal were secondarily assessed.Twenty-six patients treated at a Level I trauma center, from years 2003 to 2019, who received a digastric trochanteric osteotomy during acetabular and combined femoral head fracture ORIF through a posterior surgical approach were retrospectively identified. Osteotomies were fixed with two 3.5 mm cortical lag screws. Rates of osteotomy union, HO, femoral head osteonecrosis, and trochanteric screw removal were determined.All osteotomies went onto union without displacement or failure of fixation. Only three (12%) patients developed severe HO (modified-Brooker class III-IV). There were no instances of femoral head osteonecrosis and only one (7%) patient required trochanteric screw removal.The digastric trochanteric osteotomy heals reliably with low rates of severe HO, femoral head osteonecrosis, and screw removal for soft-tissue irritation. A review of the literature is presented and found comparable findings.

    View details for DOI 10.1007/s00590-020-02753-9

    View details for PubMedID 32743685

  • The Path to U.S. Neurosurgical Residency for Foreign Medical Graduates: Trends from a Decade 2007-2017. World neurosurgery Chandra, A. n., Brandel, M. G., Wadhwa, H. n., Almeida, N. D., Yue, J. K., Nuru, M. O., Cheng, J. n., Lu, S. n., Patel, A. n., Essayed, W. I., McDermott, M. W., Berger, M. S., Aghi, M. K. 2020


    The increasing competitiveness of the neurosurgical residency match has made it progressively difficult for foreign medical graduates (FMGs) to match in neurosurgery. We compared FMG to US medical graduate (USMG) match rates in neurosurgery and identified factors associated with match outcomes for FMG in neurosurgery.Retrospective review of AANS membership data and AAMC Charting the Outcomes match reports (2007-2017).Across 1,857 neurosurgical residents (USMG:91.1%, FMG:8.9%), average FMG match rates were 24% (range 15-35%) versus 83% (range 75-94%, p<0.001) for USMG. FMG were more male (89.5% vs. 82.0%, p=0.016), older (33.9 vs 31.8-years, p=0.008), and more likely to take research year(s) before matching (95.8% vs 78.5%, p<0.001). FMGs had greater publications (5 vs 2, p<0.001) and h-indices (3 vs 1, p<0.001). The number of matched USMGs increased by 3.3 annually, whereas that of matched FMG remained unchanged (β=0.07). Compared to USMGs, FMGs were less likely to match to NIH-Top 40 (32.7% vs. 47.5%, p<0.001) and Doximity-Top 20 (20.0% vs. 29.0%, p=0.014) programs. FMGs with prior U.S. neurosurgery program affiliation were more likely to match at NIH- and Doximity-Top 20 programs (p<0.05). For NIH-programs, FMGs were older (35.3 vs. 32.0, p=0.011), had higher h-indices (5 vs. 2, p<0.001), publications (7 vs. 2, p<0.001), and were more likely to take research year(s) (94.4% vs. 76.0%, p=0.002) than USMGs. FMGs had similar patterns for matching into Doximity-Top 20 programs.While FMGs have lower match rates into US neurosurgery residencies than USMGs, several demographic, professional, and academic factors could increase the chances of successful FMG neurosurgical match.

    View details for DOI 10.1016/j.wneu.2020.02.069

    View details for PubMedID 32084618

  • The neurosurgery applicant's "arms race": analysis of medical student publication in the Neurosurgery Residency Match. Journal of neurosurgery Wadhwa, H., Shah, S. S., Shan, J., Cheng, J., Beniwal, A. S., Chen, J. S., Gill, S. A., Mummaneni, N., McDermott, M. W., Berger, M. S., Aghi, M. K. 2019: 1-9


    Neurosurgery is consistently one of the most competitive specialties for resident applicants. The emphasis on research in neurosurgery has led to an increasing number of publications by applicants seeking a successful residency match. The authors sought to produce a comprehensive analysis of research produced by neurosurgical applicants and to establish baseline data of neurosurgery applicant research productivity given the increased emphasis on research output for successful residency match.A retrospective review of publication volume for all neurosurgery interns in 2009, 2011, 2014, 2016, and 2018 was performed using PubMed and Google Scholar. Missing data rates were 11% (2009), 9% (2011), and < 5% (all others). The National Resident Matching Program report "Charting Outcomes in the Match" (ChOM) was interrogated for total research products (i.e., abstracts, presentations, and publications). The publication rates of interns at top 40 programs, students from top 20 medical schools, MD/PhD applicants, and applicants based on location of residency program and medical school were compared statistically against all others.Total publications per neurosurgery intern (mean ± SD) based on PubMed and Google Scholar were 5.5 ± 0.6 in 2018 (1.7 ± 0.3, 2009; 2.1 ± 0.3, 2011; 2.6 ± 0.4, 2014; 3.8 ± 0.4, 2016), compared to 18.3 research products based on ChOM. In 2018, the mean numbers of publications were as follows: neurosurgery-specific publications per intern, 4.3 ± 0.6; first/last author publications, 2.1 ± 0.3; neurosurgical first/last author publications, 1.6 ± 0.2; basic science publications, 1.5 ± 0.2; and clinical research publications, 4.0 ± 0.5. Mean publication numbers among interns at top 40 programs were significantly higher than those of all other programs in every category (p < 0.001). Except for mean number of basic science publications (p = 0.1), the mean number of publications was higher for interns who attended a top 20 medical school than for those who did not (p < 0.05). Applicants with PhD degrees produced statistically more research in all categories (p < 0.05) except neurosurgery-specific (p = 0.07) and clinical research (p = 0.3). While there was no statistical difference in publication volume based on the geographical location of the residency program, students from medical schools in the Western US produced more research than all other regions (p < 0.01). Finally, research productivity did not correlate with likelihood of medical students staying at their home institution for residency.The authors found that the temporal trend toward increased total research products over time in neurosurgery applicants was driven mostly by increased nonindexed research (abstracts, presentations, chapters) rather than by increased peer-reviewed publications. While we also identified applicant-specific factors (MD/PhDs and applicants from the Western US) and an outcome (matching at research-focused institutions) associated with increased applicant publications, further work will be needed to determine the emphasis that programs and applicants will need to place on these publications.

    View details for DOI 10.3171/2019.8.JNS191256

    View details for PubMedID 31675693

  • Insurance type impacts the economic burden and survival of patients with newly diagnosed glioblastoma. Journal of neurosurgery Chandra, A., Young, J. S., Dalle Ore, C., Dayani, F., Lau, D., Wadhwa, H., Rick, J. W., Nguyen, A. T., McDermott, M. W., Berger, M. S., Aghi, M. K. 2019: 1-11


    Glioblastoma (GBM) carries a high economic burden for patients and caregivers, much of which is associated with initial surgery. The authors investigated the impact of insurance status on the inpatient hospital costs of surgery for patients with GBM.The authors conducted a retrospective review of patients with GBM (2010-2015) undergoing their first resection at the University of California, San Francisco, and corresponding inpatient hospital costs.Of 227 patients with GBM (median age 62 years, 37.9% females), 31 (13.7%) had Medicaid, 94 (41.4%) had Medicare, and 102 (44.9%) had private insurance. Medicaid patients had 30% higher overall hospital costs for surgery compared to non-Medicaid patients ($50,285 vs $38,779, p = 0.01). Medicaid patients had higher intensive care unit (ICU; p < 0.01), operating room (p < 0.03), imaging (p < 0.001), room and board (p < 0001), and pharmacy (p < 0.02) costs versus non-Medicaid patients. Medicaid patients had significantly longer overall and ICU lengths of stay (6.9 and 2.6 days) versus Medicare (4.0 and 1.5 days) and privately insured patients (3.9 and 1.8 days, p < 0.01). Medicaid patients had similar comorbidity rates to Medicare patients (67.8% vs 68.1%), and both groups had higher comorbidity rates than privately insured patients (37.3%, p < 0.0001). Only 67.7% of Medicaid patients had primary care providers (PCPs) versus 91.5% of Medicare and 86.3% of privately insured patients (p = 0.009) at the time of presentation. Tumor diameter at diagnosis was largest for Medicaid (4.7 cm) versus Medicare (4.1 cm) and privately insured patients (4.2 cm, p = 0.03). Preoperative (70 vs 90, p = 0.02) and postoperative (80 vs 90, p = 0.03) Karnofsky Performance Scale (KPS) scores were lowest for Medicaid versus non-Medicaid patients, while in subgroup analysis, postoperative KPS score was lowest for Medicaid patients (80, vs 90 for Medicare and 90 for private insurance; p = 0.03). Medicaid patients had significantly shorter median overall survival (10.7 months vs 12.8 months for Medicare and 15.8 months for private insurance; p = 0.02). Quality-adjusted life year (QALY) scores were 0.66 and 1.05 for Medicaid and non-Medicaid patients, respectively (p = 0.036). The incremental cost per QALY was $29,963 lower for the non-Medicaid cohort.Patients with GBMs and Medicaid have higher surgical costs, longer lengths of stay, poorer survival, and lower QALY scores. This study indicates that these patients lack PCPs, have more comorbidities, and present later in the disease course with larger tumors; these factors may drive the poorer postoperative function and greater consumption of hospital resources that were identified. Given limited resources and rising healthcare costs, factors such as access to PCPs, equitable adjuvant therapy, and early screening/diagnosis of disease need to be improved in order to improve prognosis and reduce hospital costs for patients with GBM.

    View details for DOI 10.3171/2019.3.JNS182629

    View details for PubMedID 31226687

  • The phenotypes of proliferating glioblastoma cells reside on a single axis of variation. Cancer discovery Wang, L. n., Babikir, H. n., Muller, S. n., Yagnik, G. n., Shamardani, K. n., Catalan, F. n., Kohanbash, G. n., Alvarado, B. n., Di Lullo, E. n., Kriegstein, A. n., Shah, S. n., Wadhwa, H. n., Chang, S. M., Philips, J. J., Aghi, M. K., Diaz, A. A. 2019


    Although tumor-propagating cells can be derived from glioblastomas (GBMs) of the proneural and mesenchymal subtypes, a glioma stem-like cell (GSC) of the classical subtype has not been identified. It is unclear if mesenchymal GSCs (mGSCs) and/or proneural GSCs (pGSCs) alone are sufficient to generate the heterogeneity observed in GBM. We performed single-cell/nuclei RNA-sequencing of 28 gliomas, and single-cell ATAC-sequencing for 8 cases. We find that GBM GSCs reside on a single axis of variation, ranging from proneural to mesenchymal. In silico lineage tracing using both transcriptomics and genetics supports mGSCs as the progenitors of pGSCs. Dual inhibition of pGSC-enriched and mGSC-enriched growth and survival pathways provides a more complete treatment than combinations targeting one GSC phenotype alone. This study sheds light on a long-standing debate regarding lineage relationships among GSCs and presents a paradigm by which personalized combination therapies can be derived from single-cell RNA signatures, to overcome intra-tumor heterogeneity.

    View details for DOI 10.1158/2159-8290.CD-19-0329

    View details for PubMedID 31554641

  • Stress Granule Assembly Disrupts Nucleocytoplasmic Transport CELL Zhang, K., Daigle, J., Cunningham, K. M., Coyne, A. N., Ruan, K., Grima, J. C., Bowen, K. E., Wadhwa, H., Yang, P., Rigo, F., Taylor, J., Gitler, A. D., Rothstein, J. D., Lloyd, T. E. 2018; 173 (4): 958-+


    Defects in nucleocytoplasmic transport have been identified as a key pathogenic event in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) mediated by a GGGGCC hexanucleotide repeat expansion in C9ORF72, the most common genetic cause of ALS/FTD. Furthermore, nucleocytoplasmic transport disruption has also been implicated in other neurodegenerative diseases with protein aggregation, suggesting a shared mechanism by which protein stress disrupts nucleocytoplasmic transport. Here, we show that cellular stress disrupts nucleocytoplasmic transport by localizing critical nucleocytoplasmic transport factors into stress granules, RNA/protein complexes that play a crucial role in ALS pathogenesis. Importantly, inhibiting stress granule assembly, such as by knocking down Ataxin-2, suppresses nucleocytoplasmic transport defects as well as neurodegeneration in C9ORF72-mediated ALS/FTD. Our findings identify a link between stress granule assembly and nucleocytoplasmic transport, two fundamental cellular processes implicated in the pathogenesis of C9ORF72-mediated ALS/FTD and other neurodegenerative diseases.

    View details for PubMedID 29628143

  • Mutant Huntingtin Disrupts the Nuclear Pore Complex NEURON Grima, J. C., Daigle, J., Arbez, N., Cunningham, K. C., Zhang, K., Ochaba, J., Geater, C., Morozko, E., Stocksdale, J., Glatzer, J. C., Pham, J. T., Ahmed, I., Peng, Q., Wadhwa, H., Pletnikova, O., Troncoso, J. C., Duan, W., Snyder, S. H., Ranum, L. W., Thompson, L. M., Lloyd, T. E., Ross, C. A., Rothstein, J. D. 2017; 94 (1): 93-+


    Huntington's disease (HD) is caused by an expanded CAG repeat in the Huntingtin (HTT) gene. The mechanism(s) by which mutant HTT (mHTT) causes disease is unclear. Nucleocytoplasmic transport, the trafficking of macromolecules between the nucleus and cytoplasm, is tightly regulated by nuclear pore complexes (NPCs) made up of nucleoporins (NUPs). Previous studies offered clues that mHTT may disrupt nucleocytoplasmic transport and a mutation of an NUP can cause HD-like pathology. Therefore, we evaluated the NPC and nucleocytoplasmic transport in multiple models of HD, including mouse and fly models, neurons transfected with mHTT, HD iPSC-derived neurons, and human HD brain regions. These studies revealed severe mislocalization and aggregation of NUPs and defective nucleocytoplasmic transport. HD repeat-associated non-ATG (RAN) translation proteins also disrupted nucleocytoplasmic transport. Additionally, overexpression of NUPs and treatment with drugs that prevent aberrant NUP biology also mitigated this transport defect and neurotoxicity, providing future novel therapy targets.

    View details for DOI 10.1016/j.neuron.2017.03.023

    View details for Web of Science ID 000398262000012

    View details for PubMedID 28384479

    View details for PubMedCentralID PMC5595097