All Publications

  • The Quality of Systematic Reviews and Meta-Analyses Assessing the Treatment and Management of Male Infertility. Andrology Bhambhvani, H. P., Greenberg, D. R., Eisenberg, M. L. 2021


    BACKGROUND: Male factor infertility (MFI) is a common medical condition which requires high quality research to guide clinical practice; however, systematic reviews (SRs) and meta-analyses (MAs) often vary in quality, raising concerns regarding the validity of their results. We sought to perform an objective analysis of SRs and MAs in MFI treatment and management and to report on the quality of published literature.METHODS: A comprehensive search in PubMed/MEDLINE and EMBASE was used to identify relevant publications. Primary search terms were male infertility, male sterility, and male subfertility. Two authors independently performed searches, screened citations for eligibility, extracted data for analysis, and graded methodological quality using the validated AMSTAR (A Measurement Tool to Assess Systematic Reviews) instrument, a validated tool used in the critical appraisal of SRs/MAs.RESULTS: 27 publications met inclusion criteria and were included in the analysis. Mean AMSTAR score (± SD) among all publications was 7.4 (1.9) out of 11, reflecting "fair to good" quality. Non-pharmacological medical treatment for MFI was the most commonly assessed intervention (n=13, 48.1%). No publications met all AMSTAR criteria. While the number of SRs/MAs has increased over time (p=0.037), the quality of publications has not significantly changed (p=0.72). SRs/MAs of the Cochrane Library had higher AMSTAR score than non-Cochrane SRs/MAs (8.5 vs 6.3, p=0.002).CONCLUSIONS: The methodological quality of SRs/MAs should be assessed to ensure high-quality evidence for clinical practice guidelines in MFI treatment and management. This review highlights a need for increased effort to publish high-quality studies in MFI treatment and management.

    View details for DOI 10.1111/andr.12972

    View details for PubMedID 33432772

  • Racial and socioeconomic disparities in retroperitoneal lymph node dissection and survival in nonseminomatous germ cell tumor: A population-based study. Urologic oncology Bhambhvani, H. P., Greenberg, D. R., Kasman, A. M., DeRouen, M. C., Cheng, I., Eisenberg, M. L., Shah, S. A. 2021


    BACKGROUND: Though testicular cancer is the most common cancer in young men, there is a paucity of epidemiologic studies examining sociodemographic disparities in adjuvant therapy and outcomes. We examined the associations of sociodemographic factors with retroperitoneal lymph node dissection (RPLND) and survival among patients with nonseminomatous germ cell tumors (NSGCTs).METHODS: Within the Surveillance Epidemiology and End Results database (2005-2015), we identified 8,573 patients with nonseminomatous germ cell tumors. Multivariable logistic regression and Fine-Gray competing-risks regression models were constructed to examine the association of sociodemographic factors (neighborhood SES (nSES), race, and insurance) with, respectively, adjuvant RPLND within 1 year of diagnosis and cancer-specific mortality.RESULTS: Patients in the lowest nSES quintile (OR 0.59, 95% CI = 0.40-0.88, P = 0.01) and Black patients (OR 0.41, 95% CI = 0.15-1.00, P= 0.058) with stage II disease were less likely to receive RPLND compared to those in the highest quintile and White patients, respectively. Stage III patients with Medicaid (OR 0.64, 95% CI = 0.46-0.89, P= 0.009) or without insurance (OR 0.46, 95% CI = 0.27-0.76, P= 0.003) were less likely to receive RPLND compared to patients with private insurance. Lowest quintile nSES patients of all disease stages and Black patients with stage I disease (HR = 2.64, 95% CI = 1.12-6.20, P = 0.026) or stage II disease (HR=4.93, 95% CI = 1.48-16.44, P = 0.009) had higher risks of cancer-specific mortality compared to highest quintile nSES and White patients, respectively.CONCLUSIONS: This national study found multilevel, stage-specific sociodemographic disparities in receipt of RPLND and survival.

    View details for DOI 10.1016/j.urolonc.2020.12.016

    View details for PubMedID 33423934

  • Reproductive sequelae of parental severe illness before the pandemic: implications for the COVID-19 pandemic. Fertility and sterility Kasman, A. M., Bhambhvani, H. P., Li, S., Zhang, C. A., Stevenson, D. K., Shaw, G. M., Simard, J. F., Eisenberg, M. L. 2020; 114 (6): 1242–49


    OBJECTIVE: To investigate, with pre-COVID-19 data, whether parental exposure to severe systemic infections near the time of conception is associated with pregnancy outcomes.DESIGN: Retrospective cohort study.SETTING: Population-based study covering births within the United States from 2009 to2016.PARTICIPANTS: The IBM MarketScan Research database covers reimbursed health care claims data on inpatient and outpatient encounters that are privately insured through employment-sponsored health insurance. Our analytic sample included pregnancies to paired fathers and mothers.INTERVENTIONS(S): Parental preconception exposure (0-6 months before conception) to severe systemic infection (e.g., sepsis, hypotension, respiratory failure, critical care evaluation).MAIN OUTCOME MEASURE(S): Preterm birth (i.e., live birth before 37 weeks) and pregnancy loss.RESULT(S): A total of 999,866 pregnancies were recorded with 214,057 pregnancy losses (21.4%) and 51,759 preterm births (5.2%). Mothers receiving intensive care in the preconception period had increased risk of pregnancy loss, as did fathers. Mothers with preconception sepsis had higher risk of preterm birth and pregnancy loss, and paternal sepsis exposure was associated with an increased risk of pregnancy loss. Similar results were noted for hypotension. In addition, a dose response was observed for both mothers and fathers between preconception time in intensive care and the risk of preterm birth and pregnancy loss.CONCLUSION(S): In a pre-COVID-19 cohort, parental preconception severe systemic infection was associated with increased odds of preterm birth and pregnancy loss when conception was soon after the illness.

    View details for DOI 10.1016/j.fertnstert.2020.09.153

    View details for PubMedID 33280730

  • Public Interest in Elective Urological Procedures in the COVID-19 Pandemic: A Google Trends Analysis UROLOGY PRACTICE Bhambhvani, H. P., Tijerina, J. D., Parham, M. J., Greenberg, D. R., Eisenberg, M. L. 2020; 7 (6): 496–501
  • Hospital Volumes of 5 Medical Emergencies in the COVID-19 Pandemic in 2 US Medical Centers. JAMA internal medicine Bhambhvani, H. P., Rodrigues, A. J., Yu, J. S., Carr, J. B., Hayden Gephart, M. 2020

    View details for DOI 10.1001/jamainternmed.2020.3982

    View details for PubMedID 33104161

  • Delayed Ejaculation After Lumbar Spine Surgery: A Claims Database Analysis. Global spine journal Bhambhvani, H. P., Kasman, A. M., Zhang, C. A., Hu, S. S., Eisenberg, M. L. 2020: 2192568220962435


    STUDY DESIGN: Retrospective cohort.OBJECTIVES: Delayed ejaculation (DE) is a distressing condition characterized by a notable delay in ejaculation or complete inability to achieve ejaculation, and there are no existing reports of DE following lumbar spine surgery. Inspired by our institutional experience, we sought to assess national rates of DE following surgery of the lumbar spine.METHODS: We queried the Optum De-identified Clinformatics Database for adult men undergoing surgery of the lumbar spine between 2003 and 2017. The primary outcome was the development of DE within 2 years of surgery. Multivariable logistic regression was performed to identify factors associated with the development of DE.RESULTS: We identified 117918 men who underwent 162646 lumbar spine surgeries, including anterior lumbar interbody fusion (ALIF), posterior lumbar fusion (PLF), and more. The overall incidence of DE was 0.09%, with the highest rate among ALIF surgeries at 0.13%. In multivariable analysis, the odds of developing DE did not vary between anterior/lateral lumbar interbody fusion, PLF, and other spine surgeries. A history of tobacco smoking (OR = 1.47, 95% CI 1.00-2.16, P = .05) and obesity (OR = 1.56, 95% CI 1.00-2.44, P = .05) were associated with development of DE.CONCLUSIONS: DE is a rare but distressing complication of thoracolumbar spine surgery, and patients should be queried for relevant symptoms at postoperative visits when indicated.

    View details for DOI 10.1177/2192568220962435

    View details for PubMedID 33047620

  • The primary sites leading to brain metastases: Shifting trends at a tertiary care center. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia Bhambhvani, H. P., Granucci, M., Rodrigues, A., Kakusa, B. W., Hayden Gephart, M. 2020; 80: 121–24


    While the majority of brain metastases arise from lung cancer, breast cancer, or melanoma, new treatments and improved prognoses have altered the profile of primary cancers that metastasize to the brain. We sought to determine the proportion of brain metastases from less common primary sites and conduct trend analyses. We reviewed the charts of 3585 patients with brain metastases seen at our institution from 2008 to 2018. We determined the primary site for each of these patients, and the Mann-Kendall test was used to evaluate temporal trends in the yearly proportion of brain metastases originating from each primary cancer. The five most common primary sites were lung (43.0%), breast (19.9%), melanoma (8.2%), renal (5.0%), and colorectal (3.8%). The proportion of yearly brain metastases originating from breast cancer (p=0.029) and melanoma (p=0.013) decreased by 23.8% and 46.7%, respectively, from 2008 (0.21 breast, 0.15 melanoma) to 2018 (0.16 breast, 0.08 melanoma), while no change was found in the proportion of brain metastases from lung, renal, and colorectal cancers. Brain metastases arising from rare primary sites, defined as those comprising at most 2% of all brain metastases, increased by 34.4% (p=0.005). Limited sample size prohibited trend analysis of other individual primary sites. We report a decrease over 11years in the proportion of brain metastases originating from breast cancer and melanoma at our institution, and an increase in brain metastases from rare primary sites. Further work with larger, multi-center databases will enable additional evaluation of brain metastases from rare primary sites.

    View details for DOI 10.1016/j.jocn.2020.08.006

    View details for PubMedID 33099333

  • Leptomeningeal Carcinomatosis: Molecular Landscape, Current Management, and Emerging Therapies. Neurosurgery clinics of North America Bhambhvani, H. P., Rodrigues, A. J., Umeh-Garcia, M. C., Hayden Gephart, M. 2020; 31 (4): 613–25


    Leptomeningeal carcinomatosis is a devastating consequence of late-stage cancer, and despite multimodal treatment, remains rapidly fatal. Definitive diagnosis requires identification of malignant cells in the cerebrospinal fluid (CSF), or frank disease on MRI. Therapy is generally palliative and consists primarily of radiotherapy and/or chemotherapy, which is administered intrathecally or systemically. Immunotherapies and novel experimental therapies have emerged as promising options for decreasing patient morbidity and mortality. In this review, the authors discuss a refined view of the molecular pathophysiology of leptomeningeal carcinomatosis, current approaches to disease management, and emerging therapies.

    View details for DOI 10.1016/

    View details for PubMedID 32921356

  • Clinicopathologic features, outcomes, and prognostic factors of testicular sarcoma: a population-based study. International urology and nephrology Bhambhvani, H. P., Greenberg, D. R., Kasman, A. M., Eisenberg, M. L. 2020


    PURPOSE: To describe clinical characteristics and identify prognostic factors among men with testicular sarcoma, and to compare survival with other testicular cancers.METHODS: The surveillance, epidemiology, and end results (SEER) database (1975-2016) was queried to identify adults with testicular sarcoma. Multivariable Cox proportional hazards, Fine and Gray competing-risks regression, propensity score matching, and Kaplan-Meier analyses were used.RESULTS: 230 men were included in this study. Median age at diagnosis was 58years (range 18-94), and median OS was 10.3years. Patients with tumors larger than 8cm in size had worse OS (HR 1.88, p=0.016) compared to patients with tumors<8cm. Disease with distant metastasis was associated with worse OS (HR 4.70, p<0.0001) and worse CSS (HR 11.41, p<0.0001) as compared to disease localized to the testis. Men with rhabdomyosarcoma had worse CSS (HR 3.25, p=0.03) as compared to men with liposarcoma. Testicular sarcoma patients had worse OS than matched patients with either seminomatous germ cell tumors (GCTs, p<0.0001) or nonseminomatous GCTs (p=0.0019), and similar survival to matched patients with sex cord stromal tumors, testicular lymphoma, or sarcomas of the lower limb-the most common anatomic site of origin of soft tissue sarcomas.CONCLUSIONS: In the largest cohort of men with testicular sarcoma to date, we identified tumor size, disease extent, and rhabdomyosarcoma histology as independent predictors of worse survival. Stage-adjusted survival was worse as compared to men with GCTs, and similar to men with sex cord stromal tumors, testicular lymphoma, and sarcomas of other primary sites.

    View details for DOI 10.1007/s11255-020-02634-4

    View details for PubMedID 32895865

  • Aneurysmal subarachnoid hemorrhage in patients with migraine and tension headache: A cohort comparison study. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia Lamsam, L., Bhambhvani, H. P., Thomas, A., Ratliff, J. K., Moore, J. M. 2020; 79: 90–94


    Migraine headache is a common condition with an estimated lifetime prevalence of greater than 20%. While it is a well-established risk factor for cardiovascular disease and ischemic stroke, its association with subarachnoid hemorrhage is largely unexplored. We sought to compare the incidence of aneurysmal subarachnoid hemorrhage in a cohort of migraine patients with a cohort of patients with tension headache. A cohort comparison study utilizing the MarketScan insurance claims database compared patients diagnosed with migraine who were undergoing treatment with abortive or prophylactic pharmacotherapy (treatment cohort) and patients diagnosed with tension headache who had never been diagnosed with a migraine and who were naive to migraine pharmacotherapy (control cohort). Patients with major pre-existing risk factors for aSAH were excluded from the study, and minor risk factors such as smoking status and hypertension were accounted for using coarsened exact matching (CEM) and subsequent cox proportional-hazards (CPH) regression. More than 679,000 patients (~125,000 treatment and~550,000 control) with an average follow-up of more than three years were analyzed for aneurysmal subarachnoid hemorrhage. CPH regression on matched data showed that treated migraine patients had a significantly lower hazard of aneurysmal subarachnoid hemorrhage compared with tension headache patients (HR=0.40, 95% CI: 0.19 - 0.86, p=0.02). This large cohort comparison study, analyzing more than 679,000 patients, demonstrated that migraine patients undergoing pharmacologic treatment had a lower hazard of aneurysmal subarachnoid hemorrhage than patients diagnosed with tension headaches. Future work specifically focusing on migraine medications may identify the mechanisms underlying this association.

    View details for DOI 10.1016/j.jocn.2020.07.017

    View details for PubMedID 33070926

  • Evaluation of Patient Treatment Preferences for 15-20mm Kidney Stones: A Conjoint Analysis. Journal of endourology Spradling, K., Bhambhvani, H. P., Chang, T. C., Pao, A. C., Liao, J. C., Leppert, J. T., Welk, B., Harris, C. R., Conti, S. L., Elliott, C. S. 2020


    INTRODUCTION AND OBJECTIVE: Ureteroscopy (URS) and percutaneous nephrolithotomy (PCNL) are standard surgical treatments for intermediate-size (15-20mm) kidney stones but differ in their postoperative recovery, stone-free rates, and complication risks. We aimed to evaluate what affects patient treatment preferences.METHODS: Patients with urinary stone disease completed a choice-based conjoint analysis exercise assessing four treatment attributes associated with URS and PCNL. A sensitivity analysis using a market simulator was performed and the relative importance of each attribute was calculated. Differences in treatment preferences by demographic subgroup were assessed.RESULTS: A total of 58 patients completed the conjoint analysis exercise. Stone-free rate was the most important treatment attribute while length of hospital stay and cosmesis were less important. Overall, sensitivity analysis based on market simulation scenarios predicted almost equal preference for URS (52.4%) compared to PCNL (47.6%) for treatment of an intermediate-size stone. Older patients (>65 yo) expressed stronger preferences for lower infection rates and shorter hospital stays, and were more likely to prefer URS (67.2%, 95% CI: 52 - 82.5%) compared to younger patients (20-34 yo) (20.3%, 95% CI: 0 - 41.5%) who preferred higher procedure success rates and fewer repeat procedures.CONCLUSION: Conjoint analysis predicts nearly equal patient preference for URS or PCNL for the treatment of intermediate-size kidney stones. Older patients prefer the lower UTI risk and shorter hospital stay associated with URS, while younger patients prefer higher stone-free rates associated with PCNL. These results can help guide urologists in counseling patients and improve the shared decision-making process.

    View details for DOI 10.1089/end.2020.0370

    View details for PubMedID 32867549

  • Assessment of the Association of Cannabis on Female Sexual Function With the Female Sexual Function Index. Sexual medicine Kasman, A. M., Bhambhvani, H. P., Wilson-King, G., Eisenberg, M. L. 2020


    INTRODUCTION: Cannabis use has increased in the last decade, and the impact of cannabis on female sexual function remains unclear.AIM: To assess the impact of frequency of use, chemovar (tetrahydrocannabinol, cannabinol, or both) type, and method of consumption on female sexual function among cannabis users.METHODS: Adults who visited a single-partner cannabis dispensary's locations were invited to participate in an uncompensated, anonymous online survey October 20, 2019 and March 12, 2020. The survey assessed baseline demographics, health status, cannabis use habits as well as used the validated Female Sexual Function Index (FSFI) to assess sexual function.MAIN OUTCOME MEASURE: The main outcomes of this study are the total FSFI score (sexual dysfunction cutoff <26.55) and subdomain scores including desire, arousal, lubrication, orgasm, satisfaction, and pain.RESULTS: A total of 452 women responded with the majority between the ages of 30-49years (54.7%) and in a relationship or married (81.6%). Of them,72.8% reported using cannabis more than 6 times per week, usually through smoking flower (46.7%). Women who reported more cannabis use, reported higher FSFI scores (29.0 vs 26.7 for lowest vs highest frequencies of reported use, P=.003). Moreover, an increase in cannabis use frequency by one additional use per week was associated with an increase in total FSFI (beta=0.61, P=.0004) and subdomains including desire domain (P=.02), arousal domain (P=.0002), orgasm domain (P=.002), and satisfaction domain (P=.003). For each additional step of cannabis use intensity (ie, times per week), the odds of reporting female sexual dysfunction declined by 21% (odds ratio: 0.79, 95% confidence interval: 0.68-0.92, P=.002). Method of consumption of cannabis and chemovar type did not consistently impact FSFI scores or odds of sexual dysfunction.CONCLUSION: Increased frequency of marijuana use is associated with improved sexual function among female users, whereas chemovar type, method of consumption, and reason for use does not impact outcomes. Kasman AM, Bhambhvani HP, Wilson-King G, etal. Assessment of the Association of Cannabis on Female Sexual Function With the Female Sexual Function Index. Sex Med 2020;XX:XXX-XXX.

    View details for DOI 10.1016/j.esxm.2020.06.009

    View details for PubMedID 32713800

  • Male and Female Sexual Dysfunction in Pediatric Cancer Survivors. The journal of sexual medicine Greenberg, D. R., Khandwala, Y. S., Bhambhvani, H. P., Simon, P. J., Eisenberg, M. L. 2020


    BACKGROUND: Pediatric cancer survivors suffer indirect long-term effects of their disease; however, there is a paucity of data regarding the effect of pediatric cancer survivorship on sexual function.AIM: To assess the prevalence and risk factors associated with sexual dysfunction among pediatric cancer survivors.METHODS: Pediatric cancer survivors were recruited to complete an online survey using the Female Sexual Function Index (FSFI) or the International Index of Erectile Function (IIEF-5), both validated questionnaires to assess female sexual dysfunction (FSD) and erectile dysfunction (ED). Patient demographics, oncologic history, prior treatment, and sexual habits were also queried. Logistic regression was used to evaluate risk factors for sexual dysfunction, and Mann-Whitney U test was used to identify factors associated with individual domains of the FSFI.OUTCOMES: The main outcome measures were FSFI and IIEF-5 score, which are used to diagnose FSD (FSFI<26.55) and ED (IIEF-5<22).RESULTS: A total of 21 (72.4%) female respondents and 20 (71.4%) male respondents were sexually active and completed the survey and FSFI or IIEF-5 questionnaire, respectively. Mean (±SD) age was 23.7 (4.1) years, andaverage age at diagnosis was 9.1 (5.0), with no difference between genders. Overall, 25.0% (5/20) of male and 52.4% (11/21) of female pediatric cancer survivors reported sexual dysfunction (P=.11). Oncologic history and prior treatment were not associated with sexual function. Females who reported difficulty relaxing during intercourse in the last 6months had higher odds of reporting sexual dysfunction (odds ratio: 13.6, 95% confidence interval: 1.2-151.2, P=.03). Subgroup analysis of FSFI domains found that previous radiation therapy was correlated with decreased lubrication and satisfaction during intercourse, whereas previous treatment to the pelvic region significantly reduced satisfaction and increased pain during intercourse.CLINICAL IMPLICATIONS: Female pediatric cancer survivors have higher odds of reporting sexual dysfunction after treatment and should be screened appropriately to provide early intervention and to mitigate risk.STRENGTH & LIMITATIONS: Our study includes validated questionnaires to assess FSD and ED and queries specific characteristics to assess their association with sexual dysfunction. However, the study is limited by sample size and its cross-sectional survey design.CONCLUSIONS: The prevalence of female sexual dysfunction in this cohort is higher than that in the general population of equivalent-aged individuals, and clinicians should be aware of these potential long-term sequelae. Greenberg DR, Khandwala YS, Bhambhvani HP, et-al. Male and Female Sexual Dysfunction in Pediatric Cancer Survivors. J Sex Med;XX:XXX-XXX.

    View details for DOI 10.1016/j.jsxm.2020.05.014

    View details for PubMedID 32622765

  • Development of robust artificial neural networks for prediction of 5-year survival in bladder cancer. Urologic oncology Bhambhvani, H. P., Zamora, A., Shkolyar, E., Prado, K., Greenberg, D. R., Kasman, A. M., Liao, J., Shah, S., Srinivas, S., Skinner, E. C., Shah, J. B. 2020


    PURPOSE: When exploring survival outcomes for patients with bladder cancer, most studies rely on conventional statistical methods such as proportional hazards models. Given the successful application of machine learning to handle big data in many disciplines outside of medicine, we sought to determine if machine learning could be used to improve our ability to predict survival in bladder cancer patients. We compare the performance of artificial neural networks (ANN), a type of machine learning algorithm, with that of multivariable Cox proportional hazards (CPH) models in the prediction of 5-year disease-specific survival (DSS) and overall survival (OS) in patients with bladder cancer.SUBJECTS AND METHODS: The National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) 18 program database was queried to identify adult patients with bladder cancer diagnosed between 1995 and 2010, yielding 161,227 patients who met our inclusion criteria. ANNs were trained and tested on an 80/20 split of the dataset. Multivariable CPH models were developed in parallel. Variables used for prediction included age, sex, race, grade, SEER stage, tumor size, lymph node involvement, degree of extension, and surgery received. The primary outcomes were 5-year DSS and 5-year OS. Receiver operating characteristic curve analysis was conducted, and ANN models were tested for calibration.RESULTS: The area under the curve for the ANN models was 0.81 for the OS model and 0.80 for the DSS model. Area under the curve for the CPH models was 0.70 for OS and 0.81 for DSS. The ANN OS model achieved a calibration slope of 1.03 and a calibration intercept of -0.04, while the ANN DSS model achieved a calibration slope of 0.99 and a calibration intercept of -0.04.CONCLUSIONS: Machine learning algorithms can improve our ability to predict bladder cancer prognosis. Compared to CPH models, ANNs predicted OS more accurately and DSS with similar accuracy. Given the inherent limitations of administrative datasets, machine learning may allow for optimal interpretation of the complex data they contain.

    View details for DOI 10.1016/j.urolonc.2020.05.009

    View details for PubMedID 32593506

  • Hepatocellular Carcinoma Brain Metastases: A Single-Institution Experience. World neurosurgery Falkson, S. R., Bhambhvani, H. P., Gephart, M. H. 2020


    BACKGROUND: Brain metastases (BM) from hepatocellular carcinoma (HCC) are rare, with a paucity of published cases. In this retrospective cohort report, we assess the proportion of BM arising from HCC and characterize related details including patient demography, clinical characteristics, treatment modalities, and survival outcomes.METHODS: We retrospectively identified and reviewed the charts of 14 patients with BM from HCC seen at our institution from 2008 to 2018.RESULTS: Among all patients with BM, the proportion originating from primary liver cancer was 0.39%. In every instance (14), the liver cancer was HCC. Median age at the time of BM diagnosis was 64 (range, 37-82). Median alpha-fetoprotein (AFP) at the time of BM was 540 ng/mL (range, 3-10,000). The median time from HCC diagnosis to BM was 31.1 months (range, 3.17-107). 8 of the 14 patients (57%) had metastases to brain parenchyma, while the remaining 6 had skull/dural metastases. For patients with brain parenchymal metastases, the median number of metastases was 1 (range, 1-5). 13 of the 14 patients are deceased, with median overall survival post BM diagnosis of 2.83 months (range, 0.430-24.0). The surviving patient is 142 months post BM diagnosis. Resection of the BM with radiosurgery was associated with increased survival as compared to radiosurgery alone (10.9 months versus 2.8 months, p=0.04).CONCLUSIONS: HCC BM is rare and constitutes a small fraction of total BM. The prognostic data provided in this report can aid medical providers in caring for patients with HCC BM.

    View details for DOI 10.1016/j.wneu.2020.03.189

    View details for PubMedID 32289508

  • Prostate Cancer Brain Metastases: A Single-Institution Experience. World neurosurgery Bhambhvani, H. P., Greenberg, D. R., Srinivas, S., Gephart, M. H. 2020


    BACKGROUND: Brain metastases from prostate cancer are rare and poorly described. We sought to assess the proportion of brain metastases arising from prostate cancer and to detail clinical characteristics, treatment modalities, and survival outcomes.METHODS: We retrospectively identified and reviewed the charts of 31 patients with intraparenchymal brain metastases from prostate adenocarcinoma seen at our institution from 2008 to 2018.RESULTS: Among all patients with brain metastases, the proportion originating from prostate adenocarcinoma was 0.86%. The median age at the time of brain metastasis diagnosis was 69 (range, 57 - 90). The median original Gleason score was 8 (range, 6 - 10), and the median PSA at the time of brain metastasis was 60 ng/ml (range, 0.34 - 4600). The median months from initial cancer diagnosis to brain metastasis was 81 (range, 3 - 195). The median number of brain metastases was 2 (range, 1 - 5). Patients had concurrent metastases to bone (100%), lung (48%), and liver (35%). Median overall survival was 3 months (range, 0.4 - 25.0). Treatment of the brain metastases was correlated with an increase in median survival from 1.2 months to 4.6 months with radiosurgery (HR = 0.11, p = 0.001) and surgical resection plus radiotherapy to 13 months (HR = 0.05, p < 0.001). All patients died of advanced, systemic disease and not of their intracranial disease.CONCLUSIONS: Brain metastasis from prostate cancer constitutes a small fraction of total brain metastases, but is associated with poor prognosis and is seen in the setting of advanced, castrate resistant disease. These data enable treating physicians to appropriately counsel their patients with prostate adenocarcinoma brain metastasis.

    View details for DOI 10.1016/j.wneu.2020.02.152

    View details for PubMedID 32147556

  • A population-level analysis of nonsquamous penile cancer: The importance of histology. Urologic oncology Bhambhvani, H. P., Greenberg, D. R., Parham, M. J., Eisenberg, M. L. 2020


    Nonsquamous penile cancers comprise 5% of penile malignancies, though their clinicopathologic features and prognostic significance remain unknown. We used a national cancer registry to detail clinical characteristics and compare cancer-specific mortality (CSM) of nonsquamous cancers with squamous cell carcinoma (SCC).The Surveillance, Epidemiology, and End Results (SEER) database (1975-2016) was queried to identify adults with nonsquamous penile cancer and penile SCC. Multivariable Fine and Gray competing-risks regression, propensity score matching, and cumulative incidence plots were used.666 men with nonsquamous penile cancer and 5,894 men with penile SCC were identified. The most commonly represented nonsquamous histological subtypes were Kaposi sarcoma (n = 183, 27.5%), melanoma (n = 74, 11.1%), basal cell carcinoma (n = 65, 9.8%), and extramammary Paget disease (n = 42, 6.3%). Cumulative incidence plots revealed a 10-year CSM rate of 32.6% in the nonsquamous penile cancer group and 25.6% in the matched penile SCC group (P < 0.0001). Among Kaposi sarcoma patients and matched SCC patients, we found a 10-year CSM rate of 29.6% in the Kaposi sarcoma group and 15.3% in the penile SCC group (P = 0.002). Similarly, a comparison of penile melanoma patients with matched SCC patients revealed a 10-year CSM rate of 38.4% in the melanoma group and 16.6% in the SCC group (P = 0.002). There was no difference in CSM between patients with basal cell carcinoma and SCC. In a sensitivity analysis limiting year of diagnosis to 2000 and onward, we found no difference in CSM between the general nonsquamous cohort or the Kaposi sarcoma cohort and matched SCC patients, but contemporary melanoma patients maintained worse CSM with a 10-year rate of 38.4% vs. 15.8% in matched SCC patients (P = 0.045).The most common nonsquamous penile cancers are Kaposi sarcoma, melanoma, and basal cell carcinoma. Overall, CSM is higher in nonsquamous penile cancers as compared to stage-matched SCC. Outcomes are similar in modern patients, likely due to improved control of systemic HIV in patients with Kaposi sarcoma. However, men with penile melanoma continue to experience a higher rate of CSM.

    View details for DOI 10.1016/j.urolonc.2020.11.025

    View details for PubMedID 33257222

  • Intracranial Tumor Control Following Immune-Related Adverse Events and Discontinuation of Immunotherapy for Melanoma. World neurosurgery Zhang, M., Rodrigues, A. J., Bhambhvani, H. P., Fatemi, P., Pollom, E. L., Gibbs, I. C., Thomas, R. P., Soltys, S. G., Hancock, S. L., Chang, S. D., Reddy, S. A., Gephart, M. H., Li, G. 2020


    Immunotherapy for melanoma patients with brain metastasis has significantly improved outcomes; however, they have also been characterized by potentially dangerous immune-related adverse events (IRAEs). Several reports suggest these reactions can precede improved treatment responses. We sought to identify if such association exists for intracranial disease control.We conducted a retrospective chart review of melanoma patients who underwent immunotherapy treatment following diagnosis of brain metastasis. The study cohort was then stratified into two groups based on their history of developing an IRAE that prompted discontinuation of that regimen. The primary outcome variable included intracranial progression-free survival (PFS). Kaplan-Meier and Cox proportional hazard analysis were used to evaluate survival and predictors of outcomes.Fifty-two patients met inclusion criteria, seventeen of whom experienced severe IRAEs that led to discontinuation of immunotherapy. Median intracranial PFS was 19.9 vs 10.5 months (p = 0.053) in patients who did and did not experience severe IRAEs prompting discontinuation, respectively. No additional outcome benefits were identified for systemic PFS or overall survival, mean (33.1 months and 27.6 months, respectively). Multivariable analysis identified BRAF mutation status as a negative prognosticator of brain progression (p = 0.013, HR = 3.90). Initial treatment with BRAF inhibitor was also a negative predictor of all-cause mortality (p = 0.015, HR = 10.73) CONCLUSION: Immune related adverse events may signify an underlying immunogenic response that has intracranial disease control benefits. Despite their associated side effects, immunotherapies continue to demonstrate promising outcomes as a first-line agent for melanoma with brain metastasis.

    View details for DOI 10.1016/j.wneu.2020.08.124

    View details for PubMedID 32853767

  • Hepatocellular Carcinoma Brain Metastases: A Single-Institution Experience & nbsp; BIOTECHNOLOGY & BIOTECHNOLOGICAL EQUIPMENT Falkson, S. R., Bhambhvani, H. P., Gephart, M. 2020; 34 (1): E27–E32
  • Deep learning enabled classification of Mayo endoscopic subscore in patients with ulcerative colitis. European journal of gastroenterology & hepatology Bhambhvani, H. P., Zamora, A. 2020


    Previous reports of deep learning-assisted assessment of Mayo endoscopic subscore (MES) in ulcerative colitis have only explored the ability to distinguish disease remission (MES 0/1) from severe disease (MES 2/3) or inactive disease (MES 0) from active disease (MES 1-3). We sought to explore the utility of deep learning models in the automated grading of each individual MES in ulcerative colitis.In this retrospective study, a total of 777 representative still images of endoscopies from 777 patients with clinically active ulcerative colitis were graded using the MES by two physicians. Each image was assigned an MES of 1, 2, or 3. A 101-layer convolutional neural network model was trained and validated on 90% of the data, while 10% was left for a holdout test set. Model discrimination was assessed by calculating the area under the curve (AUC) of a receiver operating characteristic as well as standard measures of accuracy, specificity, sensitivity, positive predictive value (PPV), and negative predictive value (NPV).In the holdout test set, the final model classified MES 3 disease with an AUC of 0.96, MES 2 disease with an AUC of 0.86, and MES 1 disease with an AUC 0.89. Overall accuracy was 77.2%. Across MES 1, 2, and 3, average specificity was 85.7%, average sensitivity was 72.4%, average PPV was 77.7%, and the average NPV was 87.0%.We have demonstrated a deep learning model was able to robustly classify individual grades of endoscopic disease severity among patients with ulcerative colitis.

    View details for DOI 10.1097/MEG.0000000000001952

    View details for PubMedID 33079775

  • Emergent neuroimaging for seizures in epilepsy: A population study. Epilepsy & behavior : E&B Lamsam, L., Bhambhvani, H. P., Ratliff, J. K., Kvam, K. A. 2020; 112: 107339


    We determined how often patients with epilepsy presented to the emergency department (ED) for seizure and the frequency and predictors for undergoing emergent neuroimaging during those visits. We conducted a retrospective population-based cohort study using administrative claims' data from 2007 to 2015. Adults with epilepsy were identified based on a diagnosis of epilepsy and an outpatient prescription for an antiepileptic medication. The Bonferroni corrected significance level was 0.0018. We identified 381,362 patients with a mean follow-up period of 1.99 years, of whom 35,015 (9.2%) patients presented to the ED for seizure at least once. Patients with at least one ED visit were younger, more likely to be male, had fewer comorbidities, and had longer follow-up as compared with those with no ED visit (all p < 0.001). Among the 35,015 patients presenting to the ED, 13.6% had neuroimaging, mostly commonly head computed tomography (CT; 95.5%). Patients undergoing neuroimaging were younger (46 versus 48 years) and with higher rates of psychosis (17.4% versus 13.8%) and depression (16.1% versus 12.2%; p < 0.001). This helps to quantify the burden of ED and emergent neuroimaging utilization for patients with epilepsy and can help inform efforts to curtail unnecessary neuroimaging.

    View details for DOI 10.1016/j.yebeh.2020.107339

    View details for PubMedID 32911297

  • Ejaculatory Dysfunction in Patients Presenting to a Men's Health Clinic: A Retrospective Cohort Study. Sexual medicine Kasman, A. M., Bhambhvani, H. P., Eisenberg, M. L. 2020


    Prevalence and bother of ejaculatory dysfunction (EjD) has yet to be evaluated in a men's health referral population.To evaluate the prevalence and associated risk factors of EjD in men presenting to a men's health clinic.A retrospective review examined patients presenting to an outpatient men's health clinic who completed the Sexual Health Inventory for Men and the Male Sexual Health Questionnaire Ejaculatory Dysfunction (MSHQ-EjD) Short Form. Patient factors including demographics, comorbidities, and medication were examined. Descriptive statistics and multivariable logistic regression were used.The main outcomes of this study are Sexual Health Inventory for Men and MSHQ-EjD scores.A total of 63 (24%) of patients presenting to the urology clinic were characterized as having EjD based on questionnaire responses. The mean age for men with EjD was 53.8 years, while those without was 42.6 years (P < .001). Of men with EjD, 74.6% were at least moderately bothered (MSHQ-EjD ≥3). Men with EjD were more likely to have erectile dysfunction (77.8%) compared with those without (21%, P < .001) as well as a history of a pelvic cancer (20.6% vs 6%, P = .001). On multivariable regression, erectile dysfunction (odds ratio: 15.04, 95% confidence interval: 6.76-35.92, P < .0001) and alpha inhibitor prescription (odds ratio: 6.82, 95% confidence interval: 1.57-30.16, P = .01) were associated with a higher odds of EjD. ED was found to be a mediator of the relationship between EjD and age, as the age association was lost in the ED population on multivariable regression compared with the non-ED population where it remained significant.EjD is common among patients presenting to a men's health clinic and may present at varying ages, though it is more common in those aged 50 years or older; it is independent of age and race. EjD is associated with erectile dysfunction, pelvic cancer history, and use of alpha inhibitors, presenting a population that could be considered for screening. Kasman AM, Bhambhvani HP, Eisenberg ML. Ejaculatory Dysfunction in Patients Presenting to a Men's Health Clinic: A Retrospective Cohort Study. J Sex Med 2020;XX:XXX-XXX.

    View details for DOI 10.1016/j.esxm.2020.05.002

    View details for PubMedID 32553504

  • A Survey Exploring the Relationship Between Cannabis Use Characteristics and Sexual Function in Men. Sexual medicine Bhambhvani, H. P., Kasman, A. M., Wilson-King, G., Eisenberg, M. L. 2020


    Cannabis is the most commonly used drug in the United States; however, the effects of cannabis use on male sexual function are poorly understood.To characterize the contemporary landscape of cannabis use and to assess the associations between male sexual function and the frequency of use, the primary method of consumption, or cannabis chemovar (tetrahydrocannabinol or cannabidiol) among current users.We surveyed adults who visited a single cannabis dispensary for baseline demographic information, medical history, cannabis use habits, and sexual function as assessed by the International Index of Erectile Function (IIEF). An IIEF-5 < 21 was considered erectile dysfunction.The main outcome measure of the study was male sexual function via the IIEF domain scores.A total of 325 men completed the survey with a mean age of 46.7 years. 71.1% of the men were Caucasian and 52.6% were married. 13 men (4%) were never users; 29 men (8.9%) used 1-2 times/week; 51 men (15.7%) used 3-5 times/week, and 232 men (71.4%) used 6+ times/week. The average IIEF-5 score was 22.3 with 19.4% of the men having erectile dysfunction. In univariate analysis, men using cannabis more frequently had a higher overall IIEF (65.36 vs 60.52, P = .001), erectile domain (27.32 vs 25.74, P = .03), orgasm domain (9.08 vs 8.12, P < .001), intercourse satisfaction domain (12.42 vs 11.31, P = .006), and overall satisfaction domain (8.11 vs 7.05, P = .002). In multivariable analysis, compared to men who used cannabis 0 times/week, those who used 6 times/week had an increased overall IIEF (69.08 vs 64.64, P-value adjusted = 0.02), intercourse satisfaction domain (P-value adjusted = 0.04), and overall satisfaction domain (P-value adjusted = 0.02). The primary method of consumption (eg, smoking, edibles, etc.) and cannabinoid composition (eg, cannabidiol vs tetrahydrocannabinol dominant) were not associated with sexual function.We report an association between the increased frequency of cannabis use and increased male sexual function. However, while the increased frequency of use was statistically significant with regard to the IIEF scores, the clinical significance of this is likely low, and selection bias may limit the generalizability of these findings. The method of consumption and cannabis chemovar were not associated with sexual function. Bhambhvani HP, Kasman AM, Wilson-King G, et al. A Survey Exploring the Relationship Between Cannabis Use Characteristics and Sexual Function in Men. J Sex Med 2020;XX:XXX-XXX.

    View details for DOI 10.1016/j.esxm.2020.06.002

    View details for PubMedID 32561331

  • Racial and socioeconomic correlates of treatment and survival among patients with meningioma: a population-based study. Journal of neuro-oncology Bhambhvani, H. P., Rodrigues, A. J., Medress, Z. A., Hayden Gephart, M. 2020


    Though meningioma is the most common primary brain tumor, there is a paucity of epidemiologic studies investigating disparities in treatment and patient outcomes. Therefore, we sought to explore how sociodemographic factors are associated with rates of gross total resection (GTR) and radiotherapy as well as survival.The National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database was queried to identify adult patients with meningioma diagnosed between 2005 and 2015. Socioeconomic status (SES) was determined using a validated composite index in which patients were stratified into tertiles and quintiles. Multivariable logistic regression and Cox proportional hazards analyses were used to identify predictors of treatment and survival, respectively.71,098 patients met our inclusion criteria. Low SES quintile was associated with reduced odds of receiving GTR (OR 0.76, 95% CI 0.69-0.83, p < 0.0001) and radiotherapy (OR 0.83, 95% CI 0.76-0.91, p < 0.0001) as well as worse survival (HR 1.48, 95% CI 1.41-1.56) as compared to the highest SES quintile. Black patients had reduced odds of GTR (OR 0.74, 95% CI 0.67-0.71, p < 0.0001) and worse survival (HR 1.23, 95% CI 1.18-1.29, p < 0.0001) as compared to white patients.This national study of patients with meningioma found socioeconomic status and race to be independent inverse correlates of likelihood of GTR, radiotherapy, and survival. Limited access to care may underlie these disparities in part, and future studies are warranted to identify specific causes for these findings.

    View details for DOI 10.1007/s11060-020-03455-2

    View details for PubMedID 32193691

  • Brain Metastases from Endometrial Cancer: Clinical Characteristics, Outcomes, and Review of the Literature. World neurosurgery Bhambhvani, H. P., Zhou, O., Cattle, C., Taiwo, R., Diver, E., Gephart, M. H. 2020


    Brain metastases from endometrial cancer are rare and poorly described. We aimed to estimate the proportion of brain metastases at our institution that arose from endometrial cancer, and to detail clinicopathologic features and survival outcomes.We retrospectively identified and reviewed the charts of 30 patients with brain metastases from endometrial cancer seen at Stanford Hospital from 2008 to 2018.Among all patients with brain metastases, the proportion arising from endometrial cancer was 0.84%. Median age at diagnosis was 62 (range, 39 - 79), and median overall survival (OS) was 6.8 months (range, 1.0 month - 58.2 months). Most patients harbored endometrioid histology (53.3%), and some had concurrent metastases to lung (50.0%), bone (36.7%), and liver (20.0%). Median time from endometrial cancer diagnosis to brain metastasis development was 20.8 months (range, 1.4 months - 11.2 years), and the median number of brain metastases was 2 (range, 1 - 20). Patients with non-endometrioid histologies had more brain metastases than those with endometrioid histology (6.21 versus 2.44, p = 0.029). There was no difference in OS by histology.We describe the largest cohort to date of patients with brain metastases originating from endometrial cancer. These patients represent a small fraction of all brain metastasis patients and have poor prognoses. These data enable providers caring for patients with brain metastases from endometrial cancer to appropriately counsel their patients.

    View details for DOI 10.1016/j.wneu.2020.11.087

    View details for PubMedID 33321250

  • Bupivacaine local anesthetic to decrease opioid requirements after radical cystectomy: Does formulation matter? Urologic oncology Schmidt, B., Bhambhvani, H. P., Greenberg, D. R., Prado, K., Shafer, S., Thong, A., Gill, H., Skinner, E., Shah, J. B. 2020


    Reduction of opioids is an important goal in the care of patients undergoing radical cystectomy (RC). Liposomal bupivacaine (LB) has been shown to be a safe and effective pain reliever in the immediate postoperative period and has been reported to reduce postoperative opioid requirements. Since the liposomal formulation is predicated on slow systemic absorption, the amount of bupivacaine administered is notably higher than that typically used with standard bupivacaine (SB) formulations. In addition, LB is costly, not universally available, and studies comparing this formulation to SB are lacking. We sought to determine if there is a difference in postoperative opioid requirements in patients who receive LB vs. high dose SB at the time of RC.In May 2019 we transitioned to administration of high-volume SB injected intraoperatively at the time of RC. This prospective cohort was compared to a historical cohort of patients who received injection of LB at the time of surgery. Primary endpoints included postsurgical opioid use measured in morphine equivalent dose (MED) and patient-reported Numeric Rating Scale (NRS) pain scores and length of stay. All patients were managed using principles of enhanced recovery after surgery (ERAS).From May 2019 through August 2019, 28 patients underwent RC and met eligibility criteria to receive SB at the time of surgery. They were compared to a historical cohort of 34 patients who received LB between November 2017 and July 2018. There was no difference in MED exposure either in the postanesthesia care unit (SB 9.0 ± 8.9 MED vs. LB 6.5 ± 9.4 MED, P= 0.29) or during the remainder of the hospital stay (SB 36.8 ± 56.9 MED vs. LB 42.1 ± 102.5 MED, P= 0.81), no difference in NRS pain scores on postoperative day 1 (SB 2.6 ± 1.6 vs. LB 2.1 ± 1.7, P= 0.23), day 2 (SB 2.4 ± 1.8 vs. LB 1.9 ± 1.6, P= 0.19), or day 3 (SB 1.9 ± 1.8 vs. LB 1.7 ± 1.7, P= 0.69) and no difference in length of stay (SB 5.0 ± 1.7 days, LB 4.9 ± 3.3 days, P= 0.93). Subgroup analysis of open RC and robotic-assisted RC showed no significant difference in MED or pain scores between LB and SB patients.Among patients undergoing RC under ERAS protocol there was no significant difference in postoperative opioid consumption, NRS pain scores, or length of stay among patients receiving SB compared to LB.

    View details for DOI 10.1016/j.urolonc.2020.11.008

    View details for PubMedID 33303378

  • Deep learning enabled prediction of 5-year survival in pediatric genitourinary rhabdomyosarcoma. Surgical oncology Bhambhvani, H. P., Zamora, A., Velaer, K., Greenberg, D. R., Sheth, K. R. 2020; 36: 23–27


    Genitourinary rhabdomyosarcoma (GU-RMS) is a rare, pediatric malignancy originating from embryonic mesenchyme. Current approaches to prognostication rely upon conventional statistical methods such as Cox proportional hazards (CPH) models and have suboptimal predictive ability. Given the success of deep learning approaches in other specialties, we sought to develop and compare deep learning models with CPH models for the prediction of 5-year survival in pediatric GU-RMS patients.Patients less than 20 years of age with GU-RMS were identified within the Surveillance, Epidemiology, and End Results (SEER) database (1998-2011). Deep neural networks (DNN) were trained and tested on an 80/20 split of the dataset in a 5-fold cross-validated fashion. Multivariable CPH models were developed in parallel. The primary outcomes were 5-year overall survival (OS) and disease-specific survival (DSS). Variables used for prediction were age, sex, race, primary site, histology, degree of tumor extension, tumor size, receipt of surgery, and receipt of radiation. Receiver operating characteristic curve analysis was conducted, and DNN models were tested for calibration.277 patients were included. The area under the curve (AUC) for the DNN models was 0.93 for OS and 0.91 for DSS. AUC for the CPH models was 0.82 for OS and 0.84 for DSS. The DNN models were well-calibrated: OS model (slope = 1.02, intercept = -0.06) and DSS model (slope = 0.79, intercept = 0.21).A deep learning-based model demonstrated excellent performance, superior to that of CPH models, in the prediction of pediatric GU-RMS survival. Deep learning approaches may enable improved prognostication for patients with rare cancers.

    View details for DOI 10.1016/j.suronc.2020.11.002

    View details for PubMedID 33276260

  • EVALUATION OF DYNAMIN 2 (DNM2) AS A THERAPEUTIC TARGET IN LEPTOMENINGEAL METASTATIC DISEASE Chernikova, S., Polyak, D., Deng, J., Tsau, S., Casey, K., Johnson, E., Bhambhvani, H., Khoeur, L., Stanley, G., Tran, K., Connolly, I., Joyce, A., Li, Y., von Eyben, R., Nagpal, S., Gephart, M. OXFORD UNIV PRESS INC. 2019: 57
  • Effect of Electronic Clinical Decision Support on Imaging for the Evaluation of Acute Low Back Pain in the Ambulatory Care Setting. World neurosurgery Chen, D., Bhambhvani, H. P., Hom, J., Mahoney, M., Wintermark, M., Sharp, C., Ratliff, J., Chen, Y. R. 2019


    To assess the effectiveness of a clinical decision support tool consisting of an electronic medical record Best Practice Alert (BPA) on the frequency of lumbar imaging in patients with acute low back pain (LBP) in the ambulatory care setting. To understand why providers order imaging outside of clinical guidelines.We implemented a BPA pop-up alert on 3/23/16 that informed the ordering physician of the Choosing Wisely recommendation to not order imaging within the first 6 weeks of low back pain in the absence of red flags. We measured imaging rates 1 year before and after implementation of the BPA. To override the BPA, providers could ignore the alert or explain their rationale for ordering imaging using either pre-set options or free-text submission. We tracked pre-set options and manually reviewed 125 free-text submissions.Significant decreases in both total imaging rate (9.6% decrease, p = 0.02) and MRI rate (14.9% decrease, p < 0.01) were observed after implementation of the BPA. No change was found in the rates of x-ray or CT ordering. 64% of providers used pre-set options in overriding the BPA, while 36% of providers entered a free-text submission. Among those providers using a free-text submission, 56% entered a non-guideline supported rationale.The present study demonstrates the effectiveness of a simple, low-cost clinical decision support tool in reducing imaging rates for patients with acute low back pain. We additionally identify reasons providers order imaging outside of clinical guidelines.

    View details for DOI 10.1016/j.wneu.2019.11.031

    View details for PubMedID 31733384

  • Intracranial Hemorrhage in Deep Vein Thrombosis/Pulmonary Embolus Patients Without Atrial Fibrillation: Direct Oral Anticoagulants Versus Warfarin. Stroke Lamsam, L., Sussman, E. S., Iyer, A. K., Bhambhvani, H. P., Han, S. S., Skirboll, S., Ratliff, J. K. 2018


    BACKGROUND AND PURPOSE: Deep vein thrombosis (DVTs) is a common disease with high morbidity if it progresses to pulmonary embolus (PE). Anticoagulation is the treatment of choice; warfarin has long been the standard of care. Early experience with direct oral anticoagulants (DOACs) suggests that these agents may be may be a safer and equally effective alternative in the treatment of DVT/PE. Nontraumatic intracranial hemorrhage (ICH) is one of the most devastating potential complications of anticoagulation therapy. We sought to compare the rates of ICH in patients treated with DOACs versus those treated with warfarin for DVT/PE.METHODS: The MarketScan Commercial Claims and Medicare Supplemental databases were used. Adult DVT/PE patients without known atrial fibrillation and with prescriptions for either a DOAC or warfarin were followed for the occurrence of inpatient admission for ICH. Coarsened exact matching was used to balance the treatment cohorts. Cox proportional-hazards regressions and Kaplan-Meier survival curves were used to estimate the association between DOACs and the risk of ICH compared with warfarin.RESULTS: The combined cohort of 218 620 patients had a median follow-up of 3.0 months, mean age of 55.4 years, and was 52.1% women. The DOAC cohort had 26 980 patients and 8 ICH events (1.0 cases per 1000 person-years), and the warfarin cohort had 191 640 patients and 324 ICH events (3.3 cases per 1000 person-years; P<0.0001). The DOAC cohort had a lower hazard ratio for ICH compared with warfarin in both the unmatched (hazard ratio=0.26; P=0.0002) and matched (hazard ratio=0.20; P=0.0001) Cox proportional-hazards regressions.CONCLUSIONS: DOACs show superior safety to warfarin in terms of risk of ICH in patients with DVT/PE.

    View details for PubMedID 29991654

  • Actin polymerization is reduced in the anterior cingulate cortex of elderly patients with schizophrenia. Translational psychiatry Bhambhvani, H. P., Mueller, T. M., Simmons, M. S., Meador-Woodruff, J. H. 2017; 7 (12): 1278


    Recent reports suggest abnormalities in the regulation of actin cytoskeletal dynamics in schizophrenia, despite consistent evidence for normal actin expression. We hypothesized that this may be explained by changes in the polymerization state of actin, rather than in total actin expression. To test this, we prepared filamentous actin (F-actin, polymeric) and globular actin (G-actin, monomeric) fractions from postmortem anterior cingulate cortex from 16 patients with schizophrenia and 14 comparison subjects. Additionally, binding of fluorescently-labeled phalloidin, a selectively F-actin-binding peptide, was measured in unfractionated samples from the same subjects. Western blot analysis of fractions revealed decreased F-actin, increased G-actin, and decreased ratios of F-actin/total actin and F-actin/G-actin in schizophrenia. Decreased phalloidin binding to F-actin in parallel experiments in the same subjects independently supports these findings. These results suggest a novel aspect of schizophrenia pathophysiology and are consistent with previous evidence of reduced dendritic spine density and altered synaptic plasticity in schizophrenia, both of which have been linked to cytoskeletal abnormalities.

    View details for DOI 10.1038/s41398-017-0045-y

    View details for PubMedID 29225346

  • Decreased expression of cortactin in the schizophrenia brain NEUROREPORT Bhambhvani, H. P., Simmons, M., Haroutunian, V., Meador-Woodruff, J. H. 2016; 27 (3): 145-150


    Schizophrenia is a severe psychiatric disorder that is characterized by a wide array of symptoms and a complex neuropathology. A well-characterized neurobiological feature of schizophrenia is abnormal synaptic plasticity, although the mechanisms underlying this are not fully understood. Numerous studies have demonstrated a link between proper functioning of the cytoskeleton and synaptic plasticity. The actin-related protein-2/3 (Arp2/3) complex is responsible for the nucleation of new actin filaments and elongation of existing actin filaments and is thus crucial to cytoskeletal dynamics, especially actin polymerization and organization. To determine whether the Arp2/3 complex is abnormally expressed in schizophrenia, we measured the protein expression of Arp2 and Arp3, as well as Arp2/3 complex binding partners and associated proteins including cortactin, neuronal-Wiskott-Aldrich syndrome protein (WASP), WASP-family verprolin homologous protein 1 (WAVE1), and Abelson interactor 1 (Abi1) in the superior temporal gyrus of paired schizophrenia and comparison participants. No changes were found in Arp2, Arp3, neuronal-WASP, WAVE1, or Abi1. However, all three isoforms of cortactin were decreased in schizophrenia. Specifically, the 62 kDa isoform was decreased by 43%; the 71 kDa isoform was decreased by 32%; and the 58 kDa isoform was decreased by 35%. Cortactin regulates branching of filamentous actin through its binding and activation of the Arp2/3 complex, and it is thus critical to the formation of stable actin networks. These findings contribute to a growing body of evidence implicating altered cytoskeletal dynamics in schizophrenia.

    View details for DOI 10.1097/WNR.0000000000000514

    View details for Web of Science ID 000373515100003

    View details for PubMedID 26691754

    View details for PubMedCentralID PMC4733612

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