All Publications


  • 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

    Abstract

    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

    Abstract

    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

    Abstract

    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

  • 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

    Abstract

    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

  • 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

    Abstract

    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

    Abstract

    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

  • 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

    Abstract

    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

    Abstract

    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

    Abstract

    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

    Abstract

    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