Shreya Malhotra

All Publications

• Retrograde endocannabinoid signaling at inhibitory synapses in vivo. Science (New York, N.Y.) Dudok, B., Fan, L. Z., Farrell, J. S., Malhotra, S., Homidan, J., Kim, D. K., Wenardy, C., Ramakrishnan, C., Li, Y., Deisseroth, K., Soltesz, I. 2024; 383 (6686): 967-970

  Abstract

  Endocannabinoid (eCB)-mediated suppression of inhibitory synapses has been hypothesized, but this has not yet been demonstrated to occur in vivo because of the difficulty in tracking eCB dynamics and synaptic plasticity during behavior. In mice navigating a linear track, we observed location-specific eCB signaling in hippocampal CA1 place cells, and this was detected both in the postsynaptic membrane and the presynaptic inhibitory axons. All-optical in vivo investigation of synaptic responses revealed that postsynaptic depolarization was followed by a suppression of inhibitory synaptic potentials. Furthermore, interneuron-specific cannabinoid receptor deletion altered place cell tuning. Therefore, rapid, postsynaptic, activity-dependent eCB signaling modulates inhibitory synapses on a timescale of seconds during behavior.

  View details for DOI 10.1126/science.adk3863

  View details for PubMedID 38422134

• Clinical outcomes and cost differences between patients undergoing primary anterior cervical discectomy and fusion procedures with private or Medicare insurance: a propensity score matched study. World neurosurgery Shah, V., Rodrigues, A. J., Malhotra, S., Johnstone, T., Varshneya, K., Haider, G., Stienen, M. N., Veeravagu, A. 2023

  Abstract

  To assess whether insurance type reflects a patient's quality of care following an ACDF procedure, by comparing differences in post-operative complications, readmission rates, reoperation rates, length of hospital stay, and cost of treatment between patients with Medicare versus private insurance.Propensity score matching (PSM) was employed to match patient cohorts insured by Medicare and private insurance in the MarketScan Commercial Claims and Encounters Database (2007-2016). Age, sex, year of operation, geographic region, comorbidities, and operative factors were used to match cohorts of patients undergoing an ACDF procedure.A total of 110,911 patients met the inclusion criteria, of which 97,543 patients (87.9%) were privately insured and 13,368 patients (12.1%) were insured by Medicare. The PSM algorithm matched 7,026 privately insured patients to 7,026 Medicare patients. After matching, there was no significant difference in 90-day post-operative complication rates, length of stay, or reoperation rates between the Medicare and privately insured cohorts. The Medicare group had lower post-operative readmission rates for all time points: 30 days (1.8% vs. 4.6%; p < 0.001), 60 days (2.5% vs. 6.3%; p < 0.001), and 90 days (4.2% vs. 7.7%; p < 0.001). The median payments to physicians were significantly lower for the Medicare group ($3,885 vs. $5,601; p < 0.001).In this study, propensity score matched patients covered by Medicare and private insurance that underwent an ACDF procedure were found to have similar treatment outcomes.

  View details for DOI 10.1016/j.wneu.2023.02.129

  View details for PubMedID 36871653

• Chronic opioid use prior to ACDF surgery is associated with inferior post-operative outcomes: a propensity-matched study of 17,443 chronic opioid users. World neurosurgery Rodrigues, A. J., Varshneya, K., Schonfeld, E., Malhotra, S., Stienen, M. N., Veeravagu, A. 2022

  Abstract

  STUDY DESIGN: Retrospective cohort OBJECTIVE: Candidates for anterior cervical discectomy and fusion (ACDF) have a higher rate of opioid use than does the public, but studies on pre-operative opioid use have not been conducted. We aimed to understand how pre-operative opioid use affects post-ACDF outcomes.METHODS: The MarketScan Database was queried from 2007-2015 to identify adult patients who underwent an ACDF. Patients were classified into separate cohorts based on the number of separate opioid prescriptions in the year before their ACDF. 90-day post-operative complications, post-operative readmission, re-operation, and total inpatient costs were compared between opioid strata. Propensity-score matching (PSM) matched patient cohorts across observed comorbidities.RESULTS: Of 81,671 ACDF patients, 31,312 (38.3%) were non-users, 30,302 (37.1%) were mild users, and 20,057 (24.6%) were chronic users. Chronic opioid users had a higher comorbidity burden, on average, than patients with less frequent opioid use (p<0.001). Chronic opioid users had higher rates of post-operative complications (9.1%) than mild opioid users (6.0%) and non-users (5.3%) (p<0.001), and higher rates of readmission and reoperation. After balancing opioid non-users vs. chronic opioid users along demographic, pre-operative comorbidity, and operative characteristics, post-operative complications remained elevated for chronic opioid users relative to opioid non-users (8.6% vs. 5.7%; p<0.001), as did rates of readmission and reoperation.CONCLUSIONS: Chronic opioid users had more comorbidities than opioid non-users and mild opioid users, longer hospitalizations, and higher rates of post-operative complication, readmission, and reoperation. After balancing patients across covariates, the outcome differences persisted, suggesting a durable association between pre-operative opioid use and negative post-operative outcomes.

  View details for DOI 10.1016/j.wneu.2022.07.002

  View details for PubMedID 35809840

• Climbing Fiber-Mediated Spillover Transmission to Interneurons Is Regulated by EAAT4. The Journal of neuroscience : the official journal of the Society for Neuroscience Malhotra, S., Banumurthy, G., Pennock, R. L., Vaden, J. H., Sugihara, I., Overstreet-Wadiche, L., Wadiche, J. I. 2021; 41 (39): 8126-8133

  Abstract

  Neurotransmitter spillover is a form of communication not readily predicted by anatomic structure. In the cerebellum, glutamate spillover from climbing fibers recruits molecular layer interneurons in the absence of conventional synaptic connections. Spillover-mediated signaling is typically limited by transporters that bind and reuptake glutamate. Here, we show that patterned expression of the excitatory amino acid transporter 4 (EAAT4) in Purkinje cells regulates glutamate spillover to molecular layer interneurons. Using male and female Aldolase C-Venus knock-in mice to visualize zebrin microzones, we find larger climbing fiber-evoked spillover EPSCs in regions with low levels of EAAT4 compared with regions with high EAAT4. This difference is not explained by presynaptic glutamate release properties or postsynaptic receptor density but rather by differences in the glutamate concentration reaching receptors on interneurons. Inhibiting glutamate transport normalizes the differences between microzones, suggesting that heterogeneity in EAAT4 expression is a primary determinant of differential spillover. These results show that neuronal glutamate transporters limit extrasynaptic transmission in a non-cell-autonomous manner and provide new insight into the functional specialization of cerebellar microzones.SIGNIFICANCE STATEMENT Excitatory amino acid transporters (EAATs) help maintain the fidelity and independence of point-to-point synaptic transmission. Whereas glial transporters are critical to maintain low ambient levels of extracellular glutamate to prevent excitotoxicity, neuronal transporters have more subtle roles in shaping excitatory synaptic transmission. Here we show that the patterned expression of neuronal EAAT4 in cerebellar microzones controls glutamate spillover from cerebellar climbing fibers to nearby interneurons. These results contribute to fundamental understanding of neuronal transporter functions and specialization of cerebellar microzones.

  View details for DOI 10.1523/JNEUROSCI.0616-21.2021

  View details for PubMedID 34400517

  View details for PubMedCentralID PMC8482868

• Training needs assessment: tool utilization and global impact. BMC medical education Markaki, A., Malhotra, S., Billings, R., Theus, L. 2021; 21 (1): 310

  Abstract

  BACKGROUND: Global demand for standardized assessment of training needs and evaluation of professional continuing education programs across the healthcare workforce has led to various instrumentation efforts. The Hennessy-Hicks Training Needs Analysis (TNA) questionnaire is one of the most widely used validated tools. Endorsed by the World Health Organization, the tool informs the creation of tailored training to meet professional development needs. The purpose of this project was to describe TNA tool utilization across the globe and critically appraise the evidence of its impact in continuous professional development across disciplines and settings.METHODS: A systematic integrative literature review of the state of the evidence across PubMed, Scopus, CINAHL, and Google Scholar databases was carried out. Full-text, peer reviewed articles and published dissertations/theses in English language that utilized the original, adapted or translated version of the TNA tool were included. Selected articles were appraised for type and level of evidence.RESULTS: A total of 33 articles were synthesized using an inductive thematic approach, which revealed three overarching themes: individual, team/interprofessional, and organizational level training needs. Included articles represented 18 countries, with more than two thirds involving high-income countries, and one third middle-income countries. Four studies (12.1%) used the original English version instrument, 23 (69.7%) adapted the original version, and 6 (18.2%) translated and culturally adapted the tool. Twenty-three studies targeted needs at the individual level and utilized TNA to determine job roles and responsibilities. Thirteen articles represented the team/interprofessional theme, applying the TNA tool to compare training needs and perceptions among professional groups. Last, three articles used the tool to monitor the quality of care across an institution or healthcare system, demonstrating the organizational training needs theme.CONCLUSIONS: Overall evidence shows that the TNA survey is widely used as a clinical practice and educational quality improvement tool across continents. Translation, cultural adaptation, and psychometric testing within a variety of settings, populations, and countries consistently reveals training gaps and outcomes of targeted continuous professional development. Furthermore, it facilitates prioritization and allocation of limited educational resources based on the identified training needs. The TNA tool effectively addresses the "know-do" gap in global human resources for health by translating knowledge into action.

  View details for DOI 10.1186/s12909-021-02748-y

  View details for PubMedID 34059018

• Differences in treatment patterns and overall survival between grade II and anaplastic pleomorphic xanthoastrocytomas. Journal of neuro-oncology Rodrigues, A., Bhambhvani, H., Medress, Z. A., Malhotra, S., Hayden-Gephart, M. 2021

  Abstract

  INTRODUCTION: Pleomorphic xanthoastrocytomas (PXAs) are classified as a grade II neoplasm, typically occur in children, and have favorable prognoses. However, their anaplastic counterparts remain poorly understood and vaguely characterized. In the present study, a large cohort of grade II PXA patients were compared with primary anaplastic PXA (APXA) patients to characterize patterns in treatment and survival.METHODS: Data were collected from the National Cancer Institute's SEER database. Univariate and multivariate Cox regressions were used to evaluate the prognostic impact of demographic, tumor, and treatment-related covariates. Propensity score matching was used to balance baseline characteristics. Kaplan-Meier curves were used to estimate survival.RESULTS: A total of 346 grade II PXA and 62 APXA patients were identified in the SEER database between 2000 and 2016. Kaplan-Meier analysis revealed substantially inferior survival for APXA patients compared to grade II PXA patients (median survival: 51months vs. not reached) (p<0.0001). After controlling across available covariates, increased age at diagnosis was identified as a negative predictor of survival for both grade II and APXA patients. In multivariate and propensity-matched analyses, extent of resection was not associated with improved outcomes in either cohort.CONCLUSIONS: Using a large national database, we identified the largest published cohort of APXA patients to date and compared them with their grade II counterparts to identify patterns in treatment and survival. Upon multivariate analysis, we found increased age at diagnosis was inversely associated with survival in both grade II and APXA patients. Receipt of chemoradiotherapy or complete surgical resection was not associated with improved outcomes in the APXA cohort.

  View details for DOI 10.1007/s11060-021-03772-0

  View details for PubMedID 33970405