Ashish Shah | University of Mumbai (original) (raw)

Papers by Ashish Shah

Brain Sciences

The mainstays of glioblastoma treatment, maximal safe resection, radiotherapy preserving neurolog... more The mainstays of glioblastoma treatment, maximal safe resection, radiotherapy preserving neurological function, and temozolomide (TMZ) chemotherapy have not changed for the past 17 years despite significant advances in the understanding of the genetics and molecular biology of glioblastoma. This review highlights the neurosurgical foundation for glioblastoma therapy. Here, we review the neurosurgeon’s role in several new and clinically-approved treatments for glioblastoma. We describe delivery techniques such as blood–brain barrier disruption and convection-enhanced delivery (CED) that may be used to deliver therapeutic agents to tumor tissue in higher concentrations than oral or intravenous delivery. We mention pivotal clinical trials of immunotherapy for glioblastoma and explain their outcomes. Finally, we take a glimpse at ongoing clinical trials and promising translational studies to predict ways that new therapies may improve the prognosis of patients with glioblastoma.

Current Cardiology Reports, 2022

Brain Sciences, 2022

Background/aims: Iatrogenic CSF leaks after endoscopic endonasal transsphenoidal surgery remain a... more Background/aims: Iatrogenic CSF leaks after endoscopic endonasal transsphenoidal surgery remain a challenging entity to manage, typically treated with CSF diversion via lumbar drainage. Objective: To assess the safety and efficacy of high-volume lumbar puncture (LP) and acetazolamide therapy to manage iatrogenic CSF leaks. Methods: We performed a prospective pilot study of four patients who developed iatrogenic postoperative CSF leaks after transsphenoidal surgery and analyzed their response to treatment with concomitant high-volume lumbar puncture followed by acetazolamide therapy for 10 days. Data collected included demographics, intra-operative findings, including methodology of skull base repair and type of CSF leak, time to presentation with CSF leak, complications associated with high-volume LP and acetazolamide treatment, and length of follow-up. Results: Mean patient age was 44.28 years, with an average BMI of 27.4. Mean time from surgery to onset of CSF leak was 7.71 days. ...

Neuro-Oncology Advances, 2021

Background Poor prognosis of glioblastoma patients and the extensive heterogeneity of glioblastom... more Background Poor prognosis of glioblastoma patients and the extensive heterogeneity of glioblastoma at both the molecular and cellular level necessitates developing novel individualized treatment modalities via genomics-driven approaches. Methods This study leverages numerous pharmacogenomic and tissue databases to examine drug repositioning for glioblastoma. RNAseq of glioblastoma tumor samples from The Cancer Genome Atlas (TCGA, n=117) were compared to “normal” frontal lobe samples from Genotype-Tissue Expression Portal (GTEX, n=120) to find differentially expressed genes (DEGs). Using compound-gene expression data and drug activity data from the Library of Integrated Network-Based Cellular Signatures (LINCS, n=66,512 compounds) CCLE (71 glioma cell lines), and Chemical European Molecular Biology Laboratory (ChEMBL) platforms, we employed a summarized reversal gene expression metric (sRGES) to “reverse” the resultant disease signature for GBM and its subtypes. A multi-parametric st...

Journal of Personalized Medicine, 2021

Human endogenous retroviruses (HERVs), which are critical to normal embryologic development and d... more Human endogenous retroviruses (HERVs), which are critical to normal embryologic development and downregulated during normal maturation, have been implicated in a variety of cancers. Abnormal persistent production of HERVs has been suggested to play a role in oncogenesis and to confer stem cell properties to cells. We recently demonstrated that the most recently incorporated HERV element (HERV-K HML-2) has been associated with the pathogenesis of the embryonal atypical teratoid rhabdoid tumor (AT/RT), shifting our understanding of embryonal tumor development. HML-2 expression is vital for proper human development and its expression is suppressed via methylation or chromatin remodeling as cells differentiate. We previously found that dysfunctional chromatin remodeling due to loss of SMARCB1 expression induces HML-2 envelope (env) expression, impairing cellular differentiation and migration, and facilitating tumor growth in AT/RT. Epigenetic dysregulation in other embryonal tumors with...

Cancers, 2021

H3K27M-mutant diffuse midline gliomas (DMGs) are rare childhood central nervous system tumors tha... more H3K27M-mutant diffuse midline gliomas (DMGs) are rare childhood central nervous system tumors that carry a dismal prognosis. Thus, innovative treatment approaches are greatly needed to improve clinical outcomes for these patients. Here, we discuss current trends in research of H3K27M-mutant diffuse midline glioma. This review highlights new developments of molecular pathophysiology for these tumors, as they relate to epigenetics and therapeutic targeting. We focus our discussion on combinatorial therapies addressing the inherent complexity of treating H3K27M-mutant diffuse midline gliomas and incorporating recent advances in immunotherapy, molecular biology, genetics, radiation, and stereotaxic surgical diagnostics.

Brain Sciences, 2021

Introduction: Melanoma brain metastases remain a devastating disease process with poor prognosis.... more Introduction: Melanoma brain metastases remain a devastating disease process with poor prognosis. Recently, there has been a surge in studies demonstrating the efficacy of oncolytic virotherapy for brain tumor treatment. Given their specificity and amenability to genetic modification, the authors explore the possible role of oncolytic virotherapy as a potential treatment option for patients with melanoma brain metastases. Methods: A comprehensive literature review including both preclinical and clinical evidence of oncolytic virotherapy for the treatment of melanoma brain metastasis was performed. Results: Oncolytic virotherapy, specifically T-VEC (Imlygic™), was approved for the treatment of melanoma in 2015. Recent clinical trials demonstrate promising anti-tumor changes in patients who have received T-VEC; however, there is little evidence for its use in metastatic brain disease based on the existing literature. To date, only two single cases utilizing virotherapy in patients wit...

Indian Journal of Otolaryngology, 1984

Vidian neurectomy, as a remedying measure for intractable vasomotor rhinitis is an accepted proce... more Vidian neurectomy, as a remedying measure for intractable vasomotor rhinitis is an accepted procedure the world over. A variety of approaches to the deep seated Vidian nerve in the pterygopalatine fossa have been described. We advocate a direct transnasal route to effect a preganglionic Vidian nerve section. It is simple, quick, safe, and does not require nasal tamponade or hospitalisation. This paper deals exclusively with the operative technique of transnasal Vidian neurectomy as practised by us.

Fuel, 2021

Abstract The application of the Livengood-Wu (LW) integral method as a tool to estimate knock ons... more Abstract The application of the Livengood-Wu (LW) integral method as a tool to estimate knock onset in spark ignited (SI) engines and combustion phasing in advanced compression ignition (ACI) engines has been demonstrated through simulations several times. In this study, the effect of uncertainties associated with parameters required for the LW integral method, when used as a tool for model based control of ignition timing in an ACI engine, were experimentally studied using five full boiling range gasoline fuels. As a first step, the method was applied to experimental data from a rapid compression machine and it was found that the ability of the LW integral method to predict ignition timing was very sensitive to the performance of the chemical kinetic model of each fuel. The method was subsequently applied to experimental data from a single-cylinder gasoline engine with simple approximations for the LW integral input parameters, and it was found that the predicted time of ignition was significantly different from the actual start of combustion. Systematic evaluation of various parametric uncertainties conducted thereafter showed that the uncertainty in cylinder charge temperature has the greatest influence. Improved methods of estimating cylinder charge temperature are proposed to account for the previously determined corrections, to enable the use of the LW integral method for model based control of ignition timing.

The Journal of Heart and Lung Transplantation, 2015

The aim of this study was to determine whether institutional volume influenced the effect of post... more The aim of this study was to determine whether institutional volume influenced the effect of postoperative complications on short-and long term survival following orthotopic heart transplantation (OHT). Methods: The United Network for Organ Sharing database was queried for adult patients (≥ 18 years of age) undergoing OHT between 2000 and 2010. Average institutional volume was calculated over the study period and modeled as both a categorical and continuous variable. Postoperative complications included rejection, dialysis dependence, infection, stroke, reoperation and a composite event. Kaplan Meier estimates and Cox regression modeling were performed for each complication to categorize the unadjusted and adjusted influence of institutional volume on survival. Results: A total of 19,849 OHT recipients were included for analysis and stratification into low (≤ 14.5/year), intermediate (14.5-26.5/year) and high (> 26.5/year) volume tertiles was performed. The overall incidences of postoperative complications were 10.2% for rejection, 7.8% for dialysis dependence, 12.0% for reoperation, 24.1% for infection and 2.3% for stroke. Low volume institutions experienced more complications following OHT than high volume institutions (43.4% v. 36.2%, p< 0.001). Survival following the composite complication outcome was significantly worse at 90-days, 1-year and 5-years in the low-volume cohort. After risk-adjustment, low institutional volume (when modeled as both a continuous and categorical variable) was also independently predictive of mortality at each time-point. Expectedly, survival at 5-years in patients without a postoperative complication (81%, CI: 80.0%-82.8%) was statistically greater (p< 0.001) than those with 1 (72.8%, CI: 69.9%-75.5%), 2 (59.8%, CI: 54.4%-64.8%) or 3 (39.9%, CI: 31.6%-48.2%) complications. Conclusion: Postoperative complications following OHT have a greater incidence and impact on short-and long-term survival at low-volume institutions. Accordingly, strategies employed at high-volume institutions could better equip lower volume hospitals to manage these events in hopes of optimizing transplant outcomes.

Circulation Journal, 2020

Cureus, 2019

Meningiomas are the most common intracranial, extra-axial neoplasms and account for a significant... more Meningiomas are the most common intracranial, extra-axial neoplasms and account for a significant proportion of all central nervous system (CNS) tumors. Regardless of the grade, treatment typically involves upfront surgical resection. However, in many instances, especially in meningiomas arising from the skull base, complete removal is often difficult given the close proximity to important anatomic structures. In this report, we discuss the use of stimulated Raman histology as a means to identify tissue boundaries during the resection of an extensive, recurrent, atypical spheno-orbital meningioma. We report a 75-year-old male with a history of a prior left frontotemporal craniotomy for a grade II meningioma three years prior, who presented with worsening left-sided visual loss and pronounced temporal bossing. Repeat magnetic resonance imaging (MRI) revealed a recurrent left spheno-orbital tumor suggestive of a meningioma extending into the middle cranial fossa, the lateral orbit, and the temporalis muscle. He underwent an extended orbito-pterional craniotomy, and intraoperative stimulated Raman histology aided in the identification of tumor margins within the orbit and the temporalis muscle in order to better preserve the normal orbital contents and muscle bulk of the infratemporal fossa. This case demonstrates the utility of stimulated Raman histology during the resection of invasive skull base tumors. The immediate intraoperative Raman histologic sections can clearly identify tissue boundaries and thus help preserve important anatomic structures. Continued development of this method can potentially improve the accuracy of intraoperative diagnoses and guide surgeons during tumor resections near eloquent anatomical regions or important normal structures.

Neuro-Oncology Practice, 2019

Background The incidence of symptomatic radiation necrosis (RN) has risen as radiotherapy is incr... more Background The incidence of symptomatic radiation necrosis (RN) has risen as radiotherapy is increasingly used to control brain tumor progression. Traditionally managed with steroids, symptomatic RN can remain refractory to medical treatment, requiring surgical intervention for control. The purpose of our study was to assess a single institution’s experience with craniotomy for steroid-refractory pure RN. Methods The medical records of all tumor patients who underwent craniotomies at our institution from 2011 to 2016 were retrospectively reviewed for a history of preoperative radiotherapy or radiosurgery. RN was confirmed histopathologically and patients with active tumor were excluded. Preoperative, intraoperative, and outcome information was collected. Primary outcomes measured were postoperative KPS and time to steroid freedom. Results Twenty-four patients with symptomatic RN were identified. Gross total resection was achieved for all patients. Patients with metastases experience...

Neuro-Oncology Practice, 2019

Background Because less-invasive techniques can obviate the need for brain biopsy in the diagnosi... more Background Because less-invasive techniques can obviate the need for brain biopsy in the diagnosis of primary central nervous system lymphoma (PCNSL), it is common practice to wait for a thorough initial work-up, which may delay treatment. We conducted a systematic review and reviewed our own series of patients to define the role of LP and early brain biopsy in the diagnosis of PCNSL. Methods Our study was divided into 2 main sections: 1) systematic review assessing the sensitivity of cerebrospinal fluid (CSF) analysis on the diagnosis of PCNSL, and 2) a retrospective, single-center patient series assessing the diagnostic accuracy and safety of early biopsy in immunocompetent PCNSL patients treated at our institution from 2012 to 2018. Results Our systematic review identified 1481 patients with PCNSL. A preoperative LP obviated surgery in 7.4% of cases. Brain biopsy was the preferred method of diagnosis in 95% of patients followed by CSF (3.1%). In our institutional series, brain bi...

Folia medica, 2018

The DNA repair process protects the cells from DNA damaging agent by multiple pathways. Majority ... more The DNA repair process protects the cells from DNA damaging agent by multiple pathways. Majority of the cancer therapy cause DNA damage which leads to apoptosis. The cell has natural ability to repair this damage which ultimately leads to development of resistance of drugs. The key enzymes involved in DNA repair process are poly(ADP-ribose) (PAR) and poly(ADP-ribose) polymerases (PARP). Tumor cells repair their defective gene via defective homologues recombination (HR) in the presence of enzyme PARP. PARP inhibitors inhibit the enzyme poly(ADP-ribose) polymerases (PARPs) which lead to apoptosis of cancer cells. Current clinical data shows the role of PARP inhibitors is not restricted to BRCA mutations but also effective in HR dysfunctions related tumors. Therefore, investigation in this area could be very helpful for future therapy of cancer. This review gives detail information on the role of PARP in DNA damage repair, the role of PARP inhibitors and chemistry of currently availabl...

Cureus, Jan 30, 2018

Despite surgical resection and adjuvant chemoradiation, survival for glioblastoma remains poor. B... more Despite surgical resection and adjuvant chemoradiation, survival for glioblastoma remains poor. Because of the dismal prognosis, attention has shifted to alternative adjuvant treatment modalities. Although traditionally limited to systemic malignancies (melanoma, lung and colon cancer), the field of immunotherapy has recently identified glioblastoma as a potential target for new treatments. Anti-tumor vaccines (dendritic cell/heat shock), checkpoint inhibitors, chimeric T-cell receptors, and virotherapy all have been preliminarily trialed in glioblastoma patients with reasonable success and safety. Although there are limitations due to autoimmune reactions and immune escape, immunotherapeutics hold much promise in the future treatment paradigms for malignant glioma.

PloS one, 2018

The honey bee has been extensively studied as a model for neuronal circuit and memory function an... more The honey bee has been extensively studied as a model for neuronal circuit and memory function and more recently has emerged as an unconventional model in biogerontology. Yet, the detailed knowledge of neuronal processing in the honey bee brain contrasts with the very sparse information available on glial cells. In other systems glial cells are involved in nutritional homeostasis, detoxification, and aging. These glial functions have been linked to metabolic enzymes, such as glutamine synthetase and glycogen phosphorylase. As a step in identifying functional roles and potential differences among honey bee glial types, we examined the spatial distribution of these enzymes and asked if enzyme abundance is associated with aging and other processes essential for survival. Using immunohistochemistry and confocal laser microscopy we demonstrate that glutamine synthetase and glycogen phosphorylase are abundant in glia but appear to co-localize with different glial sub-types. The overall sp...

Surgical neurology international, 2018

Meningiomas are the most prevalent primary tumor of the central nervous system (CNS), and althoug... more Meningiomas are the most prevalent primary tumor of the central nervous system (CNS), and although the majority of these neoplasms are classified as benign, nearly one fourth of the lesions display an aggressive profile characterized by pleomorphic histology, high recurrence rates, and overall resistance to standard treatment. Despite the ubiquitous nature of these tumors, no adjuvant therapeutic regimen has been identified which effectively controls disease recurrence and progression after surgery and radiation, leading to a dismal prognosis in this patient population. The primary focus of this research study is, hence, to assess the recently emerging use of bevacizumab, an anti-angiogenic agent, in the treatment of meningiomas. This systematic literature review analyzes the efficacy and safety of therapeutic bevacizumab for treatment-refractory meningiomas. A systematic PubMed search was conducted according to PRISMA guidelines to identify all relevant reports investigating the an...

British Journal of Neurosurgery, 2018

The first commercial High Voltage Direct Current (HVDC) transmission link was installed in 1954 b... more The first commercial High Voltage Direct Current (HVDC) transmission link was installed in 1954 between the mainland of Sweden and the island of Gotland. Since then, there is continuous and remarkable development in the HVDC technology making it an efficient way of transmitting bulk power over large distances. Due to the transition towards low carbon electricity, more renewable energy sources are being integrated into the grid. This trend has increased the use of Direct Current (DC) in the electrical networks at low voltage levels. In the past few decades, space charge phenomenon in HVDC insulation have been investigated. Many techniques have been developed for studying and understanding the space charge phenomenon in the HVDC insulation. Considering the growth of DC in electrical networks, further research into these techniques and development of novel dielectric materials suitable for DC is also progressing at a quick pace. Earlier studies on space charge phenomenon were performed mainly on Polyethylene, Epoxy, Polymethyl methacrylate and Polycarbonate insulation materials. These studies have indicated that the space charge starts accumulating beyond a threshold value of the electric field and has a strong dependency on temperature as well as the electric field. Silicon based insulation is also known as silicones. It is a highly stable and fire-resistant fluid. It is used in cable joints, traction transformers and increasingly in compact transformers where higher than normal temperatures are expected. However, it is known that when equipment is used with DC, they are expected to suffer strongly from space charge accumulation. As a result, considerable modifications in the electric field distribution with respect to the Laplacian field occurs, especially in case of voltage polarity inversion. This may cause insulation degradation and premature breakdown. The conductivity behaviour and the electric field threshold for space charge accumulation are two of the most important parameters for the design of insulation systems under DC conditions. By limiting the electric field in insulation system below the threshold value, space charge accumulation can be minimised. Reusing the existing AC cable joints under DC conditions could save considerable time as well as money in realising new DC networks. For that, conductivity behaviour and electric field threshold values of the insulation material should be investigated. The main goal of this thesis is to investigate and characterise silicon insulation material with regards to its conductivity behaviour and the electric field threshold for space charge formation. This study is a first step towards the feasibility of using silicon fluid-based AC cable joints under DC conditions. The silicon insulation samples in liquid as well as cured(solid) state are subjected to conduction current measurements and space charge measurements using pulsed electroacoustic method. Simulations are performed on a cable joint model in COMSOL Multiphysics. Presence of cured silicon layer results in a divergent current density. This resulted in high field concentration in cured silicon layer.

Journal of Neurological Surgery Part B: Skull Base, 2018

Background Assessment of the extent of resection after surgical resection of pituitary adenomas i... more Background Assessment of the extent of resection after surgical resection of pituitary adenomas is most commonly reported in terms of the presence or absence of residual tumor. A quantitative comparison of volumetric resection between endonasal endoscopy (EE) and microsurgery (MS) has rarely been done. Methods A retrospective analysis was performed on a consecutive series of 154 patients with pituitary adenomas treated by the same surgeon at a single institution. We employed volumetric analysis pre- and postoperatively on two cohorts of pituitary adenoma patients treated through MS (n = 37) versus EE approach (n = 117). Results Volumetric analysis revealed a higher incidence of complete resection (64.4 vs. 56.8%) and mean volume reduction in the EE cohort (92.7 vs. 88.4%), although not significant. Recurrence rates were significantly lower in the EE group (7.7% vs 24.3%, p = 0.015). Subgroup analysis identified that patients with preoperative tumor volumes >1 mL were less likely ...

Brain Sciences

The mainstays of glioblastoma treatment, maximal safe resection, radiotherapy preserving neurolog... more The mainstays of glioblastoma treatment, maximal safe resection, radiotherapy preserving neurological function, and temozolomide (TMZ) chemotherapy have not changed for the past 17 years despite significant advances in the understanding of the genetics and molecular biology of glioblastoma. This review highlights the neurosurgical foundation for glioblastoma therapy. Here, we review the neurosurgeon’s role in several new and clinically-approved treatments for glioblastoma. We describe delivery techniques such as blood–brain barrier disruption and convection-enhanced delivery (CED) that may be used to deliver therapeutic agents to tumor tissue in higher concentrations than oral or intravenous delivery. We mention pivotal clinical trials of immunotherapy for glioblastoma and explain their outcomes. Finally, we take a glimpse at ongoing clinical trials and promising translational studies to predict ways that new therapies may improve the prognosis of patients with glioblastoma.

Current Cardiology Reports, 2022

Brain Sciences, 2022

Background/aims: Iatrogenic CSF leaks after endoscopic endonasal transsphenoidal surgery remain a... more Background/aims: Iatrogenic CSF leaks after endoscopic endonasal transsphenoidal surgery remain a challenging entity to manage, typically treated with CSF diversion via lumbar drainage. Objective: To assess the safety and efficacy of high-volume lumbar puncture (LP) and acetazolamide therapy to manage iatrogenic CSF leaks. Methods: We performed a prospective pilot study of four patients who developed iatrogenic postoperative CSF leaks after transsphenoidal surgery and analyzed their response to treatment with concomitant high-volume lumbar puncture followed by acetazolamide therapy for 10 days. Data collected included demographics, intra-operative findings, including methodology of skull base repair and type of CSF leak, time to presentation with CSF leak, complications associated with high-volume LP and acetazolamide treatment, and length of follow-up. Results: Mean patient age was 44.28 years, with an average BMI of 27.4. Mean time from surgery to onset of CSF leak was 7.71 days. ...

Neuro-Oncology Advances, 2021

Background Poor prognosis of glioblastoma patients and the extensive heterogeneity of glioblastom... more Background Poor prognosis of glioblastoma patients and the extensive heterogeneity of glioblastoma at both the molecular and cellular level necessitates developing novel individualized treatment modalities via genomics-driven approaches. Methods This study leverages numerous pharmacogenomic and tissue databases to examine drug repositioning for glioblastoma. RNAseq of glioblastoma tumor samples from The Cancer Genome Atlas (TCGA, n=117) were compared to “normal” frontal lobe samples from Genotype-Tissue Expression Portal (GTEX, n=120) to find differentially expressed genes (DEGs). Using compound-gene expression data and drug activity data from the Library of Integrated Network-Based Cellular Signatures (LINCS, n=66,512 compounds) CCLE (71 glioma cell lines), and Chemical European Molecular Biology Laboratory (ChEMBL) platforms, we employed a summarized reversal gene expression metric (sRGES) to “reverse” the resultant disease signature for GBM and its subtypes. A multi-parametric st...

Journal of Personalized Medicine, 2021

Human endogenous retroviruses (HERVs), which are critical to normal embryologic development and d... more Human endogenous retroviruses (HERVs), which are critical to normal embryologic development and downregulated during normal maturation, have been implicated in a variety of cancers. Abnormal persistent production of HERVs has been suggested to play a role in oncogenesis and to confer stem cell properties to cells. We recently demonstrated that the most recently incorporated HERV element (HERV-K HML-2) has been associated with the pathogenesis of the embryonal atypical teratoid rhabdoid tumor (AT/RT), shifting our understanding of embryonal tumor development. HML-2 expression is vital for proper human development and its expression is suppressed via methylation or chromatin remodeling as cells differentiate. We previously found that dysfunctional chromatin remodeling due to loss of SMARCB1 expression induces HML-2 envelope (env) expression, impairing cellular differentiation and migration, and facilitating tumor growth in AT/RT. Epigenetic dysregulation in other embryonal tumors with...

Cancers, 2021

H3K27M-mutant diffuse midline gliomas (DMGs) are rare childhood central nervous system tumors tha... more H3K27M-mutant diffuse midline gliomas (DMGs) are rare childhood central nervous system tumors that carry a dismal prognosis. Thus, innovative treatment approaches are greatly needed to improve clinical outcomes for these patients. Here, we discuss current trends in research of H3K27M-mutant diffuse midline glioma. This review highlights new developments of molecular pathophysiology for these tumors, as they relate to epigenetics and therapeutic targeting. We focus our discussion on combinatorial therapies addressing the inherent complexity of treating H3K27M-mutant diffuse midline gliomas and incorporating recent advances in immunotherapy, molecular biology, genetics, radiation, and stereotaxic surgical diagnostics.

Brain Sciences, 2021

Introduction: Melanoma brain metastases remain a devastating disease process with poor prognosis.... more Introduction: Melanoma brain metastases remain a devastating disease process with poor prognosis. Recently, there has been a surge in studies demonstrating the efficacy of oncolytic virotherapy for brain tumor treatment. Given their specificity and amenability to genetic modification, the authors explore the possible role of oncolytic virotherapy as a potential treatment option for patients with melanoma brain metastases. Methods: A comprehensive literature review including both preclinical and clinical evidence of oncolytic virotherapy for the treatment of melanoma brain metastasis was performed. Results: Oncolytic virotherapy, specifically T-VEC (Imlygic™), was approved for the treatment of melanoma in 2015. Recent clinical trials demonstrate promising anti-tumor changes in patients who have received T-VEC; however, there is little evidence for its use in metastatic brain disease based on the existing literature. To date, only two single cases utilizing virotherapy in patients wit...

Indian Journal of Otolaryngology, 1984

Vidian neurectomy, as a remedying measure for intractable vasomotor rhinitis is an accepted proce... more Vidian neurectomy, as a remedying measure for intractable vasomotor rhinitis is an accepted procedure the world over. A variety of approaches to the deep seated Vidian nerve in the pterygopalatine fossa have been described. We advocate a direct transnasal route to effect a preganglionic Vidian nerve section. It is simple, quick, safe, and does not require nasal tamponade or hospitalisation. This paper deals exclusively with the operative technique of transnasal Vidian neurectomy as practised by us.

Fuel, 2021

Abstract The application of the Livengood-Wu (LW) integral method as a tool to estimate knock ons... more Abstract The application of the Livengood-Wu (LW) integral method as a tool to estimate knock onset in spark ignited (SI) engines and combustion phasing in advanced compression ignition (ACI) engines has been demonstrated through simulations several times. In this study, the effect of uncertainties associated with parameters required for the LW integral method, when used as a tool for model based control of ignition timing in an ACI engine, were experimentally studied using five full boiling range gasoline fuels. As a first step, the method was applied to experimental data from a rapid compression machine and it was found that the ability of the LW integral method to predict ignition timing was very sensitive to the performance of the chemical kinetic model of each fuel. The method was subsequently applied to experimental data from a single-cylinder gasoline engine with simple approximations for the LW integral input parameters, and it was found that the predicted time of ignition was significantly different from the actual start of combustion. Systematic evaluation of various parametric uncertainties conducted thereafter showed that the uncertainty in cylinder charge temperature has the greatest influence. Improved methods of estimating cylinder charge temperature are proposed to account for the previously determined corrections, to enable the use of the LW integral method for model based control of ignition timing.

The Journal of Heart and Lung Transplantation, 2015

The aim of this study was to determine whether institutional volume influenced the effect of post... more The aim of this study was to determine whether institutional volume influenced the effect of postoperative complications on short-and long term survival following orthotopic heart transplantation (OHT). Methods: The United Network for Organ Sharing database was queried for adult patients (≥ 18 years of age) undergoing OHT between 2000 and 2010. Average institutional volume was calculated over the study period and modeled as both a categorical and continuous variable. Postoperative complications included rejection, dialysis dependence, infection, stroke, reoperation and a composite event. Kaplan Meier estimates and Cox regression modeling were performed for each complication to categorize the unadjusted and adjusted influence of institutional volume on survival. Results: A total of 19,849 OHT recipients were included for analysis and stratification into low (≤ 14.5/year), intermediate (14.5-26.5/year) and high (> 26.5/year) volume tertiles was performed. The overall incidences of postoperative complications were 10.2% for rejection, 7.8% for dialysis dependence, 12.0% for reoperation, 24.1% for infection and 2.3% for stroke. Low volume institutions experienced more complications following OHT than high volume institutions (43.4% v. 36.2%, p< 0.001). Survival following the composite complication outcome was significantly worse at 90-days, 1-year and 5-years in the low-volume cohort. After risk-adjustment, low institutional volume (when modeled as both a continuous and categorical variable) was also independently predictive of mortality at each time-point. Expectedly, survival at 5-years in patients without a postoperative complication (81%, CI: 80.0%-82.8%) was statistically greater (p< 0.001) than those with 1 (72.8%, CI: 69.9%-75.5%), 2 (59.8%, CI: 54.4%-64.8%) or 3 (39.9%, CI: 31.6%-48.2%) complications. Conclusion: Postoperative complications following OHT have a greater incidence and impact on short-and long-term survival at low-volume institutions. Accordingly, strategies employed at high-volume institutions could better equip lower volume hospitals to manage these events in hopes of optimizing transplant outcomes.

Circulation Journal, 2020

Cureus, 2019

Meningiomas are the most common intracranial, extra-axial neoplasms and account for a significant... more Meningiomas are the most common intracranial, extra-axial neoplasms and account for a significant proportion of all central nervous system (CNS) tumors. Regardless of the grade, treatment typically involves upfront surgical resection. However, in many instances, especially in meningiomas arising from the skull base, complete removal is often difficult given the close proximity to important anatomic structures. In this report, we discuss the use of stimulated Raman histology as a means to identify tissue boundaries during the resection of an extensive, recurrent, atypical spheno-orbital meningioma. We report a 75-year-old male with a history of a prior left frontotemporal craniotomy for a grade II meningioma three years prior, who presented with worsening left-sided visual loss and pronounced temporal bossing. Repeat magnetic resonance imaging (MRI) revealed a recurrent left spheno-orbital tumor suggestive of a meningioma extending into the middle cranial fossa, the lateral orbit, and the temporalis muscle. He underwent an extended orbito-pterional craniotomy, and intraoperative stimulated Raman histology aided in the identification of tumor margins within the orbit and the temporalis muscle in order to better preserve the normal orbital contents and muscle bulk of the infratemporal fossa. This case demonstrates the utility of stimulated Raman histology during the resection of invasive skull base tumors. The immediate intraoperative Raman histologic sections can clearly identify tissue boundaries and thus help preserve important anatomic structures. Continued development of this method can potentially improve the accuracy of intraoperative diagnoses and guide surgeons during tumor resections near eloquent anatomical regions or important normal structures.

Neuro-Oncology Practice, 2019

Background The incidence of symptomatic radiation necrosis (RN) has risen as radiotherapy is incr... more Background The incidence of symptomatic radiation necrosis (RN) has risen as radiotherapy is increasingly used to control brain tumor progression. Traditionally managed with steroids, symptomatic RN can remain refractory to medical treatment, requiring surgical intervention for control. The purpose of our study was to assess a single institution’s experience with craniotomy for steroid-refractory pure RN. Methods The medical records of all tumor patients who underwent craniotomies at our institution from 2011 to 2016 were retrospectively reviewed for a history of preoperative radiotherapy or radiosurgery. RN was confirmed histopathologically and patients with active tumor were excluded. Preoperative, intraoperative, and outcome information was collected. Primary outcomes measured were postoperative KPS and time to steroid freedom. Results Twenty-four patients with symptomatic RN were identified. Gross total resection was achieved for all patients. Patients with metastases experience...

Neuro-Oncology Practice, 2019

Background Because less-invasive techniques can obviate the need for brain biopsy in the diagnosi... more Background Because less-invasive techniques can obviate the need for brain biopsy in the diagnosis of primary central nervous system lymphoma (PCNSL), it is common practice to wait for a thorough initial work-up, which may delay treatment. We conducted a systematic review and reviewed our own series of patients to define the role of LP and early brain biopsy in the diagnosis of PCNSL. Methods Our study was divided into 2 main sections: 1) systematic review assessing the sensitivity of cerebrospinal fluid (CSF) analysis on the diagnosis of PCNSL, and 2) a retrospective, single-center patient series assessing the diagnostic accuracy and safety of early biopsy in immunocompetent PCNSL patients treated at our institution from 2012 to 2018. Results Our systematic review identified 1481 patients with PCNSL. A preoperative LP obviated surgery in 7.4% of cases. Brain biopsy was the preferred method of diagnosis in 95% of patients followed by CSF (3.1%). In our institutional series, brain bi...

Folia medica, 2018

The DNA repair process protects the cells from DNA damaging agent by multiple pathways. Majority ... more The DNA repair process protects the cells from DNA damaging agent by multiple pathways. Majority of the cancer therapy cause DNA damage which leads to apoptosis. The cell has natural ability to repair this damage which ultimately leads to development of resistance of drugs. The key enzymes involved in DNA repair process are poly(ADP-ribose) (PAR) and poly(ADP-ribose) polymerases (PARP). Tumor cells repair their defective gene via defective homologues recombination (HR) in the presence of enzyme PARP. PARP inhibitors inhibit the enzyme poly(ADP-ribose) polymerases (PARPs) which lead to apoptosis of cancer cells. Current clinical data shows the role of PARP inhibitors is not restricted to BRCA mutations but also effective in HR dysfunctions related tumors. Therefore, investigation in this area could be very helpful for future therapy of cancer. This review gives detail information on the role of PARP in DNA damage repair, the role of PARP inhibitors and chemistry of currently availabl...

Cureus, Jan 30, 2018

Despite surgical resection and adjuvant chemoradiation, survival for glioblastoma remains poor. B... more Despite surgical resection and adjuvant chemoradiation, survival for glioblastoma remains poor. Because of the dismal prognosis, attention has shifted to alternative adjuvant treatment modalities. Although traditionally limited to systemic malignancies (melanoma, lung and colon cancer), the field of immunotherapy has recently identified glioblastoma as a potential target for new treatments. Anti-tumor vaccines (dendritic cell/heat shock), checkpoint inhibitors, chimeric T-cell receptors, and virotherapy all have been preliminarily trialed in glioblastoma patients with reasonable success and safety. Although there are limitations due to autoimmune reactions and immune escape, immunotherapeutics hold much promise in the future treatment paradigms for malignant glioma.

PloS one, 2018

The honey bee has been extensively studied as a model for neuronal circuit and memory function an... more The honey bee has been extensively studied as a model for neuronal circuit and memory function and more recently has emerged as an unconventional model in biogerontology. Yet, the detailed knowledge of neuronal processing in the honey bee brain contrasts with the very sparse information available on glial cells. In other systems glial cells are involved in nutritional homeostasis, detoxification, and aging. These glial functions have been linked to metabolic enzymes, such as glutamine synthetase and glycogen phosphorylase. As a step in identifying functional roles and potential differences among honey bee glial types, we examined the spatial distribution of these enzymes and asked if enzyme abundance is associated with aging and other processes essential for survival. Using immunohistochemistry and confocal laser microscopy we demonstrate that glutamine synthetase and glycogen phosphorylase are abundant in glia but appear to co-localize with different glial sub-types. The overall sp...

Surgical neurology international, 2018

Meningiomas are the most prevalent primary tumor of the central nervous system (CNS), and althoug... more Meningiomas are the most prevalent primary tumor of the central nervous system (CNS), and although the majority of these neoplasms are classified as benign, nearly one fourth of the lesions display an aggressive profile characterized by pleomorphic histology, high recurrence rates, and overall resistance to standard treatment. Despite the ubiquitous nature of these tumors, no adjuvant therapeutic regimen has been identified which effectively controls disease recurrence and progression after surgery and radiation, leading to a dismal prognosis in this patient population. The primary focus of this research study is, hence, to assess the recently emerging use of bevacizumab, an anti-angiogenic agent, in the treatment of meningiomas. This systematic literature review analyzes the efficacy and safety of therapeutic bevacizumab for treatment-refractory meningiomas. A systematic PubMed search was conducted according to PRISMA guidelines to identify all relevant reports investigating the an...

British Journal of Neurosurgery, 2018

The first commercial High Voltage Direct Current (HVDC) transmission link was installed in 1954 b... more The first commercial High Voltage Direct Current (HVDC) transmission link was installed in 1954 between the mainland of Sweden and the island of Gotland. Since then, there is continuous and remarkable development in the HVDC technology making it an efficient way of transmitting bulk power over large distances. Due to the transition towards low carbon electricity, more renewable energy sources are being integrated into the grid. This trend has increased the use of Direct Current (DC) in the electrical networks at low voltage levels. In the past few decades, space charge phenomenon in HVDC insulation have been investigated. Many techniques have been developed for studying and understanding the space charge phenomenon in the HVDC insulation. Considering the growth of DC in electrical networks, further research into these techniques and development of novel dielectric materials suitable for DC is also progressing at a quick pace. Earlier studies on space charge phenomenon were performed mainly on Polyethylene, Epoxy, Polymethyl methacrylate and Polycarbonate insulation materials. These studies have indicated that the space charge starts accumulating beyond a threshold value of the electric field and has a strong dependency on temperature as well as the electric field. Silicon based insulation is also known as silicones. It is a highly stable and fire-resistant fluid. It is used in cable joints, traction transformers and increasingly in compact transformers where higher than normal temperatures are expected. However, it is known that when equipment is used with DC, they are expected to suffer strongly from space charge accumulation. As a result, considerable modifications in the electric field distribution with respect to the Laplacian field occurs, especially in case of voltage polarity inversion. This may cause insulation degradation and premature breakdown. The conductivity behaviour and the electric field threshold for space charge accumulation are two of the most important parameters for the design of insulation systems under DC conditions. By limiting the electric field in insulation system below the threshold value, space charge accumulation can be minimised. Reusing the existing AC cable joints under DC conditions could save considerable time as well as money in realising new DC networks. For that, conductivity behaviour and electric field threshold values of the insulation material should be investigated. The main goal of this thesis is to investigate and characterise silicon insulation material with regards to its conductivity behaviour and the electric field threshold for space charge formation. This study is a first step towards the feasibility of using silicon fluid-based AC cable joints under DC conditions. The silicon insulation samples in liquid as well as cured(solid) state are subjected to conduction current measurements and space charge measurements using pulsed electroacoustic method. Simulations are performed on a cable joint model in COMSOL Multiphysics. Presence of cured silicon layer results in a divergent current density. This resulted in high field concentration in cured silicon layer.

Journal of Neurological Surgery Part B: Skull Base, 2018

Background Assessment of the extent of resection after surgical resection of pituitary adenomas i... more Background Assessment of the extent of resection after surgical resection of pituitary adenomas is most commonly reported in terms of the presence or absence of residual tumor. A quantitative comparison of volumetric resection between endonasal endoscopy (EE) and microsurgery (MS) has rarely been done. Methods A retrospective analysis was performed on a consecutive series of 154 patients with pituitary adenomas treated by the same surgeon at a single institution. We employed volumetric analysis pre- and postoperatively on two cohorts of pituitary adenoma patients treated through MS (n = 37) versus EE approach (n = 117). Results Volumetric analysis revealed a higher incidence of complete resection (64.4 vs. 56.8%) and mean volume reduction in the EE cohort (92.7 vs. 88.4%), although not significant. Recurrence rates were significantly lower in the EE group (7.7% vs 24.3%, p = 0.015). Subgroup analysis identified that patients with preoperative tumor volumes >1 mL were less likely ...