20 results on '"Ashish H. Shah"'
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2. Establishment of a new human iPSC cell line (UOMi012-A) from a patient with congenital heart defect who has undergone Fontan procedure
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Niketa Sareen, Abhay Srivastava, Ishika Mittal, Ashish H. Shah, and Sanjiv Dhingra
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Biology (General) ,QH301-705.5 - Abstract
Patients born with complex congenital heart defects, not amenable for surgical repair establishing normal bi-ventricular circulation are palliated with the Fontan Circulation (FC). Here, we report new iPSC line from a patient with tricuspid and pulmonary atresia. The patient underwent series of surgeries leading to completion of Fontan circulation at the age of 13yr., and this line was generated when she was 38yr. old. The exact genetic cause of this patient’s congenital heart defect is unknown, and this line will be used for studying molecular and cellular mechanisms responsible for cardiac dysfunction, along with screening for future potential therapeutic avenues.
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- 2024
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3. Uma Constelação de Acidente Vascular Cerebral e Hipoxemia após Extração do Eletrodo do CDI: Papel do Forame Oval Patente
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Ashish H. Shah, Petra Jenkins, and Heiko Schneider
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Forame Oval Patente ,Acidente Vascular Cerebral ,Hipóxia ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Published
- 2024
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4. Permanent Pacemaker-Mediated Exertional Hypoxemia in a Patient With Ebstein Anomaly
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Ashish H. Shah, MD, Nasir Shaikh, MD, Keivan Alizadeh, MD, Aliasgar Khadem, MD, Clarence Khoo, MD, Robin A. Ducas, MD, and Malek Kass, MD
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Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Patients with Ebstein anomaly are known to have a higher incidence of interatrial communications and shunting of blood and its components through, mainly due to either streaming of tricuspid regurgitation or due to elevated right atrial pressure. Here we describe a case where permanent pacemaker lead kept a patent foramen ovale open leading to right-to-left shunting of blood and exertional hypoxemia. This is the first such case report in the published literature.
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- 2024
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5. The epitranscriptome of high-grade gliomas: a promising therapeutic target with implications from the tumor microenvironment to endogenous retroviruses
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Christian K. Ramsoomair, Michele Ceccarelli, John D. Heiss, and Ashish H. Shah
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Glioblastoma ,Epitranscriptomics ,RNA modifications ,Endogenous retrovirus ,Microenvironment ,Medicine - Abstract
Abstract Glioblastoma (GBM) comprises 45.6% of all primary malignant brain cancers and is one of the most common and aggressive intracranial tumors in adults. Intratumoral heterogeneity with a wide range of proteomic, genetic, and epigenetic dysregulation contributes to treatment resistance and poor prognosis, thus demanding novel therapeutic approaches. To date, numerous clinical trials have been developed to target the proteome and epigenome of high-grade gliomas with promising results. However, studying RNA modifications, or RNA epitranscriptomics, is a new frontier within neuro-oncology. RNA epitranscriptomics was discovered in the 1970s, but in the last decade, the extent of modification of mRNA and various non-coding RNAs has emerged and been implicated in transposable element activation and many other oncogenic processes within the tumor microenvironment. This review provides background information and discusses the therapeutic potential of agents modulating epitranscriptomics in high-grade gliomas. A particular emphasis will be placed on how combination therapies that include immune agents targeting hERV-mediated viral mimicry could improve the treatment of GBM.
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- 2023
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6. Validation of the Emory Risk Score in the Transcatheter Aortic Valve Implantation Population: A Canadian Perspective
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Emily K. Hyde, RN, MN, Karen Throndson, RN, MN, Liane A. Arcinas, MD, Ashish H. Shah, MD, Brett Hiebert, MSc, Michael H. Yamashita, MD, CM, MPH, Donna Lee Samson, BA, Anita Maric, BSc, RQAP-GCP, CTBS, Reid Love, RN, MN, Denise Poettcker, RN, Rakesh C. Arora, MD, PhD, Colette M. Seifer, MD(Hons), and Malek Kass, MD
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Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Background: Permanent pacemaker (PPM) implantation may be indicated post-transcatheter aortic valve implantation (TAVI). The Emory Risk Score (ERS) is a validated predictive risk score of the need for a PPM post-TAVI using a balloon-expandable valve. Our objectives were to determine the validity of the ERS in our local TAVI population with both balloon-expandable and self-expanding valves and to identify additional electrocardiographic (ECG) parameters predictive of the need for a PPM post-TAVI. Methods: Retrospective chart and electronic database reviews were performed to collect demographic and procedural information. Two expert readers reviewed all ECGs. Independent factors associated with PPM implantation were examined with multivariable logistic regression via a stepwise selection process with calculation of the area under the receiver operating characteristic curve to assess model discrimination. Results: The overall PPM implantation rate was 11.7%; rates were 9% for the Sapien 3 valves, 10% for the Evolut Pro valves, and 17% for the Evolut R valves. The ERS was found to not be predictive of need for PPM post-TAVI for the entire cohort. Right bundle branch block was the only ERS parameter independently associated with new PPM implant (8.5% vs 25%, odds ratio = 3.59, P = 0.01). No additional ECG parameters met the criteria for statistical significance. Conclusions: The poor predictive value of the ERS in determining the need for a PPM post-TAVI in our patient population suggests that further refinement of a formula (or risk-calculator) is warranted. Identification of a precise risk-calculator is likely to facilitate patient mobilization and reduce inpatient healthcare resource utilization. Résumé: Introduction: L’implantation d’un stimulateur cardiaque permanent (SCP) peut être indiquée après l’implantation valvulaire aortique par cathéter (post-IVAC). L’Emory Risk Score (ERS) est un score de prédiction du risque validé de la nécessité d’un SCP post-IVAC au moyen d’une valve expansible par ballonnet. Nous avions pour objectif de déterminer la validité de l’ERS auprès de notre population ayant eu une IVAC soit par valve expansible par ballonnet ou valve auto-expansible, et de déterminer d’autres paramètres électrocardiographiques (ECG) prédictifs de la nécessité d’un SCP post-IVAC. Méthodes: Nous avons réalisé des revues rétrospectives de dossiers et de bases de données électroniques pour collecter les données démographiques et interventionnelles. Deux experts ont lu et interprété tous les ECG. Les facteurs indépendants associés à l’implantation du SCP ont été examinés en effectuant la régression logistique multivariée par processus de sélection pas-à-pas au moyen du calcul de la surface sous la courbe caractéristique d’efficacité du récepteur afin d’évaluer la discrimination du modèle. Résultats: Le taux global d’implantation d’un SCP était de 11,7 % ; les taux étaient de 9 % pour les valves Sapien 3, de 10 % pour les valves Evolut Pro et de 17 % pour les valves Evolut R. Nous avons observé que l’ERS ne permettait pas de prédire si l’implantation d’un SCP post-IVAC était nécessaire pour la cohorte entière. Le bloc de branche droit était le seul paramètre de l’ERS indépendamment associé à la nouvelle implantation d’un SCP (8,5 % vs 25 %, rapport de cotes = 3,59, P = 0,01). Aucun autre paramètre ECG ne satisfaisait au critère de signification statistique. Conclusions: La faible valeur prédictive de l’ERS à déterminer la nécessité d’un SCP post-IVAC au sein de notre population de patients montre que des améliorations de la formule (ou calculateur de risques) sont justifiées. L’identification d’un calculateur de risques précis devrait favoriser l’adhésion des patients et réduire l’utilisation des ressources en soins de santé en milieu hospitalier.
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- 2022
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7. Human endogenous retrovirus K contributes to a stem cell niche in glioblastoma
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Ashish H. Shah, Sarah R. Rivas, Tara T. Doucet-O’Hare, Vaidya Govindarajan, Catherine DeMarino, Tongguang Wang, Leonel Ampie, Yong Zhang, Yeshavanth Kumar Banasavadi-Siddegowda, Stuart Walbridge, Dragan Maric, Marta Garcia-Montojo, Robert K. Suter, Myoung-Hwa Lee, Kareem A. Zaghloul, Joseph Steiner, Abdel G. Elkahloun, Jay Chandar, Deepa Seetharam, Jelisah Desgraves, Wenxue Li, Kory Johnson, Michael E. Ivan, Ricardo J. Komotar, Mark R. Gilbert, John D. Heiss, and Avindra Nath
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Stem cells ,Virology ,Medicine - Abstract
Human endogenous retroviruses (HERVs) are ancestral viral relics that constitute nearly 8% of the human genome. Although normally silenced, the most recently integrated provirus HERV-K (HML-2) can be reactivated in certain cancers. Here, we report pathological expression of HML-2 in malignant gliomas in both cerebrospinal fluid and tumor tissue that was associated with a cancer stem cell phenotype and poor outcomes. Using single-cell RNA-Seq, we identified glioblastoma cellular populations with elevated HML-2 transcripts in neural progenitor–like cells (NPC-like) that drive cellular plasticity. Using CRISPR interference, we demonstrate that HML-2 critically maintained glioblastoma stemness and tumorigenesis in both glioblastoma neurospheres and intracranial orthotopic murine models. Additionally, we demonstrate that HML-2 critically regulated embryonic stem cell programs in NPC-derived astroglia and altered their 3D cellular morphology by activating the nuclear transcription factor OCT4, which binds to an HML-2–specific long-terminal repeat (LTR5Hs). Moreover, we discovered that some glioblastoma cells formed immature retroviral virions, and inhibiting HML-2 expression with antiretroviral drugs reduced reverse transcriptase activity in the extracellular compartment, tumor viability, and pluripotency. Our results suggest that HML-2 fundamentally contributes to the glioblastoma stem cell niche. Because persistence of glioblastoma stem cells is considered responsible for treatment resistance and recurrence, HML-2 may serve as a unique therapeutic target.
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- 2023
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8. 1-Year Mortality Prediction through Artificial Intelligence Using Hemodynamic Trace Analysis among Patients with ST Elevation Myocardial Infarction
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Seyed Reza Razavi, Tyler Szun, Alexander C. Zaremba, Ashish H. Shah, and Zahra Moussavi
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ST elevation myocardial infarction (STEMI) ,mortality ,arterial pressure ,machine learning ,classification ,Medicine (General) ,R5-920 - Abstract
Background and Objectives: Patients presenting with ST Elevation Myocardial Infarction (STEMI) due to occlusive coronary arteries remain at a higher risk of excess morbidity and mortality despite being treated with primary percutaneous coronary intervention (PPCI). Identifying high-risk patients is prudent so that close monitoring and timely interventions can improve outcomes. Materials and Methods: A cohort of 605 STEMI patients [64.2 ± 13.2 years, 432 (71.41%) males] treated with PPCI were recruited. Their arterial pressure (AP) wave recorded throughout the PPCI procedure was analyzed to extract features to predict 1-year mortality. After denoising and extracting features, we developed two distinct feature selection strategies. The first strategy uses linear discriminant analysis (LDA), and the second employs principal component analysis (PCA), with each method selecting the top five features. Then, three machine learning algorithms were employed: LDA, K-nearest neighbor (KNN), and support vector machine (SVM). Results: The performance of these algorithms, measured by the area under the curve (AUC), ranged from 0.73 to 0.77, with accuracy, specificity, and sensitivity ranging between 68% and 73%. Moreover, we extended the analysis by incorporating demographics, risk factors, and catheterization information. This significantly improved the overall accuracy and specificity to more than 76% while maintaining the same level of sensitivity. This resulted in an AUC greater than 0.80 for most models. Conclusions: Machine learning algorithms analyzing hemodynamic traces in STEMI patients identify high-risk patients at risk of mortality.
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- 2024
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9. The Critical Transfer From Paediatrics to Adult Care in Patients With Congenital Heart Disease: Predictors of Transfer and Retention of Care
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Asem Suliman, MD, MBChB, FRCPC, Ruochen Mao, MD, Brett Hiebert, MSc, James W. Tam, MD, FRCP(C), FACC, Ashish H. Shah, MD, MD-Research (UK), FRCP (UK), Reeni Soni, MD, FRCPC, and Robin A. Ducas, MD, FRCPC
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Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Background: Congenital heart disease is the most common congenital birth defect and presents with differing degrees of complexity. Patients require lifelong specialized care. The transfer from paediatric to adult care is a time of risk that may result in lapses or loss of care. A successful transfer from paediatric to adult care is integral for improved patient outcomes. Methods: In this retrospective study, we used the paediatric cardiology database and the electronic records at the adult congenital heart disease (ACHD) clinic to identify referrals and successful transfer between 2008 and 2017. Successful transfer was defined as a patient referred to the ACHD clinic who was seen in the clinic and has ongoing follow-up. We also sought to identify predictors of a successful transfer. Results: A total of 555 patients were referred to the ACHD clinic (2008-2017). Of all patients referred, 62% had a successful transfer and an ongoing specialist care. The remaining 38% either did not show for first appointments or missed 3 consecutive visits. Independent predictors of a successful transfer were the presence of moderate or complex ACHD, residing within the city limits, older age at the time of referral, and a more recent year of referral. Conclusions: Over one-third of patients did not achieve successful transfer, namely attendance at first clinic visit plus early retention in care. We were able to identify several variables that predict successful transfer. Further research is required to identify interventions that can be implemented to reduce lapses in patient care. Résumé: Contexte: La cardiopathie congénitale, qui est la malformation congénitale la plus courante, présente divers degrés de complexité. Les patients qui en sont atteints nécessitent des soins spécialisés tout au long de leur vie. La transition entre les soins pédiatriques et les soins pour adultes est un moment risqué qui peut occasionner un relâchement ou une interruption des soins. Le succès de ce transfert des soins pédiatriques aux soins pour adultes est essentiel à l’amélioration des résultats pour les patients. Méthodologie: Pour cette étude rétrospective, nous avons utilisé la base de données de cardiologie pédiatrique et les dossiers électroniques de la clinique de cardiopathie congénitale de l’adulte (CCA) pour relever les cas de réorientation et de transfert réussi survenus entre 2008 et 2017. On entendait par « transfert réussi » le fait qu’un patient orienté vers la clinique de CCA ait été vu en consultation à la clinique et qu’il fasse l’objet d’un suivi. Nous avons aussi cherché à identifier les facteurs prédictifs d’un transfert réussi. Résultats: Au total, 555 patients ont été orientés à la clinique de CCA entre 2008 et 2017. Chez 62 % de tous ces patients orientés, le transfert a été réussi et les soins spécialisés ont été poursuivis. Les patients représentant les 38 % restants ne se sont pas présentés soit à leur premier rendez-vous, soit à trois visites subséquentes consécutives. Les facteurs prédictifs indépendants du transfert réussi étaient la présence d’une CCA modérée ou complexe, le fait de résider à l’intérieur des limites de la ville, un âge plus avancé au moment de la réorientation et le caractère plus récent de la réorientation. Conclusions: Chez plus du tiers des patients, le transfert n’a pas été réussi, c’est-à-dire que ces patients ne se sont pas présentés à leur première visite à la clinique et que leurs soins n’ont pas été poursuivis rapidement après le transfert. Nous avons pu cerner plusieurs variables qui prédisent les transferts réussis. D’autres recherches seront nécessaires pour trouver les interventions à mettre en œuvre pour réduire les interruptions dans les soins aux patients.
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- 2022
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10. Differential expression of an endogenous retroviral element [HERV-K(HML-6)] is associated with reduced survival in glioblastoma patients
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Ashish H. Shah, Vaidya Govindarajan, Tara T. Doucet-O’Hare, Sarah Rivas, Leo Ampie, Catherine DeMarino, Yeshavanth Kumar Banasavadi-Siddegowda, Yong Zhang, Kory R. Johnson, Fahad Almsned, Mark R. Gilbert, John D. Heiss, and Avindra Nath
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Medicine ,Science - Abstract
Abstract Comprising approximately 8% of our genome, Human Endogenous RetroViruses (HERVs) represent a class of germline retroviral infections that are regulated through epigenetic modifications. In cancer cells, which often have epigenetic dysregulation, HERVs have been implicated as potential oncogenic drivers. However, their role in gliomas is not known. Given the link between HERV expression in cancer cell lines and the distinct epigenetic dysregulation in gliomas, we utilized a tailored bioinformatic pipeline to characterize and validate the glioma retrotranscriptome and correlate HERV expression with locus-specific epigenetic modifications. We identified robust overexpression of multiple HERVs in our cell lines, including a retroviral transcript, HML-6, at 19q13.43b in glioblastoma cells. HERV expression inversely correlated with loci-specific DNA methylation. HML-6 contains an intact open reading frame encoding a small envelope protein, ERVK3-1. Increased expression of ERVK3-1 in GBM patients is associated with a poor prognosis independent of IDH-mutational status. Our results suggest that not only is HML-6 uniquely overexpressed in highly invasive cell lines and tissue samples, but also its gene product, ERVK3-1, may be associated with reduced survival in GBM patients. These results may have implications for both the tumor biology of GBM and the role of ERVK3-1 as a potential therapeutic target.
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- 2022
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11. Population and Resource Utilization Among Patients With Adult Congenital Heart Disease: A Snapshot View of a Moderate-Size Canadian Regional Centre
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Luis A. Castro, BSc, Ashish H. Shah, MD, MD-Research (UK), FRCP, Brett Hiebert, BSc, MSc, James W. Tam, MD, FRCPC, FACC, PG Cert (Palliative Care), and Robin A. Ducas, BSc, MD, FRCPC
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Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Background: Health care resource utilization for patients with adult congenital heart disease (ACHD) has not been well characterized outside of large Canadian specialized regional centres. We sought to describe the ACHD population and resource utilization patterns seen in a medium regional Canadian centre providing specialized ACHD care. Methods: A cross-sectional retrospective study was done from a sample of patients seen in 2018 at the ACHD clinic in Manitoba, Canada. Demographic data were collected along with cardiac anatomy and repair type. Health care resource utilization, clinic visits, hospital admissions, unexpected hospital presentations, and cardiac interventions were measured over a 5-year period. Results: A random sample of 262 patients was selected from our specialized ACHD clinic. Mean age was 33.5 (±13.7) years; 48% of the population was female, and >50% resided within the major city limits. A total of 21% of the population had simple anatomy, 44% had moderate anatomy, and 35% had complex anatomy. The most commonly used imaging modality was echocardiography, followed by cardiac magnetic resonance imaging, with more frequent imaging done in patients with complex anatomy. Unexpected hospital encounters occurred at a rate of 16 per 100 person-years. Total inpatient hospital days occurred at a rate of 33 per 100 person-years, and visits to the congenital clinic occurred at a rate of 90 per 100 person-years. Conclusions: Health care resource utilization appears to be highest in older adults and those with more complex ACHD anatomy. As the overall cohort of adults with ACHD continues to age, resource needs are likely to increase. Résumé: Contexte: L'utilisation des ressources de santé à l'extérieur des grands centres spécialisés régionaux au Canada n'a pas été bien caractérisée pour les patients atteints de cardiopathie congénitale de l'adulte (CCA). Nous avons cherché à décrire la population atteinte de CCA et les schémas d'utilisation des ressources observés dans un centre régional canadien de taille moyenne fournissant des soins spécialisés en CCA. Méthodologie: Une étude transversale rétrospective a été réalisée à partir d'un échantillon de patients rencontrés en 2018 dans une clinique spécialisée en CCA du Manitoba, au Canada. Des données démographiques ont été recueillies de même que des données sur l'anatomie cardiaque et le type de réparation. L'utilisation des ressources de soins de santé, les visites à la clinique, les admissions à l'hôpital, les consultions hospitalières imprévues et les interventions cardiaques ont été mesurées sur une période de cinq ans. Résultats: Un échantillon aléatoire de 262 patients a été sélectionné dans notre clinique spécialisée en CCA. L’âge moyen des patients était de 33,5 (±13,7) ans; 48 % de la population était de sexe féminin et plus de 50 % résidait dans les limites d'une grande ville. Au total, 21 % de la population présentait une anatomie cardiaque simple, 44 % une anatomie modérément complexe et 35 % une anatomie complexe. La technique d'imagerie la plus utilisée était l’échocardiographie, suivie de l'imagerie par résonance magnétique cardiaque, l'imagerie étant plus fréquente chez les patients présentant une anatomie cardiaque complexe. Le taux de consultations hospitalières imprévues était de 16 pour 100 années-patient. Le nombre total de jours d'hospitalisation était de 33 pour 100 années-patient, et le nombre de visites à la clinique spécialisée en CCA était de 90 pour 100 années-patient. Conclusions: L'utilisation des ressources de soins de santé semble être plus élevée chez les adultes plus âgés et chez ceux qui présentent une anatomie plus complexe liée à la CCA. Puisque l'ensemble de la cohorte d'adultes atteints de CCA continue de vieillir, les besoins en ressources sont susceptibles d'augmenter.
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- 2021
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12. Oncolytic Virotherapy for High-Grade Glioma and Current Evidence and Factors to Consider for Incorporation into Clinical Practice
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Sauson Soldozy, Daniel G. Eichberg, Alexis A. Morell, Evan Luther, Victor M. Lu, Dominique M. O. Higgins, Nitesh V. Patel, Ashish H. Shah, Simon J. Hanft, Ricardo J. Komotar, and Michael E. Ivan
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oncolytic virotherapy ,glioma ,virus therapy ,glioblastoma ,brain tumor ,Medicine - Abstract
Brain tumor incidence is on the rise, and glioblastoma comprises the majority of primary tumors. Despite maximal safe resection and adjuvant chemoradiation, median survival for high-grade glioma remains poor. For this reason, it is important to develop and incorporate new treatment strategies. Oncolytic virotherapy has emerged as a viable new therapeutic entity to fill this gap. Preclinical research has shown oncolytic virotherapy to be a robust and effective treatment option for brain tumors, and clinical trials for both adult and pediatric high-grade glioma are underway. The unique and protected environment of the nervous system, in part due to the blood–brain barrier, prevents traditional systemic therapies from achieving adequate penetration. Brain tumors are also heterogenous in nature due to their diverse molecular profiles, further complicating systemic treatment efforts. Oncolytic viruses may serve to fill this gap in brain tumor treatment given their amenability to genetic modification and ability to target unique tumor epitopes. In addition, direct inoculation of the oncolytic virus agent to the tumor bed following surgical resection absolves risk of systemic side effects and ensures adequate delivery. As virotherapy transitions from bench to bedside, it is important to discuss factors to make this transition more seamless. In this article, we describe the current clinical evidence as it pertains to oncolytic virotherapy and the treatment of brain tumors as well as factors to consider for its incorporation into neurosurgical workflow.
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- 2023
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13. Cardiac failure and pulmonary hypertension secondary to renal arteriovenous malformation: a case report
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Laura J. Albak, Ashish H. Shah, and James W. Tam
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Renal arteriovenous malformation ,Pulmonary hypertension ,Medicine - Abstract
Abstract Background Heart failure is usually associated with a low-cardiac-output state; however, a minority of these patients are characterized by a high-output cardiac state, described as a cardiac index of > 4 L/minute/m2. Usually such circulation is associated with low systemic vascular resistance or arteriovenous malformation (AVM), resulting in depressurized circulation and a high-output cardiac state. Treating physicians should be cognizant of such pathology when investigating patients with heart failure. As an example, renal arteriovenous malformations are a rare vascular phenomena that are typically the result of iatrogenic, traumatic or congenital etiology. Generally, non-salient, most are detected as an incidental finding. Case presentation A 75-year-old Afro-Caribbean man with multiple comorbidities presented to the emergency department with a 6-month history of heart failure symptoms. Cardiac catheterization demonstrated a giant right renal AVM leading to a significant left-to-right, post-tricuspid shunt that was treated with transcatheter coiling. Conclusions We present this case to emphasize the significance of a detailed workup in a patient with heart failure symptoms.
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- 2021
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14. The Role of HERV-K in Cancer Stemness
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Sarah R. Rivas, Mynor J. Mendez Valdez, Vaidya Govindarajan, Deepa Seetharam, Tara T. Doucet-O’Hare, John D. Heiss, and Ashish H. Shah
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human endogenous retroviruses ,HERV-K ,stem cell phenotypes ,carcinogenesis ,Microbiology ,QR1-502 - Abstract
Human endogenous retrovirus-K (HERV-K) is the most recently integrated retrovirus in the human genome, with implications for multiple disorders, including cancer. Although typically transcriptionally silenced in normal adult cells, dysregulation of HERV-K (HML-2) elements has been observed in cancer, including breast, germ cell tumors, pancreatic, melanoma, and brain cancer. While multiple methods of carcinogenesis have been proposed, here we discuss the role of HERV-K (HML-2) in the promotion and maintenance of the stem-cell in cancer. Aberrant expression of HERV-K has been shown to promote expression of stem cell markers and promote dedifferentiation. In this review, we discuss HERV-K (HML-2) as a potential therapeutic target based on evidence that some tumors depend on the expression of its proteins for survival.
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- 2022
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15. Neurosurgical Clinical Trials for Glioblastoma: Current and Future Directions
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Ashish H. Shah and John D. Heiss
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glioblastoma ,brain mapping ,temozolomide ,radiotherapy ,connection-enhanced delivery ,immunotherapy ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
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.
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- 2022
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16. Oncolytic Virotherapy for Melanoma Brain Metastases, a Potential New Treatment Paradigm?
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Sauson Soldozy, Kathleen M. Mulligan, David X. Zheng, Melissa A. Levoska, Christopher R. Cullison, Turki Elarjani, Daniel G. Eichberg, Leonel E. Ampie, Ashish H. Shah, Kaan Yağmurlu, Mark E. Shaffrey, Jeffrey F. Scott, and Ricardo J. Komotar
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oncolytic virotherapy ,melanoma ,brain metastases ,neuroimmunology ,neuro-oncology ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
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 with metastatic brain melanoma have been reported, specifically in patients with treatment refractory disease. Currently, there is not sufficient data to support the use of T-VEC or other viruses for intracranial metastatic melanoma. In developing a virotherapy treatment paradigm for melanoma brain metastases, several factors must be considered, including route of administration, need to bypass the blood–brain barrier, viral tumor infectivity, and risk of adverse events. Conclusions: Evidence for oncolytic virotherapy treatment of melanoma is limited primarily to T-VEC, with a noticeable paucity of data in the literature with respect to brain tumor metastasis. Given the promising findings of virotherapy for other brain tumor types, oncolytic virotherapy has great potential to offer benefits to patients afflicted with melanoma brain metastases and warrants further investigation.
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- 2021
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17. Presurgical thalamocortical connectivity is associated with response to vagus nerve stimulation in children with intractable epilepsy
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George M. Ibrahim, Priya Sharma, Ann Hyslop, Magno R. Guillen, Benjamin R. Morgan, Simeon Wong, Taylor J. Abel, Lior Elkaim, Iahn Cajigas, Ashish H. Shah, Aria Fallah, Alexander G. Weil, Nolan Altman, Byron Bernal, Santiago Medina, Elysa Widjaja, Prasanna Jayakar, John Ragheb, and Sanjiv Bhatia
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Computer applications to medicine. Medical informatics ,R858-859.7 ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Although chronic vagus nerve stimulation (VNS) is an established treatment for medically-intractable childhood epilepsy, there is considerable heterogeneity in seizure response and little data are available to pre-operatively identify patients who may benefit from treatment. Since the therapeutic effect of VNS may be mediated by afferent projections to the thalamus, we tested the hypothesis that intrinsic thalamocortical connectivity is associated with seizure response following chronic VNS in children with epilepsy. Twenty-one children (ages 5–21years) with medically-intractable epilepsy underwent resting-state fMRI prior to implantation of VNS. Ten received sedation, while 11 did not. Whole brain connectivity to thalamic regions of interest was performed. Multivariate generalized linear models were used to correlate resting-state data with seizure outcomes, while adjusting for age and sedation status. A supervised support vector machine (SVM) algorithm was used to classify response to chronic VNS on the basis of intrinsic connectivity. Of the 21 subjects, 11 (52%) had 50% or greater improvement in seizure control after VNS. Enhanced connectivity of the thalami to the anterior cingulate cortex (ACC) and left insula was associated with greater VNS efficacy. Within our test cohort, SVM correctly classified response to chronic VNS with 86% accuracy. In an external cohort of 8 children, the predictive model correctly classified the seizure response with 88% accuracy. We find that enhanced intrinsic connectivity within thalamocortical circuitry is associated with seizure response following VNS. These results encourage the study of intrinsic connectivity to inform neural network-based, personalized treatment decisions for children with intractable epilepsy. Keywords: Functional connectivity, Intrinsic connectivity networks, Resting-state fMRI, Low frequency neural oscillations, VNS
- Published
- 2017
- Full Text
- View/download PDF
18. Management of immune thrombocytic purpura and acute coronary syndrome: A double-edged sword!
- Author
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Ashish H. Shah, Richard A. Anderson, Ali Raza Khan, and Timothy D. Kinnaird
- Subjects
Immune thrombocytopenic purpura ,Coronary angioplasty ,Stent thrombosis ,Optical coherence tomography ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Treating patients known to have immune thrombocytopenic purpura (ITP) presenting with acute coronary syndrome (ACS) pose challenges, especially if they undergo percutaneous coronary intervention and stenting, as they require certain period of dual anti-platelet medication based up on the type of stent been deployed. Co-existence of therapies to increase platelet number as well as anti-platelet efficacy at the same time appears contradictory; imbalance in antagonistic treatment approach of increasing platelet number to treat ITP and inhibiting their activity to treat ACS can result in life threatening complications.
- Published
- 2016
- Full Text
- View/download PDF
19. Investigating the therapeutic role and molecular biology of curcumin as a treatment for glioblastoma
- Author
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Gregor A. Rodriguez, Ashish H. Shah, Zachary C. Gersey, Sumedh S. Shah, Amade Bregy, Ricardo J. Komotar, and Regina M. Graham
- Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Objectives: Despite the aggressive standard of care for patients with glioblastoma multiforme, survival rates typically do not exceed 2 years. Therefore, current research is focusing on discovering new therapeutics or rediscovering older medications that may increase the overall survival of patients with glioblastoma. Curcumin, a component of the Indian natural spice, turmeric, also known for its antioxidant and anti-inflammatory properties, has been found to be an effective inhibitor of proliferation and inducer of apoptosis in many cancers. The goal of this study was to investigate the expanded utility of curcumin as an antiglioma agent. Methods: Using the PubMed MeSH database, we conducted a systematic review of the literature to include pertinent studies on the growth inhibitory effects of curcumin on glioblastoma cell lines based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: A total of 19 in vitro and five in vivo studies were analyzed. All of the studies indicated that curcumin decreased glioblastoma cell viability through various pathways (i.e. decrease in prosurvival proteins such as nuclear factor κB, activator protein 1, and phosphoinositide 3 kinase, and upregulation of apoptotic pathways like p21, p53, and executor caspase 3). Curcumin treatment also increased animal survival compared with control groups. Conclusions: Curcumin inhibits proliferation and induces apoptosis in certain subpopulations of glioblastoma tumors, and its ability to target multiple signaling pathways involved in cell death makes it an attractive therapeutic agent. As such, it should be considered as a potent anticancer treatment. Further experiments are warranted to elucidate the use of a bioavailable form of curcumin in clinical trials.
- Published
- 2016
- Full Text
- View/download PDF
20. An Unusual Case of Refractory Angina
- Author
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Ashish H Shah, Eduardas Subkovas, Christopher M Bellamy, Nicholas P Waterfield, and Paul Das
- Subjects
refractory ,treatment ,vasospastic angina ,Medicine - Abstract
Vasospastic angina (VA) is characterized by segments of coronary artery that have exaggerated constrictor response to a variety of stimuli, resulting in partial or complete occlusion of the vessel, leading to myocardial ischemia. Here, we are presenting a case report of a patient who was known to have VA. Initially, she was treated with pharmacotherapy. Once it became treatment-refractory and involved left main stem and exposed significant amount of myocardium at risk, it required treating with percutaneous coronary intervention, which controlled her symptoms markedly. We briefly discuss the treatment options currently available.
- Published
- 2015
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