89 results on '"Bhatia, R."'
Search Results
2. Association of virtual end-of-life care with healthcare outcomes before and during the COVID-19 pandemic: A population-based study
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Lapp, John M., primary, Stukel, Thérèse A., additional, Chung, Hannah, additional, Bell, Chaim M., additional, Bhatia, R. Sacha, additional, Detsky, Allan S., additional, Downar, James, additional, Isenberg, Sarina R., additional, Lee, Douglas S., additional, Stall, Nathan, additional, Tanuseputro, Peter, additional, and Quinn, Kieran L., additional
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- 2024
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3. Prevalence and Clinical Significance of Electrocardiographic Complete Right Bundle Branch Block in Young Individuals
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MacLachlan, H, primary, Antonakaki, A, additional, Bhatia, R, additional, Fyazz, S, additional, Chatrath, N, additional, Androulakis, E, additional, Marawaha, S, additional, Basu, J, additional, Miles, C, additional, Dhutia, H, additional, Zaidi, A, additional, Chandra, N, additional, Sheikh, N, additional, Gati, S, additional, Malhotra, A, additional, Finocchiaro, G, additional, Sharma, S, additional, and Papadakis, M, additional
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- 2024
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4. Characteristics of Walk-In Clinic Physicians and Patients in Ontario, Canada: A Cross-Sectional Study
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Lapointe-Shaw, Lauren, primary, Salahub, Christine, additional, Austin, Peter C., additional, Bai, Li, additional, Banwatt, Sundeep, additional, Berthelot, Simon, additional, Bhatia, R. Sacha, additional, Bird, Cherryl, additional, Desveaux, Laura, additional, Kiran, Tara, additional, Lofters, Aisha, additional, Maclure, Malcolm, additional, Martin, Danielle, additional, McBrien, Kerry A., additional, McCracken, Rita K., additional, Paterson, J. Michael, additional, Rahman, Bahram, additional, Shuldiner, Jennifer, additional, Tadrous, Mina, additional, Terpou, Braeden A., additional, Thakkar, Niels, additional, Wang, Ruoxi, additional, and Ivers, Noah M., additional
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- 2024
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5. The impact of drug use in athletes on resting LV systolic function and contractile reserve
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Marwaha, S, Bulleros, P, Fanton, Z, Maclachlan, H, Bhatia, R, Finocchiaro, G, Prasad, S, Gati, S, Papadakis, M, and Sharma, S
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- 2024
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6. Feasibility of novel points-based health questionnaire utilised in a nationwide cardiac screening programme for young individuals
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Maclachlan, H, Ambrogetti, R, Moulson, N, Bhatia, R, Fyyaz, S, Chatrath, N, Androulakis, E, Miles, C, Basu, J, Finocchiaro, G, Gati, S, Malhotra, A, Sharma, S, Mckinney, J, and Papadakis, M
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- 2024
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7. Longitudinal insights into coronary plaque amongst master athletes
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Fyyaz, S, Merghani, A, Al-Turaihi, S, Chatrath, N, Bhatia, R, Maclachlan, H, Finocchiaro, G, Papatheodorou, S, Parry-Williams, G, David, S, O'driscoll, J, Papadakis, M, Alfakih, K, and Sharma, S
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- 2024
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8. A longitudinal study of quantitative late gadolinium enhancement analysis in young athletes versus non-athletic individuals with acute myocarditis
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Butt, H, Androulakis, E, Bhatia, R, Maclachlan, H, Sharma, S, and Papadakis, M
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Acute myocarditis is an acute inflammatory process within the myocardium, typically caused by infections, autoimmune disease, or drug reactions. Current guidelines suggest individuals with myocarditis should refrain from intense exercise, however, it remains unclear whether exercise affects myocardial properties and fibrosis during follow-up.We analysed MRI's from 1,180 individuals referred to our dedicated Sports Cardiology service with evidence suggestive of acute myocarditis. After excluding individuals with fibrosis due to a possible arrhythmogenic cardiomyopathy, or other non-relevant causes, we identified 146 consecutive individuals with confirmed acute myocarditis: Group 1, N=57 young athletic individuals and Group 2, 89 non-athletes (table 1). All subjects underwent comprehensive appropriate evaluation in addition to cardiac magnetic resonance (CMR) with PSIR post contrast late gadolinium enhancement (LGE), at baseline and at follow up. Volumetric LGE quantification were derived by artificial intelligence-based techniques (Circle CVi42 Inc v5.13), making the necessary adjustments, and using 3 thresholding methods (2, 3, 5 SDs). Median follow-up was 71 months. Major adverse cardiovascular events (MACE), including heart failure, documented arrhythmias, recurrent myocarditis, heart transplant, stroke and death were recorded.All patients included in this cohort were positive for LGE on admission CMR. LGE was found to be significantly reduced from baseline to the follow-up scan both in athletes (2SD; 24.6% (21.1-28.1) vs 19.7% (17.2-22.2), p<0.001), and non-athletic individuals (2SD; 25.9% (22.9-29.0), vs 21.0% (18.9-23.1), p<0.001). In the analysis of regional LGE distributions, the most common distribution of LGE that was observed in both groups was in the basal and mid inferolateral segments. Interestingly, lateral wall exhibited the highest proportion of LGE reduction at follow-up scan in the whole cohort, but anterior/antero-septal LGE did not reduce, particularly in athletes (Figure 1A+B). The overall rate of major adverse cardiac events was low with 10 out of the 146 cases (6.8%). There was no significant difference in MACE in athletes compared to non-athletes. Patients who developed an adverse event were found to have a higher proportion of LGE at presentation compared to patients who did not (22.7% vs 15.6%) and septal LGE signal was found to be significantly higher at presentation in patients who developed MACE (p<0.05).Young individuals with acute myocarditis showed significant improvement of fibrosis in the follow-up assessment, particularly in lateral walls; however, athletes exhibited different regression patterns in the anterior/anteroseptal walls, compared to non-athletic individuals. There was no significant difference in prognosis between the two groups, but patients with adverse events had larger amounts of fibrosis at presentation, particularly localized in the septumFigure 1Table 1
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- 2024
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9. Ein Status repetitiver Cortical Spreading Depressions ist das electrocorticographische Korrelat verzögerter ischämischer neurologischer Defizite bei Patienten nach Subarachnoidalblutung
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Dreier, J.P., Woitzik, J., Fabricius, M., Bhatia, R., Major, S., Drenckhahn, C., Lehmann, T.N., Sarrafzadeh, A., Willumsen, L., Hartings, J., Sakowitz, O., Seemann, J.H., Thieme, A., Lauritzen, M., and Strong, A.J.
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- 2024
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10. Ethnicity and sudden cardiac death in athletes: insights from a large United Kingdom registry.
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Finocchiaro G, Radaelli D, D'Errico S, Bhatia R, Papadakis M, Behr ER, Westaby J, Sharma S, and Sheppard MN
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- Humans, United Kingdom epidemiology, Male, Female, Adult, Risk Factors, Young Adult, Adolescent, White People statistics & numerical data, Autopsy, Middle Aged, Asian People, Risk Assessment, Black People statistics & numerical data, Death, Sudden, Cardiac ethnology, Death, Sudden, Cardiac epidemiology, Death, Sudden, Cardiac etiology, Athletes, Registries, Cause of Death
- Abstract
Aims: The relationship between ethnicity and causes of sudden cardiac death (SCD) in athletes is poorly understood., Objectives: To investigate aetiology of SCD among different ethnicities in a large cohort of athletes., Methods and Results: Between 1994 and November 2022, 7880 cases of SCD were consecutively referred from all over the United Kingdom to our national cardiac pathology centre; 848 (11%) were athletes. All cases underwent detailed autopsy evaluation by expert cardiac pathologists. Clinical information was obtained from referring coroners. Most of athletes were white (n = 758; 89%). Black and Asian athletes were in number of 51 (6%) and 39 (5%), respectively. A structurally normal heart, indicative of sudden arrhythmic death syndrome (SADS) was the most common autopsy finding (n = 385; 45%), followed by myocardial diseases (n = 275; 32%), atherosclerotic coronary artery disease (CAD) (n = 58; 7%), and coronary artery anomalies (n = 29; 3%). In most of cases, death occurred during exercise (n = 737; 87%). Arrhythmogenic cardiomyopathy (ACM) was more common in black (n = 13; 25%) than in white (n = 109; 14%) and Asian (n = 3; 8%) athletes (P = 0.03 between black and white athletes; P = 0.04 between black and Asian athletes); in contrast, CAD was more common in Asians (n = 6; 15% vs. n = 51; 7% in whites vs. n = 1; 2%; in blacks, P = 0.02 between Asian and black athletes). Among white athletes, ACM was more common in individuals who died during exercise than in the ones who died at rest (P = 0.005). Such a difference was not observed in Asian and black athletes. In Asian athletes, CAD was the diagnosis at autopsy in 18% of individuals who died during exercise and in none of individuals who died at rest., Conclusion: A structurally normal heart at autopsy and myocardial diseases are the most common findings in athletes who died suddenly. While ACM is more common in black athletes, atherosclerotic CAD is more common in Asian athletes, with a strong association with exercise-induced SCD. ACM appears to be a driver of exercise-induced SCD in white athletes, however this is not the case in black and Asian athletes., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
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- 2024
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11. Breaking Barriers in Alzheimer's Disease: the Role of Advanced Drug Delivery Systems.
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Shekho D, Mishra R, Kamal R, Bhatia R, and Awasthi A
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- Humans, Animals, Biomarkers metabolism, Amyloid beta-Peptides metabolism, Brain metabolism, Brain drug effects, tau Proteins metabolism, Alzheimer Disease drug therapy, Alzheimer Disease metabolism, Drug Delivery Systems methods
- Abstract
Alzheimer's disease (AD), characterized by cognitive impairment, brain plaques, and tangles, is a global health concern affecting millions. It involves the build-up of amyloid-β (Aβ) and tau proteins, the formation of neuritic plaques and neurofibrillary tangles, cholinergic system dysfunction, genetic variations, and mitochondrial dysfunction. Various signaling pathways and metabolic processes are implicated in AD, along with numerous biomarkers used for diagnosis, risk assessment, and research. Despite these, there is no cure or effective treatment for AD. It is critically important to address this immediately to develop novel drug delivery systems (NDDS) capable of targeting the brain and delivering therapeutic agents to modulate the pathological processes of AD. This review summarizes AD, its pathogenesis, related signaling pathways, biomarkers, conventional treatments, the need for NDDS, and their application in AD treatment. It also covers preclinical, clinical, and ongoing trials, patents, and marketed AD formulations., (© 2024. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)
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- 2024
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12. The first genetically confirmed cohort of Facioscapulohumeral Muscular Dystrophy from Northern India.
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Vishnu VY, Lemmers RJLF, Reyaz A, Mishra R, Ahmad T, van der Vliet PJ, Kretkiewicz MM, Macken WL, Efthymiou S, Dominik N, Morrow JM, Bhatia R, Wilson LA, Houlden H, Hanna MG, Bugiardini E, van der Maarel SM, and Srivastava MVP
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- Humans, India, Male, Female, Adult, Middle Aged, Cohort Studies, Alleles, Muscular Dystrophy, Facioscapulohumeral genetics, Muscular Dystrophy, Facioscapulohumeral diagnosis
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Facioscapulohumeral muscular dystrophy (FSHD) is the third most common form of hereditary myopathy. Sixty per cent of the world's population lives in Asia, so a significant percentage of the world's FSHD participants is expected to live there. To date, most FSHD studies have involved individuals of European descent, yet small-scale studies of East-Asian populations suggest that the likelihood of developing FSHD may vary. Here, we present the first genetically confirmed FSHD cohort of Indian ancestry, which suggests a pathogenic FSHD1 allele size distribution intermediate between European and North-East Asian populations and more asymptomatic carriers of 4 unit and 5 unit FSHD1 alleles than observed in European populations. Our data provides important evidence of differences relevant to clinical diagnostics and underscores the need for global FSHD participation in research and trial-ready Indian FSHD cohorts., (© 2024. The Author(s).)
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- 2024
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13. Assessing the effectiveness of high frequency repetitive transcranial magnetic stimulation for post-mastectomy pain in breast cancer patients: A randomized controlled trial.
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Kataria M, Gupta N, Kumar A, Bhoriwal S, Singh A, Shekhar V, and Bhatia R
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- Humans, Female, Middle Aged, Double-Blind Method, Adult, Treatment Outcome, Aged, Neuralgia etiology, Neuralgia therapy, Breast Neoplasms complications, Breast Neoplasms surgery, Breast Neoplasms therapy, Transcranial Magnetic Stimulation methods, Quality of Life, Mastectomy adverse effects, Pain, Postoperative etiology, Pain, Postoperative therapy, Pain Measurement
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Background: Post-mastectomy pain Syndrome (PMPS), characterized by chronic neuropathic pain stemming from intercostobrachial nerve lesions, presents a formidable clinical challenge. With the incidence of breast cancer surging, effective interventions for PMPS are urgently needed. To address this, we conducted this double-blind, placebo-controlled, randomized clinical trial to study the efficacy of repetitive Transcranial Magnetic Stimulation (rTMS) therapy over the motor cortex on pain, quality of life and thermal sensitivity in PMPS patients., Methods: We delivered 15 rTMS sessions over three weeks in a cohort of 34 PMPS patients. These patients were allocated randomly to either rTMS therapy or sham therapy groups. Pain assessments, utilizing the Visual Analogue Scale (VAS) and Short Form McGill Pain Questionnaire (SF-MPQ), alongside quality-of-life evaluations through the Functional Assessment of Cancer Therapy-Breast (FACT-B), were recorded before and after the 15 sessions. Additionally, we assessed thermal sensitivity using Quantitative Sensory Testing (QST)., Results: Our findings demonstrate the superior efficacy of rTMS therapy (over sham therapy) in reducing VAS and SF-MPQ scores (p < 0.0001), improving physical (p = 0.037), emotional (p = 0.033), and functional well-being (p = 0.020) components of quality of life, as quantified by FACT-B. Our investigation also unveiled marked enhancements in thermal sensitivity within the rTMS therapy group, with statistically significant improvements in cold detection threshold (p = 0.0001), warm detection threshold (p = 0.0033), cold pain threshold (p = 0.0078), and hot pain tolerance threshold (p = 0.0078)., Conclusion: The study underscores the profound positive impact of rTMS therapy on pain, quality of life, and thermal sensitivity in patients having PMPS, opening new avenues for pain management strategies., (© 2024. The Author(s), under exclusive licence to The Japanese Breast Cancer Society.)
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- 2024
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14. In silico study on antidiabetic and antioxidant activity of bioactive compounds in Ficus carica L.
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Raman APS, Pongpaiboon S, Bhatia R, Lal Dabodhia K, Kumar A, Kumar D, Jain P, Sagar M, Singh P, and Kumari K
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- Humans, Plant Extracts chemistry, Plant Extracts pharmacology, Computer Simulation, Ficus chemistry, Hypoglycemic Agents chemistry, Hypoglycemic Agents pharmacology, Antioxidants chemistry, Antioxidants pharmacology, Molecular Docking Simulation, Molecular Dynamics Simulation, Phytochemicals chemistry, Phytochemicals pharmacology
- Abstract
Hyperglycemia is one of the diagnostic issues in diabetes mellitus and is considered as a complex metabolic condition. It has been one of the most prevalent illnesses of the twenty-first century and still rising at an alarming rate across the globe and expected to impact 693 million individuals by 2045. Therefore, it is mandatory to develop more effective and safer treatments to manage diabetes. One of the ways to manage hyperglycemia is through inhibiting carbohydrate digestion and thereby lowering the glucose formation in the human body. The enzyme salivary amylase and pancreatic amylase is responsible for cleaving α-1,4-glucoside bond. Amylase inhibitors can lower blood glucose in diabetics by slowing digestion. Ficus carica is commonly known for its medicinal properties due to its various phytochemicals. In the present study, 10 phytochemicals present in F. carica compounds named, β-carotene, lutein, cyanidin-3-glucoside, gallic acid, luteolin, catechin, kaempferol, vanillic acid, peonidin-3-glucoside, and quercetin hydrate were taken to study their inhibition potential against pancreatic amylase and salivary amylase through molecular docking and molecular dynamics simulations. Further, density functional theory calculations are used to investigate the delocalization of electron density on the molecule as well as study ADME properties of the molecules take. A QSAR model has been developed using the binding energy obtained using molecular docking and thermodynamic parameters from DFT calculations.Communicated by Ramaswamy H. Sarma.
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- 2024
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15. Contribution of veterinary sector to antimicrobial resistance in One Health compendium: an insight from available Indian evidence.
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Chakraborty D, Debnath F, Giri S, Saha S, Pyne S, Chakraverty R, Majumdar A, Deb AK, Bhatia R, and Dutta S
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The application of antibiotics in the poultry and veterinary sectors is very common practice in India. Owing to the seriousness of antimicrobial resistance (AMR), the present study has illustrated the overall scenario of AMR in the poultry and veterinary sectors in India through an in-depth scoping review and key informant interview (KII). In the poultry sector, most of the studies reviewed have reported resistant bacteria isolated from chicken meat, eggs, cloacal swabs, and fecal samples, and only a few have reported the presence of resistant bacteria in and around the environment of poultry farms. The major resistant bacteria that have been reported are E. coli , Salmonella spp., S. aureus , Campylobacter jejuni , and K. pneumoniae . These bacterial isolates exhibited resistance to various antibiotics, such as azithromycin (21.43%), tetracycline (11.30-100%), chloramphenicol (4.76-100%), erythromycin (75-83.33%), ciprofloxacin (5.7-100%), gentamicin (17-100%), amikacin (4.76%), cotrimoxazole (42.2-60%), trimethoprim (89.4%), ceftriaxone (80%), and cefotaxime (14.29-70%). Like the poultry sector, different antibiotics are also used for treating clinical and subclinical bovine mastitis, which is one of the major problems plaguing the dairy sector. Several AMR bacterial strains, such as E. coli , Staphylococcus aureus , S. epidermidis , and Klebsiella pneumoniae , have been reported by many researchers and showed resistance against tetracycline (74%), oxytetracycline (47.37%), ciprofloxacin (51%), streptomycin (57.89%), cephalosporin (100%), and trimethoprim (70%). The KIIs have revealed several reasons behind these AMR scenarios, of which the growing need for the production of food animals and their products with inadequate infrastructure and a lack of proper knowledge on farm management among the farmers are the major ones. Though several government legislations and policies have been laid down, proper implementation of these policies, strict surveillance on antibiotic application in the poultry and veterinary sectors, awareness generation among farmers, and infrastructure development can help minimize the development and transmission of AMR bacteria within and from these sectors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chakraborty, Debnath, Giri, Saha, Pyne, Chakraverty, Majumdar, Deb, Bhatia and Dutta.)
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- 2024
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16. CRISPR screen of venetoclax response-associated genes identifies transcription factor ZNF740 as a key functional regulator.
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Zhang L, Zhou X, Aryal S, Veasey V, Zhang P, Li FJ, Luan Y, Bhatia R, Zhou Y, and Lu R
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- Humans, Animals, Cell Line, Tumor, Proto-Oncogene Proteins c-bcl-2 metabolism, Proto-Oncogene Proteins c-bcl-2 genetics, Clustered Regularly Interspaced Short Palindromic Repeats genetics, Mice, Drug Resistance, Neoplasm genetics, Antineoplastic Agents pharmacology, Antineoplastic Agents therapeutic use, Transcription Factors metabolism, Transcription Factors genetics, CRISPR-Cas Systems genetics, Sulfonamides pharmacology, Bridged Bicyclo Compounds, Heterocyclic pharmacology, Leukemia, Myeloid, Acute genetics, Leukemia, Myeloid, Acute drug therapy, Leukemia, Myeloid, Acute metabolism, Leukemia, Myeloid, Acute pathology
- Abstract
BCL-2 inhibitors such as venetoclax offer therapeutic promise in acute myeloid leukemia (AML) and other cancers, but drug resistance poses a significant challenge. It is crucial to understand the mechanisms that regulate venetoclax response. While correlative studies have identified numerous genes linked to venetoclax sensitivity, their direct impact on the drug response remains unclear. In this study, we targeted around 1400 genes upregulated in venetoclax-sensitive primary AML samples and carried out a CRISPR knockout screen to evaluate their direct effects on venetoclax response. Our screen identified the transcription factor ZNF740 as a critical regulator, with its expression consistently predicting venetoclax sensitivity across subtypes of the FAB classification. ZNF740 depletion leads to increased resistance to ventoclax, while its overexpression enhances sensitivity to the drug. Mechanistically, our integrative transcriptomic and genomic analysis identifies NOXA as a direct target of ZNF740, which negatively regulates MCL-1 protein stability. Loss of ZNF740 downregulates NOXA and increases the steady state protein levels of MCL-1 in AML cells. Restoring NOXA expression in ZNF740-depleted cells re-sensitizes AML cells to venetoclax treatment. Furthermore, we demonstrated that dual targeting of MCL-1 and BCL-2 effectively treats ZNF740-deficient AML in vivo. Together, our work systematically elucidates the causal relationship between venetoclax response signature genes and establishes ZNF740 as a novel transcription factor regulating venetoclax sensitivity., (© 2024. The Author(s).)
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- 2024
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17. Epigenetic Regulation of Non-canonical Menin Targets Modulates Menin Inhibitor Response in Acute Myeloid Leukemia.
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Zhou X, Zhang L, Aryal S, Veasey V, Tajik A, Restelli C, Moreira S, Zhang P, Zhang Y, Hope K, Zhou Y, Cheng C, Bhatia R, and Lu R
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Menin inhibitors that disrupt Menin-MLL interaction hold promise for treating specific acute myeloid leukemia subtypes, including KMT2A rearrangements (KMT2A-r), yet resistance remains a challenge. Here, through systematic chromatin-focused CRISPR screens, along with genetic, epigenetic, and pharmacologic studies in a variety of human and mouse KMT2A-r AML models, we uncover a potential resistance mechanism independent of canonical Menin-MLL targets. We show that a group of non-canonical Menin targets, which are bivalently co-occupied by active Menin and repressive H2AK119ub marks, are typically downregulated following Menin inhibition. The loss of Polycomb Repressive Complex 1.1 (PRC1.1) subunits, such as PCGF1 or BCOR, leads to Menin inhibitor resistance by epigenetic reactivation of these non-canonical targets, including MYC. Genetic and pharmacological inhibition of MYC can resensitize PRC1.1-deficent leukemia cells to Menin inhibition. Moreover, we demonstrate that leukemia cells with the loss of PRC1.1 subunits exhibit reduced monocytic gene signatures and are susceptible to the BCL2 inhibition, and combinational treatment of venetoclax overcomes the resistance to Menin inhibition in PRC1.1-deficient leukemia cells. These findings highlight the important roles of PRC1.1 and its regulated non-canonical Menin targets in modulating Menin inhibitor response and provide potential strategies to treat leukemias with compromised PRC1.1 function., (Copyright © 2024 American Society of Hematology.)
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- 2024
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18. Counterintuitive Trend of Intrusion Pressure with Temperature in the Hydrophobic Cu 2 (tebpz) MOF.
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Merchiori S, Donne AL, Bhatia R, Alvelli M, Yu JJ, Wu XD, Li M, Li D, Scheller L, Lowe AR, Geppert-Rybczynska M, Trump BA, Yakovenko AA, Chorążewski M, Zajdel P, Grosu Y, and Meloni S
- Abstract
Liquid porosimetry experiments reveal a peculiar trend of the intrusion pressure of water in hydrophobic Cu
2 (3,3',5,5'-tetraethyl-4,4'-bipyrazolate) MOF. At lower temperature (T) range, the intrusion pressure (Pi ) increases with T. For higher T values, Pi first reaches a maximum and then decreases. This is at odds with the Young-Laplace law, which for systems showing a continuous decrease of contact angle with T predicts a corresponding reduction of the intrusion pressure. Though the Young-Laplace law is not expected to provide quantitative predictions at the subnanoscale of Cu2 (tebpz) pores, the physical intuition suggests that to a reduction of their hydrophobicity corresponds a reduction of the Pi . Molecular dynamics simulations and sychrothron experiments allowed to clarify the mechanism of the peculiar trend of Pi with T. At increasing temperatures the vapor density within the MOF' pores grows significantly, bringing the corresponding partial pressure to ≈5 MPa. This pressure, which is consistent with the shift of Pi observed in liquid porosimetry, represents a threshold to be overcame before intrusion takes place. Beyond some value of temperature, the phenomenon of reduction of hydrophobicity (and water surface tension) dominated over the opposite effect of increase of vapor pressure and Pi inverts its trend with T., (© 2024 The Author(s). Small published by Wiley‐VCH GmbH.)- Published
- 2024
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19. Obstructive Bilateral Renal Fungal Bezoars in an Extremely Premature Neonate Treated With Antifungals and Urokinase Irrigation: A Case Report and Review of the Literature.
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Davis K, Yap N, Clark M, Bhatia R, Johnstone L, Taghavi K, O'Brien M, Ching N, and Carr J
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Background: An ex-27-week gestation female infant developed bilateral forearm nodules at 4 weeks of life during treatment for methicillin-sensitive Staphylococcus aureus bacteremia. A pure growth of Candida albicans was isolated on culture of both sterile aspiration of the forearm abscess and urine without evidence of methicillin-sensitive Staphylococcus aureus. The patient went on to develop bilateral obstructive renal fungal bezoars at 11 weeks of life., Results: Bilateral nephrostomies were required to alleviate obstruction with the addition of local irrigation with amphotericin B deoxycholate. Two weeks later, urokinase via the nephrostomy tubes was added due to an unchanged appearance on ultrasound (US) and ongoing candiduria. A significant reduction in the size of bezoars was seen on US after 3 days. Sterilization of urine culture was achieved 7 weeks into treatment, and resolution of bezoars on US was seen 9 weeks after treatment began. No adverse events occurred from the use of local urokinase., Conclusions: Urokinase irrigation via nephrostomy is an effective and safe adjunctive treatment in refractory obstructive renal candidiasis in neonates., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)
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- 2024
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20. Sex-based Differences in Risk for Therapy-related Myeloid Neoplasms.
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Richard MA, Yan C, Chen Y, Gibson CJ, Kalra R, Bosworth A, Crossman DK, Singh P, Hageman L, He J, Armenian SH, Vose J, Weisdorf DJ, Ebert BL, Yasui Y, Cheng C, Forman SJ, Bhatia S, and Bhatia R
- Abstract
Background: Therapy-related myeloid neoplasm (t-MN) is a life-threatening complication of autologous peripheral blood stem cell (PBSC) transplantation for non-Hodgkin lymphoma (NHL). Prior studies report an association between clonal hematopoiesis (CH) in PBSC and risk of t-MN, but small samples precluded examination of risk within specific sub-populations., Methods: Targeted DNA sequencing was performed to identify CH mutations in PBSC from a retrospective cohort of 984 NHL patients (median age at transplant 57y; range: 18-78). Fine-Gray proportional subdistribution hazard regression models estimated association between number of CH mutations and t-MN, adjusting for demographic, clinical, and therapeutic variables. Secondary analyses evaluated association between CH and t-MN among males and females., Results: CH was identified in PBSC from 366 patients (37.2%). t-MN developed in 60 patients after median follow-up of 5y. Presence of ≥2 mutations conferred increased t-MN risk (adjusted hazard ratio [aHR]=2.10, 95% confidence interval [CI]=1.08-4.11, p=0.029). CH was associated with increased t-MN risk among males (aHR=1.83, 95%CI=1.01-3.31) but not females (aHR=0.56, 95%CI=0.15-2.09). Although prevalence and type of CH mutations in PBSC was comparable, the 8y cumulative incidence of t-MN was higher among males vs. females with CH (12.4% vs. 3.6%) but was similar between males and females without CH (4.9% vs. 3.9%). Expansion of CH clones from PBSC to t-MN was seen only among males., Conclusions: Presence of CH mutations in PBSC confers increased risk of t-MN after autologous transplantation in male but not female patients with NHL. Factors underlying sex-based differences in risk of CH progression to t-MN merit further investigation.
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- 2024
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21. Emerging role of vitamin D deficiency as a risk factor for retinal venous occlusions and need for public health measures for its prevention.
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Sahu PK, Gautam P, Das GK, Gogoi P, Beri N, and Bhatia R
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Purpose: To estimate levels of serum vitamin D in patients of retinal vein occlusion (RVO) and compare with age- and sex-matched controls., Methods: A prospective case-control study of 54 patients of RVO and 54 age- and sex-matched attendants of patients presenting to a tertiary care hospital in Delhi was performed. Patients on vitamin D supplementations and RVO due to infective or immunological causes or patients of glaucoma were excluded. Serum vitamin D levels of all the study participants along with relevant blood investigations with history and examination were documented. Vitamin D deficiency was defined as <20 ng/ml., Results: The mean serum vitamin D levels seen in RVO patients and the control group were 14.19 ± 5.23 ng/ml and 19.42 ± 10.27 ng/ml, respectively ( P value = 0.001) with an odds ratio of 10.558 (CI = 2.34-47.50), indicating vitamin D deficiency to be strongly correlated with RVO. Maximum patients of RVO (46.3%) were seen during the winter season. The study noted hypertension [odds ratio 20.22 (CI = 5.812-70.347)], dyslipidemia, and anemia [odds ratio 4.107 (CI = 0.62-26.90)] to be the risk factors for RVO as previously proved in the literature. Smoking, diabetes, alcohol intake, and body mass index did not emerge as risk factors for RVO., Conclusion: Vitamin D deficiency is associated with RVO; hence, estimation of serum vitamin D levels should be advised as a part of routine investigations while looking for the cause of RVOs. Public health measures like food fortification with vitamin D micronutrients and public awareness towards increased sunlight exposure in the community are simple, inexpensive measures that can decrease the burden of sight-threatening disease of RVO in the community., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Family Medicine and Primary Care.)
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- 2024
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22. Folate and Vitamin B12 Status in Women of Reproductive Age in Rural Haryana, India: Estimating Population-Based Prevalence for Neural Tube Defects.
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Das R, Duggal M, Rosenthal J, Kankaria A, Senee HK, Jabbar S, Kaur M, Kumar V, Bhardwaj S, Singh N, Dhanjal GS, Kumar A, Rose CE, Bhatia R, Gupta R, Dalpath S, Crider KS, Zhang M, Pfeiffer CM, Gupta R, Mehta R, Raina N, and Yeung LF
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- Humans, Female, India epidemiology, Adult, Prevalence, Cross-Sectional Studies, Pregnancy, Adolescent, Young Adult, Middle Aged, Bayes Theorem, Neural Tube Defects epidemiology, Neural Tube Defects etiology, Folic Acid blood, Vitamin B 12 blood, Rural Population, Vitamin B 12 Deficiency epidemiology, Folic Acid Deficiency epidemiology, Folic Acid Deficiency blood
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Background: Folate and vitamin B12 deficiencies in pregnant women are associated with increased risk for adverse maternal and infant health outcomes, including neural tube defects (NTDs)., Methods: A population-based cross-sectional survey was conducted in two rural areas in Ambala District, Haryana, India in 2017 to assess baseline folate and vitamin B12 status among women of reproductive age (WRA) and predict the prevalence of NTDs. We calculated the prevalence of folate and vitamin B12 deficiency and insufficiency by demographic characteristics among 775 non-pregnant, non-lactating WRA (18-49 years). Using red blood cell (RBC) folate distributions and an established Bayesian model, we predicted NTD prevalence. All analyses were conducted using SAS-callable SUDAAN Version 11.0.4 to account for complex survey design., Results: Among WRA, 10.1% (95% CI: 7.9, 12.7) and 9.3% (95% CI: 7.4, 11.6) had serum (<7 nmol/L) and RBC folate (<305 nmol/L) deficiency, respectively. The prevalence of RBC folate insufficiency (<748 nmol/L) was 78.3% (95% CI: 75.0, 81.3) and the predicted NTD prevalence was 21.0 (95% uncertainly interval: 16.9, 25.9) per 10,000 live births. Prevalences of vitamin B12 deficiency (<200 pg/mL) and marginal deficiency (≥200 pg/mL and ≤300 pg/mL) were 57.7% (95% CI: 53.9, 61.4) and 23.5% (95% CI: 20.4, 26.9), respectively., Conclusions: The magnitude of folate insufficiency and vitamin B12 deficiency in this Northern Indian population is a substantial public health concern. The findings from the survey help establish the baseline against which results from future post-fortification surveys can be compared., (© 2024 Wiley Periodicals LLC.)
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- 2024
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23. Scaffolds imparting anthelmintic activity: recent advancements and SAR studies.
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Kumar P, Bhatia R, and Rangra NK
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Helminthiasis, affecting billions globally, poses a significant health concern, especially in impoverished regions with inadequate sanitation. The intricate anatomical complexity of helminths requires specialized treatment approaches. There is currently no effective vaccine against helminth infections. Anthelmintics, crucial for combating these infections, target neuromuscular functions in parasites without harming the host. However, the emergence of resistance to existing anthelmintics, notably benzimidazoles, presents a growing global challenge. This review delves into the structure-activity relationship of previously synthesized core anthelmintic scaffolds-Benzimidazole, coumarin, pyrazoline, triazole, and others-to elucidate their promising anthelmintic activities. Understanding the structure-activity relationship of these novel benzimidazole derivatives, Coumarin derivatives, and others is crucial in designing potent anthelmintics, overcoming resistance, and optimizing efficacy to combat the escalating global burden of helminth infections. In the present review, we cover recently studied compounds (from the year 2019 to till date) which have promising anthelmintic activity. This review will be useful for the pharmacology and medicinal chemistry researchers working in the area anthelmintics with various scaffolds like aminobenzothiazole, benzimidazole, benzothiazole, coumarin, chromene, spiroketal, pyrazoline, triazole, etc. to design novel potent anthelmintic compound., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)
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- 2024
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24. Symmetrical brownish plaques on dorsum of hands.
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Vasisht S and Bhatia R
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- Humans, Male, Diagnosis, Differential, Hand Dermatoses diagnosis, Female, Hand
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Competing Interests: Competing interests: The BMJ has judged that there are no disqualifying financial ties to commercial companies. The authors declare the following other interests: none.
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- 2024
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25. Paclitaxel in colon cancer management: from conventional chemotherapy to advanced nanocarrier delivery systems.
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Komal, Nanda BP, Singh L, Bhatia R, and Singh A
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Paclitaxel, a potent chemotherapeutic agent derived from the bark of the Pacific yew tree, has demonstrated significant efficacy in the treatment of various cancers, including colon cancer. This comprehensive review delves into the conventional treatments for colon cancer, emphasizing the crucial role of paclitaxel in contemporary management strategies. It explores the intricate process of sourcing and synthesizing paclitaxel, highlighting the importance of its structural properties in its anticancer activity. The review further elucidates the mechanism of action of paclitaxel, its pharmacological effects, and its integration into chemotherapy regimens for colon cancer. Additionally, novel drug delivery systems, such as nanocarriers, liposomes, nanoparticles, microspheres, micelles, microemulsions, and niosomes, are examined for their potential to enhance the therapeutic efficacy of paclitaxel. The discussion extends to recent clinical trials and patents, showcasing advancements in paclitaxel formulations aimed at improving treatment outcomes. The review concludes with prospects in the field underscoring the ongoing innovation and potential breakthroughs in colon cancer therapy., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2024
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26. Clonal Hematopoiesis and Therapy-Related Myeloid Neoplasms After Autologous Transplant for Hodgkin Lymphoma.
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Yan C, Richard MA, Gibson CJ, He J, Bosworth A, Crossman DK, Singh P, Hageman L, Kalra R, Armenian SH, Vose J, Weisdorf DJ, Ebert BL, Yasui Y, Forman SJ, Bhatia R, and Bhatia S
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- Humans, Adult, Female, Male, Middle Aged, Retrospective Studies, Adolescent, Young Adult, Aged, Peripheral Blood Stem Cell Transplantation adverse effects, Tumor Suppressor Protein p53 genetics, DNA Methyltransferase 3A, Protein Phosphatase 2C genetics, DNA (Cytosine-5-)-Methyltransferases genetics, Dioxygenases, DNA-Binding Proteins genetics, Proto-Oncogene Proteins genetics, Hodgkin Disease therapy, Hodgkin Disease genetics, Transplantation, Autologous adverse effects, Clonal Hematopoiesis genetics, Neoplasms, Second Primary genetics, Neoplasms, Second Primary etiology, Mutation
- Abstract
Purpose: Therapy-related myeloid neoplasm (t-MN) is a life-threatening complication of autologous peripheral blood stem cell transplantation (aPBSCT) for Hodgkin lymphoma (HL). Although previous studies have reported an association between clonal hematopoiesis (CH) in the infused PBSC product and subsequent post-aPBSCT risk of t-MN in patients with non-HL, information about patients with HL treated with aPBSCT is not available., Methods: We constructed a retrospective cohort of 321 patients with HL transplanted at a median age of 34 years (range, 18-71). Targeted DNA sequencing of PBSC products performed for CH-associated or myeloid malignancy-associated genes identified pathogenic mutations in these patients., Results: CH was identified in the PBSC product of 46 patients (14.3%) with most prominent representation of DNMT3A (n = 25), PPM1D (n = 7), TET2 (n = 7), and TP53 (n = 5) mutations. Presence of CH in the PBSC product was an independent predictor of t-MN (adjusted hazard ratio [aHR], 4.50 [95% CI, 1.54 to 13.19]). Notably all patients with TP53 mutations in the PBSC product developed t-MN, whereas none of the patients with DNMT3A mutations alone (without co-occurring TP53 or PPM1D mutations) did. Presence of TP53 and/or PPM1D mutations was associated with a 7.29-fold higher hazard of t-MN when compared with individuals carrying no CH mutations (95% CI, 1.72 to 30.94). The presence of TP53 and/or PPM1D mutations was also associated with a 4.17-fold higher hazard of nonrelapse mortality (95% CI, 1.25 to 13.87). There was no association between CH and relapse-related mortality., Conclusion: The presence of TP53 and/or PPM1D mutations in the PBSC product increases the risk of post-aPBSCT t-MN and nonrelapse mortality among patients with HL and may support alternative therapeutic strategies.
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- 2024
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27. Idarubicin and cytarabine with and without midostaurin for FLT3-mutated acute myeloid leukemia.
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Diebold K, Bourne G, Espinoza-Gutarra M, Al-Kadhimi Z, Bachiashvili K, Rangaraju S, Vachhani P, Bhatia R, and Jamy O
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- 2024
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28. Economic Burden of Otitis Media Globally and an Overview of the Current Scenario to Alleviate the Disease Burden: A Systematic Review.
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Bhatia R, Chauhan A, Rana M, Kaur K, Pradhan P, and Singh M
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Introduction The prevalence of otitis media (OM) is substantial all over the world. Epidemiological data related to the economic burden of OM globally is minimal. The present systematic review was undertaken to estimate the economic burden of this disease in various parts of the world. Objectives An extensive literature search was done using PRISMA guidelines to identify relevant studies that estimated the economic burden of OM in monetary terms. The databases searched were PubMed Central, Ovid, and Embase. The cost estimation was done for one specific year and then compared considering the inflation rate. Data Synthesis The literature search led to the inclusion of 10 studies. The studies evaluated direct and indirect costs in monetary terms. Direct costs (health system and patient perspective) ranged from USD (United States Dollar) 122.64 (Netherlands) to USD 633.6 (USA) per episode of OM. Looking at only the patient perspective, the costs ranged from USD 19.32 (Oman) to USD 80.5 (Saudi Arabia). The total costs (direct and indirect) ranged from USD 232.7 to USD 977 (UK) per episode of OM. The economic burden per year was highest in the USA (USD 5 billion). The incidence of OM episodes was found more in children < 5 years old. Introduction of pneumococcal conjugate vaccines decreased the incidence in children and now the prevalence in adults is of concern. Conclusion The economic burden of OM is relatively high globally and addressing this public health burden is important. Approaches for the prevention, diagnosis, and treatment should be undertaken by the health system to alleviate this disease burden., Competing Interests: Conflict of Interest The authors have no conflict of interests to declare. Dr. Ragini Bhatia reported Grants or contracts from ICMR New Delhi funding agency., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit ( https://creativecommons.org/licenses/by/4.0/ ).)
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- 2024
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29. Safety and Efficacy of Injection Tenecteplase in 4.5 to 24 Hours Imaging Eligible Window Patients with Acute Ischemic Stroke (EAST-AIS) - Study Protocol.
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Pandit AK, Jatwani A, Tangri P, Srivastava MVP, Bhatia R, Kale SS, Gaikwad S, Srivastava AK, Garg A, Joseph LS, Vibha D, Vishnu VY, Singh RK, Radhakrishnan DM, Das A, and Agarwal A
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Background and Aims: Tenecteplase is used as the standard of care treatment for thrombolysis in acute ischemic stroke (AIS) patients within 4.5 h of symptom onset. Documented reports were less certain to claim the benefits of it in an extended window period. EAST-AIS (CTRI/2022/03/040718) trial is designed to determine the success rate of thrombolysis in an extended window period for good clinical outcomes., Study Design: It is a randomized, placebo-controlled trial of tenecteplase administered within 4.5-24 h of stroke onset (with or without large vessel occlusion) based on evidence of salvageable tissue through baseline computed tomography perfusion (CTP) or magnetic resonance imaging (MRI) scan. Criteria of patient inclusion are as follows: patients of both genders (male and female), age >18 years, pre-stroke modified Ranking Scale (mRS) <2, baseline NIHSS >5, CTP showing penumbra-ischemic core ratio >1.8, absolute difference in volume >10 ml, and ischemic core volume <70 ml. The sample size for the study is 100 patients: 50 in the tenecteplase arm (0.25 mg/kg body weight; maximum- 25 mg) and 50 in the placebo arm (controls)., Study Outcomes: The study's primary objective is safety endpoints along with the efficacy of tenecteplase assessed using the mRS score at 90 days of stroke onset., Conclusion: The result obtained from EAST-AIS will determine the safety and efficacy of tenecteplase injection administered 4.5-24 h following the symptom onset for AIS patients within the territory of Internal Carotid Artery (ICA), Middle Cerebral Artery (MCA), or Anterior Cerebral Artery (ACA) occlusion., (Copyright © 2024 Copyright: © 2024 Annals of Indian Academy of Neurology.)
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- 2024
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30. Development of whey protein beverage incorporating encapsulated probiotic strain Lactiplantibacillus rhamnosus NCDC 347 and its physico-chemical characteristics.
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Bhatia R, Chauhan K, Taneja NK, Kumar V, Singh G, Kaur K, and Oberoi HS
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In the present study, encapsulated strain Lactiplantibacillus rhamnosus NCDC 347 was used to prepare a novel whey protein-based beverage. The encapsulation process utilized skimmed milk powder matrix and evaluated strain viability, physico-chemical properties, sensory assessment, and shelf-life stability. Encapsulated L. rhamnosus NCDC 347 within skim milk powder maintained viability at 8.0 log CFU/g, forming spherical microcapsules with 1-12 µm concavities. Probiotic addition to whey protein beverages maintained pH and acidity within desired ranges. Physico-chemical analysis showed protein content of 8.71 ± 0.21 % to 10.05 ± 0.42 %, fat content of 0.56 ± 0.24 % to 0.67 ± 0.13 %, viscosity of 5.14 pa/s, and total soluble solids (TSS) of 14.42 ± 0.31 to 16.16 ± 0.23° Brix. The shelf-life study revealed that the beverage remained stable for up to 90 days with no significant changes ( p > 0.05) in sensory analysis. The sensory analysis scored the test sample's acceptability at 7.3 ± 0.41. The protein-rich probiotic drink exhibited favorable sensory qualities. Overall, incorporating encapsulated probiotic strain L. rhamnosus NCDC 347 into whey protein beverages could address daily protein requirements and enhance health., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)
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- 2024
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31. Repetitive Transcranial Magnetic Stimulation of the Dorsolateral Prefrontal Cortex for Phantom Limb Pain.
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Vats D, Bhatia R, Fatima S, Yadav R, Sagar S, Mir N, Khan MA, and Singh A
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- Humans, Adult, Male, Female, Middle Aged, Prefrontal Cortex, Pain Measurement, Phantom Limb therapy, Transcranial Magnetic Stimulation methods, Dorsolateral Prefrontal Cortex
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Background: Phantom limb pain (PLP) is a prevalent and distressing occurrence in 60-80% of individuals who have undergone amputations. Recent research underscores the significance of maladaptive cortical plasticity in the genesis of PLP, emphasizing the importance of targeting cortical areas for therapeutic interventions. Repetitive transcranial magnetic stimulation (rTMS), a noninvasive tool for cortical stimulation, demonstrates effectiveness in treating various chronic pain conditions of neuropathic origin. Nevertheless, there exists a limited body of research investigating the application of rTMS as a therapeutic intervention specifically for managing PLP. Notably, the dorsolateral prefrontal cortex (DLPFC) plays a crucial role in central pain processing, suggesting its potential as a key therapeutic target in PLP treatment. There is a lack of adequate data regarding the effectiveness of DLPFC-targeting rTMS in alleviating the pain experienced by PLP patients., Objective: In this study, our aim was to investigate the impact of 10 sessions of DLPFC-targeting rTMS on the pain status of individuals experiencing PLP., Study Design: Randomized controlled trial., Setting: Traumatic amputees reporting to the tertiary care center with PLP., Methods: The study was approved by the Institute Ethics Committee (IECPG-299/27.04.2022) and registered in the Clinical Trials Registry of India (CTRI/2022/07/043938). Nineteen patients suffering from PLP were recruited and randomized into real or sham rTMS groups. In the real rTMS group, patients received 10 sessions of rTMS at the DLPFC contralateral to the amputation site. The rTMS, administered at 90% of the resting motor threshold (RMT), was delivered as 8 trains of 150 pulses per train at the rate of one Hz and an inter-train interval of 60 seconds. The total number of pulses per session was 1,200. The sham group received 10 sessions of sham rTMS through the perpendicular placement of an rTMS coil over the DLPFC. These sessions lasted for the same duration and included the same sounds as the real group but involved no active stimulation. The patients' pain status was evaluated using the Visual Analog Scale (VAS) at baseline, at the end of each session of real or sham rTMS and at the 15th, 30th, and 60th day after the the completion of real or sham therapy., Results: A significant decrease in VAS scores was noted after 10 sessions of real rTMS that targeted the DLPFC, in contrast to the sham rTMS group. The real rTMS group's reduction in VAS scores also persisted during the follow-up., Limitations: A few patients had to drop out due to physical restrictions and financial constraints. Consequently, only a small number of individuals were able to complete the study protocol successfully., Conclusion: A regimen of 10 sessions of real rTMS of the DLPFC was associated with significant pain relief in patients with PLP, and the effects were sustained for 2 months. Therefore, the present study shows that rTMS of the DLPFC has potential as an effective therapeutic intervention for sustained pain relief in PLP patients.
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- 2024
32. Effect of neuronavigated repetitive Transcranial Magnetic Stimulation on pain, cognition and cortical excitability in fibromyalgia syndrome.
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Tiwari VK, Kumar A, Nanda S, Chaudhary S, Sharma R, Kumar U, Kumaran SS, and Bhatia R
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- Humans, Female, Double-Blind Method, Middle Aged, Adult, Male, Cognition physiology, Magnetic Resonance Imaging, Treatment Outcome, Pain Measurement, Fibromyalgia therapy, Fibromyalgia physiopathology, Transcranial Magnetic Stimulation methods, Cortical Excitability physiology
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Background: Fibromyalgia syndrome is a widespread chronic pain condition identified by body-wide pain, fatigue, cognitive fogginess, and sleep issues. In the past decade, repetitive transcranial magnetic stimulation has emerged as a potential management tool.. In the present study, we enquired whether repetitive transcranial magnetic stimulation could modify pain, corticomotor excitability, cognition, and sleep., Methods: Study is a randomized, sham-controlled, double-blind, clinical trial; wherein after randomizing thirty-four fibromyalgia patients into active or sham therapy (n = 17 each), each participant received repetitive transcranial magnetic stimulation therapy. In active therapy was given at 1 Hz for 20 sessions were delivered on dorsolateral prefrontal cortex (1200 pulses, 150 pulses per train for 8 trains); while in sham therapy coil was placed at right angle to the scalp with same frequency. Functional magnetic resonance imaging was used to identify the therapeutic site. Pain intensity, corticomotor excitability, cognition, and sleep were examined before and after therapy., Results: Baseline demographic and clinical parameters for both active and sham groups were comparable. In comparison to sham, active repetitive transcranial magnetic stimulation showed significant difference in pain intensity (P < 0.001, effect size = 0.29, large effect) after intervention. Other parameters of pain perception, cognition, and sleep quality also showed a significant improvement after the therapy in active therapy group only, as compared to sham., Conclusions: Findings suggest that repetitive transcranial magnetic stimulation intervention is effective in managing pain alongside cognition and sleep disturbances in patients of fibromyalgia. It may prove to be an important tool in relieving fibromyalgia-associated morbidity., (© 2024. Fondazione Società Italiana di Neurologia.)
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- 2024
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33. Cervical Artery Dissection: Clinical Outcomes and Functional Outcome Predictors from a Tertiary Care Center in India.
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Agarwal A, Garg A, Antil Y, Bhatia R, Joseph L, Sharma A, Agarwal S, Upadhyay A, Vishnu VY, and Srivastava MVP
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- 2024
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34. Oral isotretinoin with desloratadine compared with oral isotretinoin alone in the treatment of moderate to severe acne: a randomized, assessor-blinded study.
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Hazarika N, Yadav P, Bagri M, Chandrasekaran D, and Bhatia R
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- Humans, Female, Male, Administration, Oral, Young Adult, Adolescent, Adult, Drug Therapy, Combination, Single-Blind Method, Treatment Outcome, Histamine H1 Antagonists, Non-Sedating administration & dosage, Histamine H1 Antagonists, Non-Sedating adverse effects, Isotretinoin administration & dosage, Isotretinoin adverse effects, Acne Vulgaris drug therapy, Loratadine administration & dosage, Loratadine analogs & derivatives, Loratadine adverse effects, Severity of Illness Index, Dermatologic Agents administration & dosage, Dermatologic Agents adverse effects, Patient Satisfaction
- Abstract
Background: Our aim was to measure the effectiveness of oral isotretinoin with desloratadine compared with oral isotretinoin alone in treating moderate to severe acne at a tertiary care teaching hospital in North India. In this study, 90 patients with moderate to severe acne were enrolled to participate based on their fulfilling the inclusion criteria., Methods: A randomized, assessor-blinded, parallel-arm study was conducted. Randomization was done using computer-generated tables to allocate treatments in a 1:1 ratio. A low-dose oral isotretinoin at a dose of 0.3 mg/kg/day with tab desloratadine at 5 mg/day was applied to the study group and compared against the same patients going without the dosage when controls were conducted. Follow-up was at 4, 8, and 12 weeks., Results: The primary outcome was an improved global acne grading system (GAGS) score and decreased acne lesion count., Secondary Outcome: patient satisfaction with treatment. The 90 participants were randomized and 15 participants dropped out of the study, leaving 75 participants for intention to treat analysis (n = 41, n = 30). At week 12, the GAGS score and acne lesion count between the study and control groups were comparable (P > 0.05). Pruritus reported was 9.76% in the study versus 33.33% in the control group (P = 0.018). Also, 53.66% of participants reported "excellent" treatment satisfaction in the study group versus 36.67% in the control group., Conclusions: The addition of desloratadine to an isotretinoin regimen has a role in reducing disease and therapy-related pruritus in acne and leads to improved patient satisfaction., (© 2024 the International Society of Dermatology.)
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- 2024
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35. Biomarkers of bleeding and venous thromboembolism in patients with acute leukemia.
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Hisada Y, Archibald SJ, Bansal K, Chen Y, Dai C, Dwarampudi S, Balas N, Hageman L, Key NS, Bhatia S, Bhatia R, Mackman N, and Gangaraju R
- Subjects
- Humans, Male, Middle Aged, Female, Adult, Case-Control Studies, Aged, Precursor Cell Lymphoblastic Leukemia-Lymphoma blood, Precursor Cell Lymphoblastic Leukemia-Lymphoma complications, Risk Factors, Leukemia, Promyelocytic, Acute blood, Leukemia, Promyelocytic, Acute complications, Venous Thrombosis blood, Venous Thrombosis diagnosis, Venous Thrombosis etiology, Histones blood, Plasminogen Activator Inhibitor 1 blood, Thromboplastin metabolism, Thromboplastin analysis, Young Adult, Phosphatidylserines blood, Hemorrhage blood, Hemorrhage diagnosis, Venous Thromboembolism blood, Venous Thromboembolism diagnosis, Venous Thromboembolism etiology, Biomarkers blood, Leukemia, Myeloid, Acute blood, Leukemia, Myeloid, Acute complications, Blood Coagulation
- Abstract
Background: Coagulopathy and associated bleeding and deep vein thrombosis (DVT) are major causes of morbidity and mortality in patients with acute leukemia. The underlying mechanisms of these complications have not been fully elucidated., Objectives: To evaluate the associations between biomarker levels and bleeding and DVT in acute leukemia patients., Methods: We examined plasma levels of activators, inhibitors, and biomarkers of the coagulation and fibrinolytic pathways in patients aged ≥18 years with newly diagnosed acute leukemia compared with those of normal controls. Multivariable regression models were used to examine the association of biomarkers with bleeding and DVT in acute leukemia patients. The study included 358 patients with acute leukemia (29 with acute promyelocytic leukemia [APL], 253 with non-APL acute myeloid leukemia, and 76 with acute lymphoblastic leukemia) and 30 normal controls., Results: Patients with acute leukemia had higher levels of extracellular vesicle tissue factor (EVTF) activity, phosphatidylserine-positive extracellular vesicles, plasminogen activator inhibitor-1, plasmin-antiplasmin complexes, and cell-free DNA and lower levels of citrullinated histone H3-DNA complexes compared with normal controls. APL patients had the highest levels of EVTF activity and the lowest levels of tissue plasminogen activator among acute leukemia patients. There were 41 bleeding and 23 DVT events in acute leukemia patients. High EVTF activity was associated with increased risk of bleeding (subdistribution hazard ratio, 2.30; 95% CI, 0.99-5.31), whereas high levels of plasminogen activator inhibitor-1 were associated with increased risk of DVT (subdistribution hazard ratio, 3.00; 95% CI, 0.95-9.47) in these patients., Conclusion: Our study shows alterations in several biomarkers in acute leukemia and identifies biomarkers associated with risk of bleeding and DVT., Competing Interests: Declaration of competing interests R.G. has served as a consultant for Advisory Boards for Alexion, Takeda, and Sanofi and received an honorarium for presenting a webinar from Sanofi. The other authors declare no competing financial interests., (Copyright © 2024 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)
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- 2024
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36. Pre-frailty after blood or marrow transplantation and the risk of subsequent mortality.
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Balas N, Richman JS, Landier W, Shrestha S, Bruxvoort KJ, Hageman L, Meng Q, Ross E, Bosworth A, Wong FL, Bhatia R, Forman SJ, Armenian SH, Weisdorf DJ, and Bhatia S
- Subjects
- Humans, Male, Female, Middle Aged, Risk Factors, Aged, Adult, Survivors, Follow-Up Studies, Survival Rate, Young Adult, Adolescent, Bone Marrow Transplantation adverse effects, Bone Marrow Transplantation mortality, Frailty mortality
- Abstract
We examined the prevalence, risk factors, and association between pre-frailty and subsequent mortality after blood or marrow transplantation (BMT). Study participants were drawn from the BMT Survivor Study (BMTSS) and included 3346 individuals who underwent BMT between 1974 and 2014 at one of three transplant centers and survived ≥2 years post-BMT. Participants completed the BMTSS survey at a median of 9 years from BMT and were followed for subsequent mortality for a median of 5 years after survey completion. Closest-age and same-sex biological siblings also completed the survey. Previously published self-reported indices (exhaustion, weakness, low energy expenditure, slowness, unintentional weight loss) classified participants as non-frail (0-1 indices) or pre-frail (2 indices). National Death Index was used to determine vital status and cause of death. Overall, 626 (18.7%) BMT survivors were pre-frail. BMT survivors had a 3.2-fold higher odds of being pre-frail (95% CI = 1.9-5.3) compared to siblings. Compared to non-frail survivors, pre-frail survivors had higher hazards of all-cause mortality (adjusted hazard ratio [aHR] = 1.6, 95% CI = 1.4-2.0). Female sex, pre-BMT radiation, smoking, lack of exercise, anxiety, and severe/life-threatening chronic health conditions were associated with pre-frailty. The novel association between pre-frailty and subsequent mortality provides evidence for interventions as pre-frail individuals may transition back to their robust state., (© 2024. The Author(s).)
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- 2024
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37. Insights into Angiographic Recanalization of Large Arterial Occlusion: Institutional Experience with Mechanical Thrombectomy for Acute Ischemic Stroke.
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Charan BD, Gaikwad SB, Jain S, Garg A, Sebastian LJD, Srivastava MVP, Bhatia R, Pandit AK, and Kale SS
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Stroke is a leading cause of morbidity and mortality in humans. Most strokes are ischemic in nature and early recanalization of occluded vessels determines good outcomes. Recanalization of occluded vessels depends on many angiographic and demographic features. These factors need to be identified for better patient overall outcomes. Better preoperative knowledge of factors can help in customizing our treatment approach and explaining the prognosis to the guardians of the patients. We aim to share our institutional experience with mechanical thrombectomy (MT) for stroke and studied factors that affect an angiographic recanalization of vessels . A retrospective single-center study was conducted involving 104 patients who underwent MT at our institution between January 2016 and December 2019. Patient demographics, baseline characteristics, pre- and postprocedural imaging findings, and other clinical data were meticulously reviewed. We divided patients into successful recanalization (modified thrombolysis in cerebral ischemia [mTICI] 2b or 3) and unsuccessful recanalization (mTICI 2a or 1) groups and various factors were analyzed to evaluate their impact on recanalization rates. In the univariate analysis, a significant association was observed between successful recanalization and several factors: the absence of rheumatic heart disease (RHD) as a risk factor ( p = 0.035), the presence of a hyperdense vessel sign ( p = 0.003), and the use of treatment methods including aspiration ( p = 0.031), stent retriever ( p = 0.001), and Solumbra ( p = 0.019). However, in the multivariate analysis, none of these factors exhibited statistical significance. The presence of RHD is a risk factor associated with poor angiographic recanalization in all three MT treatment modalities. Based on the above variables we can guide the patients/relatives prior to MT procedure for their better outcome and risk-benefit ratio., Competing Interests: Conflict of Interest None declared., (Asian Congress of Neurological Surgeons. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)
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- 2024
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38. Is it a thrombus or a tumor? An imaging dilemma for clinicians.
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Choi J, Speirs T, Bhatia R, Sivalokanathan S, and Craft C
- Abstract
Atrial fibrillation, the most common cardiac arrhythmia in the Western world, confers a 5-fold increase in stroke, mainly due to thrombus formation in the left atrial appendage. Early rhythm control is often beneficial in reducing adverse cardiovascular events in higher-risk populations. Here, we present a patient who was found to have a 1 cm stalk-like lesion in the left atrial appendage on transesophageal echocardiogram prior to electrical cardioversion. Using multiple cardiac imaging modalities, including cardiac magnetic resonance imaging and computed tomography, the mass was eventually determined to be a chronic resolving thrombus., Competing Interests: The Authors declare that there is no conflict of interest.
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- 2024
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39. The Hidden Dangers of Meftal: A Drug Safety Alert for a Frequently Used NSAID.
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Paul P, Kamal R, and Bhatia R
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- 2024
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40. Musculocontractural type of Ehlers-Danlos syndrome with novel CHST14 pathogenic variant in two siblings.
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Ks A, Sarkar N, Bhatia R, Singh V, Sharma S, and Verma PK
- Abstract
Musculocontractural Ehlers-Danlos syndrome (MC-EDS) is a rare entity worldwide with underlying pathogenic variant in the carbohydrate sulfotransferase 14 (CHST14) gene. Previous reports of the same entity from India were of two unrelated cases. Ours is the first report of two siblings in an Indian family with craniofacial dysmorphism and distal arthrogryposis with a clinical diagnosis of EDS, where an underlying pathogenic variant in CHST14 was detected by exome sequencing., (© 2024 Wiley Periodicals LLC.)
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- 2024
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41. Liver Disease as a Potential Risk Factor for Colorectal Cancer: A Community Hospital Experience.
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Aillaud-De-Uriarte D, Hernandez-Flores LA, Zachariah PN, Bhatia R, Manzano-Cortés H, and Marines-Copado D
- Abstract
Background: Liver disease (LD) is a common pathology worldwide. Many patients remain asymptomatic and undiagnosed. Colorectal cancer (CRC) is a prevalent neoplasm and a leading cause of cancer-related deaths globally. Multiple studies suggest that inflammation in the liver could drive the initiation of colorectal cancer., Methods: This five-year (2018-2022) case-control study included 274 patients diagnosed with CRC and adenomas at a community hospital in Houston, Texas. Each patient's medical record was reviewed for pre-existing LD, including steatosis, cirrhosis, primary biliary cirrhosis, and Hepatitis B and C infections. This study aims to investigate the association between LD and CRC risk and assess differences by gender, race, and ethnicity. The study cohort comprised 124 (45.3%) women and 150 (54.7%) men. Data were compared and analyzed using a Chi-squared test for independence and binomial logistic regression. A p-value of < 0.05 was considered statistically significant. Results: Patients with LD had a two-fold increase in the odds of developing CRC compared to those without LD, in both univariate and multivariate analyses (OR 2.13 {95% CI 1.30-3.49}, p = 0.003 / OR 2.30 {95% CI 1.37-3.87}, p = 0.002, respectively). The chi-square test revealed that the association between CRC and LD was stronger in women than in men (p = 0.018 and p = 0.056, respectively)., Conclusion: Our study establishes a positive correlation between LD and CRC development, suggesting LD is a potential risk factor for CRC, particularly in women. Future research directions include exploring the underlying mechanisms of this association, evaluating the utility of early CRC screening in individuals with LD, and assessing the impact of interventions targeting LD on CRC incidence and mortality., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Research Institute Committee, Houston Methodist Willowbrook Hospital issued approval PRO00037701. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Aillaud-De-Uriarte et al.)
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- 2024
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42. Editorial: Altered metabolic traits in gastrointestinal tract cancers.
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Parte S, Pothuraju R, Kumavath R, Bhatia R, Nimmakayala RK, and Gautam S
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- Humans, Animals, Gastrointestinal Neoplasms metabolism, Gastrointestinal Neoplasms pathology
- Abstract
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.
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- 2024
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43. Spinal Cord Biopsy Revealing Primary Central Nervous System Vasculitis (PCNSV) in a Patient with Suspected Non-compressive Dorsal Myelopathy.
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Agarwal A, Vishnu VY, Garg D, Garg A, Sharma MC, Rajan R, Gupta A, Singh MB, Bhatia R, Srivastava AK, and Srivastava MVP
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- 2024
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44. Low-dose decitabine plus venetoclax as post-transplant maintenance for high-risk myeloid malignancies.
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Parks K, Diebold K, Salzman D, Di Stasi A, Al-Kadhimi Z, Espinoza-Gutarra M, Bhatia R, and Jamy O
- Abstract
Relapse remains a major cause of treatment failure following allogeneic stem cell transplantation (allo-SCT) for patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). We retrospectively investigated low-dose decitabine and venetoclax (DEC/VEN) as post-transplant maintenance in 26 older patients with AML and MDS. The cumulative incidence of day 100 gIII-IV acute graft versus host disease (GVHD) and 1-year moderate-severe chronic GVHD was 5% and 26%, respectively. One patient relapsed 14 m after transplant. The 1-year non-relapse mortality and survival were 11% and 84%, respectively. DEC/VEN is a safe and potentially effective strategy to reduce the risk of post-transplant relapse., Competing Interests: The authors declare no conflict of interest., (© 2024 The Authors. eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.)
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- 2024
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45. Masking for COVID-19 and other respiratory viral infections: implications of the available evidence.
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Halperin DT, Doron S, Hodgins S, Bailey RC, Baral S, Bhatia R, Noble J, Gandhi M, and Hearst N
- Abstract
The use of face masks has been widely promoted and at times mandated to prevent coronavirus disease 2019 (COVID-19). The 2023 publication of an updated Cochrane review on mask effectiveness for respiratory viruses as well as the unfolding epidemiology of COVID-19 underscore the need for an unbiased assessment of the current scientific evidence. It appears that the widespread promotion, adoption, and mandating of masking for COVID-19 were based not primarily on the strength of evidence for effectiveness but more on the imperative of decision-makers to act in the face of a novel public health emergency, with seemingly few good alternatives. Randomized clinical trials of masking for prevention of COVID-19 and other respiratory viruses have so far shown no evidence of benefit (with the possible exception of continuous use of N95 respirators by hospital workers). Observational studies provide lower-quality evidence and do not convincingly demonstrate benefit from masking or mask mandates. Unless robust new evidence emerges showing the effectiveness of masks in reducing infection or transmission risks in either trials or real-world conditions, mandates are not warranted for future epidemics of respiratory viral infections., Competing Interests: SD was an unpaid advisor to the Governor and the Commissioner of Education of Massachusetts on COVID-19 policy; RCB is an unpaid member of the Nyanza Reproductive Health Society., (© The Author(s) 2024.)
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- 2024
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46. Corrigendum to "Suicide during pandemic requires deeper engagement" [Asian J. Psychiatry 73 (2022) 103161].
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Sahu B, Tamysetty S, Babu GR, Shapeti S, Queeny S, Dubasi HB, Deepa R, Saldanha ND, Bhatia R, and Khetrapal S
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- 2024
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47. Getting to the Core of Stroke.
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Anand A and Bhatia R
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- 2024
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48. Treatment-Free Remission in Chronic Myeloid Leukemia.
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Bourne G, Bhatia R, and Jamy O
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With the discovery of tyrosine kinase inhibitors (TKIs), overall survival in patients with chronic myeloid leukemia (CML) now approaches that of the general population. While these TKIs have proven to be lifesaving, remaining on them lifelong creates both physical and financial burdens for patients. Recently, multiple trials have begun looking into the efficacy of trialing patients off these TKIs to see if they can sustain treatment-free remission (TFR). TFR eligibility is currently limited to a small population of patients with both robust and sustained responses to TKIs. Currently, for those who attempt a trial of TFR, the average success rates are promising, with anywhere from 38 to 54% of patients experiencing sustained TFR. For those who fail to maintain sustained TFR, safety results to date are reassuring, with almost all patients successfully responding to the re-initiation of TKIs, with death and disease progression being very rare complications. Moving forward, research is being conducted to more accurately risk stratify patients at diagnosis and pair them with optimized upfront treatment regimens aimed at increasing candidacy for the trial of TFR.
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- 2024
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49. Dermoscopic features of lichen nitidus.
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Kansal NK, Vasisht S, and Bhatia R
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- Humans, Diagnosis, Differential, Lichen Nitidus diagnostic imaging
- Abstract
Competing Interests: Competing interests: None declared.
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- 2024
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50. CBX7 reprograms metabolic flux to protect against meningioma progression by modulating the USP44/c-MYC/LDHA axis.
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Cheng H, Hua L, Tang H, Bao Z, Xu X, Zhu H, Wang S, Jiapaer Z, Bhatia R, Dunn IF, Deng J, Wang D, Sun S, Luan S, Ji J, Xie Q, Yang X, Lei J, Li G, Wang X, and Gong Y
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- Humans, Animals, Mice, Cell Line, Tumor, Glycolysis genetics, Disease Progression, Female, Meningeal Neoplasms pathology, Meningeal Neoplasms metabolism, Meningeal Neoplasms genetics, Male, Mice, Nude, Middle Aged, L-Lactate Dehydrogenase, Proto-Oncogene Proteins c-myc metabolism, Proto-Oncogene Proteins c-myc genetics, Cell Proliferation, Polycomb Repressive Complex 1 metabolism, Polycomb Repressive Complex 1 genetics, Meningioma pathology, Meningioma metabolism, Meningioma genetics, Ubiquitin Thiolesterase metabolism, Ubiquitin Thiolesterase genetics, Gene Expression Regulation, Neoplastic
- Abstract
Meningioma is one of the most common primary neoplasms in the central nervous system, but no specific molecularly targeted therapy has been approved for the clinical treatment of aggressive meningiomas. There is hence an urgent demand to decrypt the biological and molecular landscape of malignant meningioma. Here, through the in-silica prescreening and 10-year follow-up studies of 445 meningioma patients, we uncovered that CBX7 expression progressively decreases with malignancy grade and neoplasia stage in meningioma, and a high CBX7 expression level predicts a favorable prognosis in meningioma patients. CBX7 restoration significantly induces cell cycle arrest and inhibits meningioma cell proliferation. iTRAQ-based proteomics analysis indicated that CBX7 restoration triggers the metabolic shift from glycolysis to oxidative phosphorylation. The mechanistic study demonstrated that CBX7 promotes the proteasome-dependent degradation of c-MYC protein by transcriptionally inhibiting the expression of a c-MYC deubiquitinase, USP44, consequently attenuates c-MYC-mediated transactivation of LDHA transcripts, and further inhibits glycolysis and subsequent cell proliferation. More importantly, the functional role of CBX7 was further confirmed in subcutaneous and orthotopic meningioma xenograft mouse models and meningioma patients. Altogether, our results shed light on the critical role of CBX7 in meningioma malignancy progression and identify the CBX7/USP44/c-MYC/LDHA axis as a promising therapeutic target against meningioma progression., (© The Author(s) (2023). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, CEMCS, CAS.)
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- 2024
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