The Tata Memorial Hospital is situated in Parel, Mumbai, in India. Also popularly known as TMH. It is a specialist cancer treatment and research centre, closely associated with the Advanced Centre for Treatment, Research and Education in Cancer (ACTREC). The Centre is the national comprehensive cancer centre for the prevention, treatment, education and research in cancer and is recognized as one of the leading cancer centres in this part of the world. It is an autonomous body funded and controlled by Department of Atomic Energy, Government of India which also oversees the administration of institute since 1962.The Tata Memorial Hospital was initially commissioned by the Sir Dorabji Tata Trust on 28 February 1941 as a center with enduring value and a mission for concern for the Indian people. Current Director of the hospital is Dr. Rajendra A Badwe, who took over from for director Dr. K. A. Dinshaw. K.
Obesity is a global health challenge. An increasing number of patients with obesity are admitted to an intensive care unit. Airway management in these patients represents a unique challenge due to significant anatomical and physiological alterations. Increased adipose tissue in the face, cheeks, pharynx, hypopharynx, and neck narrows the upper airway, renders soft tissues more collapsible, and complicates airway management. In addition, the functional residual capacity is reduced, resulting in markedly shortened safe apnea time, contributing to severe hypoxemia during intubation. Non-invasive ventilation is effective in mitigating this risk and should be applied from pre-induction to laryngoscopy. Peri-intubation physiological optimization should include assessment of preload and cardiac contractility, with careful consideration of right ventricular strain. The transition from negative to positive intrathoracic pressure should be closely monitored, with cautious titration of positive end-expiratory pressure. Recognition of these anatomical and physiological challenges may prompt clinicians to consider awake intubation in selected patients. When rapid sequence induction is performed, both ketamine and etomidate are appropriate options; the choice between them should be guided by the clinical context, patient characteristics, local practice patterns and availability. Videolaryngoscopy increases the incidence of successful intubation on the first attempt and should be adopted routinely in the population with obesity. Several questions remain unanswered, including the safety and efficacy of pre-emptive vasopressor use to prevent post-intubation cardiovascular collapse and the optimal dosing of hypnotic agents to achieve ideal intubation conditions, while minimizing adverse events.
The clinicopathological spectrum of FET-CREB sarcomas is evolving with several distinct tumors entities described across various body sites, apart from the soft tissues. Lately, there are tumors primarily identified in the abdominal and extra-abdominal sites, including the soft tissues with an epithelioid morphology and displaying FET-CREB fusions, which are different from the established tumors showing the similar underlying gene fusions. An 18-year-old female patient presented with pain in her upper back. She underwent An An 18-year-old female patient presented with pain in her upper back. She underwent magnetic resonance imaging (MRI), which revealed a large lobulated, intraspinal, extra-axial mass, measuring 4.1 cm in the largest dimension. Histopathological examination of the biopsy revealed a tumor composed of moderate to focally, markedly pleomorphic, round to polygonal to spindle-shaped cells, including vacuolated forms in a myxoid-rich stroma with intervening branching blood vessels. By immunohistochemistry, the tumor cells were patchily positive for epithelial membrane antigen (EMA), and focally for pan keratin (AE1/AE3), S100 and desmin. A 43-year-old lady presented with a gradual, left-sided hearing loss of one year duration. On clinical examination, there was a soft palatal bulge. Computed tomogram (CT) scan showed a 4.9 cm-sized mass in the left parapharyngeal space. Microscopic examination of the excised mass revealed an infiltrating tumor composed of round to oval cells arranged in solid sheets, cords and cribriform pattern in a densely hyalinized and myxoid stroma. Few mitotic figures were noted. By immunohistochemistry, the tumor cells were focally positive for EMA, ALK and diffusely positive for S100 and SOX10. Fluorescence in-situ hybridization (FISH) revealed EWSR1 rearrangement. Next-generation sequencing (NGS) revealed EWSR1::CREB1 fusion in the former and EWSR1::ATF1 fusion in the latter tumor. The former patient is alive with the disease and the latter patient in on maintenance chemotherapy. The two tumors, occurring at distinct sites, histopathologically exhibiting a relatively atypical immunophenotype, including “myoepithelial-like” differentiation seem to further expand the clincopathological spectrum of tumors with epithelioid morphology and underlying FET-CREB fusions.
BACKGROUND:Cancer is a leading cause of death in both the USA and India. During Prime Minister Narendra Modi's State Visit to Washington, DC in June 2023, the two governments announced several cooperation commitments. One such commitment was the establishment of the US-India Cancer Dialogue, initiating a structured bilateral effort to address shared cancer challenges. The aim of this article is to outline the preparatory steps and proceedings of the inaugural joint meeting of the US-India Cancer dialogue that took place in New Delhi in August 2024. MATERIALS AND METHODS:This manuscript reports the outcomes of a structured bilateral consensus development process designed to identify priority areas for collaboration between the USA and India. Following the announcement, a high-level virtual consultation convened government, scientific, and clinical leaders to identify shared priority areas. A US-based meeting hosted by the American Society of Clinical Oncology (ASCO) refined technical workstreams, including prevention, early detection, therapeutics, clinical trials, and implementation science. Continued coordination among the US National Cancer Institute, the White House Office of Science and Technology Policy, and India's Department of Biotechnology formalized the bilateral agenda RESULTS: Over 2 days, the in-person Dialogue identified priority areas for bilateral collaboration, including expansion of human papillomavirus (HPV) vaccination and cervical cancer screening, advancement of artificial intelligence (AI)-enabled early detection technologies, improved access to immunotherapies and chimeric antigen receptor T cell (CAR-T) therapies, strengthened genomics and data-sharing infrastructure, expanded clinical trial capacity, and enhanced survivorship and palliative care. CONCLUSIONS:This collaboration establishes a durable framework to accelerate innovation, expand equitable access, and reduce preventable cancer deaths across both nations.
The post-genomic era, defined by large-scale sequencing initiatives, has generated an unprecedented catalogue of human genetic variation. Yet, the vast majority of genetic variants remain classified as variants of uncertain significance or are located within poorly characterized non-coding regions, thereby hindering the effective translation of genomic data into meaningful biological understanding and clinical application. Bridging this genotype-to-phenotype gap requires precise, high-throughput functional genomics. Early CRISPR-Cas9 knockout and CRISPR interference/activation (CRISPRi/a) screens mapped gene-level functions but could not assess single nucleotide variants (SNVs). Bridging this genotype-to-phenotype gap demands precise, high-throughput functional genomics. Multiplexed assays of variant effect (MAVEs), like saturation genome editing, systematically test all possible mutations using CRISPR-Cas9 and donor libraries. Base editors allow targeted single-base changes without double-strand breaks but are limited in scope, while prime editing can introduce any small substitution, insertion, or deletion without double-strand breaks (DSBs) or donor templates. This review traces the evolution of functional screens from gene-level knockouts to saturation genomic editing (SGE), and highlights how prime editing is driving a new paradigm for the systematic functional characterization of thousands of variants across disease-relevant genes. We also detail the architecture, mechanism, and progressive optimization of PE systems and their delivery methods. Collectively, prime editing stands as a transformative platform poised to accelerate precision functional genomics and advance the diagnosis and treatment of genetic diseases.
