9 research outputs found
Remdesivir as a choice of treatment of COVID-19: An Indian perspective
No full textMedical Science: A Peer-reviewed International Medical Journal
ISSN: 2321-5291 | Publisher: CMRA | Author guidelines | Archives | Editors | Submission
Bone metastasis in head and neck squamous cell carcinoma – 5-year experience of an Indian Cancer Institute
Full text linkINTRODUCTION: Bone metastasis (BM), a common and awful complication of advanced malignancy, is comparatively infrequent in head and neck squamous cell carcinoma (HNSCC). Having a discouraging survival of around 6-months only, BM decreases the quality of life in such patients. We reported 13 cases of BM in HNSCC patients in respect to clinical patterns, treatment modalities and outcome. MATERIAL AND METHODS: This is a retrospective study conducted in a tertiary cancer institute of India. Records of all HNSCC patients reviewed and patients having BM were identified. RESULTS: Total 13 cases of BM were found over a 5-year period; 5 patients having synchronous BM and the rest had developed metastasis later. Monostotic and polyostotic diseases were found in 8 and 5 patients, respectively, bone exclusive disease was seen in 6 patients only. Overall median survival was 6.7 months. CONCLUSIONS: Palliation seems to be the only option once BM is diagnosed in HNSCC. All of our patients received local palliative radiation, and systemic chemotherapy to increase survival. As there is no standardized treatment for such occurrence, more case series and prospective studies are welcomed
Geometry & hemodynamics of arterial stenosis: A clinical and computational study
No full textEmpirical correlation of the Modified Wheel Tracker (MWT) and the dynamic creep test for evaluating the permanent deformation of HMA
Full text linkThe Wheel Tracking Test (WTT) has been extensively used for laboratory characterization of permanent deformation of Hot Mix Asphalt (HMA). However, the fully-confined setup of the device is unable to capture the tertiary zone where shear deformation takes place. This makes the permanent deformation resistance characteristics of HMA difficult to analyze. Hence, a modified wheel tracker (MWT), with unconfined lateral sides along the wheel tracking direction was utilized in this study, which can capture the tertiary flow [referred to as the Flow Number (FN)]. The dynamic creep test, which yields FN, is a common laboratory test which has the ability to characterize permanent deformation considering the shear behavior. The study investigated the relationship of the MWT and the dynamic creep test utilizing the permanent deformation and permanent micro-strain data from the respective tests. A novel parameter, FN-Index was explored. The permanent deformation parameters derived from the MWT were well correlated with the dynamic creep test. The MWT showed promising repeatability for the FNs.The presentation of the authors' names and (or) special characters in the title of the pdf file of the accepted manuscript may differ slightly from what is displayed on the item page. The information in the pdf file of the accepted manuscript reflects the original submission by the author
Adipocyte-specific Beclin1 deletion impairs lipolysis and mitochondrial integrity in adipose tissue
No full textObjective: Beclin1 is a core molecule of the macroautophagy machinery. Although dysregulation of macroautophagy is known to be involved in metabolic disorders, the function of Beclin1 in adipocyte metabolism has not been investigated. In the present study, we aimed to study the role of Beclin1 in lipolysis and mitochondrial homeostasis of adipocytes. Methods: Autophagic flux during lipolysis was examined in adipocytes cultured in vitro and in the adipose tissue of mice. Adipocyte-specific Beclin1 knockout (KO) mice were used to investigate the activities of Beclin1 in adipose tissues. Results: cAMP/PKA signaling increased the autophagic flux in adipocytes differentiated from C3H10T1/2 cells. In vivo autophagic flux was higher in the brown adipose tissue (BAT) than that in the white adipose tissue and was further increased by the b3 adrenergic receptor agonist CL316243. In addition, surgical denervation of BAT greatly reduced autophagic flux, indicating that sympathetic nerve activity is a major regulator of tissue autophagy. Adipocyte-specific KO of Beclin1 led to a hypertrophic enlargement of lipid droplets in BAT and impaired CL316243-induced lipolysis/lipid mobilization and energy expenditure. While short-term effects of Beclin1 deletion were characterized by an increase in mitochondrial proteins, long-term Beclin1 deletion led to severe disruption of autophagy, resulting in mitochondrial loss, and dramatically reduced the expression of genes involved in lipid metabolism. Consequently, adipose tissue underwent increased activation of cell death signaling pathways, macrophage recruitment, and inflammation, particularly in BAT. Conclusions: The present study demonstrates the critical roles of Beclin1 in the maintenance of lipid metabolism and mitochondrial homeostasis in adipose tissues. (C) 2020 The Author(s). Published by Elsevier GmbH.Y
Computational pathology applied to clinical colorectal cancer cohorts identifies immune and endothelial cell spatial patterns predictive of outcome.
No full textColorectal cancer (CRC) is a histologically heterogeneous disease with variable clinical outcome. The role the tumour microenvironment (TME) plays in determining tumour progression is complex and not fully understood. To improve our understanding, it is critical that the TME is studied systematically within clinically annotated patient cohorts with long-term follow-up. Here we studied the TME in three clinical cohorts of metastatic CRC with diverse molecular subtype and treatment history. The MISSONI cohort included cases with microsatellite instability that received immunotherapy (n = 59, 24 months median follow-up). The BRAF cohort included BRAF V600E mutant microsatellite stable (MSS) cancers (n = 141, 24 months median follow-up). The VALENTINO cohort included RAS/RAF WT MSS cases who received chemotherapy and anti-EGFR therapy (n = 175, 32 months median follow-up). Using a Deep learning cell classifier, trained upon >38,000 pathologist annotations, to detect eight cell types within H&E-stained sections of CRC, we quantified the spatial tissue organisation and colocalisation of cell types across these cohorts. We found that the ratio of infiltrating endothelial cells to cancer cells, a possible marker of vascular invasion, was an independent predictor of progression-free survival (PFS) in the BRAF+MISSONI cohort (p = 0.033, HR = 1.44, CI = 1.029-2.01). In the VALENTINO cohort, this pattern was also an independent PFS predictor in TP53 mutant patients (p = 0.009, HR = 0.59, CI = 0.40-0.88). Tumour-infiltrating lymphocytes were an independent predictor of PFS in BRAF+MISSONI (p = 0.016, HR = 0.36, CI = 0.153-0.83). Elevated tumour-infiltrating macrophages were predictive of improved PFS in the MISSONI cohort (p = 0.031). We validated our cell classification using highly multiplexed immunofluorescence for 17 markers applied to the same sections that were analysed by the classifier (n = 26 cases). These findings uncovered important microenvironmental factors that underpin treatment response across and within CRC molecular subtypes, while providing an atlas of the distribution of 180 million cells in 375 clinically annotated CRC patients. © 2025 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland
Bone metastasis in head and neck squamous cell carcinoma – 5-year experience of an Indian Cancer Institute
Full text linkIntroduction. Bone metastasis (BM), a common and awful complication of advanced malignancy, is comparatively infrequent in head and neck squamous cell carcinoma (HNSCC). Having a discouraging survival of around 6-months only, BM decreases the quality of life in such patients. We reported 13 cases of BM in HNSCC patients in respect to clinical patterns, treatment modalities and outcome.
Material and methods. This is a retrospective study conducted in a tertiary cancer institute of India. Records of all HNSCC patients reviewed and patients having BM were identified.
Results. Total 13 cases of BM were found over a 5-year period; 5 patients having synchronous BM and the rest had developed metastasis later. Monostotic and polyostotic diseases were found in 8 and 5 patients, respectively, bone exclusive disease was seen in 6 patients only. Overall median survival was 6.7 months.
Conclusions. Palliation seems to be the only option once BM is diagnosed in HNSCC. All of our patients received local palliative radiation, and systemic chemotherapy to increase survival. As there is no standardized treatment for such occurrence, more case series and prospective studies are welcomed
Surgical outcomes of gallbladder cancer: the OMEGA retrospective, multicentre, international cohort study
No full textBackground Gallbladder cancer (GBC) is rare but aggressive. The extent of surgical intervention for different GBC stages is non-uniform, ranging from cholecystectomy alone to extended resections including major hepatectomy, resection of adjacent organs and routine extrahepatic bile duct resection (EBDR). Robust evidence here is lacking, however, and survival benefit poorly defined. This study assesses factors associated with recurrence-free survival (RFS), overall survival (OS) and morbidity and mortality following GBC surgery in high income countries (HIC) and low and middle income countries (LMIC).Methods The multicentre, retrospective Operative Management of Gallbladder Cancer (OMEGA) cohort study included all patients who underwent GBC resection across 133 centres between 1st January 2010 and 31st December 2020. Regression analyses assessed factors associated with OS, RFS and morbidity.Findings On multivariable analysis of all 3676 patients, wedge resection and segment IVb/V resection failed to improve RFS (HR 1.04 [0.84-1.29], p = 0.711 and HR 1.18 [0.95-1.46], p = 0.13 respectively) or OS (HR 0.96 [0.79-1.17], p = 0.67 and HR 1.48 [1.16-1.88], p = 0.49 respectively), while major hepatectomy was associated with worse RFS (HR 1.33 [1.02-1.74], p = 0.037) and OS (HR 1.26 [1.03-1.53], p = 0.022). Furthermore, EBDR (OR 2.86 [2.3-3.52], p < 0.0010), resection of additional organs (OR 2.22 [1.62-3.02], p < 0.0010) and major hepatectomy (OR 3.81 [2.55-5.73], p < 0.0010) were all associated with increased morbidity and mortality. Compared to LMIC, patients in HIC were associated with poorer RFS (HR 1.18 [1.02-1.37], p = 0.031) but not OS (HR 1.05 [0.91-1.22], p = 0.48). Adjuvant and neoadjuvant treatments were infrequently used.Interpretation In this large, multicentre analysis of GBC surgical outcomes, liver resection was not conclusively associated with improved survival, and extended resections were associated with greater morbidity and mortality without oncological benefit. Aggressive upfront resections do not benefit higher stage GBC, and international col-laborations are needed to develop evidence-based neoadjuvant and adjuvant treatment strategies to minimise surgical morbidity and prioritise prognostic benefit.Funding Cambridge Hepatopancreatobiliary Department Research Fund.Copyright & COPY; 2023 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
Efficacy and adverse events profile of videolaryngoscopy in critically ill patients: subanalysis of the INTUBE study
No full textBackground: Tracheal intubation is a high-risk procedure in the critically ill, with increased intubation failure rates and a high risk of other adverse events. Videolaryngoscopy might improve intubation outcomes in this population, but evidence remains conflicting, and its impact on adverse event rates is debated. Methods: This is a subanalysis of a large international prospective cohort of critically ill patients (INTUBE Study) performed from 1 October 2018 to 31 July 2019 and involving 197 sites from 29 countries across five continents. Our primary aim was to determine the first-pass intubation success rates of videolaryngoscopy. Secondary aims were characterising (a) videolaryngoscopy use in the critically ill patient population and (b) the incidence of severe adverse effects compared with direct laryngoscopy. Results: Of 2916 patients, videolaryngoscopy was used in 500 patients (17.2%) and direct laryngoscopy in 2416 (82.8%). First-pass intubation success was higher with videolaryngoscopy compared with direct laryngoscopy (84% vs 79%, P=0.02). Patients undergoing videolaryngoscopy had a higher frequency of difficult airway predictors (60% vs 40%, P<0.001). In adjusted analyses, videolaryngoscopy increased the probability of first-pass intubation success, with an OR of 1.40 (95% confidence interval [CI] 1.05–1.87). Videolaryngoscopy was not significantly associated with risk of major adverse events (odds ratio 1.24, 95% CI 0.95–1.62) or cardiovascular events (odds ratio 0.78, 95% CI 0.60–1.02). Conclusions: In critically ill patients, videolaryngoscopy was associated with higher first-pass intubation success rates, despite being used in a population at higher risk of difficult airway management. Videolaryngoscopy was not associated with overall risk of major adverse events. Clinical trial registration: NCT03616054
