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Degenerative retinal diseases associated with photoreceptor loss are a leading cause of visual impairment worldwide, with limited treatment options. Phenotypic profiling coupled with medicinal chemistry were used to develop a small molecule with proliferative effects on retinal stem/progenitor cells, as assessed in vitro in a neurosphere assay and in vivo by measuring Msx1-positive ciliary body cell proliferation. The compound was identified as having kinase inhibitory activity and was subjected to cellular pathway analysis in non-retinal human primary cell systems. When tested in a disease-relevant murine model of adult retinal degeneration (MNU-induced retinal degeneration), we observed that four repeat intravitreal injections of the compound improved the thickness of the outer nuclear layer along with the regeneration of the visual function, as measured with ERG, visual acuity, and contrast sensitivity tests. This serves as a proof of concept for the use of a small molecule to promote endogenous regeneration in the eye.
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Degeneração Retiniana , Humanos , Camundongos , Animais , Degeneração Retiniana/metabolismo , Metilnitrosoureia , Retina/metabolismo , Células Fotorreceptoras , Regeneração , Modelos Animais de Doenças , MamíferosRESUMO
Pediatric histiocytic neoplasms are hematopoietic disorders frequently driven by the BRAF-V600E mutation. Here, we identified two BRAF gene fusions (novel MTAP-BRAF and MS4A6A-BRAF) in two aggressive histiocytic neoplasms. In contrast to previously described BRAF fusions, MTAP-BRAF and MS4A6A-BRAF do not respond to the paradox breaker RAF inhibitor (RAFi) PLX8394 due to stable fusion dimerization mediated by the N-terminal fusion partners. This highlights a significant and clinically relevant shift from the current dogma that BRAF-fusions respond similarly to BRAF-inhibitors. As an alternative, we show suppression of fusion-driven oncogenic growth with the pan-RAFi LY3009120 and MEK inhibition.
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Histiocitose , Neoplasias , Linhagem Celular Tumoral , Criança , Humanos , Mutação , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas B-raf/genéticaRESUMO
BACKGROUND: Gene fusion events are significant sources of somatic variation across adult and pediatric cancers and are some of the most clinically-effective therapeutic targets, yet low consensus of RNA-Seq fusion prediction algorithms makes therapeutic prioritization difficult. In addition, events such as polymerase read-throughs, mis-mapping due to gene homology, and fusions occurring in healthy normal tissue require informed filtering, making it difficult for researchers and clinicians to rapidly discern gene fusions that might be true underlying oncogenic drivers of a tumor and in some cases, appropriate targets for therapy. RESULTS: We developed annoFuse, an R package, and shinyFuse, a companion web application, to annotate, prioritize, and explore biologically-relevant expressed gene fusions, downstream of fusion calling. We validated annoFuse using a random cohort of TCGA RNA-Seq samples (N = 160) and achieved a 96% sensitivity for retention of high-confidence fusions (N = 603). annoFuse uses FusionAnnotator annotations to filter non-oncogenic and/or artifactual fusions. Then, fusions are prioritized if previously reported in TCGA and/or fusions containing gene partners that are known oncogenes, tumor suppressor genes, COSMIC genes, and/or transcription factors. We applied annoFuse to fusion calls from pediatric brain tumor RNA-Seq samples (N = 1028) provided as part of the Open Pediatric Brain Tumor Atlas (OpenPBTA) Project to determine recurrent fusions and recurrently-fused genes within different brain tumor histologies. annoFuse annotates protein domains using the PFAM database, assesses reciprocality, and annotates gene partners for kinase domain retention. As a standard function, reportFuse enables generation of a reproducible R Markdown report to summarize filtered fusions, visualize breakpoints and protein domains by transcript, and plot recurrent fusions within cohorts. Finally, we created shinyFuse for algorithm-agnostic interactive exploration and plotting of gene fusions. CONCLUSIONS: annoFuse provides standardized filtering and annotation for gene fusion calls from STAR-Fusion and Arriba by merging, filtering, and prioritizing putative oncogenic fusions across large cancer datasets, as demonstrated here with data from the OpenPBTA project. We are expanding the package to be widely-applicable to other fusion algorithms and expect annoFuse to provide researchers a method for rapidly evaluating, prioritizing, and translating fusion findings in patient tumors.
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Fusão Gênica , Neoplasias/genética , RNA/metabolismo , Software , Algoritmos , Humanos , Neoplasias/patologia , Proteínas de Fusão Oncogênica/genética , Proteínas de Fusão Oncogênica/metabolismo , RNA/genéticaRESUMO
This clinical trial evaluated whether whole exome sequencing (WES) and RNA sequencing (RNAseq) of paired normal and tumor tissues could be incorporated into a personalized treatment plan for newly diagnosed patients (<25 years of age) with diffuse intrinsic pontine glioma (DIPG). Additionally, whole genome sequencing (WGS) was compared to WES to determine if WGS would further inform treatment decisions, and whether circulating tumor DNA (ctDNA) could detect the H3K27M mutation to allow assessment of therapy response. Patients were selected across three Pacific Pediatric Neuro-Oncology Consortium member institutions between September 2014 and January 2016. WES and RNAseq were performed at diagnosis and recurrence when possible in a CLIA-certified laboratory. Patient-derived cell line development was attempted for each subject. Collection of blood for ctDNA was done prior to treatment and with each MRI. A specialized tumor board generated a treatment recommendation including up to four FDA-approved agents based upon the genomic alterations detected. A treatment plan was successfully issued within 21 business days from tissue collection for all 15 subjects, with 14 of the 15 subjects fulfilling the feasibility criteria. WGS results did not significantly deviate from WES-based therapy recommendations; however, WGS data provided further insight into tumor evolution and fidelity of patient-derived cell models. Detection of the H3F3A or HIST1H3B K27M (H3K27M) mutation using ctDNA was successful in 92% of H3K27M mutant cases. A personalized treatment recommendation for DIPG can be rendered within a multicenter setting using comprehensive next-generation sequencing technology in a clinically relevant timeframe.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Tronco Encefálico/tratamento farmacológico , Glioma Pontino Intrínseco Difuso/tratamento farmacológico , Sequenciamento do Exoma/métodos , Análise de Sequência de RNA/métodos , Sequenciamento Completo do Genoma/métodos , Adolescente , Adulto , Neoplasias do Tronco Encefálico/genética , Criança , Pré-Escolar , DNA Tumoral Circulante , Glioma Pontino Intrínseco Difuso/genética , Estudos de Viabilidade , Feminino , Histonas/genética , Humanos , Masculino , Terapia de Alvo Molecular/métodos , Projetos Piloto , Medicina de Precisão , Adulto JovemRESUMO
Sclerosing epithelioid fibrosarcoma (SEF) is an uncommon neoplasm that rarely presents in bone. It is characterized by epithelioid cells arranged in nests and single-file cords within a sclerotic stromal background which may mimic neoplastic bone. SEF harbors an EWSR1 translocation, which may complicate its distinction from Ewing sarcoma in cases with histomorphologic overlap. We present a diagnostically challenging case of SEF in the mandible of a 16-year-old girl. Our experience highlights the lack of specificity of traditional morphology and EWSR1 break-apart fluorescent in situ hybridization. Open-ended RNA-based fusion gene testing coupled with MUC4 immunohistochemistry aided the eventual diagnosis in this case. Herein, we report the third case of SEF with EWSR1-CREB3L3 translocation and show that this fusion leads to aberrant upregulation of the phosphoinositide 3-kinase/mammalian target of rapamycin signaling pathway in heterologous cell models.
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Biomarcadores Tumorais/genética , Fibrossarcoma/genética , Neoplasias Mandibulares/genética , Proteínas de Fusão Oncogênica/genética , Fosfatidilinositol 3-Quinase/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Translocação Genética , Adolescente , Feminino , Fibrossarcoma/diagnóstico , Fibrossarcoma/metabolismo , Fibrossarcoma/patologia , Humanos , Neoplasias Mandibulares/diagnóstico , Neoplasias Mandibulares/metabolismo , Neoplasias Mandibulares/patologia , Transdução de Sinais , Regulação para CimaRESUMO
The Polycomb group of proteins (PcGs) are transcriptional repressor complexes that regulate important biological processes and play critical roles in cancer. Mutating or deleting EZH2 can have both oncogenic and tumor suppressive functions by increasing or decreasing H3K27me3. In contrast, mutations of SUZ12 and EED are reported to have tumor suppressive functions. EZH2 is overexpressed in many cancers, including prostate cancer, which can lead to silencing of tumor suppressors, genes regulating epithelial to mesenchymal transition (EMT), and interferon signaling. In some cases, EZH2 overexpression also leads to its use of non-histone substrates. Lastly, PRC2 associated factors can influence the progression of cancer through progressive mutations or by specific binding to certain target genes. Here, we discuss which mutations and deletions of the PRC2 complex have been detected in different cancers, with a specific focus on the overexpression of EZH2 in prostate cancer.
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Proteína Potenciadora do Homólogo 2 de Zeste/genética , Epigênese Genética , Complexo Repressor Polycomb 2/genética , Neoplasias da Próstata/genética , Linhagem Celular Tumoral , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Transição Epitelial-Mesenquimal/genética , Histonas/genética , Histonas/metabolismo , Humanos , Masculino , Mutação , Proteínas de Neoplasias , Complexo Repressor Polycomb 2/metabolismo , Próstata/metabolismo , Próstata/patologia , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Transdução de Sinais , Fatores de Transcrição , Transcrição GênicaRESUMO
Breast cancer is the second leading cause of cancer death in women, exceeded only by lung cancer, and the 5-year survival rate is largely dependent on disease stage. The American Joint Committee on Cancer (AJCC) staging system for breast cancer (7th edition) provides a tumor-node-metastasis (TNM) classification scheme for breast cancer that is important for determining prognosis and treatment. Ascertaining the correct stage of breast cancer can be challenging, and the importance of the radiologist's role has increased over the years. The radiologist should understand how breast cancer stage is assigned and should be familiar with the AJCC's TNM classification scheme. The authors review the AJCC's TNM staging system for breast cancer with emphasis on clinical and preoperative staging, the different imaging modalities used in staging, and the key information that should be conveyed to clinicians. Radiologic information that may alter stage, prognosis, or treatment includes tumor size; number of tumor lesions; total span of disease; regional nodal status (axillary levels I-III, internal mammary, supraclavicular); locoregional invasion (involvement of the pectoralis muscle, skin, nipple, or chest wall); and distant metastases to bone, lung, brain, and liver, among other anatomic structures.
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Neoplasias da Mama/diagnóstico , Diagnóstico por Imagem , Feminino , Humanos , Estadiamento de Neoplasias , Papel do Médico , RadiologiaAssuntos
Neoplasias Encefálicas/metabolismo , Carcinogênese/patologia , Glioma/metabolismo , Proteínas de Filamentos Intermediários/metabolismo , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/metabolismo , Transdução de Sinais/fisiologia , Neoplasias Encefálicas/patologia , Glioma/patologia , Humanos , Proteínas de Filamentos Intermediários/genética , Masculino , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Proteínas de Fusão Oncogênica/genética , Proteínas de Fusão Oncogênica/metabolismo , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/genética , Serina-Treonina Quinases TOR/metabolismoRESUMO
Astroblastoma is a rare tumor, which is mostly found in pediatric population. Due to scarcity of literature, the data about treatment is lacking. We are reporting case of brainstem astroblastoma in an adult female. A 45-year-old lady presented with complaint of headache, vertigo, vomiting, and nasal regurgitation for 3 months. On examination, she had weak gag, left hemiparesis. Magnetic resonance imaging brain reported medulla oblongata mass, dorsally exophytic. She underwent suboccipital craniotomy and decompression of mass. Histopathology confirmed diagnosis of astroblastoma. She underwent radiotherapy and recovered well. Brainstem astroblastoma is an extremely rare entity. The surgical resection is possible due to well-defined plane. For best outcome, maximum resection and radiation are indicated.
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Background and Aims: Laparoscopic cholecystectomy (LC) is a widely accepted surgical procedure associated with postoperative pain. This study was done to compare peripheral nerve stimulator (PNS)-guided serratus anterior plane block (SAP) and transversus abdominis plane (TAP) block for postoperative analgesia for patients undergoing LC. Methods: Following approval from the ethical committee, 70 patients for LC were randomly assigned to Group S: SAP block and Group T: TAP block. The blocks were performed under PNS guidance, and 20 ml of 0.375% ropivacaine was administered. The severity of pain was measured using a visual analogue scale (VAS). The study's primary objective was the evaluation of the postoperative VAS score. The time of the first dose of rescue analgesia and total tramadol consumption for 24 h postoperatively were secondary objectives. All the statistical calculation was done using statistical analyses for Social Sciences for Windows version 23.0 (IBM Corp, NY, USA). Results: Lower VAS score was seen in patients of TAP block at rest as well as movement at 6 h (P = 0.001), 12 h (P = 0.001) and 18 h (P = 0.001) postoperatively compared with SAP. The TAP group showed a significantly increased time of first rescue analgesic compared to the SAP group (7.97 ± 0.51 vs. 5.89 ± 1.45, P = 0.001). Tramadol usage was significantly higher in the SAP group than in the TAP group (128.9 ± 36.22 vs. 72.43 ± 44.80, P = 0.001). Conclusion: TAP block guided by the PNS improves postoperative pain with less tramadol consumption and during the postoperative period without significant complications.
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With the advent of modern antiretroviral therapy (ART), human immunodeficiency virus (HIV) infection has been modified into a chronic manageable condition, prolonging the lifespan of people living with HIV (PLHIV). This has resulted in an increased non-AIDS-related morbidity in the HIV-infected population. Our aim is to study the role of contemporary ART in tackling the risk of atherosclerosis and cardiovascular disease (CVD) in PLHIV. We searched through the databases of PubMed, PubMed Central, and Cochrane Library for pertinent articles using the medical subject headings (MeSH) "HIV infection", "Atherosclerosis", and "Antiretroviral agents". The articles published in the past five years were retrieved, screened for relevance, and assessed for quality before being included in the review. This review was performed following the PRISMA 2020 guidelines. The results indicate that the incidence of dyslipidemia with integrase strand transfer inhibitors (INSTIs) is greater than with non-nucleoside reverse transcriptase inhibitors (NNRTIs) and lesser than with protease inhibitors (PIs). INSTIs are indispensably associated with weight gain and obesity. High triglyceride (TG) and oxidized low-density lipoproteins to low-density lipoproteins (oxLDL/LDL) ratio levels and low high-density lipoprotein (HDL) levels are seen in patients taking PIs. A higher incidence of hypertension and metabolic syndrome (MetS) was noticed with INSTIs compared to NNRTIs. PI intake for >5 years increases the risk of subclinical atherosclerosis. Increased risk of myocardial infarction with INSTIs was observed in a study, while another study reported decreased risk. HIV infection independently increases the risk for atherosclerosis and CVD. Although contemporary ART decreases this enhanced risk, it inherently increases the risk for abnormal lipid profile, MetS, weight gain, and obesity. Further research into the risk of atherosclerosis and CVD with newer ART drugs is essential for decoding the underlying mechanisms and preventing adverse cardiac outcomes in PLHIV.
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Atrial fibrillation (AF) is a common arrhythmia associated with significant morbidity and mortality. The optimal approach to managing AF, specifically rate control versus rhythm control, remains a topic of debate in clinical practice. This systematic review aims to compare the rate control and rhythm control strategies based on their clinical outcomes, quality of life, and adverse events associated with them. A comprehensive search was conducted using PubMed, Google Scholar, Science Direct, Research Gate, MEDLINE (Medical Literature Analysis and Retrieval System Online), Scopus, and Embase (Excerpta Medica dataBASE) databases. A total of 1657 research papers were identified through the search strategy, and after applying the eligibility criteria, 28 studies were selected for the analysis. The studies encompassed a range of methodologies, including randomized controlled trials, observational studies, and meta-analyses. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed for study selection, data extraction, and analysis. The outcomes of interest included all: cause mortality, stroke, bleeding events, cardiovascular hospitalizations, quality of life, and adverse effects of treatment. Data were synthesized and presented in tables, charts, and forest plots for meta-analysis where appropriate. The results indicate that both rate control and rhythm control strategies have their own merits and limitations, with the outcomes varying based on patient characteristics and comorbidities. While rhythm control strategies may lead to better symptom control and improved quality of life, rate control strategies may be associated with lower risks of adverse events and complications. This systematic review provides a comprehensive overview of the current evidence regarding rate and rhythm control strategies in AF management, offering insights for clinical decision-making and highlighting the need for individualized treatment approaches.
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Pediatric brain and spinal cancers are collectively the leading disease-related cause of death in children; thus, we urgently need curative therapeutic strategies for these tumors. To accelerate such discoveries, the Children's Brain Tumor Network (CBTN) and Pacific Pediatric Neuro-Oncology Consortium (PNOC) created a systematic process for tumor biobanking, model generation, and sequencing with immediate access to harmonized data. We leverage these data to establish OpenPBTA, an open collaborative project with over 40 scalable analysis modules that genomically characterize 1,074 pediatric brain tumors. Transcriptomic classification reveals universal TP53 dysregulation in mismatch repair-deficient hypermutant high-grade gliomas and TP53 loss as a significant marker for poor overall survival in ependymomas and H3 K28-mutant diffuse midline gliomas. Already being actively applied to other pediatric cancers and PNOC molecular tumor board decision-making, OpenPBTA is an invaluable resource to the pediatric oncology community.
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Primary congenital glaucoma (PCG) is an autosomal-recessive condition characterized by high intraocular pressure (IOP), usually within the first year of life, which potentially could lead to optic nerve damage, globe enlargement, and permanent loss of vision. To date, PCG has been linked to three loci: 2p21 (GLC3A), for which the responsible gene is CYP1B1, and 1p36 (GLC3B) and 14q24 (GLC3C), for which the genes remain to be identified. Here we report that null mutations in LTBP2 cause PCG in four consanguineous families from Pakistan and in patients of Gypsy ethnicity. LTBP2 maps to chromosome 14q24.3 but is around 1.3 Mb proximal to the documented GLC3C locus. Therefore, it remains to be determined whether LTBP2 is the GLC3C gene or whether a second adjacent gene is also implicated in PCG. LTBP2 is the largest member of the latent transforming growth factor (TGF)-beta binding protein family, which are extracellular matrix proteins with multidomain structure. It has homology to fibrillins and may have roles in cell adhesion and as a structural component of microfibrils. We confirmed localization of LTBP2 in the anterior segment of the eye, at the ciliary body, and particularly the ciliary process. These findings reveal that LTBP2 is essential for normal development of the anterior chamber of the eye, where it may have a structural role in maintaining ciliary muscle tone.
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Corpo Ciliar/metabolismo , Glaucoma/genética , Proteínas de Ligação a TGF-beta Latente/genética , Mapeamento Cromossômico , Consanguinidade , Glaucoma/congênito , Humanos , Proteínas de Ligação a TGF-beta Latente/metabolismo , Mutação , LinhagemRESUMO
The diisochromenochromen-4-one 3a-3b, 4a-4c, 5a-6a & 7 have been prepared from the photocyclization reaction of bischromen-4-one 2a-2e. The later compounds are obtained from the O-alkylation of the suitable 3-hydroxy-2-aryl-4H-chromen-4-one 1a-1e with 4,4'-bischloromethyl-diphenyl in dry acetone, anhydrous K2CO3, and PTC (Bu4NâºIâ») under refluxing conditions. The structures of compounds 2a-2e, 3a-3b, 4a-4c, 5a-6a & 7 have been characterized from the rigorous analysis of their IR, ¹H-NMR, ¹³C-NMR, ESI-Mass, and elemental analysis. The antibacterial and antifungal activities of the synthesized products were also evaluated against the Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, Bacillus subtilis, and Aspergillus janus and Penicillium glabrum, respectively. Some of the tested compounds showed significant activity against the above-said microorganisms.
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Anti-Infecciosos/síntese química , Benzopiranos/síntese química , Benzopiranos/farmacologia , Processos Fotoquímicos , Anti-Infecciosos/farmacologia , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , Espectrofotometria InfravermelhoRESUMO
Introduction: The present study was undertaken to describe and quantify the spectrum of radiographic findings on coronavirus disease 2019 (COVID-19) patients. The study also aimed to analyse the changes in chest X-ray (CXR) with disease progression. Methods: COVID-19 patients admitted between the period of 15 March 2020 and 1 July 2020 were retrospectively enrolled. CXR images were assessed and reported as 'Normal' or 'Abnormal'. A severity score was calculated using Warren et al.'s Radiographic Assessment of Lung Edema scoring. Correlations of the severity score thus calculated were sought with age, sex, clinical manifestations and presence of comorbidities. Results: Five hundred patients (342 males, 158 females) were enrolled, median age being 35 years. Fever and cough were the most common symptoms but significant correlation of an abnormal CXR was found with dyspnoea. CXRs were normal in 67% and abnormal in 33% patients. The commonest comorbidities were diabetes mellitus and cardiovascular disease including hypertension, coronary artery disease and congestive heart failure. Predominant pattern was ground glass opacities, reticular alteration and consolidation peaking in the second week from symptom onset. The most frequent distribution was bilateral, peripheral with middle/lower predominance. Increasing age, male sex, presence of dyspnoea and comorbidities correlated with abnormal findings on CXR. Critical illness and mortality correlated strongly with increasing age, male sex and presence of dyspnoea, less so with presence of comorbidities. Conclusion: In the current scenario with clinicians and radiologists working in tandem, CXR seems to be a promising tool in providing relevant information in a simplified way.
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Objectives: This study aimed to find out the association of CT severity score with demographic and clinical characteristics as well as mortality in the patients who were confirmed to have COVID-19 disease in the second wave. Material and Methods: This retrospective study included collection and assessment of the demographic, clinical, laboratory data, and mortality of the patients, suspected with COVID-19 infection who underwent chest HRCT scan during March to April 2021. The findings of the chest HRCT were retrieved manually from the Medical Records section. Determination of the severity was done by the scoring system that involved the visual evaluation of the affected lobes. Results: CT severity score was mild, moderate, and severe in 21.94%, 41.60%, and 30.48% patients, respectively. Mortality rate was 5.70%. Age of the patients with mild, moderate, and severe CT severity score was significantly more than those with normal severity score (50 vs. 50 vs. 50 vs. 31, P=0.0009). When compared to patients with normal score, those with mild, moderate, and severe CT severity score had significantly higher dyspnoea (10.39% vs. 67.81% vs. 97.20% vs. 0%), significantly more cases with diabetes mellitus (16.88% vs. 25.34% vs. 31.78% vs. 9.52%, P=0.044), hypertension (27.27% vs. 21.23% vs. 32.71% vs. 4.76%, P=0.026), and obesity (6.49% vs. 8.90% vs. 23.36% vs. 0%, P=0.0005). Total leucocyte counts, absolute neutrophil counts, creatinine, serum glutamic pyruvic transaminase (SGPT), lactate dehydrogenase (LDH), ferritin, and D-dimer were deranged in significantly more patients of severe score (53.27%, 62.62%, 60.75%, 85.05%, 90.65%, 97.20%, and 95.35%, respectively). Interleukin-6 (IL-6) and C-reactive protein were deranged in significantly more patients with moderate disease (98.18% and 98.63%, respectively). Increasing severity scores were associated with increased mortality (mild vs. moderate vs. severe: 1.30% vs. 1.37 vs. 15.89%, P<.0001). Oxygen saturation (SpO2) was significantly lowest in severe score followed by moderate, mild and normal scores (87 vs. 90 vs. 96 vs. 97, P<.0001). Duration of non-rebreather mask (NRBM), noninvasive ventilation (NIV), high-flow nasal cannula (HFNC), Venture/face mask, and intubation was also associated with increasing severity scores (P<0.0001). Conclusion: CT scans play an important role in guiding physicians with their management plans and can serve as a predictor of disease severity and outcomes.
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Aim: To delineate and analyze the mortality from COVID -19 in our institute during the devastating second wave of pandemic. Settings and Design: A retrospective cohort analysis. Methods and Materials: A comprehensive mortality analysis of 142 laboratory-confirmed severe acute respiratory syndrome coronavirus 2-infected deceased patients from our hospital's medical records was done. These patients presented with severe disease at the time of admission and were managed in intensive care units. Statistical Analysis Used: Statistical Package for Social Sciences software, IBM manufacturer, Chicago, USA, version 21.0 was used. Results: The number of deceased males (82, 62.6%) was higher than females (53, 37.3%). Median age of deceased patient was 57 (44.25-69.75) years. Most frequent comorbidities were diabetes mellitus (42, 29.6%) and hypertension (41, 28.9%). Most common symptoms being shortness of breath (137, 96.5%), fever (94, 66.2%) and cough (73, 51.4%). Median peripheral capillary oxygen saturation (SpO2) at time of admission was 86% (77.25-90). Median time interval from symptom onset to admission in hospital was 3 (2.25-5) days. Neutrophil lymphocyte ratio was more than 5 in 117 (90.7%) patients. Complications seen were acute respiratory distress syndrome in 82.3%, acute liver injury in 58.4%, acute kidney injury in 26.7%, sepsis in 13.3% and acute cardiac injury in 12% patients. The median high-resolution computed tomography score was 20 (17-22). Conclusions: Male and elderly patients with underlying comorbidities had poorer outcome and involvement of multiple organ systems was common. A short time interval between symptom onset and admission/mortality, particularly encountered was worrisome.
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Background: Facial area is one of the most frequently injured area of the body, accounting for 23-97% of all facial fractures. Treatments under general anesthesia as those for maxillofacial fractures or infections is a highly complicated and a major challenging task in trismus associated patients. The main culprit in trismus is the increase muscle tone of masticatory muscles which are supplied via the mandibular nerve, blocking which could help increase the mouth opening thus, changing the whole of airway management. Material and Method: A prospective study was done on 50 patients of ASA grade I-II with unilateral mandibular fracture with trismus posted for maxillofacial surgery. Mandibular nerve block was given via extraoral approach with 5 ml of 0.5% bupivacaine using peripheral nerve stimulator to determine the difference in Pre block and Post block mouth opening and the VAS score at 2, 5, 10, 15, 20, 25, and 30 minutes. Results: The Interincisor distance measured Pre block was 1.20 ± 0.32 mm and was significantly increased after 5 mins onwards from the block (P < 0.005). The VAS score determined Pre block was 5.14 ± 1.37 which significantly decreased just 2 minutes after the application of block (P < 0.005). Conclusion: Mandibular nerve block decreases the pain and will aid in the decision making by an anesthetist regarding airway management as it helps in increasing the inter incisor distance significantly. Moreover, given the feasibility and effectiveness of the block it could be included in standard of care protocol for mandibular fracture patients.
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Introduction: Severe preeclampsia can lead to various complications including increased intracranial pressure (ICP) which can be catastrophic but difficult to detect because of variable nonspecific symptoms. Ultrasonography has been used as noninvasive measure to monitor optic nerve sheath diameter (ONSD) as a marker of raised ICP. Effect of MgSO4 on ICP can modify the management approach, need for additional monitoring, targeting hemodynamic goals, timing of delivery, and choice of anesthesia. We evaluated the effect of MgSO4 on raised ICP in severely preeclamptic patients using ultrasound-guided ONSD as a surrogate marker of ICP. Methodology: This prospective observational study was conducted after ethical committee approval and written informed consent from patients. Ultrasound-guided ONSD was measured and compared in 47 severe preeclamptic patients before and at 1 h, 4 h, 12 h, and 24 h after starting MgSO4 therapy. The analysis of data was done by one-way analysis of variance using Statistical Package for the Social Science. Results: Mean ONSD was 5.56 ± 0.30 mm in our study group. ONSD above 5.8 mm was seen in 17 (36.17%) patients and was considered as marker of raised ICP. There was a significant decrease in ONSD after 4 h of administration of MgSO4. No significant correlation was observed between mean arterial pressure, serum magnesium level, and ONSD. Conclusion: Ultrasound-guided ONSD measurement can be used as a quick, noninvasive bedside tool in severe preeclamptic patient on MgSO4 treatment as marker of ICP which help us in determining clinical severity, therapeutic response, and to decide further course of management.