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The mortality rate and association between mortality and injury severity were similar. Proportion of patients requiring intensive care unit facilities also did not change.
Despite diversion of critical care resources to deal with COVID-related admissions, we did not observe a change in mortality rate or proportion of severely injured patients requiring critical care. Our results suggest London MTCs were able to provide their usual standard of care for critically injured major trauma (Injury Severity Score >15) patients during the pandemic.
15) patients during the pandemic.Accumulating evidence suggests the role of cellular components in achieving antitumor to protumor microenvironments. Among the various types of cells within the tumor niche, the state of CD8+ T cells apparently changes from cytotoxic T effector cells and memory T cells to exhausted CD8+ T cells. These changes in the phenotype of CD8+ T cells promote the protumor microenvironment. Recently, comprehensive experimental data delineated the role of thymocyte selection-associated high-mobility group-box protein (TOX), which regulates the transcriptional process and epigenetic remodeling, with implications in tumor and chronic viral infections. This perspective summarizes the molecular mechanisms that link CD8+ T cells, TOX, and transcriptional and epigenetic reprogramming as well as future directions for determining new avenues of cancer therapeutics.Background Recent studies have demonstrated that uric acid (UA) enhances arginase activity, resulting in decreased NO in endothelial cells. However, the role of lung UA in pulmonary arterial hypertension (PAH) remains uncertain. We hypothesized that increased lung UA level contributes to the progression of PAH. Methods and Results In cultured human pulmonary arterial endothelial cells, voltage-driven urate transporter 1 (URATv1) gene expression was detected, and treatment with UA increased arginase activity. In perfused lung preparations of VEGF receptor blocker (SU5416)/hypoxia/normoxia-induced PAH model rats, addition of UA induced a greater pressure response than that seen in the control and decreased lung cGMP level. Mevastatin clinical trial UA-induced pressor responses were abolished by benzbromarone, a UA transporter inhibitor, or L-norvaline, an arginase inhibitor. In PAH model rats, induction of hyperuricemia by administering 2% oxonic acid significantly increased lung UA level and induced greater elevation of right ventricular systolic pressure with exacerbation of occlusive neointimal lesions in small pulmonary arteries, compared with nonhyperuricemic PAH rats. Administration of benzbromarone to hyperuricemic PAH rats significantly reduced lung UA levels without changing XOR (xanthine oxidoreductase) activity, and attenuated right ventricular systolic pressure increase and occlusive lesion development. Topiroxostat, a XOR inhibitor, significantly reduced lung XOR activity in PAH rats, with no effects on increase in right ventricular systolic pressure, arterial elastance, and occlusive lesions. XOR-knockout had no effects on right ventricular systolic pressure increase and arteriolar muscularization in hypoxia-exposed mice. Conclusions Increased lung UA per se deteriorated PAH, whereas XOR had little impact. The mechanism of increased lung UA may be a novel therapeutic target for PAH complicated with hyperuricemia.Background Atrial fibrillation (AF) is the most common form of clinical cardiac dysrhythmia responsible for thromboembolic cerebral stroke, congestive heart failure, and death. Aggregating evidence highlights the strong genetic basis of AF. Nevertheless, AF is of pronounced genetic heterogeneity, and in an overwhelming majority of patients, the genetic determinants underpinning AF remain elusive. Methods and Results By genome-wide screening with polymorphic microsatellite markers and linkage analysis in a 4-generation Chinese family affected with autosomal-dominant AF, a novel locus for AF was mapped to chromosome 1q24.2-q25.1, a 3.20-cM (≈4.19 Mbp) interval between markers D1S2851 and D1S218, with the greatest 2-point logarithm of odds score of 4.8165 for the marker D1S452 at recombination fraction=0.00. Whole-exome sequencing and bioinformatics analyses showed that within the mapping region, only the mutation in the paired related homeobox 1 (PRRX1) gene, NM_022716.4c.319C>T;(p.Gln107*), cosegregated with AF in the family. In addition, sequencing analyses of PRRX1 in another cohort of 225 unrelated patients with AF revealed a new mutation, NM_022716.4c.437G>T; (p.Arg146Ile), in a patient. The 2 mutations were absent in 908 control subjects. Biological analyses in HeLa cells demonstrated that the 2 mutants had significantly diminished transactivation on the target genes ISL1 and SHOX2 and markedly decreased ability to bind the promoters of ISL1 and SHOX2 (2 genes causally linked to AF), although with normal intracellular distribution. Conclusions This study first indicates that PRRX1 loss-of-function mutations predispose to AF, which provides novel insight into the molecular pathogenesis underpinning AF, implying potential implications for precisive prophylaxis and management of AF.Background Peripheral artery disease (PAD) and coronary artery disease (CAD) represent atherosclerosis in different vascular beds. We used detailed metabolic biomarker profiling to identify common and discordant biomarkers and clarify pathophysiological differences for these vascular diseases. Methods and Results We used 5 prospective cohorts from Finnish population (FINRISK 1997, 2002, 2007, and 2012, and Health 2000; n=31 657; median follow-up time of 14 years) to estimate associations between >200 metabolic biomarkers and incident PAD and CAD. Metabolic biomarkers were measured with nuclear magnetic resonance, and disease events were obtained from nationwide hospital records. During the follow-up, 498 incident PAD and 2073 incident CAD events occurred. In age- and sex-adjusted Cox models, apolipoproteins and cholesterol measures were robustly associated with incident CAD (eg, hazard ratio [HR] per SD for higher apolipoprotein B/A-1 ratio, 1.30; 95% CI, 1.25-1.36), but not with incident PAD (HR per SD for higher apolipoprotein B/A-1 ratio, 1.04; 95% CI, 0.95-1.14; Pheterogeneity0.05). link2 Lower proportion of polyunsaturated fatty acids relative to total fatty acids, and higher concentrations of monounsaturated fatty acids, glycolysis-related metabolites, and inflammatory protein markers were strongly associated with incident PAD, and many of these associations were stronger for PAD than for CAD (Pheterogeneity less then 0.001). Most differences in metabolic profiles for PAD and CAD remained when adjusting for traditional risk factors. Conclusions The metabolic biomarker profile for future PAD risk is distinct from that of CAD. This may represent pathophysiological differences.Background Family history of atherosclerotic cardiovascular disease (ASCVD) is easily accessible and captures genetic cardiovascular risk, but its prognostic value in secondary prevention is unknown. Methods and Results We followed 25 615 patients registered in SWEDEHEART (Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies) from their 1-year revisit after a first-time myocardial infarction during 2005 to 2013, until December 31, 2018. Data on relatives, diagnoses and socioeconomics were extracted from national registers. The association between family history and recurrent ASCVD was studied with Cox proportional-hazard regression, adjusting for risk factors and socioeconomics. A family history of ASCVD was defined as hospitalization due to myocardial infarction, angina with coronary revascularization, stroke, or cardiovascular death in ≥1 parent or full sibling, with early-onset defined as disease-onset before 55 years in menes secondary risk prediction. This may identify patients to target for intensified secondary prevention.Background Myocardial strain can identify subclinical left ventricular dysfunction in various cardiac diseases, but its association with clinical outcomes in genetic cardiomyopathies remains unknown. Herein, we assessed myocardial strain in patients with Danon disease (DD), a rare X-linked autophagic disorder that causes severe cardiac manifestations. Methods and Results Echocardiographic images were reviewed and used to calculate myocardial strain from a retrospective, international registry of patients with DD. Regression analyses were performed to evaluate for an association of global longitudinal strain (GLS) and ejection fraction with the composite outcome (death, ventricular assist device, heart transplantation, and implantable cardioverter defibrillator for secondary prevention). A total of 22 patients with DD (male 14 [63.6%], median age 16.5 years) had sufficient echocardiograms for analysis. Absolute GLS was reduced with a mean of 12.2% with an apical-sparing pattern observed. Univariable regression for GLS and composite outcome showed an odds ratio of 1.32 (95% CI, 1.02-1.71) with P=0.03. For receiver operating characteristic analysis, the areas under the curve for GLS and ejection fraction were 0.810 (P=0.02) and 0.605 (P=0.44), respectively. An absolute GLS cutoff of 10.0% yielded a true positive rate of 85.7% and false positive rate of 13.3%. Conclusions In this cohort of patients with DD, GLS may be a useful assessment of myocardial function and may predict clinical outcomes. This study highlights the potential use of myocardial strain phenotyping to monitor disease progression and potentially to predict clinical outcomes in DD and other genetic cardiomyopathies.According to the World Health Organization report, 5.4 million under-five children died, which is similar to under-five mortality rate of 39 deaths per 1000 live births. This rate is higher in sub-Saharan Africa with 76 deaths per 1000 live births. More than 1 out of every 2 deaths is because of diseases that can be managed with drug of low-cost and high quality. Institutional-based cross-sectional survey was conducted from January to February 2021, at the University of Gondar Comprehensive Specialized Hospital. Statistical Package for the Social Sciences software version 24 was used for data analysis. The results were presented using Figures, tables, and texts according to the nature of the data. The overall average availability of priority medicines was 75% on the day of visit and the average stock-out duration in the last 6 months was 23.85 days. Availability and utilization of priority medicines for the management of antiretroviral infections, Vitamin A deficiency, malaria, and diarrheal cases were high, whereas availability and utilization of suggested medication for neonatal sepsis were very low. A significant proportion of priority diseases was managed by non-priority medications. link3 Medicines supply sources of the country, ministry of health, policymakers as well as facility managers should work in collaboration toward ensuring sustainable and consistent availability of priority medicines through the country. Continues in-service training of healthcare professionals is also mandatory to update themselves with newly developed guidelines, standards, and recommendations.