Disseminated nocardiosis with thyroid involvement: A case report

Nocardiosis is a life-threatening infection that affects the lungs, skin, and central nervous system, particularly in immune-compromised patients. We report a case of disseminated nocardiosis with pneumonia, brain abscesses, meningitis, and thyroiditis, for an individual with recent steroid therapy. Recovery was uneventful with a 4-month course of sulfamethoxazole–trimethoprim

Performance of Six Clinical Physiological Scoring Systems in Predicting In-Hospital Mortality in Elderly and Very Elderly Patients with Acute Upper Gastrointestinal Bleeding in Emergency Department

Background and Objectives: The aim of this study is to compare the performance of six clinical physiological-based scores, including the pre-endoscopy Rockall score, shock index (SI), age shock index (age SI), Rapid Acute Physiology Score (RAPS), Rapid Emergency Medicine Score (REMS), and Modified Early Warning Score (MEWS), in predicting in-hospital mortality in elderly and very elderly patients in the emergency department (ED) with acute upper gastrointestinal bleeding (AUGIB). Materials and Methods: Patients older than 65 years who visited the ED with a clinical diagnosis of AUGIB were enrolled prospectively from July 2016 to July 2021. The six scores were calculated and compared with in-hospital mortality. Results: A total of 336 patients were recruited, of whom 40 died. There is a significant difference between the patients in the mortality group and survival group in terms of the six scoring systems. MEWS had the highest area under the curve (AUC) value (0.82). A subgroup analysis was performed for a total of 180 very elderly patients (i.e., older than 75 years), of whom 27 died. MEWS also had the best predictive performance in this subgroup (AUC, 0.82). Conclusions: This simple, rapid, and obtainable-by-the-bed parameter could assist emergency physicians in risk stratification and decision making for this vulnerable group

Comparison of Immediate and 2-Year Outcomes between Excimer Laser-Assisted Angioplasty with Spot Stent and Primary Stenting in Intermediate to Long Femoropopliteal Disease

Background. To compare the clinical outcomes between excimer laser-assisted angioplasty (ELA) with spot stent (group A) and primary stenting (group B) in intermediate to long femoropopliteal disease. Methods. Outcomes of 105 patients totaling 119 legs treated with two different strategies were analyzed retrospectively in a prospectively maintained database. Results. Baseline characteristics were similar in both groups. Better angiographic results and lesser increase of serum C-reactive protein levels (0.60 ± 0.72 versus 2.98 ± 0.97 mg/dL, P<0.001) after the intervention were obtained in Group B. Group A had inferior 1-year outcomes due to higher rate of binary restenosis (67% versus 32%, P=0.001) and lower rate of primary patency (40% versus 58%, P=0.039). Rates of amputation-free survival, target vessel revascularization, assisted primary patency, and stent fracture at 24 months were similar in both groups (80% versus 82%, P=0.979, 65% versus 45%, P=0.11, 78% versus 80%, P=0.75 and 6.3% versus 6.8%, P=0.71, resp.). Conclusion. Greater vascular inflammation after ELA with spot stent resulted in earlier restenosis and inferior 1-year clinical outcomes than primary stenting. This benefit was lost in the primary stenting group at 2 years due to late catch-up restenosis. Active surveillance with prompt intervention was required to maintain the vessel patency

The trans-ancestral genomic architecture of glycemic traits

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 x 10(-8)), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution. A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.Peer reviewe

Genetic Drivers of Heterogeneity in Type 2 Diabetes Pathophysiology

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P \u3c 5 × 10-8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care

Genetic drivers of heterogeneity in type 2 diabetes pathophysiology

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P &lt; 5 × 10-8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care.</p

Repositioning of the global epicentre of non-optimal cholesterol

High blood cholesterol is typically considered a feature of wealthy western countries(1,2). However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world(3) and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health(4,5). However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol-which is a marker of cardiovascular riskchanged from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95% credible interval 3.7 million-4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world.Peer reviewe

Rising rural body-mass index is the main driver of the global obesity epidemic in adults

Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities(.)(1,2) This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity(3-6). Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55% of the global rise in mean BMI from 1985 to 2017-and more than 80% in some low- and middle-income regions-was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing-and in some countries reversal-of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories.Peer reviewe