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Sex differences in in-hospital management in patients with sepsis and septic shock: a prospective multicenter observational study
Get PDFSex differences in the in-hospital management of sepsis exist. Previous studies either included patients with sepsis that was defined using previous definitions of sepsis or evaluated the 3-h bundle therapy. Therefore, this study sought to assess sex differences in 1-h bundle therapy and in-hospital management among patients with sepsis and septic shock, defined according to the Sepsis-3 definitions. This observational study used data from Korean Shock Society (KoSS) registry, a prospective multicenter sepsis registry. Adult patients with sepsis between June 2018 and December 2021 were included in this study. The primary outcome was adherence to 1-h bundle therapy. Propensity score matching (PSM) and multivariable logistic regression analyses were performed. Among 3264 patients with sepsis, 3129 were analyzed. PSM yielded 2380 matched patients (1190 men and 1190 women). After PSM, 1-h bundle therapy was performed less frequently in women than in men (13.0% vs. 19.2%; p < 0.001). Among the bundle therapy components, broad-spectrum antibiotics were administered less frequently in women than in men (25.4% vs. 31.6%, p < 0.001), whereas adequate fluid resuscitation was performed more frequently in women than in men (96.8% vs. 95.0%, p = 0.029). In multivariable logistic regression analysis, 1-h bundle therapy was performed less frequently in women than in men [adjusted odds ratio (aOR) 1.559; 95% confidence interval (CI) 1.245–1.951; p < 0.001] after adjustment. Among the bundle therapy components, broad-spectrum antibiotics were administered less frequently to women than men (aOR 1.339, 95% CI 1.118–1.605; p = 0.002), whereas adequate fluid resuscitation was performed more frequently for women than for men (aOR 0.629, 95% CI 0.413–0.959; p = 0.031). Invasive arterial blood pressure monitoring was performed less frequently in women than in men. Resuscitation fluid, vasopressor, steroid, central-line insertion, ICU admission, length of stay in the emergency department, mechanical ventilator use, and renal replacement therapy use were comparable for both the sexes. Among patients with sepsis and septic shock, 1-h bundle therapy was performed less frequently in women than in men. Continuous efforts are required to increase adherence to the 1-h bundle therapy and to decrease sex differences in the in-hospital management of patients with sepsis and septic shock
Impact of diabetes distress on glycemic control and diabetic complications in type 2 diabetes mellitus
Get PDFThe effect of diabetes distress on glycemic control and its association with diabetes complications is still poorly understood. We aimed to study the clinical features of patients with high diabetes distress, focusing on changes in glycemic control and risk of diabetic complications. From the Korean National Diabetes Program data, we investigated 1862 individuals with type 2 diabetes mellitus (T2DM) who completed diabetic complication studies and the Korean version of the Problem Areas in Diabetes Survey (PAID-K). A total score of PAID-K ≥ 40 was considered indicative of high distress. Individuals with high distress (n = 589) had significantly higher levels of glycated hemoglobin than those without distress (7.4% vs. 7.1%, p < 0.001). This trend persisted throughout the 3-year follow-up period. Higher PAID-K scores were associated with younger age, female gender, longer duration of diabetes, and higher carbohydrate intake (all p < 0.05). There was a significant association between high distress and diabetic neuropathy (adjusted odds ratio, 1.63; p = 0.002), but no significant association was found with other complications, including retinopathy, albuminuria, and carotid artery plaque. In conclusion, high diabetes distress was associated with uncontrolled hyperglycemia and higher odds of having diabetic neuropathy
Artificial intelligence-driven drug repositioning uncovers efavirenz as a modulator of α-synuclein propagation: Implications in Parkinson's disease
Get PDFParkinson's disease (PD) is a complex neurodegenerative disorder with an unclear etiology. Despite significant research efforts, developing disease-modifying treatments for PD remains a major unmet medical need. Notably, drug repositioning is becoming an increasingly attractive direction in drug discovery, and computational approaches offer a relatively quick and resource-saving method for identifying testable hypotheses that promote drug repositioning. We used an artificial intelligence (AI)-based drug repositioning strategy to screen an extensive compound library and identify potential therapeutic agents for PD. Our AI-driven analysis revealed that efavirenz and nevirapine, approved for treating human immunodeficiency virus infection, had distinct profiles, suggesting their potential effects on PD pathophysiology. Among these, efavirenz attenuated α-synuclein (α-syn) propagation and associated neuroinflammation in the brain of preformed α-syn fibrils-injected A53T α-syn Tg mice and α-syn propagation and associated behavioral changes in the C. elegans BiFC model. Through in-depth molecular investigations, we found that efavirenz can modulate cholesterol metabolism and mitigate α-syn propagation, a key pathological feature implicated in PD progression by regulating CYP46A1. This study opens new avenues for further investigation into the mechanisms underlying PD pathology and the exploration of additional drug candidates using advanced computational methodologies
Association of preoperative blood glucose level with delirium after non-cardiac surgery in diabetic patients
Get PDFBackground: Hyperglycemia has shown a negative association with cognitive dysfunction. We analyzed patients with high preoperative blood glucose level and hemoglobin A1c (HbA1c) level to determine the prevalence of postoperative delirium. Methods: We reviewed a database of 23,532 patients with diabetes who underwent non-cardiac surgery. Acute hyperglycemia was defined as fasting blood glucose > 140 mg/ dl or random glucose > 180 mg/dl within 24 h before surgery. Chronic hyperglycemia was defined as HbA1c level above 6.5% within three months before surgery. The incidence of delirium was compared according to the presence of acute and chronic hyperglycemia. Results: Of the 23,532 diabetic patients, 21,585 had available preoperative blood glucose level within 24 h before surgery, and 18,452 patients reported levels indicating acute hy-perglycemia. Of the 8,927 patients with available HbA1c level within three months before surgery, 5,522 had levels indicating chronic hyperglycemia. After adjustment with inverse probability weighting, acute hyperglycemia was related to higher incidence of delirium (hazard ratio: 1.33, 95% CI [1.10,1.62], P = 0.004 for delirium) compared with controls without acute hyperglycemia. On the other hand, chronic hyperglycemia did not correlate with postoperative delirium. Conclusions: Preoperative acute hyperglycemia was associated with postoperative deliri-um, whereas chronic hyperglycemia was not significantly associated with postoperative delirium. Irrespective of chronic hyperglycemia, acute glycemic control in surgical patients could be crucial for preventing postoperative delirium
NAMPT-Driven M2 Polarization of Tumor-Associated Macrophages Leads to an Immunosuppressive Microenvironment in Colorectal Cancer
Get PDFNicotinamide phosphoribosyltransferase (NAMPT) is a metabolic enzyme with key roles in inflammation. Previous studies have examined the consequences of its upregulated expression in cancer cells themselves, but studies are limited with respect to its role in the other cells within the tumor microenvironment (TME) during colorectal cancer (CRC) progression. Using single-cell RNA sequencing (scRNA-seq) data, it is founded that NAMPT is highly expressed in SPP1+ tumor-associated macrophages (TAMs), a unique subset of TAMs associated with immunosuppressive activity. A NAMPThigh gene signature in SPP1+ TAMs correlated with worse prognostic outcomes in CRC patients. The effect of Nampt deletion in the myeloid compartment of mice during CRC development is explored. NAMPT deficiency in macrophages resulted in HIF-1α destabilization, leading to reduction in M2-like TAM polarization. NAMPT deficiency caused significant decreases in the efferocytosis activity of macrophages, which enhanced STING signaling and the induction of type I IFN-response genes. Expression of these genes contributed to anti-tumoral immunity via potentiation of cytotoxic T cell activity in the TME. Overall, these findings suggest that NAMPT-initiated TAM-specific genes can be useful in predicting poor CRC patient outcomes; strategies aimed at targeting NAMPT may provide a promising therapeutic approach for building an immunostimulatory TME in CRC progression
The Long-Term View-Assessing Life Expectancy Post-Knee Arthroplasty: A Commentary on “Life Expectancy of Patients Undergoing Total Knee Arthroplasty: Comparison With General Population”
Get PDFAuthor Correction: ANKS1A regulates LDL receptor-related protein 1 (LRP1)-mediated cerebrovascular clearance in brain endothelial cells
Get PDFMelosira nummuloides Ethanol Extract Ameliorates Alcohol-Induced Liver Injury by Affecting Metabolic Pathways
No full textMelosira nummuloides is a microalga with a nutritionally favorable polyunsaturated fatty acid profile. In the present study, M. nummuloides ethanol extract (MNE) was administered to chronic-binge alcohol-fed mice and alcohol-treated HepG2 cells, and its hepatoprotective effects and underlying mechanisms were investigated. MNE administration reduced triglyceride (TG), total cholesterol (T-CHO), and liver injury markers, including aspartate transaminase (AST) and alanine transaminase (ALT), in the serum of chronic-binge alcohol-fed mice. However, MNE administration increased the levels of phosphorylated adenosine monophosphate-activated protein kinase (P-AMPK/AMPK) and PPARα, which was accompanied by a decrease in SREBP-1; this indicates that MNE can inhibit adipogenesis and improve fatty acid oxidation. Moreover, MNE administration upregulated the expression of antioxidant enzymes, including SOD, NAD(P)H quinone dehydrogenase 1, and GPX, and ameliorated alcohol-induced inflammation by repressing the Akt/NFκB/COX-2 pathway. Metabolomic analysis revealed that MNE treatment modulated many lipid metabolites in alcohol-treated HepG2 cells. Our study findings provide evidence for the efficacy and mechanisms of MNE in ameliorating alcohol-induced liver injury
Distribution of urinary trace element exposure and dietary sources in women over 50 in an agricultural region- A community-based KoGES cohort study
No full textBackground: There is a noticeable lack of information on the levels of both non-essential and essential trace elements in women aged over 50. The main objective of this study is to investigate trace element concentrations and explore the influence of sociodemographic factors and dietary sources of exposure in this demographic. Methods: We analyzed 19 trace elements, including manganese, cobalt, copper, zinc, molybdenum, chromium, nickel, arsenic, strontium, cadmium, tin, antimony, cesium, barium, tungsten, mercury, thallium, lead, and uranium, using ICP-MS and mercury analyzer. Urine samples were obtained from a cohort of 851 women aged over 50 who participated in the 8th KoGES-Ansung study (2017–2018). Multiple linear models were employed to explore associations between urinary trace element concentrations and sociodemographic factors and dietary sources of exposure. We used K-means clustering to discern patterns of exposure to trace elements and identify contributing factors and sources. Results: Our findings indicate higher concentrations of molybdenum (Mo), arsenic (As), cadmium (Cd), and lead (Pb) in our study population compared to women in previous studies. The study population were clustered into two distinct groups, characterized by lower or higher urinary concentrations. Significant correlations between age and urinary concentrations were observed in Ni. Smoking exhibited positive associations with urinary Cd and As. Associations with dietary sources of trace elements were more distinct in women in the high-exposure group. Urinary antimony (Sb) was positively linked to mushroom and egg intake, As to mushroom and fish, and Hg to egg, dairy products, fish, seaweed, and shellfish. Conclusions: Our study underscores the significant gap in understanding urinary concentrations of trace elements in women aged over 50. With higher concentrations of certain elements compared to previous studies and significant correlations between age, smoking, and specific food sources, it is imperative to address this gap through targeted dietary source-specific risk management
All-cause and cause-specific mortality in patients with Behçet disease versus the general population
No full textBackground The comparative risk of cause-specific mortality in patients with Behçet disease (BD) vs. the general population is not known. Objectives To compare the risk of all-cause and cause-specific mortality in patients with BD vs. the general population. Methods Using data from the Korea National Health Insurance Service database for the period 2002–20, we conducted a cohort study comparing patients with BD with the general population, matched according to age and sex (1: 4 ratio). We used Cox proportional hazard models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and cause-specific mortality. Subgroup analyses by age and sex were done. Results We included 24 669 patients with BD and 98 676 age- and sex-matched controls [mean (SD) age 40.5 (12.9) years; 34% male]. During a mean follow-up of 11.9 years, the incidence rate (IR) of death per 100 person-years was 0.36 in patients with BD and 0.29 in controls [hazard ratio (HR) 1.28, 95% confidence interval (CI) 1.20–1.38]. The risk of mortality was highest in the first year after BD diagnosis (HR 2.66, 95% CI 2.09–3.40). Patients with BD died more often in this period as a result of malignancy (HR 1.96, 95% CI 1.30–2.98); cardiovascular (HR 2.68, 95% CI 1.45–4.97), gastrointestinal (HR 3.50, 95% CI 1.35–9.07) and respiratory disease (HR 5.00, 95% CI 1.34–18.62); and infection (HR 3.33, 95% CI 1.02–10.92). Mortality as a result of neurological (HR 1.58, 95% CI 1.06–2.35) or genitourinary disease (HR 2.20, 95% CI 1.43–3.37) was also more common in patients with BD during the overall follow-up. Subgroup analyses showed consistent results. The risk of cardiovascular mortality vs. the general population was higher in younger patients (P=0.006) and the risk of gastrointestinal mortality was increased in women vs. men (P=0.04). Conclusions This population-based cohort study revealed that the first year after diagnosis is the highest risk period for excess mortality in people with BD. The mortality burden in BD derives from a wide spectrum of organ involvement and should serve as a warning to clinicians about the systemic nature of the disease