Acute urticaria is a common condition that can affect individuals across all age groups. Current pharmacological treatments primarily rely on antihistamines and corticosteroids. However, these therapies may be limited by suboptimal efficacy, dose- and time-dependence, and potential adverse effects. Therefore, the incorporation of effective adjunctive therapies is of considerable clinical value. This study aimed to evaluate the impact of auricular bloodletting (BL) therapy on the length of hospital stay in patients with acute urticaria. Poisson regression was used to compare differences in hospitalization duration between groups. Propensity score matching (PSM) was applied to minimize selection bias. Subgroup analyses by sex and age, as well as robustness checks using bootstrap resampling and Rosenbaum sensitivity analysis, were also performed. Before PSM, Poisson regression indicated that the bloodletting group had significantly shorter hospital stays. The effect was significant in the male, female, and adult subgroups. After PSM, the incidence rate ratios remained below 1 in all models, and statistical significance was observed. No significant differences were observed in the female or adult subgroups post-matching, whereas statistical significance was retained in the male subgroup. No adverse events were reported. Bootstrap and Rosenbaum sensitivity analyses confirmed the robustness of the findings. Patients who received auricular BL experienced shorter hospital stays. Post-matching results showed that statistical significance was retained in the male subgroup. Given the limited sample size in the intervention group, further prospective studies with larger cohorts are warranted to validate these findings and elucidate the underlying mechanisms.
Rationale: Diffuse alveolar hemorrhage (DAH) is a rare but potentially fatal condition characterized by bleeding into alveolar spaces, most often associated with autoimmune disease or severe infection. Rhinovirus is a common cause of upper respiratory tract infection but is rarely associated with DAH in immunocompetent individuals. We report 2 cases of life-threatening DAH associated with rhinovirus infection, both presenting with severe hypoxemia and showing marked improvement following corticosteroid therapy. Patient concerns: Case 1: An 85-year-old woman presented with massive hemoptysis, dyspnea, and hypoxemia. Chest computed tomography (CT) revealed diffuse ground-glass opacities (GGOs) and patchy consolidations. Case 2: A 70-year-old woman developed worsening dyspnea and hemoptysis despite antibiotics. She was hypoxemic, and chest CT showed bilateral GGOs and consolidations. Diagnoses: Bronchoalveolar lavage fluid demonstrated progressively hemorrhagic aliquots consistent with DAH in both cases. Multiplex viral polymerase chain reaction identified rhinovirus as the sole pathogen in both cases, and autoimmune serologic tests were negative. Interventions: Both patients received high-flow oxygen therapy, empirical antibiotics, and systemic corticosteroids (Case 1: intravenous methylprednisolone 1 mg/kg/day; Case 2: intravenous methylprednisolone 500 mg/day for 3 days, followed by tapering). Outcomes: After corticosteroid therapy, both patients showed rapid clinical and radiographic improvement, with resolution of hypoxemia and discharge within 10 days. Lessons: These cases suggest a potential association between rhinovirus infection and life-threatening DAH in immunocompetent patients. Both patients showed marked clinical improvement after corticosteroid therapy, suggesting a potential therapeutic role for systemic corticosteroids. Thus, clinicians should consider rhinovirus infection as a possible infectious trigger of DAH, and systemic corticosteroids may be considered in selected severe cases.
Imeglimin, a novel oral antidiabetic agent classified as a glimin, was developed for the treatment of type 2 diabetes (T2D). This single-center, single-arm interventional study evaluated the efficacy and safety of 24-week imeglimin treatment in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and T2D. Patients with MASLD and T2D were treated with imeglimin 1000 mg twice daily for 24 weeks. The primary endpoint was reduction in alanine aminotransferase (ALT) levels from baseline. Secondary endpoints included changes in metabolic parameters (including hemoglobin A1c, homeostatic model assessment of β-cell function, and homeostatic model assessment of insulin resistance), liver-related parameters (including aspartate aminotransferase [AST], gamma-glutamyl transpeptidase, hepatic fat, and fibrosis markers), and body composition. Twenty-five patients were included in the final analysis. As a primary outcome, the median ALT level was significantly reduced, from 56.00 (47.00–75.00) U/L at baseline to 34.00 (29.00–51.00) U/L at 24 weeks ( P < .001). AST level and hemoglobin A1c value were also significantly reduced. The fibrosis-4 index showed a significant reduction at 12 weeks. By contrast, no significant changes were observed for gamma-glutamyl transpeptidase, homeostatic model assessment of β-cell function, homeostatic model assessment of insulin resistance, hepatic fat content parameters, other fibrosis-related parameters (excluding fibrosis-4 index), and body composition. All adverse events were grade 1, and no patients discontinued treatment due to adverse events. Imeglimin treatment was associated with improvements in serum ALT and AST levels after 24 weeks in patients with MASLD and T2D. These findings provide preliminary evidence of the potential clinical utility of imeglimin in this population and warrant confirmation in larger randomized controlled studies.
This cross-sectional study aimed to compare obesity indicators for predicting insulin resistance using machine learning. Data were obtained from NHANES 2015 to 2018, focusing on a nondiabetic adult population. Insulin resistance was defined as HOMA-IR ≥ 75th percentile of the training set. Key predictors were selected via bootstrap stability selection with elastic net. Logistic regression, random forest, and extreme gradient boosting (XGBoost) models were built using body mass index (BMI) and waist-to-height ratio (WHtR). Performance was assessed by area under the curve (AUC), sensitivity, specificity, accuracy, calibration, and decision curve analysis. Race-stratified and nested regression analyses were performed. A total of 3562 subjects were included. BMI, WHtR, Glycated hemoglobin, and triglycerides were identified as key predictors. All models achieved AUC > 0.79; logistic regression (LR) performed best (BMI-based LR: AUC = 0.811; WHtR-based LR: AUC = 0.811). WHtR-based LR showed slightly better accuracy (0.746 vs 0.715) and specificity (0.744 vs 0.678). Obesity indicators had the highest feature importance, and race-stratified analyses confirmed general robustness across subgroups. WHtR and BMI are strong independent predictors of IR. LR models using these simple indices performed well in discrimination, calibration, and net benefit, offering cost-effective screening options, particularly where resources are scarce. Future work should prioritize external validation and race-specific thresholds.
Thyroid disorders frequently coexist with cardiovascular disease, including hypertension, but whether long-term modulation of antihypertensive drug targets influences thyroid disease risk remains uncertain. We aimed to evaluate the associations of 7 antihypertensive drug-target classes with thyroid diseases in European and East Asian populations using a trans-ancestry drug-target Mendelian randomization (MR) framework. We performed a two-sample, trans-ancestry drug-target MR analysis of 7 antihypertensive target classes. Target-proximal single-nucleotide polymorphisms associated with systolic blood pressure (SBP) were used as genetic proxies. Estimates were scaled per 1-mm Hg genetically predicted increase in SBP; the putative effect of target inhibition that lowers SBP was therefore interpreted in the opposite direction. Summary statistics were obtained for 4 primary thyroid diseases, benign thyroid tumors where available, and 3 thyroid-related proteins in European and East Asian datasets. Hypertension was used as a positive-control outcome. Random-effects inverse-variance weighting was the primary method, with Wald ratio estimation for single-nucleotide polymorphism instruments and weighted-median, Cochran’s Q , MR-Egger, and Mendelian Randomization Pleiotropy RESidual Sum and Outlier analyses as sensitivity assessments. Within the European populace, genetic surrogates for β-blockers exhibit (odds ratio = 0.93; 95% confidence interval = 0.87–0.99) a close association with heightened susceptibility to thyroid carcinoma, whereas KCNH2 (1.15; 1.01–1.32) demonstrates an inverse correlation with thyroid cancer risk. Moreover, calcium channel blockers exhibit a conspicuous linkage with an elevated incidence of hyperthyroidism (0.97; 0.96–0.99) alongside a diminished likelihood of thyroid cancer (1.07; 1.03–1.10). CYP17A1 exerts a protective influence against hyperthyroidism (1.04; 10.1–1.07) and Graves disease (1.10; 1.05–1.16) but manifests a pathogenic effect concerning hypothyroidism (0.99; 0.97–1.00) and thyroid cancer (0.92; 0.86–0.98). Conversely, KCNJ11 demonstrates a proximate correlation between diminished hypothyroidism risk and augmented thyroid cancer susceptibility (0.83; 0.73–0.95). Analogous estimations were noted for CYP17A1 within the East Asian cohort. Genetically proxied perturbation of several antihypertensive drug targets was associated with thyroid disease risk, with CYP17A1 showing the broadest cross-ancestry pattern. These estimates reflect lifelong target-proximal genetic effects rather than the clinical effects of prescribed drugs and should be considered hypothesis-generating pending replication, pharmacoepidemiological studies, and randomized clinical trials.
