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A higher heart rate is recognized as an independent risk factor for all-cause mortality and cardiovascular events in the general population. However, the association between elevated heart rate and clinical adverse outcomes in patients with non-dialysis-dependent chronic kidney disease (CKD) has not been sufficiently investigated. A total of 1353 participants enrolled in the Fukushima CKD Cohort Study were examined to investigate associations between resting heart rate and clinical adverse outcomes using Cox proportional hazards analysis. The primary outcome of the present study was all-cause mortality, with cardiovascular events as the secondary outcome. Participants were stratified into four groups based on resting heart rate levels at baseline (heart rate < 70/min, ≥ 70 and < 80/min, ≥ 80 and < 90/min, and ≥ 90/min). During the median observation period of 4.9 years, 123 participants died, and 163 cardiovascular events occurred. Compared with the reference level heart rate < 70/min group, the adjusted hazard ratios (HRs) for all-cause mortality were 1.74 (1.05–2.89) and 2.61 (1.59–4.29) for the heart rate ≥ 80 and < 90/min group and heart rate ≥ 90/min group, respectively. A significantly higher risk of cardiovascular events was observed in the heart rate ≥ 80/min and < 90/min group (adjusted HR 1.70, 1.10–2.62), but not in the heart rate ≥ 90/min group (adjusted HR 1.45, 0.90–2.34). In patients with non-dialysis-dependent CKD, a higher resting heart rate was associated with increased all-cause mortality. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to compare the effects of mitiglinide/voglibose with those of glimepiride on glycemic variability and vascular endothelial function in patients with type 2 diabetes. Materials and Methods: It was a multicenter, open‐label, randomized, crossover study. Hospitalized patients received either mitiglinide/voglibose (three times daily administration of 10 mg mitiglinide and 0.2 mg voglibose) or glimepiride (once‐daily 2 mg) in random order, each for 5 days. The reactive hyperemia index (RHI) and the mean amplitude of glycemic excursions (MAGE) were measured as co‐primary endpoints using reactive hyperemia peripheral arterial tonometry and continuous glucose monitoring. Results: The analysis included 30 patients (15 in each group). The RHI was 1.670 ± 0.369 during treatment with mitiglinide/voglibose and 1.716 ± 0.492 during treatment with glimepiride, with no significant difference between the two. MAGE was significantly lower in the mitiglinide/voglibose group (47.6 ± 18.5 mg/dL) than in the glimepiride group (100.6 ± 32.2 mg/dL). Although the mean blood glucose levels over the entire 24 h period were comparable between the two groups, the use of mitiglinide/voglibose was associated with a lower standard deviation of mean glucose, coefficient of variation, and mean postprandial glucose excursion compared with glimepiride. The time below range (<70 mg/dL) and the time above range (>180, >200, and 250 mg/dL) were lower in the mitiglinide/voglibose group, while the time in range (70–180 mg/dL) was higher. Conclusions: In our short‐duration randomized crossover study, although not impacting vascular endothelial function, mitiglinide/voglibose demonstrated potential benefits in reducing glycemic variability, postprandial hyperglycemia, and hypoglycemia in patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Background: Identifying programmed death-ligand-1 (PD-L1) expression is crucial for optimizing treatment strategies involving immune checkpoint inhibitors. However, the role of intratumoral metabolic heterogeneity specifically derived from 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) images in predicting PD-L1 expression in patients with newly diagnosed non-small cell lung cancer (NSCLC) remains unexplored. Here, we investigated the association between FDG PET texture features and PD-L1 expression by retrospectively analyzing the data of patients newly diagnosed with NSCLC who underwent FDG PET/CT scans and PD-L1 immunohistochemical staining before treatment. Methods: Patients were categorized based on their tumor proportion scores (TPSs) into negative-, low-, and high-PD-L1 expression groups. We computed the maximum standardized uptake value and 31 texture features for the primary tumor from PET images and compared differences in parameters among the groups. Results: Of the 83 patients, 12, 45, and 26 were assigned to the negative-, low-, and high-PD-L1 expression groups, respectively. Six specific texture features (low gray-level run emphasis, short-run low gray-level emphasis, long-run high gray-level emphasis, low gray-level zone emphasis, high gray-level zone emphasis, and short-zone low gray-level emphasis) helped distinguish among all possible combinations. Conclusions: Our findings revealed that FDG PET texture features are potential imaging biomarkers for predicting PD-L1 expression in patients newly diagnosed with NSCLC. [ABSTRACT FROM AUTHOR]

Cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) is a late‐onset, autosomal recessive neurodegenerative disorder caused by biallelic AAGGG/ACAGG repeat expansion (AAGGG‐exp/ACAGG‐exp) in RFC1. The recent identification of patients with CANVAS exhibiting compound heterozygosity for AAGGG‐exp and truncating variants supports the loss‐of‐function of RFC1 in CANVAS patients. We investigated the pathological changes in 2 autopsied patients with CANVAS harboring biallelic ACAGG‐exp and AAGGG‐exp. RNA fluorescence in situ hybridization of the 2 patients revealed CCTGT‐ and CCCTT‐containing RNA foci, respectively, in neuronal nuclei of tissues with neuronal loss. Our findings suggest that RNA toxicity may be involved in the pathogenesis of CANVAS. ANN NEUROL 2024;95:607–613 [ABSTRACT FROM AUTHOR]

Background: Allergen-specific immunotherapy (AIT), an established treatment for allergic diseases, prevents the development of other allergic manifestations. Although the mechanisms remain unclear, AIT has been shown to reduce basophil activation (BA) against nontarget allergens. Objectives: The aim of this study was to assess immunological changes in Dermatophagoides farinae (Der f) after Japanese cedar pollen (JCP)-based subcutaneous immunotherapy (SCIT) monotherapy. Method: The data of 16 patients (age: 6–37 years) with JCP-induced allergic rhinitis who were sensitive to Der f (serum Der f-specific immunoglobulin E [IgE] level >0.34 kUA/L) and received JCP-based SCIT for 5 years were reviewed retrospectively. BA by Der f and JCP extracts and serum-specific IgE and immunoglobulin G4 (IgG4) levels against these allergens were evaluated before and after completing 5 years of JCP-based SCIT monotherapy. Results: The areas under the dose-response curves of BA by Der f and JCP extracts were significantly reduced (p = 0.02 and p = 0.002, respectively). JCP-specific IgE levels decreased and JCP-specific IgG4 levels increased significantly (p < 0.001 for both), whereas Der f-specific IgE and IgG4 levels did not change significantly. Conclusions: JCP-based SCIT monotherapy reduced Der f-specific BA. These findings suggest that JCP-based SCIT has the potential to modulate immune response toward nontarget allergens. [ABSTRACT FROM AUTHOR]

E x vivo viscoelastic testing can be used to assess the concentration responses to tranexamic acid in blood samples obtained from pregnant women across the three trimesters and in non-pregnant controls. Minor variations in fibrinolysis across pregnancy suggest a target tranexamic acid blood concentration of 12.5 mg L−1 for complete inhibition of fibrinolysis. Although the data support the potential utility of viscoelastic testing using the ClotPro® TPA test in maintaining therapeutic tranexamic acid concentrations during postpartum haemorrhage, it might obscure potentially crucial endogenous fibrinolysis inhibitor interactions essential to the microcirculation. [ABSTRACT FROM AUTHOR]

This study in vitro comprehensively assessed reversal of the anticoagulant effects of rivaroxaban, an oral factor Xa inhibitor, using andexanet alfa and various prothrombin complex concentrate (PCC) products in a battery of tests. In static coagulation assays, andexanet alpha outperformed PCCs except for activated PCC being more effective in standard coagulation times. However, in a flow chamber model mimicking arterial shear, both andexanet alpha and high-concentration PCC restored fibrin formation, but not platelet adhesion. In the Russell's viper venom test and anti-Xa assay, only andexanet alpha could be tested for efficacy. The antidote effects of andexanet alpha and PCCs in restoring coagulation can be qualitatively or selectively demonstrated using in vitro coagulation tests. [ABSTRACT FROM AUTHOR]

This article discusses a study on factors influencing blood transfusion in adolescent idiopathic scoliosis correction surgery. The authors raise concerns about certain aspects of the study's methodology and analysis. They highlight the need for standardized protocols for fluid management, including the use of esophageal doppler monitoring. The authors also question the exclusion of certain known risk factors from the statistical model and suggest that further research with a larger sample size is needed. Overall, caution should be exercised when applying the current findings in clinical practice. [Extracted from the article]

The article discusses a study that developed a model to predict the length of stay in the intensive care unit (ICU) after pediatric liver transplantations. The authors identified certain risk factors, such as pretransplant hospital admission and postoperative adverse events, that were associated with prolonged ICU stay. However, the article points out that the model has limitations, such as not providing details on the factors that led to hospital admission or return to the operating room (OR), which limits its practical application. The authors suggest that further clarification and additional information would strengthen the predictive model and improve clinical decisions. [Extracted from the article]