Background: systemic inflammation disorders were observed in chronic kidney disease (CKD). Whether the systemic inflammatory indicators could be optimal predictors for the survival of CKD remains less studied.Methods: In this study, participants were selected from the datasets of the National Health and Nutrition Examination Survey (NHANES) between 1999 to 2018 years. Four systemic inflammatory indicators were evaluated by the peripheral blood tests including systemic immune-inflammation index (SII, platelet*neutrophil/lymphocyte), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR). Kaplan-Meier curves, restricted cubic spline (RCS), and Cox regression analysis were used to evaluate the association between the inflammatory index with the all-cause mortality of CKD. Receiver operating characteristic (ROC) and concordance index (C-index) were used to determine the predictive accuracy of varied systemic inflammatory indicators. Sensitive analyses were conducted to validate the robustness of the main findings.Results: A total of 6,880 participants were included in this study. The mean age was 67.03 years old. Among the study population, the mean levels of systemic inflammatory indicators were 588.35 in SII, 2.45 in NLR, 133.85 in PLR, and 3.76 in LMR, respectively. The systemic inflammatory indicators of SII, NLR, and PLR were all significantly positively associated with the all-cause mortality of CKD patients, whereas the high value of LMR played a protectable role in CKD patients. NLR and LMR were the leading predictors in the survival of CKD patients [Hazard ratio (HR) =1.21, 95% confidence interval (CI): 1.07-1.36, p = 0.003 (3^rd quartile), HR = 1.52, 95%CI: 1.35-1.72, p<0.001 (4^th quartile) in NLR, and HR = 0.83, 95%CI: 0.75-0.92, p<0.001 (2^nd quartile), HR = 0.73, 95%CI: 0.65-0.82, p<0.001 (3^rd quartile), and = 0.74, 95%CI: 0.65-0.83, p<0.001 (4^th quartile) in LMR], with a C-index of 0.612 and 0.624, respectively. The RCS curves showed non-linearity between systemic inflammatory indicators and all-cause mortality risk of the CKD population.Conclusion: Our study highlights that systemic inflammatory indicators are important for predicting the survival of the U.S. population with CKD. The systemic inflammatory indicators would add additional clinical value to the health care of the CKD population.

We aimed to develop a machine-learning based predictive model to identify 30-day readmission risk in Acute heart failure (AHF) patients. In this study 2232 patients hospitalized with AHF were included. The variance inflation factor value and 5-fold cross-validation were used to select vital clinical variables. Five machine learning algorithms with good performance were applied to develop models, and the discrimination ability was comprehensively evaluated by sensitivity, specificity, and area under the ROC curve (AUC). Prediction results were illustrated by SHapley Additive exPlanations (SHAP) values. Finally, the XGBoost model performs optimally: the greatest AUC of 0.763 (0.703–0.824), highest sensitivity of 0.660, and high accuracy of 0.709. This study developed an optimal XGBoost model to predict the risk of 30-day unplanned readmission for AHF patients, which showed more significant performance compared with traditional logistic regression (LR) model.

Objective: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease. Among its various complications, heart failure (HF) has been recognized as the second leading cause of cardiovascular death in RA patients. The objective of this study was to investigate the relationship between RA and HF using epidemiological and genetic approachesMethods: The study included 37,736 participants from the 1999-2020 National Health and Nutrition Examination Survey. Associations between RA and HF in the US population were assessed with weighted multivariate logistic regression analysis. A two-sample Mendelian randomization (MR) analysis was employed to establish the causal relationship between the two variables. The primary analysis method utilized was inverse variance weighting (IVW). Additionally, horizontal pleiotropy and heterogeneity were assessed to account for potential confounding factors. In cases where multiple independent datasets were accessible during MR analysis, we combined the findings through a meta-analytical approach.Results: In observational studies, the prevalence of HF in combination with RA reached 7.11% (95%CI 5.83 to 8.39). RA was positively associated with an increased prevalence of HF in the US population [odds ratio (OR):1.93, 95% confidence interval (CI):1.47-2.54, P < 0.0001]. In a MR analysis utilizing a meta-analytical approach to amalgamate the results of the IVW method, we identified a significant causal link between genetically predicted RA and a heightened risk of HF (OR = 1.083, 95% CI: 1.028-1.141; P = 0.003). However, this association was not deemed significant for seronegative RA (SRA) (OR = 1.028, 95% CI: 0.992-1.065; P = 0.126). These findings were consistent across sensitivity analyses and did not indicate any horizontal pleiotropy.Conclusion: RA correlates with an elevated prevalence of HF within the US population. Furthermore, genetic evidence derived from European populations underscores a causal link between RA and the risk of HF. However this association was not significant in SRA.

Aim: Cutaneous adverse events (CAEs) after treatment with BRAF and MEK inhibitors in patients with melanoma remain incompletely characterized. To determine the association of BRAF and MEK inhibitor treatment with CAEs in patients with melanoma compared with BRAF inhibitor alone.Method: PubMed, Cochrane, Embase and Web of Science were systematically searched for BRAF and MEK inhibitors from database inception through 10 May 2024. Randomized clinical trials reporting on CAEs in patients with melanoma being treated with BRAF and MEK inhibitors compared with patients with melanoma being treated with BRAF inhibitor monotherapy were selected. Pooled Risk ratios (RRs) and 95% CIs were determined using random-effects analyses. The selected end points were alopecia, cutaneous squamous-cell carcinoma, hyperkeratosis, keratoacanthoma, palmoplantar erythrodysaesthesia syndrome, palmoplantar keratoderma, rash, photosensitivity reaction, and skin papilloma. All-grade and high-grade (≥3) CAEs were recorded.Results: Comparing with BRAF and MEK inhibitors, treatment with BRAF inhibitors alone was associated with an increased risk of rash (RR, 0.73; 95% CI, 0.54–0.99; p = 0.039; I² = 88%), alopecia (RR, 0.28; 95% CI, 0.20–0.41; P < 0.001; I² = 76%), hyperkeratosis (RR, 0.30; 95% CI, 0.22–0.41; P < 0.001; I² = 56%), palmoplantar erythrodysaesthesia syndrome (RR, 0.21; 95% CI, 0.10–0.47; P < 0.001; I² = 81%), palmoplantar keratoderma (RR, 0.39; 95% CI, 0.26–0.57; P < 0.001; I² = 29%), Skin papilloma (RR, 0.25; 95% CI, 0.12–0.52; P < 0.001; I² = 77%), cutaneous squamous-cell carcinoma (RR, 0.21; 95% CI, 0.11–0.42; P < 0.001; I² = 50%), and keratoacanthoma (RR, 0.22; 95% CI, 0.12–0.40; P < 0.001; I² = 0%).Conclusion: Therapy with BRAF and MEK inhibitors was associated with a lower risk of CAEs, especially rash, alopecia, hyperkeratosis, palmoplantar erythrodysaesthesia syndrome, palmoplantar keratoderma, skin papilloma, cutaneous squamous-cell carcinoma, and keratoacanthoma, compared with BRAF inhibitor alone. The risks of photosensitivity reaction was similar between the assessed groups. The findings may help to balance between beneficial melanoma treatment and cutaneous morbidity and mortality.

This study was performed to assess the efficacy and safety of a topical diclofenac solution in patients with knee osteoarthritis (OA). PubMed, Embase, Cochrane Library, Web of Science, and Scopus databases were searched for randomized controlled trials until June 2020. The WOMAC pain, stiffness, physical function subscales, pain on walking, and the occurrence of adverse events were pooled to comprehensively analyse the efficacy and safety of topical diclofenac solution. All statistical analyses were conducted using Review Manager 5.3 software. Five RCTs were included, which provided high‐quality evidence. In comparison to the vehicle control, the mean differences for WOMAC pain, stiffness, and physical function subscales, as well as pain on walking, were all statistically significant in favor of topical diclofenac solution. The safety of topical diclofenac solution was similar to the vehicle control, apart from adverse events involving application‐site skin reactions. Topical diclofenac solution is effective and safe for use in patients with knee OA, but may cause minor skin reactions.

Background: Immune checkpoint inhibitor (ICI) plus chemotherapy is effective in advanced gastric or gastroesophageal junction (G/GEJ) cancer. This study aims to evaluate the clinical effect of first-line immunotherapy in combination with chemotherapy for advanced G/GEJ cancer. Methods: PubMed, Web of Science, Embase and Cochrane databases were systematically searched from the inception of the databases to December 2021. Randomized trials comparing ICI plus chemotherapy with chemotherapy in first-line treatment for advanced G/GEJ cancer were included. The outcomes were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs). Analyses were performed in Stata 14.0 software. The study protocol was registered with PROSPERO, number CRD42022300907. Results: Five trials were included for analysis, involving 2, 814 patients. ICI plus chemotherapy can significantly improve OS (hazards ratio [HR], 0.86; 95% CI 0.78-0.94; P = .002), PFS (HR, 0.79; 95% CI 0.63-0.99; P ＜ .001) and ORR (relative ratio [RR], 1.20; 95% CI 1.11-1.30; P < .001). In safety analyses, there were no significant differences in incidence of all AEs, treatment-related adverse event (TRAE), TRAE of grade 3 or higher, serious TRAE and TRAE leading to death between two arms ( P > .05). Conclusions: ICI plus chemotherapy is more effective first-line treatment for advanced G/GEJ cancer in contrast to chemotherapy regrading to improving OS, PFS and ORR, without increasing TRAE risk. This study will redefine the role of ICI in combination with chemotherapy in the first-line setting for G/GEJ cancer, and provide reference for clinical treatment.