Radiomics based on HRCT can predict RP-ILD and mortality in anti-MDA5 + dermatomyositis patients: a multi-center retrospective study.

OBJECTIVES: To assess the effectiveness of HRCT-based radiomics in predicting rapidly progressive interstitial lung disease (RP-ILD) and mortality in anti-MDA5 positive dermatomyositis-related interstitial lung disease (anti-MDA5 + DM-ILD). METHODS: From August 2014 to March 2022, 160 patients from Institution 1 were retrospectively and consecutively enrolled and were randomly divided into the training dataset (n = 119) and internal validation dataset (n = 41), while 29 patients from Institution 2 were retrospectively and consecutively enrolled as external validation dataset. We generated four Risk-scores based on radiomics features extracted from four areas of HRCT. A nomogram was established by integrating the selected clinico-radiologic variables and the Risk-score of the most discriminative radiomics model. The RP-ILD prediction performance of the models was evaluated by using the area under the receiver operating characteristic curves, calibration curves, and decision curves. Survival analysis was conducted with Kaplan-Meier curves, Mantel-Haenszel test, and Cox regression. RESULTS: Over a median follow-up time of 31.6 months (interquartile range: 12.9-49.1 months), 24 patients lost to follow-up and 46 patients lost their lives (27.9%, 46/165). The Risk-score based on bilateral lungs performed best, attaining AUCs of 0.869 and 0.905 in the internal and external validation datasets. The nomogram outperformed clinico-radiologic model and Risk-score with AUCs of 0.882 and 0.916 in the internal and external validation datasets. Patients were classified into low- and high-risk groups with 50:50 based on nomogram. High-risk group patients demonstrated a significantly higher risk of mortality than low-risk group patients in institution 1 (HR = 4.117) and institution 2 cohorts (HR = 7.515). CONCLUSION: For anti-MDA5 + DM-ILD, the nomogram, mainly based on radiomics, can predict RP-ILD and is an independent predictor of mortality.

Insulin resistance levels predicted metabolic improvement and weight loss after metabolic surgery in Chinese patients with type 2 diabetes.

BACKGROUND: The causes for failure of metabolic improvement and inadequate weight loss after metabolic surgery (MS) in Chinese patients with type 2 diabetes (T2D) have not been fully elucidated. The effect of insulin resistance (IR) on the outcome of T2D, hypertension, hyperlipidemia, and obesity after MS in Chinese patients with T2D and a body mass index (BMI) of 25-32.5 kg/m2 warrants further study. OBJECTIVES: Patients with T2D and a BMI of 25-32.5 kg/m2 who underwent MS between July 2019 and June 2021 were included. SETTING: University hospital, China. METHODS: IR levels were evaluated with the glucose disposal rate (GDR). Improvement of T2D, hypertension, and hyperlipidemia was assessed with the composite triple endpoint (CTEP), and weight loss was assessed with the percent of total weight loss (%TWL). Partial correlation analysis, binary logistic regression analysis, multiple linear regression analysis, receiver operating characteristic curve (ROC) analysis, and subgroup analysis were used to analyze the relationship between the CTEP, %TWL at 1 year postoperative, and GDR preoperative. RESULTS: This study analyzed the data of 51 patients with T2D and a BMI of 25-32.5 kg/m2 (30 men and 21 women) with a mean preoperative GDR of 3.72 ± 1.48 mg/kg/min. Partial correlation coefficients between CTEP, %TWL, and GDR were .303 (P = .041) and .449 (P = .001), respectively. The preoperative GDR was significantly positively correlated with CTEP (OR = 1.610, P = .024) and %TWL (ß = 1.38, P = .003). The preoperative GDR predicted cutoff values of 4.36 and 5.35 mg/kg/min for CTEP attainment and %TWL ≥ 20%, respectively. CONCLUSION: IR levels predicted metabolic improvement and weight loss 1 year after MS in Chinese patients with T2D and a BMI of 25-32.5 kg/m2.

Sex-Specific Changes in Body Composition Following Metabolic and Bariatric Surgery Are Associated with the Remission of Metabolic Syndrome.

PURPOSE: Metabolic and bariatric surgery (MBS) is the most effective treatment for metabolic syndrome (MetS). However, the mechanism of MetS remission after MBS remains unclear. We aimed to explore the relationship between sex differences, body composition, and the remission of MetS after MBS. MATERIALS AND METHODS: Cross-sectional study of 80 patients with obesity and MetS who underwent MBS with case-control design. The International Diabetes Federation criteria were used to define MetS. Body composition was measured using dual-energy X-ray absorptiometry before and 1 year after the operation. In addition to calculating changes in MetS and its prevalence, we performed a multiple logistic regression to determine predictors of MetS remission. RESULTS: There were significant differences in body composition between males and females after MBS. Both males and females had significant improvements in the overall prevalence of MetS, decreasing from 100 to 21.74% (P <0.001) and from 100 to 35.29% (P <0.001), respectively. A higher percentage of visceral adipose tissue (VAT) reduction tends to be associated with a higher chance of MetS remission in men. In females, the MetS nonremission subgroup had a higher %Trunk lean body mass (LBM), and %Android LBM reduction than the remission subgroup, but the multiple logistic regression analysis result was not statistically significant. CONCLUSION: After MBS, reduced VAT might be related to MetS reversibility in males, while reduced LBM may result in MetS nonremission in females.

Effect of laparoscopic sleeve gastrectomy on mobilization of site-specific body adipose depots: a prospective cohort study.

BACKGROUND: Effect of bariatric surgery on mobilization of site-specific body adipose depots is not well investigated. Herein, the authors conducted a prospective cohort study to assess whether bariatric surgery can differentially affect specific fat storage pools and to further investigate correlations between site-specific fat mobilization and clinical outcomes. MATERIALS AND METHODS: In this single-centre prospective cohort study, 49 participants underwent laparoscopic sleeve gastrectomy (LSG) from 24 May 2022 to 20 October 2022 and underwent MRI to estimate subcutaneous fat area, visceral fat area (VFA), hepatic and pancreatic proton density fat fraction (PDFF) at baseline and 3 months after surgery. The protocol for this study was registered on clinicaltrials.gov. RESULTS: Among 49 patients who met all inclusion criteria, the median [interquartile range (IQR)] age was 31.0 (23.0-37.0) years, the median (IQR) BMI was 38.1 (33.7-42.2) kg/m 2 and 36.7% were male. Median (IQR) percentage hepatic PDFF loss was the greatest after bariatric surgery at 68.8% (47.3-79.7%), followed by percentage pancreatic PDFF loss at 51.2% (37.0-62.1%), percentage VFA loss at 36.0% (30.0-42.4%), and percentage subcutaneous fat area loss at 22.7% (17.2-32.4%) ( P <0.001). By calculating Pearson correlation coefficient and partial correlation coefficient, the positive correlations were confirmed between change in VFA and change in glycated haemoglobin ( r =0.394, P =0.028; partial r =0.428, P =0.042) and between change in hepatic PDFF and change in homoeostatic model assessment of insulin resistance ( r =0.385, P =0.025; partial r =0.403, P =0.046). CONCLUSIONS: LSG preferentially mobilized hepatic fat, followed by pancreatic fat and visceral adipose tissue, while subcutaneous adipose tissue was mobilized to the least extent. Reduction in visceral adipose tissue and hepatic fat is independently associated with the improvement of glucose metabolism after LSG.

Visible-Light-Promoted Direct C3-H Cyanomethylation of 2H-Indazoles.

The efficient visible-light-promoted cyanomethylation of 2H-indazoles in the presence of Ir(ppy)3 as the photocatalyst and bromoacetonitrile as the cyanomethyl radical source was achieved under mild conditions, providing a series of C3-cyanomethylated derivatives in good yields.

Disease-specific mortality and major adverse cardiovascular events after bariatric surgery: a meta-analysis of age, sex, and BMI-matched cohort studies.

BACKGROUND: Obesity is associated with a significant predisposition towards cardiovascular events and acts as an important risk factor for mortality. Herein, we conducted a comprehensive meta-analysis to estimate the protective effect of bariatric surgery on disease-specific mortality and major adverse cardiovascular events (MACEs) in patients with severe obesity. METHODS: PubMed and Embase were searched from inception to 4 June 2022. Eligible studies were age, sex, and BMI-matched cohort studies. The protocol for this meta-analysis was registered on PROSPERO (ID: CRD42022337319). RESULTS: Forty matched cohort studies were identified. Bariatric surgery was associated with a lower risk of disease-specific mortality including cancer mortality [hazard ratio with 95% confidence interval: 0.46 (0.37-0.58)], cardiovascular mortality [0.38 (0.29-0.50)], and diabetes mortality [0.25 (0.11-0.57)]. Bariatric surgery was associated with a lower incidence of MACEs [0.58 (0.51-0.66)] and its components including all-cause mortality [0.52 (0.47-0.58)], atrial fibrillation [0.79 (0.68-0.92)], heart failure [0.52 (0.42-0.65)], myocardial infarction [0.55 (0.41-0.74)], and stroke [0.75 (0.63-0.89)]. According to subgroup analysis on all-cause mortality, patients with severe obesity and type 2 diabetes benefited more from bariatric surgery than those with severe obesity only (heterogeneity between groups: P =0.001), while different surgical approaches brought similar benefits (heterogeneity between groups: P =0.87). CONCLUSIONS: This meta-analysis of 40 matched cohort studies supports that bariatric surgery reduces disease-specific mortality and incidence of both MACEs and its components in patients with severe obesity compared with nonsurgical subjects. Bariatric surgery deserves a more aggressive consideration in the management of severe obesity.

Evaluating the threshold limit value of acceptable exposure concentration for exposure to bioaerosols in a wastewater treatment plant: Reverse-quantitative microbial risk assessment and sensitivity analysis.

Agitation operations produce numerous pathogenic bioaerosols in WWTPs1. QMRA2 can determine risks of persons exposed to these bioaerosols. However, QMRA framework cannot help stakeholders in immediately deciding whether a risk is intolerable. Thus, evaluating threshold of acceptable exposure concentration is an urgent issue but is still rarely addressed in WWTPs. This study analyzed TLV3 benchmarks of E. coli and S. aureus bioaerosols emitted from a WWTP by reverse-QMRA. Furthermore, variance of input parameters was clarified by sensitivity analysis. Results showed that, under conservative and optimistic estimates, TLV of technicians was 1.52-2.06 and 1.26-1.68 times as large as those of workers, respectively; wearing mask drive TLV up to 1-2 orders of magnitude; TLV of M4 was at most 1.33 and 1.31 times as large as that of RD5, respectively. For sensitivity analysis, removal fraction by equipping PPE enlarge TLV for effortlessly obtaining an acceptable assessment result; exposure time was dominant when without PPE excepting the scenario of technicians exposed to E. coli bioaerosol. This study helps establish threshold guidelines for bioaerosols in WWTPs and contribute innovative perspectives for stakeholders.

The predictive value of trunk/leg fat ratio for type 2 diabetes mellitus remission after bariatric surgery: A new observation and insight.

Background: Emerging evidence supported the significant role of body composition and fat distribution in the etiology and pathogenesis of Type 2 diabetes mellitus (T2DM). Objective: To assess the predictive value of representative parameters of body composition and fat distribution for T2DM remission after bariatric surgery. Methods: A total of 72 patients with T2DM who underwent bariatric surgery in our center between September 2010 and December 2018 were included in this retrospective observational study. Diabetes remission was defined according to the American Diabetes Association criteria released in 2021. Body fat percentage, skeletal muscle index, Android/Gynoid ratio and trunk/leg fat ratio were derived from dual-energy X-ray absorptiometry and assessed. Results: A total of 40 patients (56%) achieved remission among 72 patients. Patients in the remission group had higher body fat percentage and lower trunk/leg fat ratio than those in the non-remission group. The area under the receiver operating characteristic curve (AUC) for predicting T2DM remission was higher for trunk/leg fat ratio (0.784), compared to BMI (AUC 0. 0.690) and body fat percentage (AUC 0.688). The prediction model (AUC 0.883) including age, duration of T2DM, and trunk/leg fat ratio performed better than the ABCD score (AUC 0.809) and the DiaRem score (AUC 0.792). A nonlinear relationship was observed between trunk/leg fat ratio and BMI. Conclusion: Trunk/leg fat ratio is a promising predictor for T2DM remission after bariatric surgery.

Telitacicept for Recalcitrant Cutaneous Manifestations of Systemic Lupus Erythematosus: A Case Report and Review of the Literature.

Telitacicept is a novel humanized, recombinant transmembrane activator and calcium modulator and cyclophilin ligand interactor and the Fc portion (TACI-Fc) fusion protein, designed to neutralize the activity of both B-cell lymphocyte stimulator (BLyS) and a proliferation-inducing ligand (APRIL). On March 9, 2021, telitacicept received its first approval in China for the treatment of adult patients with active, autoantibody-positive systemic lupus erythematosus (SLE). Additionally, on April 15, 2020, the U.S. Food and Drug Administration (FDA) granted fast track designation to telitacicept for the treatment of SLE. Clinical studies of telitacicept in several other indications, including IgA nephropathy, multiple sclerosis, myasthenia gravis, neuromyelitis optica spectrum disorders, rheumatoid arthritis and Sjögren's syndrome are underway in China. This is the first case that reports telitacicept successfully treated a SLE patient with refractory cutaneous involvement, which provides a potential therapeutic option for recalcitrant cutaneous manifestations of SLE. Furthermore, we review reported studies of BLyS targeted treatments for mucocutaneous lupus. Telitacicept appears to have activity in refractory cutaneous involvement of SLE and clinical trials are warranted to further assess this potential therapy.

Clinical value of YKL-40 in patients with polymyositis/dermatomyositis: A cross-sectional study and a systematic review.

INTRODUCTION: We performed a cross-sectional study to investigate the clinical usefulness of YKL-40 in patients with dermatomyositis (DM) and conducted a systematic review to summarize the clinical value of YKL-40 in patients with polymyositis (PM)/DM. MATERIALS AND METHODS: A cross-sectional study and a systematic review were performed to study the clinical value of YKL-40 in patients with PM/DM. Serum YKL-40 level was detected using enzyme-linked immunosorbent assay, and its association with clinical and laboratory parameters was analyzed. In the systematic review, electronic databases of OVID Embase, OVID Medline, and web of science were searched to collect studies that reported clinical use of YKL-40 in patients with PM/DM. RESULTS: In the cross-sectional study, serum YKL-40 level was higher in patients with DM than in healthy controls (median [interquartile range]: 84.09 [52.72-176.4] ng/ml versus 27.37 [12.30-53.58] ng/ml, p < 0.0001). Serum levels of YKL-40 were associated with the course of DM (r = -0.469, p < 0.001), CRP (r = 0.303, p = 0.043), CK (r = 0.263, p = 0.037), and global disease activity (r = 0.628, p < 0.001). The area under the ROC curve was 0.835 (95% confidence interval 0.751-0.920). In the systematic review, a total of four studies were included with moderate to high quality. Serum level of YKL-40 has the possibility for diagnosing PM/DM, identifying PM/DM patients with interstitial lung disease (ILD) or rapid progress ILD, and predicting death. CONCLUSION: Serum YKL-40 level is a possible useful biomarker for PM/DM diagnosis and may be used to predict prognosis.

Bioinformatics analysis of potential Key lncRNA-miRNA-mRNA molecules as prognostic markers and important ceRNA axes in gastric cancer.

Gastric cancer (GC), the fifth most common malignancy worldwide, has an extremely poor prognosis at the advanced stage or the early stage if inadequately treated. Long noncoding RNAs (lncRNAs), microRNAs (miRNAs) and mRNAs all function as competing endogenous RNAs (ceRNAs) that target and regulate each other. Changes in their expression and their regulatory bioprocesses play important roles in GC. However, the roles of key RNAs and their regulatory networks remain unclear. In this study, RNA profiles were extracted from The Cancer Genome Atlas database, and R language was used to discover the differentially expressed (DE) lncRNAs, miRNAs and mRNAs in GC. Then, the DERNAs were paired by miRcode, miRDB, TargetScan and DIANA, and the ceRNA network was further constructed and visualized using Cytoscape. Moreover, a functional enrichment analysis was performed using Metascape. Afterward, the "survival" package was employed to identify candidate prognostic targets (DERNA-os) in the ceRNA network. Ultimately, the ceRNA network was analyzed to identify crucial lncRNA/miRNA/mRNA axes. Based on 374 gastric adenocarcinoma and gastric adenoma samples, 283 DEceRNAs (69 lncRNAs, 10 miRNAs, and 204 mRNAs) were identified. The 204 mRNAs were significantly enriched in some interesting functional clusters, such as the trans-synaptic signaling cluster and the protein digestion and absorption cluster. The ceRNA network consisted of 43 ceRNAs (13 lncRNAs, 2 miRNAs, and 28 mRNAs) that were related to prognosis. Among them, 2 lncRNAs (LNC00469 and AC010145.1) and 1 mRNA (PRRT4) were potential new biomarkers. In addition, according to the lncRNA/miRNA/mRNA regulatory relationships among the 43 ceRNAs, we identified four axes that might play important roles in the progression of GC and investigated the potential mechanism of the most promising axis (POU6F2-AS2/hsa-mir-137/OPCML) in promoting the proliferation and invasiveness of GC.

The effect of community-acquired pneumonia on myocardial injury in systemic lupus erythematosus: Insights from cardiac magnetic resonance.

OBJECTIVES: Myocardial injury (MInj) in systemic lupus erythematosus (SLE) has been observed in several studies. However, clinical predictors of MInj remain unclear. We aim to explore the effects of community-acquired pneumonia (CAP) on MInj in SLE patients according to cardiac magnetic resonance (CMR) T1 mapping. METHODS: SLE patients with or without CAP and healthy controls underwent CMR screening. The CMR protocol included: cines, T1- and T2 mapping, and late gadolinium enhancement (LGE). Clinical characteristics, CMR findings, and T1 mapping measuremments were compared between subgroups. Clinical assessment was performed on the subjects. RESULTS: Thirty-eight SLE patients were screened, including 18 patients with CAP (CAP group) and 20 age- and gender-matched patients without CAP (non-CAP group) as well as 26 healthy controls. The platelet count of CAP group was higher than the non-CAP group (p = 0.015). Compared with the health control group, native T1 was higher in the CAP group (p < 0.001) and the non-CAP group (p = 0.002). ECV was higher in the CAP group (p < 0.001) and the non-CAP group (p = 0.002). The LV ejection fraction (p = 0.049) and RV ejection fraction (p = 0.026) of the CAP group was lower than that of the healthy control group, whereas no significant difference was observed between non-CAP and healthy control groups. CONCLUSIONS: This is the first study that assesses the effects of CAP on MInj of SLE patients by CMRI T1 mapping. We highlight SLE patients with CAP who are at increased risk of MInj, manifesting as myocardial inflammation, diffuse myocardial fibrosis, and decreased ventricular function.

Effects of medications on incidence and risk of knee and hip joint replacement in patients with osteoarthritis: a systematic review and meta-analysis.

BACKGROUND: This systematic review and meta-analysis aimed to investigate the incidence and risk of knee and hip replacement in patients with osteoarthritis (OA) treated with different medications. METHODS: OVID MEDLINE, OVID EMBASE, Cochrane and Web of Science electronic databases were searched from inception to May 4th, 2022. Clinical trials, including randomized controlled trials, cohort studies and case-control studies, were selected. The meta-analysis effect size was estimated using either incidence with 95% confidence intervals (CIs) or odds ratio (OR)/relative risk (RR) with 95% CIs. The risk of bias and heterogeneity among studies were assessed and analyzed. RESULTS: Forty studies were included, involving 6,041,254 participants. The incidence of joint replacement in patients with OA varied according to the study design and treatments. The incidence of knee arthroplasty varied from 0 to 70.88%, while the incidence of hip arthroplasty varied from 11.71 to 96.43%. Compared to non-users, bisphosphonate users had a reduced risk of knee replacement (RR = 0.71, 95% CI: 0.66-0.77; adjusted hazard ratio [aHR] = 0.76, 95% CI: 0.70-0.83). Compared to intra-articular corticosteroid users, hyaluronic acid (HA) users had a higher risk of knee arthroplasty (RR = 1.76, 95% CI: 1.38-2.25). No publication bias was observed. CONCLUSIONS: Bisphosphonate treatment is associated with a reduced risk of knee replacement. More studies are needed to validate our results due to the limited number of eligible studies and high heterogeneity among studies.

What are the disease burden and its sensitivity analysis of workers exposing to Staphylococcus aureus bioaerosol during warm and cold periods in a wastewater treatment plant?

Biological treatment in wastewater treatment plants releases high amounts of pathogenic bioaerosols. Quantitative microbial risk assessment is a framework commonly used for quantitative risk estimation for occupational exposure scenarios. However, the quantitative contributions of health-risk-estimate inputted parameters remain ambiguous. Therefore, this research aimed to study the disease burden of workers exposed to Staphylococcus aureus bioaerosol during warm and cold periods and strictly quantify the contributions of the inputted parameters by sensitivity analysis on the basis of Monte Carlo simulation. Results showed that the disease health risk burden of workers in the warm period was 1.15-6.11 times higher than that of workers in the cold period. The disease health risk burden of workers without personal protective equipment was 23.83-36.55 times higher than that of workers with personal protective equipment. Sensitivity analysis showed that exposure concentration and aerosol ingestion rate were the first and second predominant factors, respectively; the sensitivity partitioning coefficient of the former was 1.17-1.35 times the value of the latter. In addition, no remarkable differences were revealed in the sensitivity percentage ratio between warm and cold periods. The findings could contribute to the mitigation measures for the management of public health risks.

Bariatric Surgery Improves Nonalcoholic Fatty Liver Disease: Systematic Review and Meta-Analysis.

PURPOSE: Bariatric surgery has been uncovered to relieve nonalcoholic fatty liver disease (NAFLD) in patients with obesity, while current studies have neutral or opposite results. This systematic review and meta-analysis aimed to evaluate the effects of bariatric surgery on NAFLD in patients with obesity. MATERIALS AND METHODS: PubMed, Embase, Cochrane Central, and Web of Science databases were performed to obtain publications containing comparison results of liver biopsy before and after bariatric surgery in obesity. Primary outcomes were biopsy-confirmed remission of NAFLD and NAFLD activity scores. Secondary outcomes were liver function. This study was registered with PROSPERO, CRD42021240346. RESULTS: Thirty-seven studies were included. After bariatric surgery, a biopsy-confirmed resolution of steatosis was improved in 56% of patients, ballooning degeneration in 49%, inflammation in 45%, and fibrosis in 25%. Bariatric surgery significantly decreased mean NAFLD activity scores. RYGB achieved the most obviously improvements in steatosis, and SG attained the most notably ameliorations in fibrosis. The percentage of patients with improved steatosis and hepatic fibrosis in Asian countries was higher than non-Asian countries. The reduction of ALT and AST was 11.95U/L and 6.44 U/L after surgery. CONCLUSION: Our study has revealed that bariatric surgery brought out significantly resolution of NAFLD in individuals with obesity. RYGB and SG have been proved to be of benefit to many hepatic parameters, and the improvement of liver steatosis and fibrosis, particularly in Asian countries. It is strongly suggested that bariatric surgery should be considered as a novel treatment for NAFLD.

Effects of Roux-en-Y Gastric Bypass Versus Sleeve Gastrectomy on Body Composition for Patients with a BMI > 35 kg/m2 at 1 Year After Surgery.

PURPOSE: Effects of Roux-en-Y gastric bypass (RYGB) versus sleeve gastrectomy (SG) on body composition have not been well compared. This meta-analysis aimed to compare changes in fat mass (FM) and lean tissue mass (LTM) for patients with a BMI > 35 kg/m2 at 1 year after RYGB and SG. METHODS: PubMed, EMBASE, the Cochrane Library, and ClinicalTrials.gov were searched ending in December 2021 for eligible studies which reported baseline and postsurgical BMI, FM, and LTM. RESULTS: Of 17 eligible studies, 831 patients were included, 484 following RYGB and 347 following SG. Weighted mean differences (WMD) and 95% confidence intervals (CI) were from a random-effects model. For patients with a BMI > 35 kg/m2, RYGB resulted in a more substantial reduction of BMI (- 14.13 kg/m2 [95%CI - 14.74, - 13.53] versus - 11.96 kg/m2 [95%CI - 12.81, - 11.11], P < 0.001) and FM (- 26.22 kg [95%CI - 28.31, - 24.12] versus - 21.50 kg [95%CI - 25.52, - 17.48], P = 0.042) than SG, and a relatively weaker impact on LTM (- 8.28 kg [95%CI - 9.33, - 7.22] versus - 10.12 kg [95%CI - 11.55, - 8.68], P = 0.043). CONCLUSION: This meta-analysis study indicates that RYGB is superior to SG in reducing excess FM for patients with a BMI > 35 kg/m2 and seems to be more beneficial when LTM preservation is taken into consideration.

Safety and efficacy of SHR4640 combined with febuxostat for primary hyperuricemia: a multicenter, randomized, double-blind, phase II study.

BACKGROUND: To evaluate the safety, tolerability, and efficacy of SHR4640, a highly selective urate transporter-1 inhibitor, in combination with febuxostat, in patients with primary hyperuricemia. METHODS: In this randomized, double-blind, parallel-controlled phase II study, patients whose fasting serum uric acid (sUA) levels were ⩾ 480 µmol/L at screening with gout or sUA levels were ⩾ 420 µmol/L lasting for at least 3 months without gout, either with sUA levels ⩾ 540 µmol/L at screening or sUA levels ⩾ 480 µmol/L with comorbidities at screening, were enrolled. Patients were randomized (1:1:1) to receive SHR4640 10 mg plus febuxostat 80 mg, SHR4640 10 mg plus febuxostat 40 mg, and SHR4640 5 mg plus febuxostat 20 mg orally once daily. The primary end point was the incidence of treatment-emergent adverse events (TEAEs). RESULTS: A total of 93 patients were randomized and received treatment. TEAEs occurred in 55.9% of patients. The incidence of TEAEs was comparable among all the groups. Serious TEAEs occurred in one patient (1.1%), with no deaths observed. The proportion of patients who achieved the target sUA levels by week 4 was 79.3%, 96.6%, and 75.0% in the SHR4640 10 mg plus febuxostat 80 mg, SHR4640 10 mg plus febuxostat 40 mg, and SHR4640 5 mg plus febuxostat 20 mg groups, respectively. The mean percent reduction of sUA was 59.7%, 63.7%, and 41.8%, respectively. CONCLUSION: SHR4640 plus febuxostat exhibited a tolerable safety profile and substantial sUA lowering activity in patients with primary hyperuricemia. REGISTRATION: www.chinadrugtrials.org.cn; CTR 20192429.

Characterization and clinical significance of biventricular mechanics in patients with systemic lupus erythematosus by 3T cardiovascular magnetic resonance tissue tracking.

BACKGROUND: Detecting impaired left ventricle (LV) or right ventricle (RV) mechanics could aid in fully understanding the process of cardiac involvement in patients with systemic lupus erythematosus (SLE). This study aimed to evaluate biventricular strain parameters derived from cardiac magnetic resonance (CMR) tissue tracking in SLE patients and their association with other clinical variables. METHODS: A group of 47 SLE patients and 27 healthy controls were enrolled and underwent CMR examination, including cine and late gadolinium enhancement (LGE) imaging. Aside from RV strain parameters in the radial direction, biventricular global peak strain and peak systolic/diastolic global strain rate in radial, circumferential, and longitudinal directions were assessed for each participant. Multivariate linear regression analysis was used to analyze the factors related to the biventricular strain parameters. Receiver operating characteristic (ROC) analysis was used to identify RV dysfunction. RESULTS: Compared with the controls, part of the biventricular strain parameters in the SLE subgroup with preserved ejection fraction (EF) were impaired, which was more significant in the SLE subgroup with reduced EF (all P<0.05). The SLE patients with RV dysfunction (15/47) included patients with LV dysfunction (8/47). The RVEF was associated with impaired LV global peak strain and peak diastolic strain rate in the SLE patients (absolute value of ß=0.406-0.715, all P<0.05). The LV LGE in SLE patients (12/47) was associated with LV global longitudinal peak strain and peak diastolic global longitudinal strain rate (ß=0.378 and -0.342; all P<0.05). There were independent correlations between pulmonary arterial hypertension and RV global longitudinal peak strain, anti-ribonucleoprotein (RNP) antibody and RV global circumferential peak strain, and pericardial effusion and RV peak diastolic global circumferential strain rate, respectively (ß=0.319, 0.359, and -0.285, respectively; all P<0.05). The LV global longitudinal peak strain had greater diagnostic accuracy for RV dysfunction RV dysfunction [area under curve (AUC): 0.933, cut-off value: -13.38%). CONCLUSIONS: Biventricular strain parameters derived from CMR are sensitive markers of subclinical ventricular function impairment before EF reduction at an early stage of SLE. Biventricular strain analysis could be considered for inclusion in early cardiac functional assessment in SLE patients, particularly LV global longitudinal peak strain, which might assist in therapeutic decision-making and disease monitoring.

Cardiovascular events in adult polymyositis and dermatomyositis: a meta-analysis of observational studies.

OBJECTIVES: We aimed to review whether PM and DM patients have an increased cardiovascular (CV) risk, including ischaemic heart disease (IHD), cerebrovascular accidents (CVA) and venous thromboembolism. METHODS: We searched PubMed, Embase and the Cochrane database for relevant studies from inception to February 2021. RESULTS: Twenty-two studies comprising 25 433 patients were included. With PM/DM vs general populations, the risk was significantly increased for CV events [relative risk (RR) = 2.37, 95% CI: 1.86, 3.02]. The RR of CV events for males with PM/DM was higher than for females (RR = 1.43; 95% CI: 1.17, 1.74). PM/DM patients followed for one to five years had a significantly higher CV risk than those followed for five to ten years (RR = 3.51, 95% CI: 1.95, 6.32). The risk was increased for North Americans (RR = 4.28, 95% CI: 2.57, 7.11), Europeans (RR = 2.29, 95% CI: 1.58, 3.31) and Asians (RR = 2.03, 95% CI: 1.41, 2.90). Our meta-analysis found that the elevated CV event risk was related to PM (RR = 2.35, 95% CI: 1.51, 3.66) and DM (RR = 2.55, 95% CI: 1.66, 3.93). Subgroup analyses showed that the risk was significantly increased for IHD (RR = 1.76, 95% CI: 1.40, 2.21), CVA morbidity (RR = 1.31, 95% CI: 1.03, 1.67) and ischaemic stroke (IS) (RR = 1.47, 95% CI: 1.26, 1.73), with no statistically significant increased risk of haemorrhagic stroke mortality (RR = 1.43, 95% CI: 0.92, 2.21). The CV event risk was increased for venous thromboembolism (RR = 4.60, 95% CI: 3.17, 6.66), deep venous thrombosis (RR = 5.53, 95% CI: 3.25, 9.39) and pulmonary embolism (RR = 5.26, 95% CI: 2.62, 10.55). CONCLUSION: This meta-analysis found that PM/DM patients had a ∼2.37 times increased CV risk, particularly males diagnosed in the previous five years. PM/DM may be an independent risk factor for developing IHD, IS, deep venous thrombosis and pulmonary embolism.

Effects of medications on incidence and risk of knee and hip joint replacement in patients with osteoarthritis: a systematic review and meta-analysis

Abstract Background: This systematic review and meta-analysis aimed to investigate the incidence and risk of knee and hip replacement in patients with osteoarthritis (OA) treated with different medications. Methods: OVID MEDLINE, OVID EMBASE, Cochrane and Web of Science electronic databases were searched from inception to May 4th, 2022. Clinical trials, including randomized controlled trials, cohort studies and case-control studies, were selected. The meta-analysis effect size was estimated using either incidence with 95% confidence intervals (CIs) or odds ratio (OR)/relative risk (RR) with 95% CIs. The risk of bias and heterogeneity among studies were assessed and analyzed. Results: Forty studies were included, involving 6,041,254 participants. The incidence of joint replacement in patients with OA varied according to the study design and treatments. The incidence of knee arthroplasty varied from 0 to 70.88%, while the incidence of hip arthroplasty varied from 11.71 to 96.43%. Compared to non-users, bisphosphonate users had a reduced risk of knee replacement (RR = 0.71, 95% CI: 0.66-0.77; adjusted hazard ratio [aHR] = 0.76, 95% CI: 0.70-0.83). Compared to intra-articular corticosteroid users, hyaluronic acid (HA) users had a higher risk of knee arthroplasty (RR = 1.76, 95% CI: 1.38-2.25). No publication bias was observed. Conclusion: Bisphosphonate treatment is associated with a reduced risk of knee replacement. More studies are needed to validate our results due to the limited number of eligible studies and high heterogeneity among studies.