Macrophage-Derived GSDMD Plays an Essential Role in Atherosclerosis and Cross Talk Between Macrophages via the Mitochondria-STING-IRF3/NF-κB Axis.

BACKGROUND: Macrophages play a crucial role in atherosclerotic plaque formation, and the death of macrophages is a vital factor in determining the fate of atherosclerosis. GSDMD (gasdermin D)-mediated pyroptosis is a programmed cell death, characterized by membrane pore formation and inflammatory factor release. METHODS: ApoE-/- and Gsdmd-/- ApoE-/- mice, bone marrow transplantation, and AAV (adeno-associated virus serotype 9)-F4/80-shGSDMD (shRNA-GSDMD) were used to examine the effect of macrophage-derived GSDMD on atherosclerosis. Single-cell RNA sequencing was used to investigate the changing profile of different cellular components and the cellular localization of GSDMD during atherosclerosis. RESULTS: First, we found that GSDMD is activated in human and mouse atherosclerotic plaques and Gsdmd-/- attenuates the atherosclerotic lesion area in high-fat diet-fed ApoE-/- mice. We performed single-cell RNA sequencing of ApoE-/- and Gsdmd-/- ApoE-/- mouse aortas and showed that GSDMD is principally expressed in atherosclerotic macrophages. Using bone marrow transplantation and AAV-F4/80-shGSDMD, we identified the potential role of macrophage-derived GSDMD in aortic pyroptosis and atherosclerotic injuries in vivo. Mechanistically, GSDMD contributes to mitochondrial perforation and mitochondrial DNA leakage and subsequently activates the STING (stimulator of interferon gene)-IRF3 (interferon regulatory factor 3)/NF-κB (nuclear factor kappa B) axis. Meanwhile, GSDMD regulates the STING pathway activation and macrophage migration via cytokine secretion. Inhibition of GSDMD with GSDMD-specific inhibitor GI-Y1 (GSDMD inhibitor Y1) can effectively alleviate the progression of atherosclerosis. CONCLUSIONS: Our study has provided a novel macrophage-derived GSDMD mechanism in the promotion of atherosclerosis and demonstrated that GSDMD can be a potential therapeutic target for atherosclerosis.

Efficacy and safety of Water Vapor Thermal Therapy in the treatment of benign prostate hyperplasia: a systematic review and single-arm Meta-analysis.

BACKGROUND: Benign prostatic hyperplasia (BPH) is a common chronic condition among men aged 50 or older, causing voiding and obstructive lower urinary tract symptoms. Water vapor thermal therapy (WVTT) using the Rezum® system is a new minimally invasive surgical technique that is increasingly reported as a treatment for BPH. METHODS: The protocol was submitted to the PROSPERO registry. We searched PubMed, Web of Science, Embase, Cochrane Library and ClinicalTrials.gov up to July 29, 2022. Quality assessment was carried out by a 20-item checklist form prepared by the Institute of Health Economics (IHE). Double arcsine transformation was performed to stabilize the variance of the original ratio. When I2 > 50%, the random effect model was used to calculate the pooled parameters. Otherwise, the fixed effect model was used. 95% confidence intervals (CIs) were calculated. A leave-one-out sensitivity analysis was performed to evaluate the impact of each study on the pooled outcomes, and finally, Egger's test was used to assess publication bias. RESULTS: A total of seven single-arm observational studies and one random controlled trial, including 1015 patients, were included. One year after WVTT, the International Prostate Symptom Score decreased by 11.37 (95% CI: -12.53, -10.21), the IPSS Quality of Life scale decreased by 2.59 (95% CI: -2.92, -2.26), the maximum urine flow rate increased by 5.26 ml/s (95% CI: 4.53, 5.99), and the postvoid residual decreased by 13.18 ml (95% CI: -24.32, -2.03). The most common complication was dysuria, with a pooled incidence of 21% (95% CI: 14%, 29%), and the second most common complication was hematuria, with a pooled incidence of 14% (95% CI: 10%, 18%). The pooled incidence of retreatment was 3% (95% CI: 2%, 5%). CONCLUSIONS: WVTT is an attractive alternative to medication or more invasive surgical procedures and can serve as first-line therapy for men with BPH.

Association Between Thromboelastography and Coronary Heart Disease.

BACKGROUND Thromboelastography (TEG) is a novel blood viscoelasticity detection method revealing blood coagulation status and has been reported to be helpful in predicting clinical outcomes in patients with cardiovascular diseases (CVD). In this study, we aimed to investigate the association between TEG and CVD. MATERIAL AND METHODS A single-center case-control study was performed. Individuals who took TEG tests at Tongji Hospital in Wuhan, China from 2015 to 2019 were included. The nearest-neighbor Mahalanobis matching with replacement, within propensity score calipers of 0.25 was used to control the covariate imbalance between CVD patients and controls. Logistic regression analyses were conducted to assess the relationship between TEG and CVD. Subgroup and sensitivity analyses were performed to evaluate the robustness of the association between TEG and CVD. RESULTS After matching, a total of 151 participants were included in this study, with 83 patients having CVD (49 patients having coronary heart disease [CHD] and 34 patients having an ischemic stroke). By comparison, CHD patients had a significantly higher maximum amplitude (MA) (P=0.02) than controls. After multivariable adjustment, MA (OR 1.11, 95% CI 1.01-1.24, P=0.04) was independently associated with CHD. The association between MA and CHD remained robust across subgroups and in sensitivity analyses. CONCLUSIONS The current study suggests that MA is significantly associated with CHD. Enhanced platelet reactivity as described by high MA might be associated with risk of CHD. The exact role of MA in the measurement of CHD risk needs to be further examined in large-scale prospective cohort studies.

Comparison of Thulium Laser Resection of Bladder Tumors and Conventional Transurethral Resection of Bladder Tumors for Non-Muscle-Invasive Bladder Cancer.

INTRODUCTION: The thulium laser resection of bladder tumors (TmLRBT) was increasingly used in the treatment of non-muscle-invasive bladder cancer (NMIBC) recently, and here we report the relevant outcomes of our institution to evaluate its efficacy and safety. METHODS: We retrospectively collected the data of NMIBC patients who underwent either TmLRBT or transurethral resection of bladder tumor (TURBT). The baseline characteristics and perioperative outcomes were compared in these 2 groups. RESULTS: The TmLRBT had a higher rate of detrusor identification than TURBT (97.4 vs. 87.6%, p = 0.001). After screening, 134 patients who underwent TmLRBT and 152 patients who received TURBT were enrolled in the analysis, and their baseline characteristics were similar. During the TURBT, 24 (15.8%) obturator nerve reflexes and 9 (5.9%) bladder perforations occurred, while none happened during the TmLRBT. After surgery, TmLRBT patients had fewer postoperative gross hematuria (38.1 vs. 96.7%, p < 0.001) and postoperative irrigation (27.6 vs. 92.7%, p < 0.001), and its irrigation duration was significantly shorter (2.3 vs. 3.3 day, p < 0.001). During the follow-up, no significant difference in the recurrence rate was detected (p = 0.315). CONCLUSIONS: TmLRBT is a safer technique than conventional TURBT in the treatment of NMIBC, and it could offer better specimens for pathologic assessment while the cancer control was not compromised.

Revealing the coexistence of differentiation and communication in an endemic hare, Lepus yarkandensis (Mammalia, Leporidae) using specific-length amplified fragment sequencing.

BACKGROUND: The Yarkand hare (Lepus yarkandensis Günther, 1875) is endemic to oasis and desert areas around the Tarim Basin in the Xinjiang Uyghur Autonomous Region of northwest China; however, genome-wide information for this species remains limited. Moreover, the genetic variation, genetic structure, and phylogenetic relationships of Yarkand hare from the plateau mountain regions have not been reported. Thus, we used specific-length amplified fragment sequencing (SLAF-seq) technology to evaluate the genetic diversity of 76 Yarkand hares from seven geographic populations in the northern and southwestern parts of the Tarim Basin to investigate single-nucleotide polymorphism (SNP) marker-based population differentiation and evolutionary processes. Selective sweep analysis was conducted to identify genetic differences between populations. RESULTS: Using SLAF-seq, a total of 1,835,504 SNPs were initially obtained, of which 308,942 high-confidence SNPs were selected for further analysis. Yarkand hares exhibited a relatively high degree of genetic diversity at the SNP level. Based on pairwise FST estimates, the north and southwest groups showed a moderate level of genetic differentiation. Phylogenetic tree and population structure analyses demonstrated evident systematic phylogeographical structure patterns consistent with the geographical distribution of the hares. Hierarchical analysis of molecular variation further indicated that genetic variation was mainly observed within populations. Low to moderate genetic differentiation also occurred among populations despite a common genomic background, likely due to geographical barriers, genetic drift, and differential selection pressure of distinct environments. Nevertheless, the observed lineage-mixing pattern, as indicated by the evolutionary tree, principal component analysis, population structure, and TreeMix analyses, suggests a certain degree of gene flow between the north and southwest groups. This may be related to the migration of hares to high-altitude water sources southwest of the basin during glacial climatic oscillations, as well as river re-diffusion and oasis restoration in the basin following the glacial period. We also identified candidate genes, and their associated gene ontology terms and pathways, related to the adaptation of Yarkand hares to different environmental habitats. CONCLUSIONS: The identified genome-wide SNPs, genetic diversity, and population structure of Yarkand hares expand our understanding of the genetic background of this endemic species and provide valuable insights into its environmental adaptation, allowing for further exploration of the underlying mechanisms.

Safety and efficacy of thulium laser resection of bladder tumors versus transurethral resection of bladder tumors: a systematic review and meta-analysis.

The thulium laser resection of bladder tumor (TmLRBT) is widely used in the treatment of non-muscle-invasive bladder cancer (NMIBC), and we conduct this study to compare the safety and efficacy of TmLRBT with transurethral resection of bladder tumor (TURBT). A comprehensive literature research was conducted using multiple databases, and comparative studies evaluating the safety and efficacy of TmLRBT and TURBT were included. For continuous outcomes, the weighted mean difference (WMD) was used to measure the difference, whereas the risk ratio (RR) with a 95% confidence interval (CI) was calculated for binary variables. Overall, ten studies with 1558 patients enrolled were included in the meta-analysis. The baseline characteristics of two groups were comparable. The operative time (p = 0.24) and catheterization time (p = 0.41) of two groups were similar but the TmLRBT group had a shorter length of hospital stay (p = 0.04). TmLRBT was related to fewer intraoperative complications including obturator nerve reflex (p < 0.001) and bladder perforation (p < 0.001). Although the rate of postoperative irrigation did not significantly differ in our analysis (p = 0.28), the TmLRBT was related to a significantly shorter duration of irrigation (p = 0.004). Besides, the TmLRBT group had a higher rate of identification of detrusor (p = 0.02). However, TmLRBT did not suggest significantly better cancer control than TURBT including the overall recurrence (p = 0.052), 1-year recurrence (p = 0.23), and 2-year recurrence (p = 0.40). Compared with conventional TURBT, the TmLRBT showed superior safety and non-inferior efficacy in cancer control. TmLRBT could also provide high-quality specimens for pathology diagnosis; therefore, it is an as effective option for NMIBC.

Adjunctive medical expulsive therapy with tamsulosin for repeated extracorporeal shock wave lithotripsy: a systematic review and meta-analysis.

PURPOSE: To evaluate the efficacy of adjunctive medical expulsive therapy (MET) with tamsulosin for the promotion of stone fragments clearance for repeated extracorporeal shock wave lithotripsy (ESWL). MATERIALS AND METHODS: This meta-analysis was conducted by systematic search for randomized controlled trial (RCT) studies in PubMed/Medline, Scopus, Cochrane Library, Web of Science databases in January 2020, which compared tamsulosin with either placebo or non-placebo control for repeated ESWL. The primary endpoint was stone-free rate (SFR), the second endpoints were stone clearance time and complications. The quality assessment of included studies was performed by using the Cochrane System and Jadad score. RESULTS: 7 RCTs were included in this meta-analysis. Tamsulosin provided higher SFR (for stones larger than 1cm, OR: 5.56, p=0.0003), except for patients with stones less than 1cm. For patients with renal stones (OR: 2.97, p=0.0005) or upper ureteral stones (OR: 3.10, p=0.004), tamsulosin can also provide a higher SFR. In addition, tamsulosin provided a shorter stone clearance time (WMD: -9.40, p=0.03) and lower pain intensity (WMD=-17.01, p< 0.0001) and incidences of steinstrasse (OR: 0.37, p=0.0002). CONCLUSION: Adjunctive MET with tamsulosin is effective in patients with specific stone size or location that received repeated ESWL. However, no well-designed RCT that used computed tomography for the detection and assessment of residual stone fragments was found. More studies with high quality and the comparison between tamsulosin and secondary ESWL are needed in the future.

Biatrial enlargement as a predictor for reablation of atrial fibrillation.

Purpose: We aimed to determine whether biatrial enlargement could predict reablation of atrial fibrillation after first ablation. Methods: 519 consecutive patients with drug resistant atrial fibrillation [paroxysmal AF (PAF) 361, non-PAF 158] who underwent catheter ablation in Capital Medical University Xuanwu hospital between 2009 and 2014 were enrolled. Biatrial enlargement (BAE) was diagnosed according to trans-thoracic echocardiography (TTE). Ablation strategies included complete pulmonary vein isolation (PVI) in all patients and additional linear ablation across mitral isthmus, left atrium roof, left atrium bottom and tricuspid isthmus, or electrical cardioversion on the cases that AF could not be terminated by PVI. Anti-arrhythmic drugs or cardioversion were used to control the recurred atrial arrhythmia in patients with recurrence of atrial fibrillation after ablation. Reablation was advised when the drugs were resistant or that patient could not tolerate. Risk factors for reablation were analyzed. Results: After 33.11±21.45months, 170 patients recurred atrial arrhythmia, and reablation were applied in 117 patients. Multivariate Cox regression analysis demonstrated that that biatrial enlargement (BAE, HR 1.755, 95%CI 1.153-2.670, P=0.009) was an independent predictor for reablation and was associated with reablation (Log rank P=0.007). Conclusion: Biatrial enlargement is an independent risk predictor for the reablation in atrial fibrillation patients after first ablation.

First-line atezolizumab in addition to bevacizumab plus chemotherapy for metastatic, nonsquamous non-small cell lung cancer: A United States-based cost-effectiveness analysis.

BACKGROUND: The IMpower150 trial found that adding atezolizumab to the combination of bevacizumab and chemotherapy improved survival for patients with metastatic, nonsquamous non-small cell lung cancer (NSCLC). However, considering the high cost of immunotherapy, there is a need to assess its value by considering both efficacy and cost. The current study evaluated the cost-effectiveness of atezolizumab in the first-line setting for the treatment of patients with metastatic NSCLC from the US payer perspective. METHODS: A Markov model was developed to compare the lifetime cost and effectiveness of the combination of atezolizumab, bevacizumab, carboplatin, and paclitaxel (ABCP) with the combination of bevacizumab, carboplatin, and paclitaxel (BCP) and carboplatin and paclitaxel (CP) in the first-line treatment of patients with metastatic NSCLC. Life-years (LYs), quality-adjusted LYs (QALYs), and lifetime costs were estimated. One-way and probabilistic sensitivity analyses were performed to evaluate the model uncertainty. Additional subgroup analyses were performed. RESULTS: ABCP provided an additional 0.413 QALYs (0.460 LYs) and 0.738 QALYs (0.956 LYs), respectively, compared with BCP and CP. The corresponding incremental costs were $234,998 and $381,116, respectively. The incremental cost-effectiveness ratio for ABCP was $568,967 per QALY compared with BCP and $516,114 per QALY compared with CP. The subgroup analysis demonstrated that PD-L1 expression of ≥50% on tumor cells (TC3) or ≥10% on immune cells (IC3) decreased the incremental cost-effectiveness ratio to $464,703 per QALY. CONCLUSIONS: From the perspective of the US payer, ABCP is estimated to not be cost-effective compared with BCP or CP in the first-line setting for patients with metastatic, nonsquamous NSCLC at a willingness-to-pay threshold of $100,000 per QALY.

Ubiquitous expressed transcript promotes tumorigenesis by acting as a positive modulator of the polycomb repressive complex 2 in clear cell renal cell carcinoma.

BACKGROUND: The ubiquitous expressed transcript (UXT) plays a key role in various tumors by regulating transcriptional activity of multiple transcription factors, including androgen receptor (AR). However, the role of UXT in clear cell renal cell carcinoma (ccRCC) is still unknown. METHODS: Yeast two-hybrid screening, GST pull-down and co-immunoprecipitation assays were performed to detect the interacting protein of UXT. Chromatin immunoprecipitation (ChIP) was performed to investigate the levels of histone H3 lysine 27 trimethylation at the HOXA9 promoters. CCK-8 assays, colony formation assays and Transwell assays were performed to detect the proliferation, colony formation, migration and invasion of renal cancer cells. Quantitative PCR analysis was performed to detect the expressions of UXT in human ccRCC samples. RESULTS: The enhancer of zeste homolog 2 (EZH2) is a novel UXT interacting protein and UXT interacts with EZH2 in the nucleus. In addition, UXT interacts with the polycomb repressive complex 2 (PRC2) through directly binding to EZH2 and suppressor of zeste 12 homolog (SUZ12), but not to embryonic ectoderm development (EED). Moreover, the UXT activates EZH2 histone methyltransferase activity by facilitating EZH2 binding with SUZ12. We further provided striking evidences that knockdown of UXT inhibits proliferation, colony formation, migration and invasion of renal cancer cells, in an EZH2-dependent manner. Importantly, the upregulation of UXT expression was observed in clinical ccRCC samples, and the high expression level of UXT was associated with advanced stage, distant metastasis and poor overall survival in patients with ccRCC. CONCLUSION: The UXT is a novel regulator of the PRC2 and acts as a renal cancer oncogene that affects the progression and survival of ccRCC patients.

Efficacy of low-intensity extracorporeal shock wave therapy for the treatment of chronic prostatitis/chronic pelvic pain syndrome: A systematic review and meta-analysis.

AIMS: Low-intensity extracorporeal shock wave therapy (Li-ESWT) has been applied in urolithiasis and some chronic diseases. We performed a systematic review and meta-analysis to assess the efficacy of Li-ESWT for the treatment of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). METHODS: A comprehensive search of MEDLINE, Web of Science, EMBASE, and the Cochrane Library to January 6, 2019 was performed for randomized controlled trials (RCTs) reporting on patients with CP/CPPS treated with Li-ESWT compared with the sham group. Outcomes were evaluated based on the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI). The quality assessment of included studies was performed by the Cochrane System. RESULTS: Six publications involving five RCTs with 280 patients were assessed in this review. NIH-CPSI total score, pain domain and quality of life (QOL) were significantly better in the Li-ESWT group than those in the control group at the endpoint (P < 0.00001, P = 0.003, and P < 0.00001), 4 weeks (P < 0.00001, P = 0.0002 and P < 0.00001) and 12 weeks (P < 0.00001, P < 0.00001, and P = 0.0002) after the treatment. For urinary score, significant difference existed at 12 weeks after the treatment (P = 0.006). At 24 weeks after treatment, there was no significant difference between the two groups in NIH-CPSI total score (P = 0.26), pain domain (P = 0.32), urinary score (P = 0.07), and QOL (P = 0.29). CONCLUSIONS: Li-ESWT showed great efficacy for the treatment of CP/CPPS at the endpoint and during the follow-up of 4 and 12 weeks, though the efficacy of 24-week follow-up was not significantly different due to insufficient data. Generally, Li-ESWT is a promising minimal invasive method for the treatment of CP/CPPS.

Mini-Percutaneous Nephrolithotomy with Ureter Catheter: A Safe and Effective form of mPCNL Offers Better Quality of Life.

OBJECTIVE: To compare outcomes and postoperative quality of life (QoL) among patients with kidney stone who received mini-percutaneous nephrolithotomy (mPCNL), partial tubeless mPCNL or mPCNL with ureter catheter in a prospective randomized clinical trial. METHODS: From May 2017 to December 2017, 60 patients with kidney stone who underwent mPCNL were randomized into 3 groups: Group I (mPCNL), Group II (partial tubeless mPCNL), Group III (mPCNL with ureter catheter). We evaluated perioperative characteristics, stone clearance, analgesic requirements and QoL by using the Wisconsin Stone QOL questionnaire. RESULTS: The age, gender, stone diameter, body mass index, length of operation, drop in hemoglobin and stone-free rates for the 3 groups were similar among these groups. However, the postoperative visual analog scale and the analgesic requirement in Group II were significantly the lowest (p < 0.05). According to Wisconsin Stone QOL questionnaire, compared to Group I, statistical significant difference in the QoL was seen in Group II and III, indicating a meaningful and immediate improvement in the postoperative QoL following mPCNL. CONCLUSION: Compared with standard and partial tubeless mPCNL, mPCNL with ureter catheter is a safe and useful form of mPCNL, which can offer better QoL and is more cost effective.

Secondary Management for Recurrent Ureteropelvic Junction Obstruction after Pyeloplasty: A Comparison of Re-Do Robot-Assisted Laparoscopic Pyeloplasty and Conventional Laparoscopic Pyeloplasty.

OBJECTIVE: To describe and analyze our experience with secondary robot-assisted laparoscopic pyeloplasty (RALP) and conventional laparoscopic pyeloplasty (LP) in treating recurrent ureteropelvic junction obstruction (UPJO) after primary pyeloplasty. METHODS: Patients who underwent secondary RALP or LP for recurrent UPJO were retrospectively analyzed. Baseline characteristics, detailed history of previous pyeloplasty, operative profile and follow-up data were collected and analyzed. RESULTS: Among 29 patients presented with recurrent UPJO, 15 patients underwent secondary RALP. Both groups (RALP or LP) were comparable in baseline characteristics and detailed history of previous pyeloplasty. The mean operative time, suturing time, and hospitalization time of patients in RALP group were significantly less than those in LP group. The mean operative time of RALP group was 2.1 h, while the mean operative time of LP group was 3.23 h. The average suturing time of LP (62.43 min) is about 3 times that of RALP (21.47 min). The overall mean follow-up data was 23 months. The success rate of the RALP group and LP group was 87.7 and 85.7% respectively. CONCLUSION: Compared to LP, RALP may be a better choice for the treatment of recurrent UPJO. Further high-quality clinical studies are needed to confirm the superior nature of RALP.

Pure Small Cell Carcinoma of Prostate: A Report of 8 Cases.

PURPOSE: To describe characteristics of pure small cell carcinoma of prostate (SCCP) and assess the prognostic factors. PATIENTS AND METHODS: We summarized data of pure SCCP from published studies and ours and made Kaplan-Meier analysis and Cox regression to evaluate prognosis factors. RESULTS: A total of 2,213 patients with prostate cancer was identified, of which eight (0.36%) patients were pure SCCP. The mean age at diagnosis was 61 years old. And there were 2 patients diagnosed at 34 and 50 years old respectively. Symptoms of these patients were similar to patients with prostate adenocarcinoma. Serum prostate specific antigen of 7 patients was at normal level. Five patients received chemotherapy, average overall survival (OS) was 9.75 months; 3 only received conservative treatment, average OS was 4 months. By univariate and multivariate Cox analysis, chemotherapy is an independent predictor of survival. Kaplan-Meier analysis demonstrated that chemotherapy was associated with longer OS. CONCLUSION: Clinical characteristics, examination and treatment strategy of pure SCCP are very different from prostate adenocarcinoma. According to the data from published studies and from our studies, the average survival of patients receiving chemotherapy is longer than those who received other treatment modalities.

Use of Implantable Cardioverter Defibrillators in Heart Failure Patients and Risk of Mortality: A Meta-Analysis.

BACKGROUND: The purpose of this study was to evaluate the effect of implantable cardioverter defibrillators (ICD) in heart failure (HF) patients compared to pharmacologic/conventional management. MATERIAL AND METHODS: We searched PubMed, Embase, and Springer Link Library databases up to February 10th, 2014. Pooled risk ratio (RR) and 95% confidence interval (CI) for the mortality of the patients with HF were collected and calculated in a fixed-effects model or a random-effects model, as appropriate. Summary effect estimates were also stratified by sex and follow-up time. Egger's regression asymmetry tests were utilized for publication bias detection. RESULTS: A total of 7 separate studies including 15 520 patients (10 801 ICD cases and 4719 controls) with HF were considered in the meta-analysis. The overall estimates showed that ICD could statistically significantly reduce the mortality of male (RR=0.73, 95% CI: 0.66-0.80) and female (RR=0.75, 95% CI: 0.63-0.90) patients. In addition, the further stratification subgroup analysis indicated that ICD presented a significant reduction (male: RR=0.72, 95% CI: 0.64-0.81; female: RR=0.69, 95% CI: 0.56-0.85) of mortality after 2-3 years of ICD therapy. The RR (95% CI) effects of mortality after 4-5 years of ICD therapy for males and females were 0.76 (0.51-1.14) and 0.96 (0.68-1.37), respectively. CONCLUSIONS: This meta-analysis suggests that ICD could reduce HF patient mortality despite the sex difference.

Case report: Regression after low-dose glucocorticoid therapy in a case of acute immune myocarditis induced by anti-PD-1 therapy for NSCLC.

Background: PD-1 inhibitors exhibit efficacy in managing unresectable/metastatic driver gene-negative NSCLC, albeit with potential immune-related adverse events (irAEs). Among these, immune checkpoint inhibitor-associated myocarditis (ICI-M) is rare yet lethal. This study presents the initial successful instance of ICI-M in a lung cancer patient, rescued by low-dose glucocorticoids post-deterioration during treatment. Case summary: A 78-year-old male with a medical history of stage IV pT3N2M1 NSCLC underwent four cycles of palliative chemotherapy, resulting in stable disease (SD). Subsequent to declining further chemotherapy, the patient was transitioned to a targeted therapy regimen comprising Anlotinib in conjunction with PD-1 inhibitor immunotherapy. On the 26th day post-administration of the PD-1 inhibitor, the patient manifested Grade 2 immune-mediated myocarditis. Treatment encompassing 1mg/kg methylprednisolone combined with immunoglobulin shock therapy was initiated for 3 days, achieving symptomatic control. Nonetheless, upon tapering methylprednisolone dosage to 4-8mg/3-4d, the condition deteriorated, necessitating transfer to the intensive care unit. Methylprednisolone dosage was escalated to 80mg/day for 3 days, followed by gradual reduction by one-third to two-thirds weekly, culminating in the patient's safe discharge from the hospital. Conclusion: Immune-related myocarditis linked to checkpoint inhibitors is often managed effectively with high-dose glucocorticoid therapy. However, in Asian populations, low-dose glucocorticoids are increasingly utilized for salvage therapy, yielding favorable outcomes and improving prognosis compared to European populations.

Prediction of initial objective response to drug-eluting beads transcatheter arterial chemoembolization for hepatocellular carcinoma using CT radiomics-based machine learning model.

Objective: A prognostic model utilizing CT radiomics, radiological, and clinical features was developed and validated in this study to predict an objective response to initial transcatheter arterial chemoembolization with drug-eluting beads (DEB-TACE) for hepatocellular carcinoma (HCC). Methods: Between January 2017 and December 2022, the baseline clinical characteristics and preoperative and postoperative follow-up imaging data of 108 HCC patients who underwent the first time treatment of DEB-TACE were analyzed retrospectively. The training group (n = 86) and the validation group (n = 22) were randomly assigned in an 8:2 ratio. By logistic regression in machine learning, radiomics, and clinical-radiological models were constructed separately. Finally, the integrated model construction involved the integration of both radiomics and clinical-radiological signatures. The study compared the integrated model with radiomics and clinical-radiological models using calibration curves, receiver operating characteristic (ROC) curves, and decision curve analysis (DCA). Results: The objective response rate observed in a group of 108 HCC patients who received initial DEB-TACE treatment was found to be 51.9%. Among the three models, the integrated model exhibited superior predictive accuracy in both the training and validation groups. The training group resulted in an area under the curve (AUC) of 0.860, along with sensitivity and specificity values of 0.650 and 0.913, respectively. Based on the findings from the validation group, the AUC was estimated to be 0.927. Additionally, it was found that values of sensitivity and specificity were 0.875 and 0.833, respectively. In the validation group, the AUC of the integrated model showed a significant improvement when contrasted to the clinical-radiological model (p = 0.042). Nevertheless, no significant distinction was observed in the AUC when comparing the integrated model with the radiomics model (p = 0.734). The DCA suggested that the integrated model demonstrates advantageous clinical utility. Conclusion: The integrated model, which combines the CT radiomics signature and the clinical-radiological signature, exhibited higher predictive efficacy than either the radiomics or clinical-radiological models alone. This suggests that during the prediction of the objective responsiveness of HCC patients to the first DEB-TACE treatment, the integrated model yields superior outcomes.

The effect of obesity on the outcome of thoracic endovascular aortic repair: a systematic review and meta-analysis.

Background: Obesity is a well-known predictor for poor postoperative outcomes of vascular surgery. However, the association between obesity and outcomes of thoracic endovascular aortic repair (TEVAR) is still unclear. This systematic review and meta-analysis was performed to assess the roles of obesity in the outcomes of TEVAR. Methods: We systematically searched the Web of Science and PubMed databases to obtain articles regarding obesity and TEVAR that were published before July 2023. The odds ratio (OR) or hazard ratio (HR) was used to assess the effect of obesity on TEVAR outcomes. Body mass index (BMI) was also compared between patients experiencing adverse events after TEVAR and those not experiencing adverse events. The Newcastle-Ottawa Scale was used to evaluate the quality of the enrolled studies. Results: A total of 7,849 patients from 10 studies were included. All enrolled studies were high-quality. Overall, the risk of overall mortality (OR = 1.49, 95% CI [1.02-2.17], p = 0.04) was increased in obese patients receiving TEVAR. However, the associations between obesity and overall complications (OR = 2.41, 95% CI [0.84-6.93], p = 0.10) and specific complications were all insignificant, including stroke (OR = 1.39, 95% CI [0.56-3.45], p = 0.48), spinal ischemia (OR = 0.97, 95% CI [0.64-1.47], p = 0.89), neurological complications (OR = 0.13, 95% CI [0.01-2.37], p = 0.17), endoleaks (OR = 1.02, 95% CI [0.46-2.29], p = 0.96), wound complications (OR = 0.91, 95% CI [0.28-2.96], p = 0.88), and renal failure (OR = 2.98, 95% CI [0.92-9.69], p = 0.07). In addition, the patients who suffered from postoperative overall complications (p < 0.001) and acute kidney injury (p = 0.006) were found to have a higher BMI. In conclusion, obesity is closely associated with higher risk of mortality after TEVAR. However, TEVAR may still be suitable for obese patients. Physicians should pay more attention to the perioperative management of obese patients.

Metabolic clues to aging: exploring the role of circulating metabolites in frailty, sarcopenia and vascular aging related traits and diseases.

Background: Physical weakness and cardiovascular risk increase significantly with age, but the underlying biological mechanisms remain largely unknown. This study aims to reveal the causal effect of circulating metabolites on frailty, sarcopenia and vascular aging related traits and diseases through a two-sample Mendelian Randomization (MR) analysis. Methods: Exposures were 486 metabolites analyzed in a genome-wide association study (GWAS), while outcomes included frailty, sarcopenia, arterial stiffness, atherosclerosis, peripheral vascular disease (PAD) and aortic aneurysm. Primary causal estimates were calculated using the inverse-variance weighted (IVW) method. Methods including MR Egger, weighted median, Q-test, and leave-one-out analysis were used for the sensitive analysis. Results: A total of 125 suggestive causative associations between metabolites and outcomes were identified. Seven strong causal links were ultimately identified between six metabolites (kynurenine, pentadecanoate (15:0), 1-arachidonoylglycerophosphocholine, androsterone sulfate, glycine and mannose) and three diseases (sarcopenia, PAD and atherosclerosis). Besides, metabolic pathway analysis identified 13 significant metabolic pathways in 6 age-related diseases. Furthermore, the metabolite-gene interaction networks were constructed. Conclusion: Our research suggested new evidence of the relationship between identified metabolites and 6 age-related diseases, which may hold promise as valuable biomarkers.

Physical frailty, genetic predisposition, and incident arrhythmias.

BACKGROUND: Cross-sectional evidence suggests a possible link between frailty and atrial fibrillation (AF). It remains unclear whether frailty and incident arrhythmias are longitudinally associated. This study aimed to determine whether the frailty phenotype is longitudinally associated with incident arrhythmias, especially AF. METHODS: In this prospective cohort of UK Biobank, individuals with arrhythmias at baseline, those without data for frailty phenotype, and no genetic data were excluded. Five domains of physical frailty, including weight loss, exhaustion, low physical activity, low grip strength, and slow gait speed, were assessed. A total of 142 single-nucleotide polymorphisms was used to calculate the polygenic risk score (PRS) for AF. Hospital inpatient records and death records were used to identify incident arrhythmias. RESULTS: This study included 464 154 middle-aged and older adults (mean age 56.4 ± 8.1 years, 54.7% female) without arrhythmia at baseline. During a median follow-up of 13.4 years (over 5.9 million person-years), 46 454 new-onset arrhythmias cases were recorded. In comparison with non-frailty, the multivariable-adjusted hazard ratios (HRs) of AF were 1.12 (95% CI: 1.09, 1.15, P < 0.0001) and 1.44 (95% CI: 1.36, 1.51, P < 0.0001) for participants with pre-frailty and frailty, respectively. Similar associations were observed for other arrhythmias. We found that slow gait speed presented the strongest risk factor in predicting all arrhythmias, including AF (HR 1.34, 95% CI: 1.30, 1.39), bradyarrhythmias (HR 1.30, 95% CI: 1.22, 1.37), conduction system diseases (HR 1.29, 95% CI: 1.22, 1.36), supraventricular arrhythmias (HR 1.32, 95% CI: 1.19, 1.47), and ventricular arrhythmias (HR 1.37, 95% CI: 1.25, 1.51), with all P values <0.0001. In addition to slow gait speed, weight loss (HR 1.13, 95% CI: 1.09, 1.16, P < 0.0001) and exhaustion (HR 1.11, 95% CI: 1.07, 1.14, P < 0.0001) were significantly associated with incident AF, whereas insignificant associations were observed for physical activity (HR 1.03, 95% CI: 0.996, 1.08, P = 0.099) and low grip strength (HR 1.00, 95% CI: 0.97, 1.03, P = 0.89). We observed a significant interaction between genetic predisposition and frailty on incident AF (P for interaction <0.0001), where those with frailty and the highest tertile of PRS had the highest risk of AF (HR 3.34, 95% CI: 3.08, 3.61, P < 0.0001) compared with those with non-frailty and the lowest tertile of PRS. CONCLUSIONS: Physical pre-frailty and frailty were significantly and independently associated with incident arrhythmias. Although direct causal inference still needs to be further validated, these results suggested the importance of assessing and managing frailty for arrhythmia prevention.