Baihetiya Azhati

Objectives: Neoadjuvant therapy with immune checkpoint inhibitors and tyrosine kinase inhibitors has been shown to reduce the tumour size and thrombus length in patients with renal cell carcinoma with venous tumour thrombus (RCC‐VTT). This study aimed to evaluate the effectiveness and safety of neoadjuvant tislelizumab plus pazopanib in patients with RCC‐VTT. Patients and Methods: From November 2021 to January 2024, nine patients with RCC‐VTT were included in this retrospective study. All patients received neoadjuvant tislelizumab (200 mg intravenously every 3 weeks) and pazopanib (800 mg orally once daily), followed by surgery. Key effectiveness outcomes included the objective response rate (ORR) of the primary tumour, the percentage change in VTT length and safety. Results: Among the nine patients with RCC‐VTT, the median age was 58 years (range, 39–78). Following neoadjuvant tislelizumab plus pazopanib, six patients achieved partial response in the primary tumour and three had stable disease, yielding an ORR of 66.7%. The VTT length decreased from 4.9 cm (range, 1.1–9.3 cm) to 3.8 cm (range, 0–8.1 cm), with a median reduction of 29.2% (range, −153.1% to 100.0%). Treatment‐related adverse events (TRAEs) of any grade and grade 3 were reported in 88.9% and 55.6% of patients, respectively. The common TRAEs of any grade were vomiting (77.8%), fatigue (33.3%), pruritus (33.3%), weight loss (33.3%), poor appetite (33.3%), pruritus (33.3%) and hepatic impairment (33.3%). No grade 4–5 TRAEs or deaths were observed. Conclusion: The neoadjuvant combination of tislelizumab and pazopanib effectively reduced tumour size and thrombus length, narrowing the surgical scope and potentially leading to better postoperative outcomes.

First and foremost, we extend our sincere gratitude to Zhang et al for their dedication to advancing scientific knowledge. True scientific progress is achieved through iterative research, critical discourse, and persistent pursuit of accurate solutions. We are deeply inspired by the commitment demonstrated by Zhang et al and aspire to emulate their dedication in our future endeavors. It is imperative to acknowledge, however, that while we hold great respect for the perspectives presented by Zhang et al, endorsing them may pose challenges. Whether considering contemporary methodological standards or the findings of previously published Mendelian randomization (MR) studies, convincing a broad audience presents inherent complexities. Their letter lacks sufficient evidence to support their views and urges us, along with many other researchers who have published ED-related MR studies, to reconsider and update our methodologies and article content.

Objective We aimed to explore the association between the leucocyte telomere length (LTL) and erectile dysfunction (ED) among a nationally representative sample of US adults. Design Secondary population-based study. Setting The National Health and Nutrition Examination Survey (NHANES) (2001–2002). Participants A total of 1694 male participants were extracted from the NHANES database for 2001–2002. Primary and secondary outcome measures The primary focus of the study was to determine the association between the LTL and ED, using multivariate logistic regression and restricted cubic spline models for examination. The secondary outcome measures involved conducting stratified subgroup analyses to exclude interactions of different variables with the LTL. Results Participants with ED had shorter LTLs than those without ED (pConclusion Our results demonstrated an inverted J-curve relationship between the LTL and ED. When the LTL was ≥1.037, the incidence of ED decreased with increasing LTL.

Previous observational studies have found a potential link between prostate disease, particularly prostate cancer (PCa), and kidney disease, specifically chronic renal disease (CKD), in relation to erectile dysfunction (ED), yet the causal relationship between these factors remains uncertain. The study sought to explore the potential causal association between prostate diseases, renal diseases, renal function, and risk of ED. In this study, 5 analytical approaches were employed to explore the causal relationships between various prostate diseases (PCa and benign prostatic hyperplasia), renal diseases (CKD, immunoglobulin A nephropathy, membranous nephropathy, nephrotic syndrome, and kidney ureter calculi), as well as 8 renal function parameters, with regard to ED. All data pertaining to exposure and outcome factors were acquired from publicly accessible genome-wide association studies. The methods used encompassed inverse variance weighting, MR-Egger, weighted median, simple mode, and weighted mode residual sum and outlier techniques. The MR-Egger intercept test was utilized to assess pleiotropy, while Cochran’s Q statistic was employed to measure heterogeneity. We employed inverse variance weighting MR as the primary statistical method to assess the causal relationship between exposure factors and ED. Genetically predicted PCa demonstrated a causal association with an elevated risk of ED (odds ratio, 1.125; 95% confidence interval, 1.066-1.186; P < .0001). However, no compelling evidence was found to support associations between genetically determined benign prostatic hyperplasia, CKD, immunoglobulin A nephropathy, membranous nephropathy, nephrotic syndrome, kidney ureter calculi, and the renal function parameters investigated, and the risk of ED. The risk of ED is considerably amplified in patients diagnosed with PCa, thereby highlighting the importance of addressing ED as a significant concern for clinicians treating individuals with PCa. This study’s strength lies in validating the PCa-ED association using genetic analysis, while its limitation is the heterogeneity in study results. The results of this study suggest a potential link between PCa and a higher risk of ED.

Aims: Female sexual dysfunction (FSD) is a considerably underestimated condition. It has been repeatedly reported that patients with cardiovascular diseases (CVD) may suffer from an increased risk of FSD. However, there is still a lack of comprehensive and systematic evaluation of various CVD and FSD. We aimed to elucidate the association between CVD and FSD through a comprehensive literature review and meta-analysis. Methods and results: The PubMed, Scopus, Embase, and Cochrane Library databases were systematically searched from inception to 28 February 2023. We identified all relevant studies reporting the risk of FSD in subjects with or without CVD. The associations between CVD and the risk of FSD were assessed by calculating pooled odds ratios (ORs) (cross-sectional studies) and risk ratios (RRs) (longitudinal studies) with 95% CIs. We employed random-effects models to account for potential heterogeneity, and the quality of the included studies was assessed using the Newcastle–Ottawa Scale. Fifty-four articles with 148 946 individuals were included in our meta-analysis. Compared with control subjects, subjects with CVD had a 1.51-fold increased risk of FSD (OR 1.51 95% CI, 1.34–1.69, P < 0.001, heterogeneity I2 = 91.4%, P < 0.001). Subgroup analyses indicated that the association between CVD and FSD remained significant in longitudinal studies (RR 1.50 95% CI, 1.21–1.86, P < 0.001, heterogeneity I2 = 86.7%, P < 0.001). Particularly, hypertension (OR 1.41 95% CI, 1.23–1.62, P < 0.001, heterogeneity I2 = 82.7%, P < 0.001), stroke (OR 1.81 95% CI, 1.54–2.12, P < 0.001, heterogeneity I2 = 0%, P < 0.423), and myocardial infarction (OR 2.07 95% CI, 1.60–2.67, P < 0.001 heterogeneity I2 = 82.4%, P < 0.001) were significantly associated with FSD. Meta-regression revealed that the primary sources of heterogeneity in FSD are attributable to adjustments for covariates, study design, and study population. Conclusion: Our meta-analysis indicated that patients with CVD suffer from a greater risk of developing FSD. Meanwhile, we validated these findings in longitudinal queues. Notably, conditions such as hypertension, stroke, and myocardial infarction demonstrated a significant association with the incidence of FSD.

The associations between sexual dysfunction (SD) and sleep disorders, sleep quality, and sleep duration remain unclear. To assess the relationship between sleep and SD through a literature review and meta-analysis. The PubMed, Scopus, Embase, Ovid MEDLINE, and Cochrane Library databases were systematically searched from inception to November 10, 2022. Pooled relative risks and 95% CIs were used to examine the association of sleep disorders with SD in longitudinal studies. Pooled odds ratios (ORs) and 95% CIs were used to examine the associations between SD and sleep disorders, sleep quality, and sleep duration in cross-sectional studies. Forty-three articles, including 11 longitudinal studies and 32 cross-sectional studies, were included in the quantitative analysis. The pooled relative risk of SD in patients with sleep disorders was 1.97 in longitudinal studies (95% CI, 1.46-2.67, P < .001; heterogeneity: I² = 95.0%, P < .001), while the pooled OR of SD in patients with sleep disorders was 2.05 in cross-sectional studies (95% CI, 1.76-2.39, P < .001; heterogeneity: I² = 91.4%, P < .001). When compared with controls, subjects with poor sleep quality had a 1.49-fold increased risk of SD (OR, 1.49; 95% CI, 1.31-1.71, P < .001; heterogeneity: I² = 73.4%, P < .001). In addition, short sleep duration was associated with the risk of SD (OR, 1.14; 95% CI, 1.06-1.22, P < .001; heterogeneity: I² = 0.0%, P = .849). The risk of SD is significantly increased in patients with sleep disorders and poor sleep quality, indicating that clinicians should monitor sleep among patients with SD. This study is the most comprehensive meta-analysis of the association between sleep and SD to date. However, different sleep disorders may have varying associations with sleep duration and sleep quality; thus, we could not identify the independent effects across the studies. Our systematic review and meta-analysis results suggest that sleep disorders, especially obstructive sleep apnea, increase the risk of SD in men and women. Poor sleep quality is significantly associated with SD. Short sleep duration is associated with an increased risk of SD.

Whether there is a connection between sexual dysfunction (SD) and prostate cancer (PCa) is controversial. We sought to review the interrelationship between SD and PCa and to determine whether there is a definitive risk of men developing PCa after suffering from SD. A complete search of the PubMed, Web of Science, Ovid MEDLINE, Embase, and Cochrane Library databases was performed to search for eligible studies published up to October 2022. The protocol for this meta-analysis is available from PROSPERO (ID: CRD42022342381). The associations between SD and the risk of PCa were assessed by calculating pooled ORs with 95% CIs, and the standard mean difference (SMD) and its 95% CI were used to assess the relationship between SD and prostate-specific antigen (PSA) levels or prostate volume (PV). Random-effects models were used to account for potential heterogeneity, and the Newcastle–Ottawa Scale (NOS) was used to evaluate the quality of the included studies. Twenty studies involving 215,626 individuals were included in our meta-analysis. Compared with controls, subjects with SD had a 1.62-fold increased risk of PCa (OR = 1.62, 95% CI, 1.77-2.23, P = .003; heterogeneity: I² = 97.8%, P < .001). Patients with SD had higher PSA levels than controls (SMD =0.07, 95% CI, 0.00 to 0.13, P = .041; heterogeneity: I² = 55.6%, P = .027). However, there was no association between SD and PV (SMD = 0.03, 95% CI, −0.05 to 0.11, P = .122; heterogeneity: I² = 48.5%, P = .100). Current evidence confirms a potential link between SD and the risk of PCa and that SD in PCa patients should be of concern to clinicians. The strength of this study is that it is to our knowledge the first meta-analysis of studies on the risk of PCa in men with SD. A limitation is that most of the studies included in this meta-analysis focused on ED. Our systematic review and meta-analysis results suggest that men with SD have a higher risk of PCa and higher PSA levels than men without SD. However, this is merely inferential, and causality cannot be determined based on the current data. Further longitudinal studies should be performed to validate our preliminary findings.

Bladder cancer is one of the most lethal malignancy in urological system, and 20–25% of bladder cancer patients are muscle invasive with unfavorable prognosis. However, the role of alternative splicing (AS) in muscle-invasive bladder cancer (MIBC) remains to be elucidated. Percent spliced in (PSI) data obtained from the Cancer Genome Atlas (TCGA) SpliceSeq database (n = 394) were utilized to evaluate the AS events in MIBC. Prognosis-associated AS events were screened out by univariate Cox regression. LASSO Cox regression was used to identify reliable prognostic patterns in a training set and further validated in a test set. Splicing regulatory networks were constructed by correlations between PSI of AS events and RNA expression of splicing factors. As a result, a total of 2589 prognosis-related AS events in MIBC were identified. Pathways of spliceosomal complex (FDR = 0.017), DNA-directed RNA polymerase II, core complex (FDR = 0.032), and base excision repair (FDR = 0.038) were observed to be significantly enriched. Additionally, we noticed that most of the prognosis-related AS events were favorable factors. According to the LASSO and multivariate Cox regression analyses, 15-AS-based signature was established with the area under curve (AUC) of 0.709, 0.823, and 0.857 at 1-, 3-, and 5- years, respectively. The MIBC patients were further divided into high- and low-risk groups based on median risk sores. Interestingly, we observed that the prevalence of FGFR3 with mutations and focal amplification was significantly higher in low-risk group. Functional and immune infiltration analysis suggested potential signaling pathways and distinct immune states between these two groups. Moreover, splicing correlation network displayed a regulatory mode of prognostic splicing factors (SF) in MIBC patients. This study not only provided novel insights into deciphering the possible mechanism of tumorgenesis and pathogenesis but also help refine risk stratification systems and potential treatment of decision-making for MIBC.