Marcelo Antonio Pinheiro Braga

Introduction The cardiovascular safety of testosterone-replacement therapy (TRT) for middle-aged and older men with low to low-normal levels of testosterone remains unclear. Methods We systematically searched PubMed, Embase, Cochrane Library, and ClinicalTrials.gov for randomized controlled trials (RCTs) comparing TRT versus placebo for men aged ≥ 40 years old with hypogonadism or low to low-normal testosterone levels (≤ 14 nmol/L), and at least 12 months of follow-up. We pooled risk ratios (RRs) with 95% confidence intervals (CIs) applying a random-effects model and using R version 4.3.1 for statistical analyses. Results We included 23 RCTs comprising 9280 men with testosterone deficiency, of whom 4800 (51.7%) were randomized to TRT. The mean age was 64.6 years, and the baseline total testosterone was 9.17 nmol/L. Placebo and TRT had similar rates of all-cause mortality (RR 0.85; 95% CI 0.60–1.19; p = 0.33). There was a significant increase in the incidence of cardiac arrhythmias (RR 1.53; 95% CI 1.20–1.97; p < 0.01). There was no significant difference between groups in cardiovascular mortality (RR 0.85; 95% CI 0.65–1.12; p = 0.25), stroke (RR 1.00; 95% CI 0.67–1.50; p = 0.99), and myocardial infarction (RR 0.94; 95% CI 0.69–1.28; p = 0.70). Conclusion In men with low to low-normal testosterone, aged 40 and above, TRT did not increase all-cause mortality, cardiovascular mortality, stroke, or myocardial infarction, but increased the incidence of cardiac arrhythmias. Registration PROSPERO identifier number CRD42024502421.

Aims: The comparative effectiveness of specific antihypertensive agents in preventing new-onset or recurrent atrial fibrillation (AF) remains under debate. This study aimed to evaluate the impact of different antihypertensive agents on AF risk. Methods and results: Medline, Cochrane, EMBASE, and ClinicalTrials.gov databases were searched for randomized controlled trials (RCTs) reporting AF events as a predefined outcome. Angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), dihydropyridine calcium channel blockers (CCBs), β-blockers, mineralocorticoid antagonists (MRAs), and thiazide diuretics (TDs) were analyzed. The risk ratio (RR) with a 95% credible interval (CrI) was calculated within a Bayesian random-effects network meta-analysis (NMA). Treatments were ranked using the surface under the cumulative ranking (SUCRA). Twenty-two RCTs randomising 66,156 patients with hypertension, diabetes, or AF were included. ACE inhibitors plus TD (RR 0.44; 95% CrI 0.23–0.82), ACE inhibitors (RR 0.66; 95% CrI 0.44–0.95), and ARBs (RR 0.52; 95% CrI 0.38–0.70) were associated with lower rates of new-onset or recurrent AF compared with CCBs. SUCRA ranked ACE inhibitors plus TD (0.86) as the best, followed by ARBs (0.77), MRAs (0.75), and ACE inhibitors (0.53) for preventing AF events. These findings were consistent across secondary and sensitivity analyses. Conclusion: In this NMA comparing multiple antihypertensive regimens in patients with hypertension, diabetes, or AF, ACE inhibitors plus TD, ACE inhibitors, and ARBs were the most effective in reducing AF events, outperforming CCBs. Registration: PROSPERO Database (CRD42024588765).

Background: The decision to perform segmental or extended colectomy in Lynch syndrome (LS) patients with colorectal cancer (CRC) is still controversial. Therefore, this systematic review and meta‐analysis aims to provide updated evidence for segmental versus extended colectomy in LS carriers with CRC.Methods: PubMed, Embase, and Cochrane Library were systematically searched for studies published until January 2024 comparing segmental and extended colectomies for CRC in patients with LS. Risk ratio (RR) was used to evaluate binary endpoints with 95% confidence intervals (CIs). Heterogeneity was assessed with the Cochran’s Q test and I² statistics. Statistical analysis was performed using the R Software, version 4.2.3.Results: A total of 14 studies comprising 2303 LS carriers with CRC, of whom 1724 (74.9%) patients underwent segmental colectomy and 579 (25.1%) patients underwent extended colectomy. Segmental colectomy significantly increased metachronous CRC (mCRC) (RR 2.87; 95% CI 2.03–4.07; and p < 0.01). There were no significant differences between groups for 5‐year overall survival (OS) (RR 0.92; 95% CI 0.82–1.03; and p = 0.14), 10‐year OS (RR 0.99; 95% CI 0.96–1.04; and p = 0.80), and mortality (RR 1.63; 95% CI 0.90–2.97; and p = 0.11). There were no significant linear associations between the outcome of mCRC and age at the time of primary CRC, sex, primary CRC location, and pathogenic LS variant.Conclusion: In this meta‐analysis, segmental colectomy significantly increased mCRC compared with extended colectomy after the first surgery for CRC in patients with LS. However, there were no significant differences between groups for 5‐ and 10‐year OS and mortality.

Background: The efficacy and safety of adjunctive low‐voltage area (LVA) ablation on outcomes of catheter ablation (CA) for atrial fibrillation (AF) remains uncertain.Methods: PubMed, Embase, Cochrane Library, and ClinicalTrials.gov were searched for randomized controlled trials (RCTs) comparing CA with versus without LVA ablation for patients with AF. Risk ratios (RR) with 95% confidence intervals (CI) were pooled with a random‐effects model. Our primary endpoint was recurrence of atrial tachyarrhythmia (ATA), including AF, atrial flutter, or atrial tachycardia. We used R version 4.3.1 for all statistical analyses.Results: Our meta‐analysis included 10 RCTs encompassing 1780 patients, of whom 890 (50%) were randomized to LVA ablation. Adjunctive LVA ablation significantly reduced recurrence of ATA (RR 0.76; 95% CI 0.67−0.88; p < .01) and reduced the number of redo ablation procedures (RR 0.54; 95% CI 0.35−0.85; p < .01), as compared with conventional ablation. Among 691 (43%) patients with documented LVAs on baseline substrate mapping, adjunctive LVA ablation substantially reduced ATA recurrences (RR 0.57; 95% CI 0.38−0.86; p < .01). There was no significant difference between groups in terms of periprocedural adverse events (RR 0.78; 95% CI 0.39−1.56; p = .49).Conclusions: Adjunctive LVA ablation is an effective and safe strategy for reducing recurrences of ATA among patients who undergo CA for AF.

Background Cancer survivors are at increased risk for atrial fibrillation (AF). However, data on the efficacy and safety of catheter ablation (CA) in this population remain limited. Therefore, we aimed to perform a systematic review and meta-analysis comparing outcomes after CA for AF in patients with versus without prior or active cancer. Methods We systematically searched PubMed, Cochrane Library, and Embase from inception to April 2023 for studies comparing the safety and efficacy of CA for AF in cancer survivors. Outcomes of interest were bleeding events, late AF recurrence, and need for repeat ablation. Statistical analyses were performed using Review Manager 5.4.1. We pooled odds ratios (OR) with 95% confidence intervals (CI) for binary endpoints. Results We included 5 retrospective cohort studies comprising 998 patients, of whom 41.4% had a history of cancer. Cancer survivors were at significantly higher risk of clinically relevant bleeding (OR 2.17; 95% CI 1.17-4.0; p=0.01) as compared with those without cancer. The efficacy of CA for AF was similar between groups. Late AF recurrence at 12 months was not significantly different between patients with vs. without a history of cancer (OR 1.29; 95% CI 0.78–2.13; p=0.32). Similar findings were observed in the outcome of repeat ablations (OR 0.71; 95% CI 0.37-1.37; p=0.31). Conclusions These findings suggest that cancer survivors have an increased risk of bleeding after CA for AF relative to patients without cancer, with no significant difference in the efficacy of CA for maintenance of sinus rhythm between groups. Study registration This systematic review is registered in the International Prospective Register of Systematic Reviews (PROSPERO) under registration number CRD42023394538. Graphical abstract