The application of transcranial direct current stimulation (tDCS) to targeted cortices has been found to improve in skill acquisition; however, these beneficial effects remained unclear in fine and complicated skill. The aim of the current meta-analysis was to investigate the association between tDCS application and the efficacy of surgical performance during surgical skill training. We included randomized controlled trials (RCTs) investigating the efficacy of tDCS in enhancing surgical skill acquisition. This meta-analysis was conducted under a random-effect model. Six RCTs with 198 participants were included. The main result revealed that tDCS was associated with significantly better improvement in surgical performance than the sham control (Hedges’ g = 0.659, 95% confidence intervals (95%CIs) = 0.383 to 0.935, p < 0.001). The subgroups of tDCS over the bilateral prefrontal cortex (Hedges’ g = 0.900, 95%CIs = 0.419 to 1.382, p < 0.001) and the primary motor cortex (Hedges’ g = 0.599, 95%CIs = 0.245 to 0.953, p = 0.001) were both associated with significantly better improvements in surgical performance. The tDCS application was not associated with significant differences in error scores or rates of local discomfort compared with a sham control. This meta-analysis supported the rationale for the tDCS application in surgical training programs to improve surgical skill acquisition.
Background: Anti-phospholipid syndrome (APS) has emerged as a significant issue in autoimmune diseases over recent decades. Its hallmark feature is thromboembolic events, potentially affecting any vascularized area including the microcirculation of the inner ear. Since the first case report of APS-related audiovestibular dysfunction described in 1993, numerous reports have explored the association between APS-related antibodies and audiovestibular dysfunction. These studies indicate a higher prevalence of APS-related antibodies in patients with sensorineural hearing loss compared to healthy controls. Unlike other idiopathic hearing loss disorders, audiovestibular dysfunction associated with APS may respond to appropriate treatments, highlighting the importance of timely recognition by clinicians to potentially achieve favorable outcomes. Therefore, this systematic review aims to consolidate current evidence on the characteristics, pathophysiology, assessment, and management of audiovestibular dysfunction linked to APS. Methods: This systematic review utilized electronic searches of the PubMed, Embase, ClinicalKey, Web of Science, and ScienceDirect online platforms. The initial search was performed on 27 January 2024, with the final update search completed on 20 June 2024. Results: Based on theoretical pathophysiology, anticoagulation emerges as a pivotal treatment strategy. Additionally, drawing from our preliminary data, we propose a modified protocol combining anticoagulants, steroids, and non-invasive brain stimulation to offer clinicians a novel therapeutic approach for managing these symptoms. Conclusions: Clinicians are encouraged to remain vigilant about the possibility of APS and its complex audiovestibular manifestations, as prompt intervention could stabilize audiovestibular function effectively.
11 September 2025 in International Journal of Surgery
Background: Recent evidence has raised concerns about potential pro-oncogenic effects associated with glucagon-like peptide-1 (GLP-1) receptor agonists and sodium–glucose cotransporter 2 (SGLT2) inhibitors, particularly regarding gastrointestinal malignancies. Colorectal tumors, the third most diagnosed cancer globally, already show increased incidence in patients with metabolic disorders who typically require these medications. For example, obese subjects had a significantly higher risk of colorectal tumors than healthy subjects. However, existing evidence on this association remains inconsistent. This network meta-analysis (NMA) evaluated the comparative incidence of colorectal tumors associated with specific GLP-1 receptor agonists and SGLT2 inhibitors. Materials and Methods: We conducted a confirmatory NMA focused specifically on colorectal tumor incidence as an adverse effect, following Cochrane methodological recommendations. We performed a frequentist-based NMA of randomized controlled trials (RCTs) evaluating GLP-1 receptor agonists or SGLT2 inhibitors. Our primary outcome was colorectal tumor incidence, with safety profiles assessed by dropout rates as a secondary outcome. Results: This NMA encompassing 68 RCTs with 207 200 participants found that only semaglutide was associated with increased incidence of colorectal tumors compared to controls. A dose-stratified analysis revealed that high-dose injectable semaglutide (2.4 mg/week) was the only regimen associated with increased incidence. Furthermore, when focusing on RCTs of obese subjects, the increased colorectal tumor rate related to semaglutide still existed. Neither other GLP-1 receptor agonists nor any SGLT2 inhibitors demonstrated significant associations with colorectal tumor development. Conclusion: Our study provides the first comprehensive NMA addressing the incidence of colorectal tumors related to individual GLP-1 receptor agonists and SGLT2 inhibitors, suggesting a dose–dependent relationship to semaglutide, particularly in its high-dose injectable form (2.4 mg/week). These findings represent a potential risk signal that requires further validation, given the already elevated baseline colorectal tumor risk in the target population, especially in subjects with obesity. Future research should focus on long-term follow-up studies to better characterize the mechanisms and clinical implications of this semaglutide-specific risk signal. What this adds to the existing literature: This network meta-analysis, based on 68 randomized controlled trials, suggested that only semaglutide, especially in highdose injectable form (2.4 mg/week), was associated with increased incidence of colorectal tumors compared to controls, especially in obese patients. Neither other GLP-1 receptor agonists nor any SGLT2 inhibitors demonstrated significant associations with colorectal tumor development. Learning points: Our study provides evidence regarding the increased incidence of colorectal tumors related to semaglutide in a dose dependent way (2.4 mg/week).
Background/Objectives: Emerging evidence suggests an association between glucagon-like peptide-1 (GLP-1) receptor agonists and sodium–glucose co-transporter 2 (SGLT2) inhibitors with altered risk of damage in the inner ear system. However, limited research exists on the relationship between these medications and subsequent irreversible hearing loss. We conducted this network meta-analysis (NMA) to evaluate the comparative risk of hearing loss associated with such medications. Methods: In this NMA, we used a confirmatory approach to specifically focus on particular adverse effects of interest (i.e., incidence of hearing loss here) based on the Cochrane recommendation. A Bayesian-based NMA of randomized controlled trials (RCTs) of GLP-1 receptor agonists or SGLT2 inhibitors was conducted. The primary outcome was the hearing loss events. Results: Our NMA of 29 RCTs with 145,895 participants found that only two exendin-4 derivatives—lixisenatide and high-dose efpeglenatide (i.e., 6 mg/week)—showed increased hearing loss events compared to controls. No other GLP-1 receptor agonists or SGLT2 inhibitors demonstrated significantly elevated hearing loss risk. Lixisenatide ranked highest in risk among all investigated regimens. Conclusions: This comprehensive NMA identifies a significant association between exendin-4 derivatives (lixisenatide and efpeglenatide) and potential ototoxicity. Clinicians should carefully consider this potential ototoxicity when prescribing exendin-4 derivatives, particularly in patients with pre-existing hearing loss risk factors.
Metastatic cancer, characterized by poor survival outcomes and grim prognosis, represents the final stage of malignancy. The current evidence regarding the prophylactic effects of glucagon-like peptide-1 (GLP-1) receptor agonists and sodium–glucose cotransporter 2 (SGLT2) inhibitors on metastatic cancer remains largely unexamined. With a confirmatory approach based on the Cochrane recommendation, we conducted a frequentist-based network meta-analysis (NMA) of randomized controlled trials (RCTs) evaluating such medications. The primary outcome was the incidence of metastatic cancer, while secondary outcomes included safety profiles assessed through dropout rates. The findings were reaffirmed by sensitivity analysis with a Bayesian-based NMA. This NMA of 207,606 participants from 67 RCTs revealed that only efpeglenatide demonstrated a statistically significant reduction in metastatic cancer events compared to controls (odds ratio = 0.26, 95% confidence intervals = 0.09 to 0.70, p = 0.010, number needed to treat = 188.4). Efpeglenatide’s efficacy was not confined to specific cancer types. Safety profiles were comparable across all treatments. These findings indicate that efpeglenatide may possess a broad, systemic preventive effect against metastatic cancers, potentially operating through mechanisms that are not restricted to individual organ systems. Further research is warranted to elucidate the molecular pathways underlying its anti-metastatic properties and to explore its role in preventive oncology.
Background: Although glucagon-like peptide-1 (GLP-1) receptor agonists and sodium–glucose cotransporter 2 (SGLT2) inhibitors have gained attention for their broad therapeutic effects, their influence on hematologic malignancy remains underexplored. Given the high mortality associated with hematologic cancers, clarifying the impact of these agents on such malignancies is essential. Objectives: This pilot network meta-analysis (NMA) aimed to assess the comparative risk of hematologic malignancies—including lymphoma, leukemia, and myeloma—associated with various GLP-1 receptor agonists and SGLT2 inhibitors. Methods: Following Cochrane-recommended confirmatory methods, we systematically searched multiple databases for randomized controlled trials (RCTs) published through 4 December 2024. The primary outcome was the incidence of overall hematologic malignancies. A frequentist random-effects NMA via the netmeta package was conducted, with additional validation through Bayesian NMA for solely sensitivity analyses. Results: Fifty-five RCTs (n = 200,606) were analyzed. Dulaglutide showed a significantly higher risk of overall hematologic malignancy [odds ratio (OR) = 2.18, 95% confidence interval (95%CI) = 1.14–4.19). In contrast, tirzepatide was linked to a significantly reduced risk (OR = 0.14, 95%CI = 0.03–0.60), especially for lymphoma. No statistically significant associations were identified for SGLT2 inhibitors (i.e., 95%CI across 1.0). Conclusions: Our preliminary findings reveal distinct and agent-specific effects of GLP-1 receptor agonists on hematologic malignancy risk. While dulaglutide may elevate the risk, tirzepatide appears protective, particularly against lymphoma. These results call for further long-term mechanistic studies to clarify causality and underlying pathways.