Comparative efficacy and safety of sodium fluorescein-guided surgery versus standard white light for resection of brain metastases: a systematic review and meta-analysis.

PURPOSE: Recent studies have investigated if the sodium fluorescein-guided (SFg) improves the extent of resection of BMs when compared to standard white light (sWL). Therefore, we aimed to assess the comparative efficacy and safety of SFg and sWL for resection of BMs. METHODS: We searched Medline, Embase, and Cochrane Library databases following Cochrane and PRISMA guidelines for studies reporting comparative data of SFg and WL resection of BMs. We pooled odds ratios (OR) with 95% confidence intervals under random effects and applied I² statistics and leave-one-out sensitivity analysis to assess heterogeneity. I² > 40% was considered significant for heterogeneity. RESULTS: Five studies involving 816 patients were included, of whom 390 underwent BMs resection with SFg and 426 with sWL, and ages ranging between 26 and 86.2 years old. Analysis revealed a statistically significant higher likelihood of complete resection in the SFg group when compared to the sWL group (OR = 2.15, 95%CI: 1.18-3.92, p = 0.01; I² = 47%). Sensitivity analysis revealed a consistent result in all five scenarios, with low heterogeneity in two of the five scenarios. Three studies reported significant improvement in OS in the SFg group, and the qualitative assessment of complications and procedure-related mortality did not provide sufficient information for conclusions. CONCLUSION: This systematic review and meta-analysis identified a higher likelihood of complete resection in the SFg group when compared to the standard sWL group. This study is the first to directly compare the impact of SFg and sWL on resection outcomes for BMs.

Decompressive Craniectomy with or Without Dural Closure: Systematic Review and Meta-analysis.

Decompressive craniectomy is used to alleviate intracranial pressure in cases of traumatic brain injury and stroke by removing part of the skull to allow brain expansion. Traditionally, this procedure is followed by a watertight dural suture, although evidence supporting this method is not strong. This meta-analysis examines the feasibility of the open-dura (OD) approach versus the traditional closed-dura (CD) technique with watertight suturing. A systematic review and comparative meta-analysis were conducted on OD and CD dural closure techniques. Medline, Embase, and Cochrane were searched for relevant trials. The primary end point was the rate of complications, with specific analyses for infection and cerebrospinal fluid (CSF) leaks. Mortality, poor neurological outcomes, and operation duration were also assessed. Odds ratios with 95% confidence intervals (CIs) were calculated using a random-effects model. Following a comprehensive search, 930 studies were screened, from which four studies and a total of 368 patients were ultimately selected. The primary outcome analysis showed a reduced likelihood of complications in the OD group when compared with the CD group (368 patients, odds ratio 0.54 [95% CI 0.32-0.90]; I2 = 17%; p < 0.05). Specific analysis of infections and CSF leaks did not show statistically significant results, as well as the evaluation of the mortality rates and poor neurological outcome differences between groups. Assessment of operation duration, however, demonstrated a significant difference between techniques, with a mean reduction of 52.50 min favoring the OD approach (mean difference - 52.50 [95% CI - 92.13 to - 12.87]; I2 = 96%). This study supports the viability of decompressive craniectomy without the conventional time-spending watertight duraplasty closure, exhibiting no differences in the rate of infections or CSF leaks. Furthermore, this approach has been associated with improved rates of complications and faster surgery, which are important aspects of this technique, particularly in its potential to reduce both costs and procedure length.

The Effect of Time Pressure on Surgical Skill Retention in Novices: A Randomized Controlled Trial.

BACKGROUND: There are limited opportunities to practice surgical skills and techniques in residency. Therefore, it is important to explore strategies which optimize surgical simulation experiences to enhance learning outcomes and skill retention. METHODS: Novice medical students (n = 29) were recruited to participate in a Fundamentals of Laparoscopic Surgery (FLS) peg transfer task training. Participants were randomly assigned to a control group, practicing the peg transfer task independently, or an experimental group, practicing with time pressure. Participant skill assessments were completed before the training, after the training, and 8-weeks after the training. Subjective and objective stress measurements were taken in the form of self-report surveys and heart rate variability data, respectively. RESULTS: For all the skill assessment measurements, there was no difference between groups in performance on the FLS task. Both groups showed improvement in performance after the training compared to before. The experimental group reported higher stress during and after the training period compared to the control group; however, there was no difference between groups on heart rate variability metrics. CONCLUSION: Time pressure while practicing an FLS task did not significantly impact learning acquisition or retention. However, the experimental group reported higher levels of stress. This preliminary study suggests time pressure does not confer an enhanced surgical skill learning experience for novices.

The effect of sodium-glucose transporter 2 inhibitors on stroke in patients with type 2 diabetes: A meta-analysis.

OBJECTIVES: To provide an update on the effect of sodium-glucose cotransporter 2 (SGLT2) inhibitors on stroke in patients with type 2 diabetes (T2D). METHODS: PubMed, Embase, and Cochrane Library were systematically searched for randomized controlled trials (RCTs) comparing SGLT2 inhibitors versus placebo or other therapies in patients with T2D and reporting stroke endpoint. We computed the risk ratios (RRs) to binary endpoints, with 95 % confidence intervals (CIs). RESULTS: A total of 71 RCTs and 105,914 patients were included, of whom 62,488 (59 %) were randomized to the SGLT2 inhibitors group. The follow-up ranged from 12 weeks to 4.2 years. There were no significant differences between groups in all types of stroke (RR 0.96; 95 % CI 0.89-1.04), ischemic stroke (RR 0.89; 95 % CI 0.76-1.04), and transient ischemic attack (RR 0.96; 95 % CI 0.79-1.16). Patients on SGLT2 inhibitors experienced lower rates of hemorrhagic stroke (RR 0.62; 95 % CI 0.39-0.98). In the subgroup analysis of the type of drug, sotagliflozin significantly reduced all types of stroke (RR 0.74; 95 % CI 0.56-0.97). CONCLUSION: In this meta-analysis of 71 RCTs comprising 105,914 patients with T2D, SGLT2 inhibitors were not associated with a reduced risk of stroke and transient ischemic attack compared to placebo or other therapies; however, there was a trend toward reduced risk of hemorrhagic stroke. Among all SGLT2 inhibitors, sotagliflozin significantly reduced the risk of stroke.

Mesenchymal-Epithelial Transition Kinase Inhibitor Therapy in Patients with Advanced Papillary Renal-Cell Carcinoma: A Systematic Review and Meta-Analysis.

Papillary subtypes of renal-cell carcinoma (pRCC) represent 10-15% of the cases and commonly have MET alterations. This systematic review and single-arm meta-analysis evaluated MET inhibitor therapy (METi) efficacy and safety in adults with confirmed advanced pRCC. The search strategy included PubMed, Web-of-science, Cochrane, and Scopus. We used the DerSimonian/Laird random effect model for all analyses; p-value < 5% was considered significant, and heterogeneity was assessed with I2. Three clinical trials and six cohort studies were included with 504 patients; 31% were MET-driven. Our pooled analysis demonstrated an objective response rate (ORR) in MET-driven, MET-independent, and overall patients of: 36% (95%CI: 10-62), 0% (95%CI: 0-3), and 21% (95%CI: 1-41), respectively. One-year disease control and progression-free survival rates were, respectively, 70% (95%CI: 52-88) and 15% (95%CI: 10-20). Twelve- and twenty-four-month survival rates were, respectively, 43% (95%CI: 23-64) and 10% (95%CI: 0-30). The prevalence of adverse events of any grade and grades 3-5 were 96% (95%CI: 91-100) and 44% (95%CI: 37-50), respectively. We suggest METi has anti-tumor activity and is tolerable in patients with advanced pRCC.

Safety and efficacy of sotagliflozin in patients with type II diabetes mellitus and chronic kidney disease: a meta-analysis of randomized controlled trials.

BACKGROUND: Sotagliflozin is a dual sodium-glucose co-transporter 1 and 2 inhibitor that increases glucosuria and natriuresis in patients with type 2 diabetes mellitus (T2DM). However, the safety and efficacy in patients with concomitant chronic kidney disease (CKD) remains unclear. Therefore, we aimed to conduct a meta-analysis to evaluate the current evidence in this regard. METHODS: We searched PubMed, Embase, Cochrane, and Web of Science for randomized controlled clinical trials on the safety and efficacy of Sotagliflozin in patients with T2DM and CKD compared with placebo. Statistical analysis was performed using RevMan 5.4. Heterogeneity was assessed with I2 statistics. The study was recorded in PROSPERO registry (CRD42023449631). RESULTS : We included three studies totaling 11,648 patients followed for 15.7 ± 5.9 months. Reduction in HbA1C (mean difference - 0.33%; 95% CI [- 0.54, - 0.11]; p = 0.003; I2 = 100%) and weight (mean difference - 1.01 kg; 95% CI [- 1.17, - 0.86]; p < 0.00001; I2 = 96%) were significantly higher in the Sotagliflozin group compared with placebo. All-cause mortality (RR 0.98; 95% CI [0.81, 1.20]; p = 0.87; I2 = 0%) and major adverse cardiovascular events (RR 0.70; 95% CI [0.40, 1.21]; p = 0.20; I2 = 39%) were not significantly different between groups. However, estimated glomerular filtration rate reduction (mean difference - 0.95; 95% CI [- 1.32, - 0.58]; p < 0.00001; I2 = 98%), genital mycotic infections (RR 2.73; 95% CI [1.96, 3.79]; p < 0.00001; I2 = 0%), diarrhea (RR 1.42; 95% CI [1.24. 1.63]; p < 0.00001; I2 = 0%) and volume depletion (RR 1.31; 95% CI [1.11, 1.56]; p = 0.002; I2 = 0%) were more common with Sotagliflozin. CONCLUSIONS: In patients with T2DM and CKD, Sotagliflozin appears to be effective for glycemic control and weight loss. Although the medication seemed safe concerning mortality and cardiovascular events, it induced estimated glomerular filtration rate reduction, and was associated with a higher risk of genital mycotic infections, diarrhea, and volume depletion.

Cardiovascular Benefits of GLP-1 Receptor Agonists in Patients Living with Obesity or Overweight: A Meta-analysis of Randomized Controlled Trials.

BACKGROUND: GLP-1 receptor agonists (GLP-1 RAs) have emerged as an effective therapeutic class for weight loss. However, the efficacy of these agents in reducing cardiovascular endpoints among patients living with obesity or overweight is unclear. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing GLP-1 RAs versus placebo in patients with obesity or overweight. We searched PubMed, Cochrane, and Embase databases. A random-effects model was used to calculate risk ratios (RRs) and mean differences (MDs), with 95% confidence intervals (CIs). RESULTS: A total of 13 RCTs were included, with 30,512 patients. Compared with placebo, GLP-1 RAs reduced systolic blood pressure (MD - 4.76 mmHg; 95% CI - 6.03, - 3.50; p < 0.001; I2 = 100%) and diastolic blood pressure (MD - 1.41 mmHg; 95% CI - 2.64, - 0.17; p = 0.03; I2 = 100%). GLP-1 RA significantly reduced the occurrence of myocardial infarction (RR 0.72; 95% CI 0.61, 0.85; p < 0.001; I2 = 0%). There were no significant differences between groups in unstable angina (UA; RR 0.84; 95% CI 0.65, 1.07; p = 0.16; I2 = 0%), stroke (RR 0.91; 95% CI 0.74, 1.12; p = 0.38; I2 = 0%), atrial fibrillation (AF; RR 0.49; 95% CI 0.17, 1.43; p = 0.19; I2 = 22%), and deep vein thrombosis (RR 0.30; 95% CI 0.06, 1.40; p = 0.13; I2 = 0%). CONCLUSIONS: In patients living with obesity or overweight, GLP-1 RA reduced systolic and diastolic blood pressure and the occurrence of myocardial infarction, with a neutral effect on the occurrence of UA, stroke, AF, and deep vein thrombosis. REGISTRATION: PROSPERO identifier number CRD42023475226.

Cyclin-Dependent Kinase 4/6 Inhibitors Plus Endocrine Therapy versus Endocrine Therapy Alone for HR-Positive, HER-2-Negative Early Breast Cancer: Meta-Analysis of Phase III Randomized Clinical Trials.

BACKGROUND: Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors are approved for advanced breast cancer combined with endocrine therapy (ET). The efficacy of CDK4/6 inhibitors plus ET in hormone estrogen-positive, human epidermal growth factor 2-negative (HR+/HER2-) early-stage breast cancer (esBC) is still to be confirmed. METHODS: We performed a systematic review and a meta-analysis to investigate the efficacy of CDK4/6i plus ET in esBC. Main outcomes included invasive disease-free survival (iDFS), distant relapse-free survival (DRFS), and overall survival (OS). We included only phase III randomized controlled trials. We used RStudio version 4.2.3, and we considered p < 0.05 to be statistically significant. RESULTS: Four studies were selected, including 14,168 patients, of which 7089 were treated with CDK4/6i plus ET and 7079 received ET monotherapy. Regarding patient characteristics, 6828 (48.2%) were premenopausal. Compared with ET alone, iDFS rates (HR 0.81; 95% CI: 0.67, 0.98; p = 0.034) were significantly in favor of CDK4/6 inhibitors plus ET. However, there were no significant differences in DRFS (HR 0.79; 95% CI: 0.58, 1.07; p = 0.132) nor OS (HR 0.96; 95% CI: 0.69, 1.35; p = 0.829). CONCLUSIONS: Our results show that the addition of CDK4/6 inhibitors is associated with a significant benefit for HR+/HER2- esBC patients in iDFS. More studies and longer follow-up are needed to assess overall survival benefits.

Cardiovascular benefits of statin plus ezetimibe combination therapy versus statin monotherapy in acute coronary syndrome: a meta-analysis of randomized controlled trials.

BACKGROUND: The efficacy of adding ezetimibe to statin therapy for event reduction in patients with acute coronary syndromes (ACS) remains a topic of ongoing debate. METHODS: We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing ezetimibe plus statin versus statin monotherapy in patients with ACS. We searched PubMed, Embase, and Cochrane for eligible trials. The random-effects model was used to calculate the risk ratios with 95% confidence intervals (CIs). Statistical analyses were performed using RStudio version 4.2.3 (RStudio, PBC). RESULTS: Six RCTs comprising 20 574 patients with ACS were included, of whom 10 259 (49.9%) were prescribed ezetimibe plus statin. The patient population had an average age of 63.8 years, and 75.1% were male. Compared with statin monotherapy, ezetimibe plus statin significantly reduced major adverse cardiovascular events (MACE) (risk ratio 0.93; 95% CI 0.90-0.97; P < 0.01) and nonfatal myocardial infarction (risk ratio 0.88; 95% CI 0.81-0.95; P < 0.01). There was no significant difference between groups for revascularization (risk ratio 0.94; 95% CI 0.90-1.00; P = 0.03), all-cause mortality (risk ratio 0.87; 95% CI 0.63-1.21; P = 0.42), or unstable angina (risk ratio 1.05; 95% CI 0.86-1.27; P = 0.64). CONCLUSION: In this meta-analysis of patients with ACS, the combination of ezetimibe plus statin was associated with a reduction in MACE and nonfatal myocardial infarction, compared with statin monotherapy.