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INTRODUCTION: Brugada syndrome (BrS) is a genetic heart disease that predisposes individuals to malignant ventricular arrhythmias and sudden cardiac death (SCD). Although implantable cardioverter-defibrillators (ICDs) and quinidine are primary treatments, recurrent BrS-triggered cardiac ventricular arrhythmias necessitating ICD therapies can persist. In this setting, epicardial substrate ablation has emerged as a promising alternative for high-risk symptomatic patients. OBJECTIVE:Evaluate the effectiveness and safety of epicardial substrate ablation in patients with BrS. METHODS: In this systematic review and single-arm meta-analysis, we systematically searched PubMed, Embase, and Cochrane databases following PRISMA guidelines for studies including BrS patients who had epicardial substrate ablation. Data was extracted and statistical analysis was performed using random-effects modeling for proportional meta-analysis. Heterogeneity was examined with I² statistics. RESULTS: Seventeen observational cohort studies comprising 695 BrS patients were included. The mean patient age at enrollment was 40.4 ± 14.2 years, 89.9% were males and 77.6% exhibited spontaneous type 1 Brugada ECG pattern. Pooled analysis demonstrated resolution of the type 1 pattern in 89% of cases (95% CI 74-98%; I²=91%) and elimination of abnormal electrograms in 93% (95% CI 84-99%, I²=71%). Post-procedure VF/VT inducibility was 8% (95% CI 1-18%; I²=83%). The overall complication rate was 3% (95% CI 0-8%, I²=78%) with pericarditis being the most common. Rates of recurrent VT/VF and appropriate ICD therapies during post-ablation follow-up were 13% (95% CI 5-23%; I²=87%) and 10% (95% CI 3-21%; I²=87%), respectively. CONCLUSIONS: Epicardial substrate ablation shows promise for BrS patients experiencing recurrent BrS-triggered ventricular arrhythmias, offering demonstrable therapeutic efficacy in eliminating arrhythmogenic substrates with an acceptable safety profile. However, high heterogeneity among studies highlights the need for further research and standardized protocols in this field.

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PURPOSE: Magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) is a novel, minimally invasive alternative to traditional open surgery corpus callosotomy (CC). We aim to compare both approaches in terms of time of hospitalization and surgical procedure, complications, and efficacy outcomes. METHODS: A systematic search on PubMed, Embase, Web of Science, and Cochrane Library databases was performed for studies directly comparing MRgLITT and open surgery for refractory epilepsy in children. RESULTS: A total of 240 patients from five studies were included. There was no statistically significant difference observed between the two groups regarding the favorable Engel outcome. (RR 0.89; 95 % CI 0.70-1.14; p = 0.36; I2=0 %) The mean hospital length of stay (LOS) was significantly shorter in the patients who underwent MRgLITT. (MD -2.84 days; 95 % CI [-3.17]-[-2.51] days; p < 0.00001; I2=90 %) The mean operation duration was significantly longer in the intervention group. (MD 1.38 h; 95 % CI 0.64- 2.12 h; p = 0.00002; I2=55 %). The mean blood loss was significantly lower in patients who underwent MRgLITT. (MD -75.15 ml; 95 % CI [-92.82]-[-57.48] ml; p < 0.00001; I2=0 %) CONCLUSION: CC is a valuable option for treating RE, especially in children. The open surgery bears the stigma of an invasive and complicated technique which might justify its underuse. MRgLITT is a great alternative and possibly a way to widen the use of callosotomy in children, however, its cost and availability may be a challenge.

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CONTEXTO: A doença de Chagas continua sendo uma das principais causas não isquêmicas de cardiomiopatia na América Latina. No entanto, nossa compreensão dos parâmetros ecocardiográficos prognósticos além da fração de ejeção do ventrículo esquerdo (FEVE) permanece limitada. Objetivo: Conduzir uma revisão sistemática e metanálise para avaliar a relação entre o strain longitudinal global do ventrículo esquerdo (GLS-VE), o diâmetro diastólico final do ventrículo esquerdo (DDFVE) e a FEVE com o risco de mortalidade por todas as causas, transplante cardíaco ou necessidade de dispositivo de assistência ventricular mecânica. MÉTODOS: Realizamos uma busca sistemática nas bases de dados Elsevier, PubMed e Cochrane por estudos que avaliassem GLS-VE, DDFVE e FEVE em pacientes com doença de Chagas, abrangendo tanto as fases indeterminada quanto de cardiomiopatia. A análise estatística foi realizada utilizando o RevMan 5.1.7, e a heterogeneidade foi avaliada usando estatísticas I². Calculamos razões de risco (HR) combinadas com intervalos de confiança (IC) de 95% sob um modelo de efeitos aleatórios. Também realizamos uma análise de subgrupos de análises multivariáveis para minimizar o efeito de variáveis de confusão. RESULTADOS: Incluímos 1.277 pacientes de 10 estudos observacionais, com idade média variando de 53 a 66 anos, sendo 60,3% do sexo masculino. Desses pacientes, 1.138 (89%) apresentavam cardiomiopatia chagásica, enquanto 139 estavam na fase indeterminada. A FEVE média variou de 26% a 52%. A redução do GLS-VE (HR 1,14; IC 95% 1,01-1,29; p= 0,04; Figura 1A) e o aumento do DDFVE (HR 1,07; IC 95% 1,02-1,12; p< 0,0001; Figura 1B) foram associados a maior risco de mortalidade por todas as causas, transplante cardíaco ou necessidade de dispositivo de assistência ventricular mecânica. Em contrapartida, maiores índices de FEVE foram associados a menor risco desse desfecho composto (HR 0,93; IC 95% 0,90-0,96; p= 0,002), o que permaneceu estatisticamente significativo após análise de subgrupos com apenas resultados ajustados por multivariáveis (HR 0,95; IC 95% 0,91- 0,99; p= 0,001; Figura 1C). CONCLUSÃO: Nesta revisão sistemática e metanálise de pacientes com doença de Chagas, a redução do GLS-VE e o aumento do DDFVE foram associados a maior risco de mortalidade por todas as causas, transplante cardíaco ou necessidade de dispositivo de assistência ventricular mecânica, enquanto o aumento da FEVE foi fator protetor prognóstico independente para esse desfecho.

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BACKGROUND AND OBJECTIVES: Cerebral aneurysms in complex anatomical locations and intraoperative rupture can be challenging. Many methods to reduce blood flow can facilitate its exclusion from the circulation. This study evaluated the safety and efficacy of using adenosine, rapid ventricular pacing, and hypothermia in cerebral aneurysm clipping. METHODS: Databases (PubMed, Embase, and Web of Science) were systematically searched for studies documenting the use of adenosine, rapid ventricular pacing, and hypothermia in cerebral aneurysm clipping and were included in this single-arm meta-analysis. The primary outcome was 30-day mortality. Secondary outcomes included neurological outcomes by mRs and GOS, and cardiac outcomes. We evaluated the risk of bias using ROBIN-I, a tool developed by the Cochrane Collaboration. OpenMetaAnalyst version 2.0 was used for statistical analysis and I2 measured data heterogeneity. Heterogeneity was defined as an I2 > 50%. RESULTS: Our systematic search yielded 10,100 results. After the removal of duplicates and exclusion by title and abstract, 64 studies were considered for full review, of which 29 were included. The overall risk of bias was moderate. The pooled proportions of the adenosine analysis for the different outcomes were: For the primary outcome: 11,9%; for perioperative arrhythmia: 0,19%; for postoperative arrhythmia: 0,56%; for myocardial infarction incidence: 0,01%; for follow-up good recovery (mRs 0-2): 88%; and for neurological deficit:14.1%. In the rapid ventricular pacing analysis, incidences were as follows: peri operative arrhythmia: 0,64%; postoperative arrhythmia: 0,3%; myocardial infarction: 0%. In the hypothermia analysis, the pooled proportion of 30-day mortality was 11,6%. The incidence of post-op neurological deficits was 35,4% and good recovery under neurological analysis by GOS was present in 69.2%. CONCLUSION: The use of the three methods is safe and the related complications were very low. Further studies are necessary, especially with comparative analysis, for extended knowledge.

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BACKGROUND AND OBJECTIVES: Mechanical thrombectomy (MT) has been established as the gold standard of treatment for patients with Acute Ischemic Stroke (AIS) who present up to 6 h after the onset of the stroke. Recently, the DEFUSE-3 and DAWN trials established the safety of starting the MT procedure up to 16 and 24 h after the patient was last seen well, respectively. The purpose of this study is to assess the safety and functional effects of thrombectomy in individuals with AIS detected at a late stage (> 24 h). MATERIALS AND METHODS: PubMed, Web of Science, Embase, and Cochrane databases were thoroughly searched for research on MT in patients in the extremely late time window after AIS. The primary outcomes were symptomatic cerebral hemorrhage, 90-day mortality, Thrombolysis in Cerebral Infarction (TICI) 2b-3, and Modified Rankin Scale (mRS) 0-2. RESULTS: Our study included fifteen studies involving a total of 1,221 patients who presented with AIS and an extended time window. The primary outcome of interest was the favorable functional outcome, mRS 0-2 at 90 days. The pooled proportion for this outcome was 45% (95% confidence interval 34-58%). Other outcomes included the TICI 2b or 3 (successful recanalization), which was reported in 12 studies and had a 79% incidence in the study population (95% CI 68-87%). Complications included: symptomatic intracranial hemorrhage (sICH), which revealed an incidence of 7% in the study population (95% CI 5-10%); and 90-day mortality, which reported a 27% incidence (95% CI 24-31%). In addition, we conducted a comparative analysis between endovascular treatment and standard medical therapy. CONCLUSION: Our meta-analysis provides evidence that supports the need of further randomized and prospective clinical trials to better assess the effectiveness and safety of MT in these patients.

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BACKGROUND: Acute myocardial infarction (AMI) is an important cause of cardiogenic shock (CS). There is lack of evidence regarding the safety and efficacy of venoarterial extracorporeal membrane oxygenation (VA-ECMO) compared with Impella in this population. METHODS: We systematically searched PubMed, EMBASE, and Cochrane Library for studies comparing VA-ECMO with Impella in patients with CS related to AMI. The systematic review and meta-analysis followed Cochrane recommendations and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We used R version 4.3.1 for all statistical analyses. Odds ratios (OR) and 95% confidence intervals (CI) were pooled with a random-effects model. RESULTS: We included seven observational studies with 15.903 patients, of whom 12.943 (81.3%) were treated with Impella. There was no significant difference between groups regarding in-hospital mortality (OR 0.79; 95% CI 0.37-1.69; p=0.54; Figure 1A), ischemic stroke (OR 0.69; 95% CI 0.14-3.35; p=0.64; Figure 1B), acute kidney injury (OR 1.22; 95% CI 0.55-2.70; p=0.62), renal replacement therapy or dialysis (OR 1.02; 95% CI 0.33-3.19; p=0.97; Figure 1C), and blood transfusion (OR 0.52; 95% CI 0.16-1.72; p=0.28). CONCLUSION: In this meta-analysis, there was no significant difference between VA-ECMO and Impella among patients with CS and AMI for the outcomes of in-hospital mortality, ischemic stroke, acute kidney injury, renal replacement therapy, or blood transfusion.

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BACKGROUND: Weaning patients with COPD from mechanical ventilation (MV) presents a challenge, as literature on this topic is limited. This study compares PSV and T-piece during spontaneous breathing trials (SBT) in this specific population. METHODS: A search of PubMed, EMBASE, and Cochrane in September 2023 yielded four randomized controlled trials (RCTs) encompassing 560 patients. Among these, 287 (51%) used T-piece during SBTs. RESULTS: The PSV group demonstrated a significant improvement in the successful extubation rate compared to the T-piece (risk ratio [RR] 1.14; 95% confidence interval [CI] 1.03-1.26; p = 0.02). Otherwise, there was no statistically significant difference in the reintubation (RR 1.07; 95% CI 0.79-1.45; p = 0.67) or the ICU mortality rates (RR 0.99; 95% CI 0.63-1.55; p = 0.95). CONCLUSION: Although PSV in SBTs exhibits superior extubation success, consistent weaning protocols warrant further exploration through additional studies.

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BACKGROUND AND OBJECTIVE: Painful peripheral neuropathy is a common and challenging complication of diabetes mellitus. Combination therapy is used widely by clinicians, although strong evidence for efficacy and safety is lacking. The goal of this study is to compare the efficacy and safety of combination versus monotherapy of first-line medications for peripheral diabetic neuropathy. METHODS: PubMed, Embase, Cochrane Central, and clinicaltrials.gov databases were searched on December 5, 2022, for randomized clinical trials comparing combined therapy with gabapentinoids and either tricyclic antidepressants (TCAs) or serotonin and norepinephrine reuptake inhibitors (SNRIs) versus monotherapy with any of these drugs. Pooled mean differences (MD) with a 95% confidence interval (CI) were computed for pain outcomes, measured on an 11-point numeric rating scale averaging pain scores in the last 7 days. Risk ratios (RRs) were computed for binary endpoints. Risk assessment was performed using the Risk of Bias 2 tool. RESULTS: A total of five randomized studies and 916 patients were included. Follow-up ranged from 6 to 12 weeks. Mean pain reduction was greater for combination therapy than monotherapy (MD - 0.39; 95% CI - 0.67 to - 0.12; p = 0.005). Similarly, there was an improvement in ≥ 30% reduction in average pain (RR 1.16; 95% CI 1.07-1.26; p < 0.01) with combination therapy. In contrast, there was no significant difference between groups in ≥ 50% reduction in average pain (RR 1.21; 95% CI 0.99-1.49; p = 0.06). When comparing combination therapy versus gabapentinoid monotherapy, there was also a significant reduction in average pain (MD - 0.61; 95% CI - 0.85 to - 0.37; p < 0.01) with combination therapy. CONCLUSION: In patients with painful diabetic peripheral neuropathy, the combination of gabapentinoids with TCAs or SNRIs is associated with a greater reduction in pain as compared with monotherapy, although this difference may not translate into a clinically important difference.

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OBJECTIVE: To evaluate the effectiveness and side-effect profile of the modified Atkins diet (MAD) compared to the usual diet (UD) in reducing seizure frequency among patients with drug-resistant epilepsy (DRE). METHODS: In February 2023, we conducted an extensive search in PubMed, EMBASE, and Cochrane databases to find randomized controlled trials (RCTs) comparing MAD to UD in patients with drug-resistant epilepsy (DRE) on standard anti-seizure medication (ASM). We used random-effects meta-analyses and the Risk of Bias 2 tool to evaluate treatment effects and assess the quality of the included RCTs, respectively. RESULTS: Six studies were evaluated in the meta-analysis, including 575 patients, of whom 288 (50.1 %) were randomized to the MAD. Average follow-up period was 12 weeks. MAD plus standard drug therapy was associated with a higher rate of 50 % or greater reduction in seizure frequency compared to UD plus drug therapy (RR 6.28; 95 % CI 3.52-10.50; p<0.001), both in children (RR 6.28; 95 % CI 3.43-11.49; p<0.001) and adults with DRE (RR 6.14; 95 % CI 1.15-32.66; p = 0.033). MAD was also associated with a higher seizure freedom rate compared to UD (RR 5.94; 95 % CI 1.93-18.31; p = 0.002). Five studies reported adverse events with MAD; constipation was reported in 17 % of patients (95 % CI 5-44 %), lethargy in 11 % (95 % CI 4-25 %), and anorexia in 12 % (95 % CI 8-19 %). Due to limited information about the ASM regimens, we were unable to further analyze the interaction between MAD and ASM. SIGNIFICANCE: This meta-analysis, comprising 575 patients from 6 RCTs, revealed that MAD led to higher rates of seizure freedom and underscored its role in seizure frequency reduction by 50 % or more in both adults and children, with no significant adverse events concerns.

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INTRODUCTION: Pituitary adenomas, benign tumors, can lower quality of life. Pituitary adenomas that invade the medial wall and cavernous sinus (CS) indicate tumor recurrence and partial surgical excision. Despite the cavernous sinus's complexity and risks, new research has improved the surgical procedure and made excision safer. This comprehensive review and single-arm meta-analysis evaluates endocrinological remission and resection rates in pituitary adenomas to determine the benefits and risks of MWCS resection. METHODS: Databases were systematically searched for studies documenting the resection of the medial wall of the cavernous sinus. The primary outcome was endocrinological remission in patients who underwent resection of the MWCS. RESULTS: Eight studies were included in the final analysis. The pooled proportion of endocrinological remission (ER) was 63.3%. The excision of MWCS pooled a gross total resection (GTR) proportion of 72.9%. Finally, ICA injury attained a pooled ratio of 0.5%, indicating minimal morbidity in the procedure. CONCLUSION: The cavernous sinus was ruled out, proving the MWCS excision is safe. Limiting population selection to Knosp 3A or lower enhanced GTR frequencies and lowered recurrence, according to subgroup analyses. This meta-analysis shows that MWCS resection can be a beneficial treatment option for pituitary tumors, when there is no macroscopic medial wall invasion and careful patient selection is done, especially for GH- and ACTH-producing tumors that can cause life-threatening metabolic changes.

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BACKGROUND: Pretreatment with oral P2Y12 inhibitors is a standard practice for ST-elevation myocardial infarction (STEMI) patients undergoing percutaneous coronary intervention (PCI). However, the efficacy and safety of P2Y12 inhibitors pretreatment remain unclear. OBJECTIVES: We conducted a meta-analysis to investigate the impact of P2Y12 inhibitor pretreatment on thrombotic and hemorrhagic endpoints in STEMI patients. METHODS: We searched multiple databases for studies that compared P2Y12 inhibitor pretreatment with no pretreatment in STEMI patients and reported endpoints of interest. Random effects model was used for the meta-analysis. RESULTS: Our meta-analysis included 3 randomized controlled trials and 14 observational studies, comprising 70,465 patients assigned to either P2Y12 inhibitor pretreatment (50,328 patients) or no pretreatment (20,137 patients). Compared to no pretreatment, P2Y12 inhibitor pretreatment did not result in significant reductions in all-cause mortality (risk ratio [RR] 0.73; 95% confidence interval [CI]: 0.52-1.03; p = 0.07), myocardial infarction (RR 0.75; 95% CI: 0.53-1.07; p = 0.11), or major bleeding (RR 0.80; 95% CI: 0.56-1.16; p = 0.22) at 30 days. However, our subgroup analysis revealed that P2Y12 inhibitor pretreatment administered in the pre-hospital setting was associated with a significant reduction in the incidence of myocardial infarction compared to no pretreatment (RR 0.73; 95% CI: 0.56-0.91; p < 0.01). CONCLUSION: Our analysis suggests that pretreatment with oral P2Y12 inhibitors before PCI in patients with STEMI was not associated with reduced all-cause mortality, myocardial infarction, or major bleeding. However, pretreatment with P2Y12 inhibitors in the pre-hospital setting appears to be beneficial in reducing reinfarction.

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Robotic assistance has improved electrode implantation precision in stereoelectroencephalography (SEEG) for refractory epilepsy patients. We sought to assess the relative safety of the robotic-assisted (RA) procedure compared to the traditional hand-guided one. A systematic search on PubMed, Web of Science, Embase, and Cochrane was performed for studies directly comparing robot-assisted vs. manually guided SEEG to treat refractory epilepsy. The primary outcomes included target point error (TPE), entry point error (EPE), time of implantation of each electrode, operative time, postoperative intracranial hemorrhage, infection, and neurologic deficit. We included 427 patients from 11 studies, of whom 232 (54.3%) underwent robot-assisted surgery and 196 (45.7%) underwent manually guided surgery. The primary endpoint, TPE, was not statistically significant (MD 0.04 mm; 95% CI - 0.21, - 0.29; p = 0.76). Nonetheless, EPE was significantly lower in the intervention group (MD - 0.57 mm; 95% CI - 1.08; - 0.06; p = 0.03). Total operative time was significantly lower in the RA group (MD - 23.66 min; 95% CI - 32.01, - 15.31; p < 0.00001), as well as the individual time of implantation of each electrode (MD - 3.35 min; 95% CI - 3.68, - 3.03; p < 0.00001). Postoperative intracranial hemorrhage did not differ between groups: robotic (9/145; 6.2%) vs. manual (8/139; 5.7%) (RR 0.97; 95% CI 0.40-2.34; p = 0.94). There was no statistically relevant difference in infection (p = 0.4) and postoperative neurological deficit (p = 0.47) incidence between the two groups. In this analysis, there is a potential relevance in the RA procedure when comparing the traditional one, since operative time, time of implantation of each electrode, and EPE were significantly lower in the robotic group. More research is needed to corroborate the superiority of this novel technique.

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Animal models of cerebral ischemia have improved our understanding of the pathophysiology and mechanisms involved in stroke, as well as the investigation of potential therapies. The potential of zebrafish to model human diseases has become increasingly evident. The availability of these models allows for an increased understanding of the role of chemical exposure in human conditions and provides essential tools for mechanistic studies of disease. To evaluate the potential neuroprotective properties of minocycline against ischemia and reperfusion injury in zebrafish and compare them with other standardized models. In vitro studies with BV-2 cells were performed, and mammalian transient middle cerebral artery occlusion (tMCAO) was used as a comparative standard with the zebrafish stroke model. Animals were subjected to ischemia and reperfusion injury protocols and treated with minocycline. Infarction size, cytokine levels, oxidative stress, glutamate toxicity, and immunofluorescence for microglial activation, and behavioral test results were determined and compared. Administration of minocycline provided significant protection in the three stroke models in different parameters analyzed. Both experimental models complement each other in their particularities. The proposal also strengthens the findings in the literature in rodent models and allows the validation of alternative models so that they can be used in further research involving diseases with ischemia and reperfusion injury.

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