Safety and feasibility of rotational atherectomy (RA) versus conventional stenting in patients with chronic total occlusion (CTO) lesions: a systematic review and meta-analysis.

BACKGROUND AND AIM: Interventional cardiologists face challenges in managing chronic total occlusion (CTO) lesions, with conflicting results when comparing rotational atherectomy (RA) to conventional PCI. This meta-analysis aims to provide a critical evaluation of the safety and feasibility of RA in CTO lesions. METHODS: PubMed, Scopus, Web of Science, Ovid, and Cochrane central library until April 2023 were searched for relevant studies. MACE was our primary outcomes, other outcomes were all cause of death, cardiac death, MI, and TVR. Also, we reported angiographic outcomes as technical success, procedural success, and procedural complications in a random effect model. The pooled data was analyzed using odds ratio (OR) with its 95% CI using STATA 17 MP. RESULTS: Seven studies comprising 5494 patients with a mean follow-up of 43.1 months were included in this meta-analysis. Our pooled analysis showed that RA was comparable to PCI to decrease the incidence of MACE (OR = 0.98, 95% CI [0.74 to 1.3], p = 0.9). Moreover, there was no significant difference between RA and conventional PCI in terms of other clinical or angiographic outcomes. CONCLUSION: Our study showed that RA had comparable clinical and angiographic outcomes as conventional PCI in CTO lesions, which offer interventional cardiologists an expanded perspective when addressing calcified lesions. PROSPERO REGISTRATION: CRD42023417362.

Cognitive behavioral therapy for the treatment of insomnia in patients with cardiovascular diseases: a meta-analysis with GRADE analysis.

Insomnia, as a difficulty in initiating and maintaining sleep, coupled with cardiovascular diseases (CVDs) increase the risk of aggravate daytime symptoms, mortality, and morbidity. Cognitive behavioral therapy (CBT) is thought to have a significant impact on insomnia treatment, but in patients with CVDs, there is a paucity of data. To provide a comprehensive appraisal on the impact of CBT on the treatment of insomnia in patients with CVDs. We searched Ovid, Scopus, Web of science, and Cochrane central, to randomized controlled trials (RCTs) from inception till November 2022. Outcomes of interest were insomnia severity index (ISI), Pittsburgh Sleep Quality Index (PSQI), sleep efficiency (SE), Dysfunctional Beliefs and Attitudes about Sleep Scale (DBAS), and sleep disorders questionnaire (SDQ). Pooled data were analyzed using mean difference (MD) with its 95% confidence interval (CI) in a random effect model using STATA 17 for Mac. Nine RCTs comprising 365 patients were included in the analysis. CBT significantly reduced scores of ISI (MD = - 3.22, 95%  CI - 4.46 to - 1.98, p < 0.001), PSQI (MD = - 2.33, 95%  CI - 3.23 to - 1.44, p < 0.001), DBAS (MD = - 0.94, 95%  CI - 1.3 to - 0.58, p < 0.001), SDQ (MD = - 0.38, 95%  CI - 0.56 to - 0.2, p < 0.001). Also, it increased the score of SE (MD = 6.65, 95% CI 2.54 to 10.77, p < 0.001). However, there was no difference in terms of ESS. CBT is an easy and feasible intervention with clinically significant improvement in insomnia symptoms. Further large-volume studies are needed to assess sustained efficacy.

Drug-coated balloons versus drug-eluting stents in patients with acute myocardial infarction undergoing percutaneous coronary intervention: an updated meta-analysis with trial sequential analysis.

BACKGROUND: Drug-coated balloons (DCBs) are an established strategy for coronary artery disease. However, the new generation drug-eluting stent (DES) is recommended for patients with Acute myocardial infarction (AMI) for coronary artery revascularization. Our aim is to provide a comprehensive appraisal of the efficacy of DCBs in patients with AMI undergoing PCI. METHODS: We searched the WOS, PubMed, Scopus, and Cochrane CENTRAL till March 2023, for studies that compared DCBs versus DES in patients with AMI undergoing PCI. We used a random-effects model to compare major adverse cardiac events (MACE), cardiac death, all-cause death, myocardial infarction, target lesion revascularization (TLR), stent thrombosis, Late lumen Loss (LLL), and minimum lumen diameter (MLD) between the two groups. RESULTS: Thirteen studies comprising 2644 patients were included. The pooled OR showed non-inferiority of DCB over DES in terms of MACE (OR = 0.89, 95% CI [0.57 to 1.40], p = 0.63). When we defined MACE as a composite of cardiac death, MI, and TLR; the pooled OR favored DCB over DES (OR = 0.50, 95% CI [0.28 to 0.9], p = 0.02). Moreover, DCB was not inferior to DES in terms of all-cause mortality (OR = 0.88, 95% CI: 0.43 to 1.8, p = 0.73), cardiac mortality, (OR = 0.59, 95% CI: 0.22 to 1.56, p = 0.29), MI (OR = 0.88, 95% CI: 0.34 to 2.29, p = 0.79), stent thrombosis (OR = 1.21, 95% CI: 0.35 to 4.23, p = 0.76), TLR (OR = 0.9, 95% CI: 0.43 to 1.93, p = 0.8), LLL (MD = -0.6, 95% CI: -0.3 to 0.19, p = 0.64), or MLD (MD = -0.4, 95% CI: -0.33 to 0.25, p = 0.76). CONCLUSION: Our meta-analysis indicated that DCB intervention was not inferior to DES in the PCI setting in patients with AMI, and can be recommended as a feasible strategy in AMI. PROSPERO REGISTRATION: CRD42023412757.

Physical therapy interventions for the management of hand tremors in patients with Parkinson's disease: a systematic review.

BACKGROUND: Several physical therapy modalities have been used to improve hand tremors in patients with Parkinson's disease (PD). However, little is known about the efficacy of these techniques. Therefore, we conducted this study to synthesize evidence from published studies on the efficacy of physical therapy techniques for hand tremors in PD patients. METHODS: We followed the PRISMA statement and Cochrane handbook guidelines when conducting this study. We conducted an electronic literature search of PubMed, Cochrane Central Register of Clinical Trials, Web of Science, Ovid, and Embase, and then we selected clinical trials assessing the efficacy of any physical therapy intervention for hand tremors in patients with PD. Study outcomes were extracted, and evidence was synthesized narratively. RESULTS: A total of six modalities described in six studies were included in this systematic review. Out of the six interventions, the tremor's glove and electrical stimulation showed significant improvements in root mean square angular velocity (59% and 43.8%, respectively) and UPDRS tremor score (P < 0.05 for both). Also, eccentric exercises were associated with significant reductions in the mean resting tremor amplitude (P < 0.05). These data were dependent on single studies; therefore, a meta-analysis was not feasible. CONCLUSION: Several physical therapy interventions, such as electrical stimulation, exercises, transcranial low voltage pulsed electromagnetic fields, weights, and virtual reality showed promising results in reducing hand tremors. However, this evidence was based on a limited number of included studies, and more RCTs with larger sample sizes are required to confirm the efficacy of these interventions.

Effect of intra-arterial thrombolysis following successful endovascular thrombectomy on functional outcomes in patients with large vessel occlusion acute ischemic stroke: A post-CHOICE meta-analysis.

INTRODUCTION: Endovascular thrombectomy (EVT) is the standard treatment of acute ischemic stroke (AIS) due to large vessel occlusion (LVO). Although > 70% of patients in the trials assessing EVT for AIS-LVO had successful recanalization, only a third ultimately achieved favorable outcomes. A "no-reflow" phenomenon due to distal microcirculation disruption might contribute to such suboptimal outcomes. Combining intra-arterial (IA) tissue plasminogen activator (tPA) and EVT to reduce the distal microthrombi burden was investigated in a few studies. We present a pooled-data meta-analysis of the existing evidence of this combinatorial treatment. METHODS: We followed the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) recommendations. We aimed to include all original studies investigating EVT plus IA tPA in AIS-LVO patients. Using R software, we calculated pooled odds ratios (ORs) with corresponding 95% confidence intervals (CI). A fixed-effects model was adopted to evaluate pooled data. RESULTS: Five studies satisfied the inclusion criteria. Successful recanalization was comparable between the IA tPA and control groups at 82.9% and 82.32% respectively. The 90-day functional independence was similar between both groups (OR= 1.25; 95% CI= 0.92-1.70; P= 0.154). Symptomatic intracranial hemorrhage (sICH) was also comparable between both groups (OR= 0.66; 95% CI= 0.34-1.26; P= 0.304). CONCLUSION: Our current meta-analysis does not show significant differences between EVT alone and EVT plus IA tPA in terms of functional independence or sICH. However, with the limited number of studies and included patients, more randomized controlled trials (RCTs) are needed to further investigate the benefits and safety of combined EVT and IA tPA.

Impact of pre-treatment cerebral microbleeds on the outcomes of endovascular thrombectomy: A systematic review and meta-analysis.

OBJECTIVE/AIM: To investigate the effect of cerebral microbleeds (CMBs) on the functional and safety outcomes of endovascular thrombectomy (EVT) in patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO). METHODS: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines for systematic review and meta-analysis. We included observational studies that recruited AIS-LVO patients, used susceptibility-sensitive magnetic resonance imaging (MRI) to detect CMBs, and examined the association between them and predefined outcome events. The extracted data included study and population characteristics, risk of bias domains, and outcome measures. The outcomes of interest included functional independence, revascularization success, procedural and hemorrhagic adverse events. We conducted a meta-analysis using the Mantel-Haenszel method and calculated the risk ratios. RESULTS: Four studies with a total of 1,514 patients were included. A significant reduction in the likelihood of achieving a favorable functional outcome was observed in patients with CMBs (Risk ratio (RR) 0.69, 95% confidence interval (CI): 0.52 to 0.91, P=0.01). No significant differences were observed between the CMBs and no CMBs groups in terms of successful revascularization, mortality, intracranial hemorrhage (ICH), subarachnoid hemorrhage (SAH), and parenchymal hematoma. CONCLUSIONS: The presence of CMBs significantly reduced the likelihood of achieving functional independence post-EVT in AIS-LVO patients. However, CMBs did not impact the rates of successful revascularization, mortality, or the occurrence of various hemorrhagic events. Future research should explore the mechanisms of this association and strategies to mitigate its impact.

Efficacy of Hibiscus sabdariffa on Reducing Blood Pressure in Patients With Mild-to-Moderate Hypertension: A Systematic Review and Meta-Analysis of Published Randomized Controlled Trials.

We aimed to assess the efficacy of Hibiscus sabdariffa in patients with mild-to-moderate hypertension or metabolic syndrome (MetS) by comparing it against placebo, antihypertensive drugs, or other herbal products. Four databases were searched for randomized clinical trials (RCTs) examining the efficacy of H. sabdariffa in patients with mild-to-moderate hypertension or hypertension associated with MetS. Data on the change in systolic blood pressure (SBP) and diastolic blood pressure (DBP) were extracted and analyzed using Review Manager Version 5.3. A total of 13 RCTs (1205 participants) were analyzed. Hibiscus sabdariffa significantly reduced both SBP and DBP compared with placebo (mean difference -6.67, P = 0.004 and -4.35 mm Hg, P = 0.02). Subgroup analysis showed that change in SBP and DBP was statistically significant in patients with only hypertension, whereas not significant in patients with hypertension associated with MetS. When H. sabdariffa was compared with active controls (antihypertensive drugs or other herbals), the change in SBP and DBP was not statistically significant (all P > 0.05). Hibiscus sabdariffa is effective in reducing the SBP and DBP in patients with mild-to-moderate hypertension, but was neither effective in those with MetS nor superior to antihypertensive drugs. Further RCTs are required to determine the long-term efficacy of H. sabdariffa and to describe patients who would benefit most from this treatment.

A systematic review of vaccine-induced thrombotic thrombocytopenia in individuals who received COVID-19 adenoviral-vector-based vaccines.

Reports of thrombotic response after receiving COVID-19 Adenoviral-Vector Based Vaccines raise concerns about vaccine-induced thrombotic thrombocytopenia (VITT); therefore, we conduct this systematic review to report susceptible demographics outcomes, commonalities, and prognosis of reporting cases. We identified published articles by searching PubMed, SCOPUS, and Web of Science from December 2020 till May 2021, with an updated search in September 2021. All case reports and case series reporting thrombotic response after receiving COVID-19 Adenoviral-Vector Based Vaccines were eligible for including. In addition, two authors independently extracted data and assessed the quality of the included studies. A total of 157 patients with thrombotic events after the ChAdOx1 nCoV-19 vaccine and 16 patients with thrombotic events after Ad26.COV2. S vaccine was included in our study. 72% of the ChAdOx1 nCoV-19 cases were females, while in Ad26.COV2.S subgroup, all reported patients were females. The commonest presentations were deep vein thrombosis 20 (12.7%) and cerebral venous sinus thrombosis 18 (11.5%) in the ChAdOx1 nCoV-19 subgroup while cerebral venous sinus thrombosis 14 (87.5%) and pulmonary embolism 2 (12.5%) in the Ad26.COV2. S subgroup. In this study, we described the certain demographics associated with VITT and the clinical presentations of those cases in the ChAdOx1 nCoV-19 and Ad26.COV2. S vaccines. Young individuals, particularly females, may be more susceptible to VITT, and future studies should seek to confirm this association. In addition, the clinical presentation of VITT commonly includes cerebral thrombi, pulmonary embolism, and deep venous thrombosis, but other presentations are also possible, highlighting the importance of clinical vigilance in recent vaccine recipients.

Intravenous thrombolysis before mechanical thrombectomy for acute ischemic stroke due to large vessel occlusion; should we cross that bridge? A systematic review and meta-analysis of 36,123 patients.

BACKGROUND: The use of intravenous thrombolysis (IVT) before mechanical thrombectomy (MT) for acute ischemic stroke due to large vessel occlusion (AIS-LVO) is a debatable subject in the field of neuro-interventional surgery. We conducted this systematic review and meta-analysis to synthesize evidence from published studies on the outcomes of IVT + MT compared with MT alone in AIS-LVO patients. METHODS: We searched PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials from inception to January 2022 for relevant clinical trials and observational studies. Eligible studies were identified, and all relevant outcomes were pooled in the meta-analysis DerSimonian-Liard random-effects model. RESULTS: Forty-nine studies, with a total of 36,123 patients, were included in this meta-analysis. IVT + MT was significantly superior to MT alone in terms of successful recanalization (RR 1.06, 95% CI 1.03 to 1.09), mortality (RR 0.75, 95% CI 0.68-0.82), favorable functional outcome (RR 1.21, 95% CI 1.13 to 1.29), and complete recanalization (RR 1.06, 95% CI 1.00 to 1.11). There were no significant differences between the two groups in terms of improvement of the National Institute of Health Stroke Scale (NIHSS) score at 24 h or at discharge (p > 0.05). Complications including symptomatic intracranial hemorrhage, symptomatic intracerebral hemorrhage (sICH), procedure-related complications, and parenchymal hematoma were comparable between the two groups (p > 0.05). CONCLUSION: For AIS-LVO, IVT + MT is associated with slightly better rates of survival, successful and complete recanalization, and favorable functional outcome as compared with MT alone. Further clinical trials are needed to corroborate such benefits of bridging IVT.

Tranexamic acid for patients with aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis of 2991 patients.

OBJECTIVE: We aimed to synthesize evidence from published clinical trials on the efficacy and safety of tranexamic acid (TXA) administration in patients with aneurysmal subarachnoid hemorrhage (aSAH). METHODS: We followed the standard methods of the Cochrane Handbook of Systematic Reviews for interventions and the PRISMA statement guidelines 2020 when conducting and reporting this study. A computer literature search of PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials was conducted from inception until 1 January 2022. We selected observational studies and clinical trials comparing TXA versus no TXA in aSAH patients. Data of all outcomes were pooled as the risk ratio (RR) with the corresponding 95% confidence intervals in the meta-analysis models. RESULTS: Thirteen studies with a total of 2991 patients were included in the analysis. TXA could significantly cut the risk of rebleeding (RR 0.56, 95% CI 0.44 to 0.72) and mortality from rebleeding (RR 0.60, 95% CI 0.39 to 0.92, p = 0.02). However, TXA did not significantly improve the overall mortality, neurological outcome, delayed cerebral ischemia, or hydrocephalus (all p > 0.05). In terms of safety, no significant adverse events were reported. No statistical heterogeneity or publication bias was found in all outcomes. CONCLUSION: In patients with aSAH, TXA significantly reduces the incidence of rebleeding and mortality from rebleeding. However, current evidence does not support any benefits in overall mortality, neurological outcome, delayed cerebral ischemia, or hydrocephalus.

Mavoglurant (AFQ056) for the treatment of levodopa-induced dyskinesia in patients with Parkinson's disease: a meta-analysis.

BACKGROUND: Mavoglurant (AFQ056), a selective metabotropic glutamate receptor 5 (mGluR5) inhibitor, was tested for t levodopa-induced dyskinesia (LID) in patients with Parkinson's Disease (PD). However, clinical trials showed inconsistent results regarding the efficacy of mavoglurant in treating LID in patients with Parkinson's disease (PD). METHODS: A computer literature search of PubMed, Scopus, Web of science, and Cochrane CENTRAL was conducted until March 2021. We selected relevant randomized controlled trials comparing mavoglurant to placebo. Study data were extracted and pooled as mean difference (MD) in the meta-analysis model. RESULTS: Six RCTs were included in this meta-analysis with a total of 485 patients. Mavoglurant was not significantly superior to placebo in terms of the "off-time" (MD -0.27 h, 95% CI -0.65 to 0.11), "on time" (MD 0.29 h, 95% CI -0.09 to 0.66), Lang-Fahn activities of daily living dyskinesia scale (MD -0.95, 95% CI -1.98 to 0.07), UPDRS-III (MD -0.51, 95% CI -1.66 to 0.65), or UPDRS-IV (MD -0.41, 95% CI -0.85 to 0.03). However, the pooled modified abnormal involuntary movement scale favored the mavoglurant group than the placebo group (MD -2.53, 95% CI -4.23 to -0.82). CONCLUSIONS: This meta-analysis provides level one evidence that mavoglurant is not effective in treating the LID in patients with PD.

Endovascular thrombectomy for large ischemic strokes: An updated living systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: Recent studies indicate endovascular thrombectomy (EVT) as a safe, effective treatment for acute ischemic stroke (AIS) with large ischemic regions. Our study updates an ongoing living systematic review and meta-analysis of randomized controlled trials (RCTs) comparing outcomes of EVT to medical management only. METHODS: We searched MEDLINE, EMBASE, and the Cochrane Library for RCTs comparing EVT to medical management in AIS patients with large ischemic areas. Using fixed-effect models, we conducted a meta-analysis to compare functional independence, mortality, and symptomatic intracranial hemorrhage (sICH) between EVT and standard medical management. We evaluated bias risk with the Cochrane tool and graded the certainty of evidence using the GRADE approach. RESULTS: Of 1363 new citations, we included six RCTs with a total of 1876 patients. We found low-certainty evidence of improved functional independence (risk difference [RD] 29.9%, 95% CI 17.2% to 46.9%), increase in sICH (RD 2.6%, 95% CI 0.3% to 6.4%), and a non-significant decrease in mortality (RD -1.8%, 95% CI -3.9% to 0.6%) for AIS patients with large infarcts who underwent EVT compared to medical management only. CONCLUSION: Our revised meta-analysis suggests low-certainty evidence that there is improved functional independence, a non-significant decrease in mortality, and an increase in sICH among AIS patients with large infarcts who undergo EVT compared to those receiving medical management alone. SYSTEMATIC REVIEW PROTOCOL REGISTRATION: PROSPERO (CRD42023398742).

Rigid ring vs. flexible band for tricuspid valve repair in patients with tricuspid valve regurgitation: A systematic review and meta-analysis.

Background & objectives: Rigid ring and Flexible band are techniques used to repair tricuspid valve regurgitation. The comparison between both techniques' effectiveness is controversial in the literature. We conducted this systematic review and meta-analysis to compare the safety and efficacy of rigid ring versus flexible band for tricuspid valve repair in patients with tricuspid valve regurgitation. Methods: We conducted a PRISMA-compliant systematic review and meta-analysis. A systematic search was performed in major databases, including PubMed, Scopus, Web of Science, and Cochrane CENTRAL to identify relevant published studies. Data were extracted and analyzed using Stata (version 17 for Mac) and Revman (version 5.4 for Windows). Results: Twelve studies were included in this meta-analysis. Total number of patients was 4259. The rigid ring wasn't superior to the flexible band in terms of postoperative tricuspid regurgitation RR 0.74, 95 % CI (0.43-1.27) (P = 0.29). However, the results were not homogeneous. After employing sensitivity analysis, the significance of the pooled effect estimate didn't change, showing no significant difference between the two annuloplasty RR 0.72, 95%CI (0.45-1.15). On the other hand, the rigid ring was associated with a higher bypass time than the flexible band (RR 4.85, P = 0.00). There were no differences between the two groups in terms of hospital stay, ICU stays, prolonged ventilation, mechanical ventilation time, annuloplasty size, stroke, concomitant mitral valve surgery, concomitant aortic valve surgery, atrial fibrillation, pacemaker implantation, low cardiac output, in-hospital death, or late death (all P > 0.05). Conclusion: Our study findings suggested no difference between rigid ring compared to flexible band regarding the rates of postoperative tricuspid regurgitation; however, rigid ring may encompass a higher bypass time. Therefore, further research is required to ensure our findings.

A comprehensive guide on the optimal timing of PCI in the setting of acute coronary syndrome: An updated meta-analysis.

BACKGROUND: Invasive revascularization is recommended for cohorts of patients with ST-elevation myocardial infarction (STEMI) and non-ST-elevation acute coronary syndrome (NSTE-ACS). However, the optimal timing of invasive revascularization is still controversial and no defined consensus is established. We aim to give a comprehensive appraisal on the optimal timing of invasive strategy in the heterogenous population of ACS. METHODS: Relevant studies were assessed through PubMed, Scopus, Web of science, and Cochrane Library from inception until April 2023. Major adverse cardiovascular events (MACE) and all-cause mortality were our primary outcomes of interest, other secondary outcomes were cardiac death, TVR, MI, repeat revascularization, recurrent ischemia, and major bleeding. The data was pooled as odds ratio (OR) with its 95% confidence interval (CI) in a random effect model using STATA 17 MP. RESULTS: A total of 26 studies comprising 21,443 patients were included in the analysis. Early intervention was favor to decrease all-cause mortality (OR = 0.79, 95% CI: 0.64 to 0.98, p = 0.03), when compared to delayed intervention. Subgroup analysis showed that early intervention was significantly associated with all-cause mortality reduction in only NSTE-ACS (OR = 0.83, 95% CI [0.7 to 0.99], p = 0.04). However, there was no significant difference between early and delayed intervention in terms of MACE, cardiac death, TVR, MI, repeat revascularization, recurrent ischemia, and major bleeding. CONCLUSION: An early intervention was associated with lower mortality rates compared to delayed intervention in NSTE-ACS with no significant difference in other clinical outcomes. PROSPERO registration: CRD42023415574.

Combined saline and vildagliptin induced M2 macrophage polarization in hepatic injury induced by acute kidney injury.

Acute kidney injury (AKI) is a prevalent medical condition accompanied by mutual affection of other organs, including the liver resulting in complicated multiorgan malfunction. Macrophages play a vital role during tissue injury and healing; they are categorized into "classically activated macrophages" (M1) and "alternatively activated macrophages" (M2). The present study investigated and compared the conventional fluid therapy vs Dipeptidyl peptidase 4 inhibitor (DPP-4i) vildagliptin on the liver injury induced by AKI and evaluated the possible molecular mechanisms. Thirty rats comprised five groups (n = 6 rats/group): control, AKI, AKI+saline (received 1.5 mL of normal saline subcutaneous injection), AKI+vildagliptin (treated with oral vildagliptin 10 mg/kg), AKI+saline+vildagliptin. AKI was induced by intramuscular (i.m) injection of 50% glycerol (5 ml/kg). At the end of the work, we collected serum and liver samples for measurements of serum creatinine, blood urea nitrogen (BUN), alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrotic factor-α (TNF-α), and interleukin-10 (IL-10). Liver samples were processed for assessment of inducible nitric oxide synthase (iNOS) as a marker for M1, arginase 1 (Arg-1) as an M2 marker, c-fos, c-Jun, mitogen-activated protein kinase (MAPK), activator protein 1 (AP-1), and high-mobility-group-box1 (HMGB1) protein. The difference was insignificant regarding the relative expression of AP-1, c-Jun, c-fos, MAPK, and HMGB between the AKI+saline group and the AKI+Vildagliptin group. The difference between the same two groups concerning the hepatic content of the M1 marker (iNOS) and the M2 marker Arg-1 was insignificant. However, combined therapy produced more pronounced changes in these markers, as the difference in their relative expression between the AKI+saline+Vildagliptin group and both the AKI+saline group and the AKI+Vildagliptin group was significant. Accordingly, we suggest that the combined saline and vildagliptin hepatoprotective effect involves the downregulation of the MAPK/AP-1 signaling pathway.

Do cerebral microbleeds increase the risk of dementia? A systematic review and meta-analysis.

Background: Dementia is a neurological disorder that commonly affects the elderly. Cerebral microbleeds (CMBs) are small, tiny lesions of the cerebral blood vessels and have been suggested as a possible risk factor for dementia. However, data about the association between CMBs and dementia risk are inconsistent and inconclusive. Therefore, we conducted this systematic review and meta-analysis to investigate the association between CMBs and dementia and highlight the possible explanations. Methods: We followed the standard PRISMA statement and the Cochrane Handbook guidelines to conduct this study. First, we searched medical electronic databases for relevant articles. Then, we screened the retrieved articles for eligibility, extracted the relevant data, and appraised the methodological quality using the Newcastle-Ottawa Scale. Finally, the extracted data were pooled as risk ratios (RR) and hazard ratios (HR) in the random-effects meta-analysis model using the Review Manager software. Results: We included nine studies with 14,221 participants and follow-up periods > 18 months. Overall, CMBs significantly increased the risk of developing dementia (RR 1.84, 95% CI [1.27-2.65]). This association was significant in the subgroups of studies on high-risk populations (RR 2.00, 95% CI [1.41-2.83], n = 1657 participants) and those in the general population (RR 2.30, 95% CI [1.25-4.26], n = 12,087 participants) but not in the memory clinic patients. Further, CMBs increased the risk of progressing to incident dementia over time (HR 2, 95% CI [1.54-2.61]). Conclusion: Individuals with CMBs have twice the risk of developing dementia or progressing to MCI than those without CMBs. The detection of CMBs will help identify the population at higher risk of developing dementia. Physicians should educate individuals with CMBs and their families on the possibility of progressing to dementia or MCI. Regular cognitive assessments, cognitive training, lifestyle modifications, and controlling other dementia risk factors are recommended for individuals with CMBs to decrease the risk of cognitive decline and dementia development.

Endovascular Thrombectomy for Large Ischemic Strokes: A Living Systematic Review and Meta-Analysis of Randomized Trials.

BACKGROUND AND PURPOSE: New studies have shown that endovascular thrombectomy (EVT) is safe and effective for acute ischemic stroke (AIS) patients with large ischemic areas. The aim of our study is to conduct a living systematic review and meta-analysis of randomized trials comparing EVT versus medical management only. METHODS: We searched MEDLINE, Embase, and the Cochrane Library to identify randomized controlled trials (RCTs) comparing EVT versus medical management alone in AIS patients with large ischemic regions. We conducted our meta-analysis using fixed-effect models to compare functional independence, mortality, and symptomatic intracranial hemorrhage (sICH) between EVT and standard medical management only. We assessed the risk of bias using the Cochrane risk-of-bias tool and the certainty of evidence for each outcome using the Grading of Recommendations, Assessment, Development, and Evaluations approach. RESULTS: Of 14,513 citations, we included 3 RCTs with a total of 1,010 participants. We found low-certainty evidence of possibly a large increase in the proportion of patients with functional independence (risk difference [RD] 30.3%, 95% CI 15.0% to 52.3%), low-certainty evidence of possibly a small non-significant decrease in mortality (RD -0.7%, 95% CI -3.8% to 3.5%), and low-certainty evidence of possibly a small non-significant increase in sICH (RD 3.1%, 95% CI -0.3% to 9.8%) for AIS patients with large infarcts who underwent EVT compared to medical management only. CONCLUSION: Low-certainty evidence shows that there is possibly a large increase in functional independence, a small non-significant decrease in mortality, and a small non-significant increase in sICH amongst AIS patients with large infarcts undergoing EVT compared to medical management only.

The Role of RIN3 Gene in Alzheimer's Disease Pathogenesis: a Comprehensive Review.

Alzheimer's disease (AD) is a globally prevalent form of dementia that impacts diverse populations and is characterized by progressive neurodegeneration and impairments in executive memory. Although the exact mechanisms underlying AD pathogenesis remain unclear, it is commonly accepted that the aggregation of misfolded proteins, such as amyloid plaques and neurofibrillary tau tangles, plays a critical role. Additionally, AD is a multifactorial condition influenced by various genetic factors and can manifest as either early-onset AD (EOAD) or late-onset AD (LOAD), each associated with specific gene variants. One gene of particular interest in both EOAD and LOAD is RIN3, a guanine nucleotide exchange factor. This gene plays a multifaceted role in AD pathogenesis. Firstly, upregulation of RIN3 can result in endosomal enlargement and dysfunction, thereby facilitating the accumulation of beta-amyloid (Aß) peptides in the brain. Secondly, RIN3 has been shown to impact the PICLAM pathway, affecting transcytosis across the blood-brain barrier. Lastly, RIN3 has implications for immune-mediated responses, notably through its influence on the PTK2B gene. This review aims to provide a concise overview of AD and delve into the role of the RIN3 gene in its pathogenesis.

Short- and Long-term Outcomes of Percutaneous Coronary Interventions in Chronic and Non-chronic Total Occlusions: A Meta-analysis of 690,123 Patients.

The use of percutaneous coronary intervention (PCI) in patients with chronic total occlusion (CTO) is still a subject of debate, with conflicting outcomes reported in different studies when compared to non-CTO lesions. This meta-analysis aims to clarify the clinical outcomes of PCI in CTO cases compared to non-CTO lesions, both in the short and long-term. PubMed, Scopus, Web of Science, Ovid, and Cochrane Central were searched until March 2023 for relevant studies addressing short- and long-term outcomes of PCI in CTO vs non-CTO lesions. Dichotomous data were pooled as odds ratio (OR) with its 95% confidence interval (CI) in a random Der-Simonian lair effect model using STATA 17 MP. Eight studies with a total of 690,123 patients were included. In terms of short-term outcomes, CTO PCI was associated with higher rates of vessel perforation (OR = 2.16, 95% CI: 1.31-3.57) and cardiac tamponade (OR = 5.19, 95% CI: 4.29-6.28). Additionally, CTO PCI showed lower rates of procedural success (OR = 0.84, 95% CI: 0.73-0.96). Moreover, in the long-term, CTO PCI had higher rates of MACE (OR = 1.02, 95% CI: 1.01-1.04), however, it showed lower rates of cardiac death (OR = 0.61, 95% CI: 0.38-0.98), with no significant difference in other reported outcomes. Our findings underscore the challenges and adverse outcomes associated with using PCI to treat CTO lesions in the short term. This suggests that interventional cardiologists should carefully evaluate the risks and benefits before proceeding with PCI in CTO lesions.