Role of adjunctive cariprazine for treatment-resistant depression in patients with major depressive disorder: A systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: Cariprazine is an orally active dopamine D3-preferring D3/D2 receptor and serotonin 5-HT1A receptor partial agonist, being considered as a treatment for refractory MDD. Therefore, we aim to perform the first meta-analysis of current literature, to collate changes in depression from baseline and assess tolerability of adjunctive cariprazine in MDD populace. METHODS: PubMed, Embase, Google Scholar, ClinicalTrials.Gov, and Cochrane Library were searched from inception till 1st September 2023. RCTs of adult patients with refractory MDD under adjunctive cariprazine vs. placebo were included. Primary outcomes included improvement in MADRS, CGI-S, and HAM-D 17 scores. Secondary outcomes included treatment-emergent adverse events. The statistical analysis was performed using generic inverse variance with random-effects model. The overall risk ratios (RR) were calculated for dichotomous outcomes. RESULTS: A total of five RCTs were analysed, enrolling 2013 participants (cariprazine: 959 participants, Placebo: 1054). Supplementation of ADT with cariprazine demonstrated a significant improvement in MADRAS, CGI-S and HAMD-17 scores from baseline (LSMD: -1.88, 95% CI [-2.94, -0.83], p=0.0005), (LSMD: -0.18, 95% CI [-0.29, -0.07], p=0.002), and (LSMD: -0.96, 95% CI [-1.70, -0.21], p=0.01) respectively. Treatment with adjunctive cariprazine therapy demonstrated significantly increased incidence of akathisia, nausea, dizziness, fatigue, restlessness, somnolence, and tremors when compared with placebo. CONCLUSION: Our meta-analysis provides evidence supporting the efficacy of adjunctive cariprazine in patients with refractory MDD. However, it is essential to consider the safety profile of cariprazine, particularly the increased risk of adverse events. The vigilant monitoring and management of these side effects should be integrated into clinical practice to minimize discontinuation rates and optimize patient outcomes.

Comparative efficacy and safety of mitral valve repair versus mitral valve replacement in Rheumatic heart disease: A high-value care systematic review and meta-analysis.

Rheumatic Heart Disease (RHD) remains a leading cause of cardiovascular death (CVD) globally. Mitral Valve repair (MVP) and mitral valve replacement (MVR) are the two most commonly and successfully used techniques to treat the disease. MVP is associated with reduced post-operative complications compared to MVR; however, it carries the risk of valvular fibrosis and scarring. Given the lack of recommendations, inconsistent findings, and paucity of pathophysiological evidence at present, we aimed to conduct a meta-analysis and systematically review the available literature to determine the efficacy and safety of MVP compared to MVR in improving clinical outcomes among patients with RHD. A comprehensive literature search was conducted on MEDLINE (PubMed), Cochrane Central and Scopus from inception till September 2023. The primary objective was early mortality defined as any cause-related death occurring 30 days following surgery. Secondary outcomes included long-term survival defined as the time duration between hospital discharge and all-cause death. Infectious endocarditis, thromboembolic events (including stroke, brain infarction, peripheral embolism, valve thrombosis, and transient ischemic attack), and haemorrhagic events (any serious bleeding event that required hospitalisation, resulted in death, resulted in permanent injury, or required blood transfusion) were all considered as post- operative complications. Additionally aggregated Kaplan-Meier curves were reconstructed for long term survival, freedom from reoperation, and freedom from valve-related adverse events by merging the reconstructed individual patient data (IPD) from each individual study. A significant decrease in early mortality with MV repair strategy versus MV replacement [RR 0.63; P = 0.003) irrespective of mechanical or bioprosthetic valves was noted. The results reported significantly higher long-term survival in patients undergoing MVP versus MVR (HR 0.53; P = 0.0009). Reconstructed Kaplan-Meier curves showed that the long term survival rates at 4, 8, and 12 years were 88.6, 82.0, 74.6 %, in the MVR group and 91.7, 86.8, 81.0 %, in the MVP group, respectively. MVP showed statistically significant reduction in early mortality, adverse vascular events, and better long-term survival outcomes compared to the MVR strategy in this analysis.

Left bundle branch pacing vs biventricular pacing in heart failure patients with left bundle branch block: A systematic review and meta-analysis.

BACKGROUND: Left bundle branch pacing (LBBP) is a novel pacing modality of cardiac resynchronization therapy (CRT) that achieves more physiologic native ventricular activation than biventricular pacing (BiVP). AIM: To explore the validity of electromechanical resynchronization, clinical and echocardiographic response of LBBP-CRT. METHODS: Systematic review and Meta-analysis were conducted in accordance with the standard guidelines as mentioned in detail in the methodology section. RESULTS: In our analysis, the success rate of LBBP-CRT was determined to be 91.1%. LBBP-CRT significantly shortened QRS duration, with significant improvement in echocardiographic parameters, including left ventricular ejection fraction, left ventricular end-diastolic diameter and left ventricular end-systolic diameter in comparison with BiVP-CRT. CONCLUSION: A significant reduction in New York Heart Association class and B-type natriuretic peptide levels was also observed in the LBBP-CRT group vs BiVP-CRT group. Lastly, the LBBP-CRT cohort had a reduced pacing threshold at follow-up as compared to BiVP-CRT.

Safety and efficacy of percutaneous Watchman 2.5 device versus Amplatzer Amulet for left atrial appendage closure in patients with non-valvular atrial fibrillation: A systematic review and study-level meta-analysis.

INTRODUCTION: In patients with non-valvular atrial fibrillation (NVAF), mechanical occlusion of the left atrial appendage (LAA) using a permanently implanted device may be an effective alternative to oral anti-coagulants (OAC). To facilitate left atrial appendage closure (LAAC), multiple percutaneous devices have been proposed. Watchman Generation 2.5 and Amplatzer Amulet are the two most popular used devices for preventing stroke in patients with NVAF. We sought to compare safety and efficacy outcomes between Watchman 2.5 and Amplatzer Amulet in patients undergoing LAAC procedure. METHODS: We carried out a comprehensive and systematic search of the databases PubMed and Scopus, for all studies that compared the safety and efficacy of Watchman 2.5 and Amplatzer Amulet devices, from inception, till June 2023. We performed the statistical analysis using Review Manager (V.5.4.1 Cochrane Collaboration, London, United Kingdom). The safety outcomes of interest included device success, device-related thrombus, device embolization perioperatively and at follow-up, perioperative pericardial perfusion events, and perioperative cardiac tamponade events. Efficacy outcomes were all-cause mortality perioperatively and at follow-up, cardiovascular (CV) mortality at follow-up, stroke, major and minor bleeding events at follow-up, transient ischemic attack (TIA) in follow-up period, thromboembolic events in follow-up period, and peri-device leakage in perioperative period. All data was analysed using a random-effects model, and presented as risk ratios (RRs) with 95% confidence intervals (95%CIs). RESULTS: Regarding safety outcomes, device success was non-significantly reduced in Watchman group when compared with Amulet (RR 0.99, p = 0.57; I2 = 34%). In contrast, device-related thrombus was non-significantly increased in Watchman 2.5 group in comparison to Amulet (RR 1.44, p = 0.11; I2 = 0%). There was no significant difference between the devices in terms of device embolization in the perioperative (RR 0.36, p = 0.38; I2 = 22%) and follow-up (RR 2.24, p = 0.13; I2 = 0%) periods. Likewise, there was no significant difference in the risks of pericardial effusion (RR 0.98, p = 0.98; I2 = 0%), and cardiac tamponade (RR 0.65, p = 0.76; I2 = 62%) perioperatively. Regarding efficacy outcomes, no significant difference was observed in all-cause mortality between devices perioperatively (RR 0.51, p = 0.32; I2 = 0%) and at follow-up (RR 1.08, p = 0.56; I2 = 0%). CV-mortality was non-significantly reduced in Watchman group when compared with Amulet (RR 0.57, p = 0.20; I2 = 0%). The Amulet device was not superior to the Watchman device in terms of stroke at follow-up (RR 1.13, p = 0.63; I2 = 0%). Sub-group analysis showed comparable ischaemic and haemorrhagic stroke events between two devices. Furthermore, at follow-up, there was no significant difference in major (RR 1.06, p = 0.63; I2 = 0%) and minor bleeding events (RR 1.81, p = 0.17; I2 = 0%) between the two devices. No difference was observed for trans-ischemic attack (RR 1.89, p = 0.24; I2 = 0%) and thromboembolic events (RR 0.96, p = 0.96; I2 = 0%) at follow-up. No significant difference was observed between devices for peri-device leakage in perioperative period (RR 2.16, p = 0.05; I2 = 0%). CONCLUSION: The data suggested that LAAC is safe and efficacious procedure irrespective of device used, with generally low complication rates. Watchman generation 2.5 remains non-superior to Amplatzer Amulet in terms of safety and efficacy outcomes.

Efficacy and safety of bedaquiline and delamanid in the treatment of drug-resistant tuberculosis in adults: A systematic review and meta-analysis.

Multi and extensively drug-resistant tuberculosis is a grave cause of global public health concern due to its high mortality and limited treatment options. We conducted this systemic review and meta-analysis to evaluate the efficacy and safety of bedaquiline and delamanid, which have been added to the WHO-recommended regimen for treating drug-resistant tuberculosis. Electronic databases were searched from their inception until December 1st, 2021, for eligible studies assessing the efficacy and safety of bedaquiline and delamanid for treating drug-resistant tuberculosis. Binary outcomes were pooled using a DerSimonian-Laird random-effects model and arcsine transformation and reported on a log scale with a 95% confidence interval (CIs). Twenty-one studies were shortlisted in which bedaquiline, delamanid, and a combination of both were administered in 2477, 937, and 169 patients. Pooled culture conversion at 6 months was 0.801 (p < 0.001), 0.849 (p = 0.059) for bedaquiline and delamanid, respectively, and 0.823 (p = 0.017), concomitantly. In the bedaquiline cohort, the pooled proportion of all-cause mortality at 6 months was reported as 0.074 (p < 0.001), 0.031 (p = 0.372) in the delamanid cohort, and 0.172 in the combined cohort. The incidence of adverse events in the bedaquiline cohort ranged from 11.1% to 95.2%, from 13.2% to 86.2% in the delamanid cohort, and 92.5% in a study in the combined cohort. The incidence of QTC prolongation reported in each cohort is as follows: bedaquiline 0.163 (p < 0.001), delamanid 0.344 (p = 0.272) and combined 0.340 (p < 0.001). Our review establishes the efficacy of delamanid, bedaquiline, and their combined use in treating drug-resistant tuberculosis with reasonable rates of culture conversion, low mortality rates, and safety of co-administration, as seen with their effect on the QTc interval.

Efficacy of Intravascular Imaging-Guided Drug-Eluting Stent Implantation: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

Intravascular imaging (IVI) namely intravascular ultrasound (IVUS) and optical coherence tomography (OCT), presents as a promising imaging modality for drug-eluting stent (DES) implantation compared to the gold-standard conventional two-dimensional angiography. IVI provides detailed information on vessel lumen, lesion length, and degree of calcification. For this purpose, we conducted a meta-analysis by pooling recently conducted randomized control trials (RCTs) to compare IVI with angiography for DES implantation. Scopus and MEDLINE were searched till May 2023 for RCTs comparing IVI with traditional angiography-guided stent implantation in coronary artery disease patients undergoing percutaneous coronary intervention. The primary outcome of interest was target-lesion revascularization (TLR). Secondary outcomes included target vessel revascularization (TVR), all-cause mortality, and major adverse cardiovascular events (MACE). A random-effects meta-analysis with metaregression was performed to derive risk ratios with corresponding 95% CIs from dichotomous data. Fourteen RCTs with a total of 8946 CAD patients (IVI 4751 vs angiography 4195; mean age 61.7 years) and a median follow-up of 15 months (12-24.3) were included. IVI was associated with significantly reduced TLR (RR 0.63 [0.49, 0.79]) vs conventional angiography. Similarly, TVR incidence (RR 0.66 [0.53, 0.83]), and MACE (RR 0.69 [0.58, 0.78]) were also significantly decreased with IVI vs conventional angiography for PCI. However, no significant difference was observed in all-cause mortality between the 2 imaging modalities (RR 0.85 [0.63, 1.15]). Metaregression analysis showed no significant impact of follow-up duration, baseline comorbidities such as hypertension, smoking status, previous MI, and stent length on TLR incidence. IVI was associated with improved clinical outcomes in terms of reduced TLR, TVR, and MACE incidence when compared with traditional angiography in CAD patients for stent implantation.

Efficacy and safety of finerenone in chronic kidney disease and type 2 diabetes patients: a systematic review and meta-analysis.

Background and objectives: The incidence of morbidity and mortality in patients with type 2 diabetes mellitus is substantially correlated with cardiovascular disease and chronic kidney disease. The current guidelines recommend the use of renin-angiotensin system blockers, but recent studies probed into the effects of finerenone to mitigate the risk of cardiorenal events. This meta-analysis was performed to demonstrate the effects of finerenone on cardiorenal events, comprising cardiovascular mortality, heart failure, change in estimated glomerular filtration rate, and serum potassium levels. Methods: After screening with our eligibility criteria, 350 articles were identified with an initial literature search on multiple databases, including PubMed, Science Direct, and Cochrane Central. Seven randomized controlled trials with a total of 15 462 patients (n=8487 in the finerenone group; n=6975 in the control group) were included. Results: Patients receiving finerenone were at a reduced risk for cardiovascular mortality [HR: 0.84 (0.74, 0.95)], heart failure [OR: 0.79 (0.68, 0.92)], decrease in estimated glomerular filtration rate by 40% [OR: 0.82 (0.74, 0.91)] and by 57% [OR: 0.70 (0.59, 0.82)]; and a higher incidence of moderate hyperkalemia [OR: 2.25 (1.78, 2.84)]. Conclusion: Finerenone, owing to its better mineralocorticoid affinity, and a much lower risk of adverse effects, promises to be a much better alternative than other renin-angiotensin system blockers available for the treatment of chronic kidney disease patients with type 2 diabetes. Further trials should be conducted to provide more definitive evidence to assess the safety and efficacy of finerenone compared to spironolactone and eplerenone.

Adverse events following COVID-19 mRNA vaccines: A systematic review of cardiovascular complication, thrombosis, and thrombocytopenia.

BACKGROUND AND OBJECTIVES: Since publishing successful clinical trial results of mRNA coronavirus disease 2019 (COVID-19) vaccines in December 2020, multiple reports have arisen about cardiovascular complications following the mRNA vaccination. This study provides an in-depth account of various cardiovascular adverse events reported after the mRNA vaccines' first or second dose including pericarditis/myopericarditis, myocarditis, hypotension, hypertension, arrhythmia, cardiogenic shock, stroke, myocardial infarction/STEMI, intracranial hemorrhage, thrombosis (deep vein thrombosis, cerebral venous thrombosis, arterial or venous thrombotic events, portal vein thrombosis, coronary thrombosis, microvascular small bowel thrombosis), and pulmonary embolism. METHODS: A systematic review of original studies reporting confirmed cardiovascular manifestations post-mRNA COVID-19 vaccination was performed. Following the PRISMA guidelines, electronic databases (PubMed, PMC NCBI, and Cochrane Library) were searched until January 2022. Baseline characteristics of patients and disease outcomes were extracted from relevant studies. RESULTS: A total of 81 articles analyzed confirmed cardiovascular complications post-COVID-19 mRNA vaccines in 17,636 individuals and reported 284 deaths with any mRNA vaccine. Of 17,636 cardiovascular events with any mRNA vaccine, 17,192 were observed with the BNT162b2 (Pfizer-BioNTech) vaccine, 444 events with mRNA-1273 (Moderna). Thrombosis was frequently reported with any mRNA vaccine (n = 13,936), followed by stroke (n = 758), myocarditis (n = 511), myocardial infarction (n = 377), pulmonary embolism (n = 301), and arrhythmia (n = 254). Stratifying the results by vaccine type showed that thrombosis (80.8%) was common in the BNT162b2 cohort, while stroke (39.9%) was common with mRNA-1273 for any dose. The time between the vaccination dosage and the first symptom onset averaged 5.6 and 4.8 days with the mRNA-1273 vaccine and BNT162b2, respectively. The mRNA-1273 cohort reported 56 deaths compared to the 228 with BNT162b2, while the rest were discharged or transferred to the ICU. CONCLUSION: Available literature includes more studies with the BNT162b2 vaccine than mRNA-1273. Future studies must report mortality and adverse cardiovascular events by vaccine types.

Role of laparoscopic surgery in the management of gallbladder cancer: Systematic review & meta-analysis.

BACKGROUND: This meta-analysis evaluates the safety and short-term oncological outcomes of laparoscopic vs. open surgery for gallbladder carcinoma(GBC). METHODS: Meta-analysis was performed on laparoscopic(LG) and open group(OG) studies. Data for survival outcomes were extracted from Kaplan-Meier curves and combined with Tierney's method to estimate hazard ratios(HRs) and 95% CIs. RESULTS: There was no significant difference in overall survival(HR: 1.01), disease-free survival(HR: 0.84), 30-day mortality(RR:1.10), overall recurrence(RR:0.93), intraoperative gallbladder violation(RR:1.17), operative time(WMD:8.32), number of patients receiving adjuvant chemotherapy(RR:1.06) and blood transfusion(RR: 0.81). A significant difference was seen in survival of T3 subgroup(HR:0.77) and number of lymph node dissections (LND)(WMD: 0.63) favoring OG, along with a decrease in postoperative complications(RR:0.65), greater incidence of R0 resections(RR:1.04), lower volume of intraoperative blood loss(WMD: 128.62), lower time in removing drainage tube(WMD: 1.35), shorter diet recovery time(WMD: 1.88), shorter hospital stay(WMD: 3.51), lower incidence of 90-day mortality(RR:0.49) favoring LG. A higher incidence of port-site recurrence(RR:1.99) was reported in LG. CONCLUSION: Laparoscopic surgery is non-inferior to the open approach in terms of oncological outcomes and has an improved rate of postoperative complications.

No difference in myocardial iron concentration and serum ferritin with deferasirox and deferiprone in pediatric patients with hemoglobinopathies: A systematic review and meta-analysis.

OBJECTIVES: Iron overload is a common complication experienced by transfusion-dependent children with hemoglobin disorders. Chelators such as deferasirox (DFX) and deferiprone (DFP) are effective in overcoming this problem. We conducted this systematic review and meta-analysis to evaluate the effectiveness of DFX compared to DFP in treating iron overload amongst pediatric patients with hemoglobin disorders. MATERIAL AND METHODS: PubMed and Cochrane Central were searched from their inception until Dec 21 2021, for randomized clinical trials (RCTs) and observational studies, which assessed the efficacy of DFX compared to DFP in the treatment of inherited hemoglobin disorders. The outcomes of interest included myocardial iron concentration (MRI T2*) at the end of the trial and change in mean serum ferritin (SF) levels at the 6 and 12 months mark. Weighted mean differences (WMDs) with their corresponding 95% confidence intervals (CIs) were calculated for continuous outcomes using random effects model. RESULTS: A total of 5 studies comprising 607 children were included. The results of our analysis revealed no significant difference between DFX and DFP in MRI T2* at the end of treatment (WMD: -0.92; 95% CI [-3.35, 1.52]; p = 0.46; I2 = 0). Moreover, there has been no significant difference noted in SF levels at both 6 months (WMD: 97.31; 95% CI [-236.16, 430.77]; p = 0.57; I2 = 0) and 12 months (WMD: 46.99; 95% CI [-191.42, 285.40]; p = 0.70; I2 = 0) respectively. CONCLUSION: Our analysis shows no significant difference between the efficacy of DFX and DFP in the management of iron overload in children with inherited blood disorders. Future large-scale clinical trials are required to further validate our results.

Causes and Determinants of Heart Failure Readmissions Post Transcutaneous Aortic Valve Replacement: A Systematic Review and Meta-Analysis.

Transcutaneous aortic valve implantation (TAVI) has transformed the management of aortic stenosis (AS) and is increasingly being used for patients with symptomatic, severe aortic stenosis who are ineligible or at high risk for conventional cardiac surgery. PUBMED, Google Scholar, and SCOPUS databases were searched to identify studies reporting heart failure hospitalization after TAVI. Major factors evaluated for HF hospitalization were age, comorbidities such as hypertension, atrial fibrillation (AF), chronic pulmonary disease including COPD, chronic kidney disease, baseline LVEF before the procedure, NYHA symptom class, and society of thoracic surgeons (STS) score. Hazard ratio (HR) with a 95% confidence interval were computed using random-effects models. A total of eight studies were included comprising 77,745 patients who underwent TAVI for severe aortic stenosis. The presence of diabetes mellitus (HR: 1.39, 95% CI [1.17, 1.66], chronic kidney disease (CKD) (HR: 1.39, 95% CI [1.31, 1.48], atrial fibrillation (HR: 1.69, 95% CI [1.42, 2.01], chronic pulmonary disease (HR: 1.33, 95% CI [1.12, 1.58], and a high STS score (HR: 1.07, 95% CI [1.03, 1.11] were positive predictors of 1-year HF hospitalization after TAVI. Patients with diabetes mellitus, AF, CKD, chronic pulmonary disease, and a high STS score are at an increased risk of heart failure hospitalization at 1-year of TAVI, whereas increasing age, hypertension, LVEF <50%, and NYHA class III/IV symptoms did not predict HF hospitalization. Careful follow-up after TAVI in high-risk patients, with closer surveillance for HF particularly, is key to preventing HF hospitalizations and death.

Early Transcatheter or Surgical Aortic Valve Replacement Versus Conservative Management in Asymptomatic Patients With Severe Aortic Stenosis: A Systematic Review and Meta-analysis.

The merits of conservative management vs early intervention in patients with asymptomatic severe aortic stenosis remains unknown. Digital databases (MEDLINE, Google Scholar, and Embase) were searched for all relevant studies from inception through September 2022. Studies comparing conservative management with early intervention were compared using a random-effects model to calculate risk ratios (RRs) with 95% confidence interval (CI). A total of 12 studies comprising 3624 asymptomatic aortic stenosis patients (1747 receiving surgery, and 1877 receiving conservative treatment) were included in the analysis. The average follow-up time was 4.45 (IQR 3.5-5) years. Early intervention was associated with a significantly reduced risk of cardiac (RR 0.42, 95% CI 0.25-0.72; P = 0.001; I2 = 54%), non-cardiac (RR 0.46, 95% CI 0.32-0.68; P < 0.0001; I2 = 0%), all-cause mortality (RR 0.40, 95% CI 0.32-0.51; P < 0.00001; I2 = 58%), heart failure hospitalization (RR 0.21, 95% CI 0.13-0.36; P < 0.00001; I2 = 0%), sudden cardiac death (RR 0.29, 95% CI 0.12-0.66; P = 0.004, I2 = 24%), and MACE (RR 0.46, 95% CI; 0.28-0.75; P = 0.002; I2 = 68%), compared with conservative management. There was no significant difference in the 30-day mortality (RR 0.63, 95% CI 0.19-2.04; P = 0.44; I2 = 28%), myocardial infarction (RR 0.44, 95% CI 0.19-1.06; P = 0.07, I2=0%), and 90-day mortality (RR 0.68, 95% CI 0.20-2.37; P = 0.55; I2 = 61%) between the 2 groups. This meta-analysis shows statistically significant reductions in the risk for all-cause mortality, cardiac specific mortality, non-cardiac mortality, heart failure hospitalization, MACE, and sudden cardiac death among asymptomatic aortic stenosis patients who underwent early intervention as opposed to conservative management.

Efficacy of bariatric surgery in COVID-19 patients: An updated systematic review and meta-analysis.

Introduction: Obesity is linked with poor outcomes in patients with SARS-CoV-2 infection. In patients with BMI > 35 kg/m2, increased rates of hospital and subsequently ICU admissions have been noted. Bariatric surgery resulting in sustained weight loss is hypothesized to decrease the morbid outcomes associated with COVID. In this review, we update the evidence on the topic. Methods: An extensive literature search was conducted of electronic databases. Screening of the articles based on the eligibility criteria was followed by relevant data extraction. In addition to articles used in a previous meta-analysis, relevant databases were searched to filter for any new articles. Initially, two independent reviewers screened Pubmed and the Cochrane database followed by a thorough search of additional databases such as Google scholar and Medrxiv. Articles were first screened using title and abstract, followed by a full text read. Duplicates, meta-analysis, letter to the editors, and commentaries were excluded. No language restrictions were applied. Results: A total of nine articles with a population of 1,130,341 were entered into RevMan. Patients with bariatric surgery displayed significantly decreased hospitalization (OR: 0.52, 95% CI [0.45, 0.61]), were less likely to be admitted to the ICU (OR: 0.44, 95% CI [0.29, 0.67]), and had reduced overall mortality (OR: 0.42, 95% CI [0.25, 0.70]). Conclusion: Surgically induced weight loss is beneficial in reducing morbidity and mortality of COVID-19.

Apheresis: A cell-based therapeutic tool for the inflammatory bowel disease.

Inflammatory Bowel Disease (IBD) is a hallmark of leukocyte infiltration, followed by the release of cytokines and interleukins. Disease progression to Ulcerative Colitis (UC) or Crohn's Disease (CD) remained largely incurable. The genetic and environmental factors disrupt enteral bacteria in the gut, which hampers the intestinal repairing capability of damaged mucosa. Commonly practiced pharmacological therapies include 5-aminosalicylic acid with corticosteroids and tumor necrosis factor (TNF)-α. New interventions such as CDP571 and TNF-blocking RDP58 report the loss of patient response. This review discusses the non-pharmacologic selective granulocyte-monocyte-apheresis (GMA) and leukocytapheresis (LCAP) that have been proposed as treatment modalities that reduce mortality. GMA, an extracorporeal vein-to-vein technique, presents a strong safety profile case for its use as a viable therapeutic option compared to GMA's conventional medication safety profile. GMA reported minimal to no side effects in the pediatric population and pregnant women. Numerous studies report the efficacious nature of GMA in UC patients, whereas data on CD patients is insufficient. Its benefits outweigh the risks and are emerging as a favored non-pharmacological treatment option. On the contrary, LCAP uses a general extracorporeal treatment that entraps leukocytes and suppresses cytokine release. It has been deemed more efficacious than conventional drug treatments, the former causing better disease remission, and maintenance. Patients with UC/CD secondary to complications have responded well to the treatment. Side effects of the procedure have remained mild to moderate, and there is little evidence of any severe adverse event occurring in most age groups. LCAP decreases the dependence on steroids and immunosuppressive therapies for IBD. The review will discuss the role of GMA and LCAP.

Efficacy and Safety of Concomitant Tricuspid Repair in Patients Undergoing Mitral Valve Surgery: a Systematic Review and Meta-Analysis.

Tricuspid valve repair (TVR) is recommended for patients with moderate primary tricuspid regurgitation (TR), those with moderate TR, and a history of heart failure without annular dilation, while being essential for patients with severe secondary TR undergoing MVS. The meta-analysis aimed to evaluate the efficacy and safety of tricuspid valve repair in patients undergoing MVS. We systematically searched PubMed, Embase, and Google Scholar through January 2022, and studies comparing patients with TVR and those without TVR were selected. The primary outcomes were 30-day, and all-cause mortality. In this meta-analysis, 20 studies were included with a patient population of 72,422. No significant differences were observed between patients undergoing TVR with MVS, in comparison to MVS group only for the primary outcomes i.e., 30-day mortality (RR: 1.14, 95% CI [0.69, 1.87], and all-cause mortality (RR: 1.16, 95% CI [0.86, 1.57]. From the secondary outcomes, pacemaker insertion (RR: 2.62, 95% CI [2.24, 3.06]), new-onset TR or progression (RR: 0.32, 95% CI [0.16, 0.66]), stroke (RR: 1.22, 95% CI [1.05, 1.42]), cross-clamp time (WMD: 17.67, 95% CI [13.96, 21.37]), surgery time (WMD: 43.59, 95% CI [37.07, 50.10]), ICU time (WMD: 19.50, 95% CI [9.31, 29.67]), and ventilation time (WMD: 6.62, 95% CI [0.69, 12.55]) were significant. However, major bleeding events, atrial fibrillation, renal failure, heart failure hospitalization, postoperative MI, wound infection, early or prolonged morbidity, cardiopulmonary bypass time, and duration of hospital stay were non-significant. Our meta-analysis has furthered the discussion for weighing the risks and benefits of pursuing TVR during MVS.

Willingness and Perceptions Regarding COVID-19 Vaccine Booster Dose in Pakistani Vaccinated Population: A Cross-Sectional Survey.

Objectives: This study was conducted to evaluate COVID-19 vaccine booster dose willingness and identify predictors and factors of willingness and hesitance in the vaccinated population of Pakistan. Methods: A cross-sectional web-based survey was undertaken between January and February 2022 to highlight the public perceptions regarding the COVID-19 booster dose and evaluate the willingness to get the additional dose. Demographic information and booster dose willingness were recorded through the questionnaire. Additionally, a 5-point Likert scale was employed to explore fears and beliefs regarding COVID-19 vaccinations. Univariate and multivariate regression was performed to identify booster dose willingness and hesitance factors. Results: Of the 787 respondents, 69.6% were females, 75.3% fell in the 18-30 years age group, 53.5% were university students or had a Bachelor's degree. Overall, a 77.8% booster dose willingness was reported. Participants showed absence or low fear levels associated with a booster dose (47.3%). 60.1% agreed it was safe to receive an additional vaccine dose, with 44.1% agreeing that boosters are effective against coronavirus variants. Independent predictors of willingness included the absence of comorbidities, whereas not being willing to pay for the booster dose was a predictor of hesitance. Conclusion: This study showed a suboptimal willingness level of booster dose uptake among the vaccinated Pakistani population. Public health policymakers must undertake necessary awareness campaigns to strategize vaccination drives and dispel myths.

Novel drug delivery systems for inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a chronic illness characterized by relapsing inflammation of the intestines. The disorder is stratified according to the severity and is marked by its two main phenotypical representations: Ulcerative colitis and Crohn's disease. Pathogenesis of the disease is ambiguous and is expected to have interactivity between genetic disposition, environmental factors such as bacterial agents, and dysregulated immune response. Treatment for IBD aims to reduce symptom extent and severity and halt disease progression. The mainstay drugs have been 5-aminosalicylates (5-ASAs), corticosteroids, and immunosuppressive agents. Parenteral, oral and rectal routes are the conventional methods of drug delivery, and among all, oral administration is most widely adopted. However, problems of systematic drug reactions and low specificity in delivering drugs to the inflamed sites have emerged with these regular routes of delivery. Novel drug delivery systems have been introduced to overcome several therapeutic obstacles and for localized drug delivery to target tissues. Enteric-coated microneedle pills, various nano-drug delivery techniques, prodrug systems, lipid-based vesicular systems, hybrid drug delivery systems, and biologic drug delivery systems constitute some of these novel methods. Microneedles are painless, they dislodge their content at the affected site, and their release can be prolonged. Recombinant bacteria such as genetically engineered Lactococcus Lactis and eukaryotic cells, including GM immune cells and red blood cells as nanoparticle carriers, can be plausible delivery methods when evaluating biologic systems. Nano-particle drug delivery systems consisting of various techniques are also employed as nanoparticles can penetrate through inflamed regions and adhere to the thick mucus of the diseased site. Prodrug systems such as 5-ASAs formulations or their derivatives are effective in reducing colonic damage. Liposomes can be modified with both hydrophilic and lipophilic particles and act as lipid-based vesicular systems, while hybrid drug delivery systems containing an internal nanoparticle section for loading drugs are potential routes too. Leukosomes are also considered as possible carrier systems, and results from mouse models have revealed that they control anti- and pro-inflammatory molecules.

NFATc1 signaling drives chronic ER stress responses to promote NAFLD progression.

OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) can persist in the stage of simple hepatic steatosis or progress to steatohepatitis (NASH) with an increased risk for cirrhosis and cancer. We examined the mechanisms controlling the progression to severe NASH in order to develop future treatment strategies for this disease. DESIGN: NFATc1 activation and regulation was examined in livers from patients with NAFLD, cultured and primary hepatocytes and in transgenic mice with differential hepatocyte-specific expression of the transcription factor (Alb-cre, NFATc1c.a . and NFATc1Δ/Δ ). Animals were fed with high-fat western diet (WD) alone or in combination with tauroursodeoxycholic acid (TUDCA), a candidate drug for NAFLD treatment. NFATc1-dependent ER stress-responses, NLRP3 inflammasome activation and disease progression were assessed both in vitro and in vivo. RESULTS: NFATc1 expression was weak in healthy livers but strongly induced in advanced NAFLD stages, where it correlates with liver enzyme values as well as hepatic inflammation and fibrosis. Moreover, high-fat WD increased NFATc1 expression, nuclear localisation and activation to promote NAFLD progression, whereas hepatocyte-specific depletion of the transcription factor can prevent mice from disease acceleration. Mechanistically, NFATc1 drives liver cell damage and inflammation through ER stress sensing and activation of the PERK-CHOP unfolded protein response (UPR). Finally, NFATc1-induced disease progression towards NASH can be blocked by TUDCA administration. CONCLUSION: NFATc1 stimulates NAFLD progression through chronic ER stress sensing and subsequent activation of terminal UPR signalling in hepatocytes. Interfering with ER stress-responses, for example, by TUDCA, protects fatty livers from progression towards manifest NASH.