The caspase-activated DNase promotes cellular senescence.

Cellular senescence is a response to many stressful insults. DNA damage is a consistent feature of senescent cells, but in many cases its source remains unknown. Here, we identify the cellular endonuclease caspase-activated DNase (CAD) as a critical factor in the initiation of senescence. During apoptosis, CAD is activated by caspases and cleaves the genomic DNA of the dying cell. The CAD DNase is also activated by sub-lethal signals in the apoptotic pathway, causing DNA damage in the absence of cell death. We show that sub-lethal signals in the mitochondrial apoptotic pathway induce CAD-dependent senescence. Inducers of cellular senescence, such as oncogenic RAS, type-I interferon, and doxorubicin treatment, also depend on CAD presence for senescence induction. By directly activating CAD experimentally, we demonstrate that its activity is sufficient to induce senescence in human cells. We further investigate the contribution of CAD to senescence in vivo and find substantially reduced signs of senescence in organs of ageing CAD-deficient mice. Our results show that CAD-induced DNA damage in response to various stimuli is an essential contributor to cellular senescence.

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.

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.

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.

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.

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.

Impact of non-alcoholic fatty liver disease on coronavirus disease 2019: A systematic review.

BACKGROUND: Many studies have revealed a link between non-alcoholic fatty liver disease (NAFLD) and coronavirus disease 2019 (COVID-19), making understanding the relationship between these two conditions an absolute requirement. AIM: To provide a qualitative synthesis on the currently present data evaluating COVID-19 and NAFLD. METHODS: This systematic review was conducted in accordance with the guidelines provided by preferred reporting items for systematic reviews and meta-analyses and the questionnaire utilized the population, intervention, comparison, and outcome framework. The search strategy was run on three separate databases, PubMed/MEDLINE, Scopus, and Cochrane Central, which were systematically searched from inception until March 2024 to select all relevant studies. In addition, ClinicalTrials.gov, Medrxiv.org, and Google Scholar were searched to identify grey literature. RESULTS: After retrieval of 11 studies, a total of 39282 patients data were pooled. Mortality was found in 11.5% and 9.4% of people in NAFLD and non-NAFLD groups. In all, 23.2% of NAFLD patients and 22% of non-NAFLD admissions diagnosed with COVID-19 were admitted to the intensive care unit, with days of stay varying. Ventilatory support ranged from 5% to 40.5% in the NAFLD cohort and from 3.1% to 20% in the non-NAFLD cohort. The incidence of acute liver injury showed significance. Clinical improvement on days 7 and 14 between the two classifications was significant. Hospitalization stay ranged from 9.6 days to 18.8 days and 7.3 days to 16.4 days in the aforementioned cohorts respectively, with 73.3% and 76.3% of patients being discharged. Readmission rates varied. CONCLUSION: Clinical outcomes except mortality consistently showed a worsening trend in patients with NAFLD and concomitant COVID-19. Further research in conducting prospective longitudinal studies is essential for a more powerful conclusion.

Recent advances in Del Nido cardioplegia: A comprehensive analysis of randomized clinical trials in adult cardiac surgery.

BACKGROUND: Del Nido cardioplegia (DNC) has extensively been used for pediatric population undergoing cardiac surgery. However, its use in adult cardiac surgeries have been limited thus, its benefits are not yet fully known. This analysis was performed to evaluate the impact of DNC versus any other type of cardioplegia in adult patients who are undergoing cardiac surgery. METHODS: We systematically searched PubMed, Cochrane Library, and Scopus from database inception till March 2023, and moderate to high-quality randomized controlled trials were included which compared DNC to other cardioplegia. The primary outcome was postoperative stroke and/or transient ischemic attack (TIA). Secondary outcomes included spontaneous rhythm return, postoperative myocardial infarction, all-cause mortality, postoperative atrial fibrillation, defibrillation after coronary reperfusion, postoperative intra-aortic balloon pump, postoperative kidney injury, postoperative low cardiac output syndrome, inotropic support, cardiopulmonary bypass time, cross-clamp time, blood transfusion, cardioplegia volume, hospital stay, intensive care unit stay, mechanical ventilation stay, postoperative left ventricular ejection fraction, and cardiac markers. RESULTS: In this meta-analysis, 13 studies were included with a patient population of 2207. Stroke and/or TIA studies (risk ratio [RR]: 0.54, 95% CI [0.29, 1.00]) and all-cause mortality studies (RR: 1.30, 95% CI [0.66, 2.56]) were insignificant. From the secondary outcomes, spontaneous rhythm return (RR: 1.58, 95% CI [1.02, 2.45]), defibrillation after coronary reperfusion (RR: 0.49, 95% CI [0.30, 0.79]), inotropic support (RR: 0.70, 95% CI [0.57, 0.85]), composite risk of stroke and/or TIA and/or acute kidney injury and mortality (RR: 0.72, 95% CI [0.53, 0.99]), cross-clamp time (mean difference [MD]: -6.01, 95% CI [-11.14, -0.89]), blood transfusion (RR: 0.73, 95% CI [0.60, 0.90]), cardioplegia volume (MD: -537.17, 95% CI [-758.89, -315.45]), troponin T (MD: -1.71, 95% CI [-2.11, -1.32]), creatine phosphokinase-MB (MD: -2.96, 95% CI [-5.84, -0.07]) were significant. Whereas all other secondary outcomes were found to be insignificant. CONCLUSION: No significant difference was observed between patients undergoing Del Nido administration in comparison to other cardioplegia solutions for the primary outcome, stroke or/and TIA.

Outcomes after transcatheter aortic valve replacement in cancer survivors with prior chest radiation therapy: an updated systematic review and meta-analysis.

Clinical outcomes for TAVR in cancer survivors with prior chest radiation therapy (C-XRT) who develop symptomatic aortic-valve stenosis are not adequately assessed in major clinical trials leading to conflicting results. Hence, we conducted this meta-analysis to evaluate the, safety, efficacy, and mortality outcomes of cancer survivors with prior C-XRT undergoing TAVR. MEDLINE and Scopus were searched up to March 2024. Observational studies and randomized controlled trials comparing severe aortic stenosis patients with and without prior C-XRT undergoing TAVR with at least one outcome of interest were shortlisted. Data were analyzed using random-effects model to derive weighted mean differences, and risk ratios with 95% confidence intervals. Six studies with 6,191 patients (278 C-XRT and 5,913 no-C-XRT) were included. All-cause mortality at 30-day (RR 1.63, p = 0.12) and 1-year interval (RR 1.59, p = 0.08) showed no significant differences with prior C-XRT versus no-C-XRT. Worsening CHF was the only post-procedural safety outcome significantly higher in patients with prior C-XRT (RR 1.98, p = 0.0004) versus no- C-XRT. The efficacy end-points i.e., improvement in LVEF (MD 1.24; -0.50, 2.98), and aortic valve gradient (MD -0.63; -1.32, 0.05) were not significantly different. TAVR has similar all-cause mortality, efficacy and safety (except CHF worsening) among cancer survivors with and without a prior history of C-XRT.

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.

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.

Long-term outcomes of titanium-nitride-oxide coated stents and drug-eluting stents in acute coronary syndrome: A systematic review and meta-analysis.

BACKGROUND: In severe cases of coronary artery disease, percutaneous coronary intervention provide promising results. The stent used could be a drug-eluting stent (DES) or a titanium-nitride-oxide coated stent (TiNOS). AIM: To compare the 5-year effectiveness and safety of the two stent types. METHODS: The following systematic review and meta-analysis was conducted in accordance with the preferred reporting items for systematic reviews and meta-analysis guidelines, and PubMed/MEDLINE, Scopus, and Cochrane Central were searched from inception till August 2023. Primary outcomes were major adverse cardiac events (MACE), cardiac death, myocardial infarction (MI), cardiac death or MI, and ischemia-driven total lesion revascularization (ID-TLR). RESULTS: Four randomized controlled trials (RCT), which analyzed a sum total of 3045 patients with acute coronary syndrome (ACS) after a median follow-up time of 5 years were included. Though statistically insignificant, an increase in the ID-TLR was observed in patients receiving TiNOSs vs DESs. In addition, MI, cardiac death and MI, and definite stent thrombosis (DST) were significantly decreased in the TiNOS arm. Baseline analysis revealed no significant results with meta-regression presenting non-ST elevated MI (NSTEMI) as a statistically significant covariate in the outcome of MACE. CONCLUSION: TiNOS was found to be superior to DES in terms of MI, cardiac death or MI, and DST outcomes, however, the effect of the two stent types on ID-TLR and MACE was not significant. A greater number of studies are required to establish an accurate comparison of patient outcomes in TiNOS and DES.

The Caspase-Activated DNase drives inflammation and contributes to defense against viral infection.

Mitochondria react to infection with sub-lethal signals in the apoptosis pathway. Mitochondrial signals can be inflammatory but mechanisms are only partially understood. We show that activation of the caspase-activated DNase (CAD) mediates mitochondrial pro-inflammatory functions and substantially contributes to host defense against viral infection. In cells lacking CAD, the pro-inflammatory activity of sub-lethal signals was reduced. Experimental activation of CAD caused transient DNA-damage and a pronounced DNA damage response, involving major kinase signaling pathways, NF-κB and cGAS/STING, driving the production of interferon, cytokines/chemokines and attracting neutrophils. The transcriptional response to CAD-activation was reminiscent of the reaction to microbial infection. CAD-deficient cells had a diminished response to viral infection. Influenza virus infected CAD-deficient mice displayed reduced inflammation in lung tissue, higher viral titers and increased weight loss. Thus, CAD links the mitochondrial apoptosis system and cell death caspases to host defense. CAD-driven DNA damage is a physiological element of the inflammatory response to infection.

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.

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.