Alcohol Relapse After Early Liver Transplantation in Patients With Alcoholic Liver Disease: A Meta-Analysis.

Background: Alcohol use disorder (AUD) is a significant source of end-stage liver disease and liver failure and an indication for liver transplant (LT). Historically, LT for alcoholic liver disease (ALD) required 6 months of alcohol abstinence. Recently, it has been demonstrated that early LT (< 6 months of abstinence) in strictly selected group of patients provides survival benefit while keeping the relapse to harmful drinking at acceptable levels. This practice has been reflected in the Dallas consensus, but more data are needed to appropriately risk stratify the patient from the perspective of return to harmful alcohol drinking post-transplant. This "6-month rule" has been highly debated and recent data demonstrated that the duration of pre-transplant sobriety is not related with an increased risk of relapse to alcohol post-transplant. We performed a meta-analysis to compare the rate of alcohol relapse in individuals having standard vs. early LT. Methods: MEDLINE and SCOPUS were searched for randomized controlled trials (RCTs), observational studies, and case-control studies from their inception through June 2022. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMSA) 2009 checklist guidelines were followed for this meta-analysis. Studies comparing post-transplant outcomes, such as alcohol relapse, in individuals following standard vs. early LT, were included. Reviews, case studies, conference abstracts, clinical trials with only an abstract, and studies with inadequate data for extraction were all disqualified. The data were retrieved, gathered, and examined. The random effects model was used to generate forest plots. For the analysis, a P-value of 0.05 was considered significant. Results: Thirty-four studies were discovered in the initial search. Three studies were included in this systematic review and meta-analysis incorporating 367 patients. Mean age was 51.7 years. Out of 367 patients, 173 (47%) underwent early LT. Out of three studies included, one study demonstrated decreased probability of alcohol relapse in patients undergoing early LT, whereas the other two showed the opposite result. All of the included studies were analyzed and had minimal risk of bias. Pooled analysis demonstrates that the difference in alcohol relapse between early vs. standard LT was insignificant (odds ratio: 1.24, 95% confidence interval: 0.75 - 2.06, P = 0.40). Conclusion: Our results show that early LT is not associated with increased risk of alcohol relapse post-transplant when compared with a mandatory 6-month abstinence period. Hence, individuals with ALD should not be categorically rejected from LT merely on the criteria of 6 months of abstinence. Other selection criteria based on the need and post-transplant outcomes should be utilized.

Acetazolamide as an Adjunctive Diuretic Therapy for Patients with Acute Decompensated Heart Failure: A Systematic Review and Meta-Analysis.

BACKGROUND: Recent evidence suggests that acetazolamide may be beneficial as an adjunctive diuretic therapy in patients with acute decompensated heart failure (HF). We aim to pool all the studies conducted until now and provide updated evidence regarding the role of acetazolamide as adjunctive diuretic in patients with acute decompensated HF. METHODS: PubMed/Medline, Cochrane Library, and Scopus were searched from inception until July 2023, for randomized and nonrandomized studies evaluating acetazolamide as add-on diuretic in patients with acute decompensated HF. Data about natriuresis, urine output, decongestion, and the clinical signs of congestion were extracted, pooled, and analyzed. Data were pooled using a random effects model. Results were presented as risk ratios (RRs), odds ratios (ORs), or weighted mean differences (WMD) with 95% confidence intervals (95% CIs). Certainty of evidence was assessed using the grading of recommendation, assessment, development, and evaluation (GRADE) approach. A P value of < 0.05 was considered significant in all cases. RESULTS: A total of 5 studies (n = 684 patients) were included with a median follow-up time of 3 months. Pooled analysis demonstrated significantly increased natriuresis (MD 55.07, 95% CI 35.1-77.04, P < 0.00001; I2 = 54%; moderate certainty), urine output (MD 1.04, 95% CI 0.10-1.97, P = 0.03; I2 = 79%; moderate certainty) and decongestion [odds ratio (OR) 1.62, 95% CI 1.14-2.31, P = 0.007; I2 = 0%; high certainty] in the acetazolamide group, as compared with controls. There was no significant difference in ascites (RR 0.56, 95% CI 0.23-1.36, P = 0.20; I2 = 0%; low certainty), edema (RR 1.02, 95% CI 0.52-2.0, P = 0.95; I2 = 45%; very low certainty), raised jugular venous pressure (JVP) (RR 0.86, 95% CI 0.63-1.17, P = 0.35; I2 = 0%; low certainty), and pulmonary rales (RR 0.82, 95% CI 0.44-1.51, P = 0.52; I2 = 25%; low certainty) between the two groups. CONCLUSIONS: Acetazolamide as an adjunctive diuretic significantly improves global surrogate endpoints for decongestion therapy but not all individual signs and symptoms of volume overload. SYSTEMATIC REVIEW REGISTRATION: This systematic review was prospectively registered on the PROSPERO ( https://www.crd.york.ac.uk/PROSPERO/ ), registration number CRD498330.

Clinical Outcomes With Nurse-Coordinated Multidisciplinary Care in Patients With Heart Failure: A Systematic Review and Meta-analysis.

The American Heart Association (AHA) and the European Society of Cardiology (ESC) recommend nurse-inclusive multidisciplinary care for patients with heart failure (HF). However, there is no meta-analysis that focuses specifically on the impact of nurse-coordinated multidisciplinary care. Considering this literature gap, we conducted this review that seeks to systematically synthesize the current evidence available regarding the impact of nurse-coordinated multidisciplinary care on clinical outcomes in patients with HF. A comprehensive search was done using PubMed/Medline, Cochrane Library, and EMBASE from inception till July 2023 for randomized controlled trials (RCTs) comparing nurse-coordinated multidisciplinary care with usual care in adult patients (>18 years) with acute or chronic HF. Data about all-cause mortality, HF-related hospitalizations, and all-cause hospitalizations was extracted, pooled, and analyzed. Forrest plots were generated using the random effects model. A total of 30 RCTs were included in the analysis with a total of 7950 HF patients. Our pooled analysis demonstrated a significant reduction in all-cause mortality in HF patients who received nurse-coordinated multidisciplinary care (RR = 0.80, 95% CI: 0.72-0.88, P = 0.0001). Similarly, there was a significantly lesser risk of HF-related hospitalizations (RR = 0.56, 95% CI: 0.45-0.71, P = 0.00001) and all-cause hospitalizations (RR = 0.78, 95% CI: 0.70-0.87, P = 0.0001) among HF patients with nurse-coordinated multidisciplinary care as compared to the usual care. Nurse-coordinated multidisciplinary care significantly reduces the risk of all-cause mortality, HF-related hospitalizations, and all-cause hospitalizations in HF patients' posthospital discharge.

Clinical Outcomes With Furosemide Versus Torsemide in Patients With Heart Failure: An Updated Systematic Review and Meta-Analysis.

Despite potential advantages of torsemide over furosemide, <10% of the patients with heart failure (HF) are on torsemide in clinical practice. Prior studies comparing furosemide to torsemide in patients with HF have shown conflicting findings, regarding hospitalizations and mortality. We aimed to pool all the studies conducted to date and provide the most updated and comprehensive evidence, regarding the effect of furosemide vs torsemide in reducing mortality and hospitalizations in patients with HF. We conducted a comprehensive literature search of the PubMed/Medline, Cochrane Library and Scopus from inception till June 2023, for randomized and nonrandomized studies comparing furosemide to torsemide in adult patients (>18 years) with acute or chronic HF. Data about all-cause mortality, HF-related hospitalizations and all-cause hospitalizations was extracted, pooled, and analyzed. Forest plots were created based on the random effects model. A total of 17 studies (n = 11,996 patients) were included in our analysis with a median follow-up time of 8 months. Our pooled analysis demonstrated no difference in all-cause mortality between furosemide and torsemide groups in HF patients (OR = 0.98, 95% CI: 0.75-1.29, P = 0.89). However, torsemide was associated with a significantly lesser incidence of HF-related hospitalizations (OR = 0.73, 95% CI: 0.54-0.99, P = 0.04), and all-cause hospitalizations (OR = 0.84, 95% CI: 0.73-0.98, P = 0.03), as compared to furosemide. Torsemide significantly reduces HF-related and all-cause hospitalizations as compared to furosemide, with no difference in mortality. We recommend transitioning from furosemide to torsemide in HF patients who are not attaining symptomatic control.

Cerebrovascular disease in COVID-19: a systematic review and meta-analysis.

Background: The association between COVID-19 and acute cerebrovascular disease (CVD) has not been explored extensively. New data has come to light which may change previous results. Methods: We queried the PubMed electronic database from its inception until February 2022 for studies evaluating the incidence of stroke in COVID-19 patients. Results of the analysis were pooled using a random-effects model and presented as odds ratios (ORs) with 95% confidence intervals (95% CIs). Results: 37 studies consisting of 294,249 patients were included in our analysis. Pooled results show that the incidence of acute CVD events in COVID-19 positive patients is 2.6% (95% CI: 2.0-3.3; P<0.001). Cardioembolic (OR=14.15, 95% CI: 11.01 to 18.19, P<0.00001) and cryptogenic (OR=2.87, 95% CI: 1.91 to 4.32, P<0.00001) etiologies were associated with COVID-19 positivity. Risk factors for CVD events in patients with COVID-19 were atrial fibrillation (OR=2.60, 95% CI: 1.15 to 5.87, P=0.02), coronary artery disease (OR=2.24, 95% CI: 1.38 to 3.61, P=0.0010), diabetes (OR=2.46, 95% CI: 1.36 to 4.44, P=0.003) and hypertension (OR=3.65, 95% CI: 1.69 to 7.90, P=0.005). Conclusion: COVID-19 infection is associated with an increased risk for acute CVD and is associated with cardioembolic and cryptogenic etiologies and the risk factors of atrial fibrillation, coronary artery disease, diabetes and hypertension in COVID-19 positive patients.

Use of abdominal compression device in colonoscopy: a systematic review and meta-analysis.

BACKGROUND/AIMS: Colonoscopy for screening is associated with unpleasant experiences for patients, and abdominal compression devices have been developed to minimize these problems. However, there is a paucity of data supporting the therapeutic benefits of this strategy. This study examined the effects of using an abdominal compression device during colonoscopy on the cecal intubation time (CIT), abdominal compression, patient comfort, and postural changes. METHODS: We searched PubMed and Scopus (from inception to November 2021) for randomized controlled trials that assessed the effects of an abdominal compression device during colonoscopy on CIT, abdominal compression, patient comfort, and postural change. A random-effects meta-analysis was performed. Weighted mean differences (WMDs) and Mantel-Haenszel odds ratios (ORs) were calculated. RESULTS: Our pooled analysis of seven randomized controlled trials revealed that abdominal compression devices significantly reduced CIT (WMD, -0.76 [-1.49 to -0.03] minutes; p=0.04), abdominal compression (OR, 0.52; 95% confidence interval [CI], 0.28-0.94; p=0.03), and postural changes (OR, 0.46; 95% CI, 0.27-0.78; p=0.004) during colonoscopy. However, our results did not show a significant change in patient comfort (WMD, -0.48; 95% CI, -1.05 to 0.08; p=0.09) when using an abdominal compression device. CONCLUSION: Our findings demonstrate that employing an abdominal compression device may reduce CIT, abdominal compression, and postural change but have no impact on patient comfort.

Association of Electronic Cigarette Exposure on Cardiovascular Health: A Systematic Review and Meta-Analysis.

Despite the growing use of electronic cigarettes (EC) in the Unites States, particularly among young people, and their perceived safety, current evidence suggests that EC usage may cause adverse clinical cardiovascular effects. Therefore, we aim to pool all studies evaluating the association of EC exposure with cardiovascular health. Medline, Cochrane CENTRAL, and Scopus were searched for studies from January 1, 2006 until December 31, 2022. Randomized and observational studies reporting cardiovascular outcomes, hemodynamic parameters, and biomarkers of platelet physiology, before and after acute or chronic EC exposure were pooled using a random-effects model. Overall, 27 studies (n = 863) were included. Heart rate increased significantly after acute EC exposure (weighted mean difference [WMD]: 0.76 bpm; 95% confidence interval [CI], 0.48, 1.03; P < 0.00001; I2 = 92%). Significant increases in systolic blood pressure (WMD: 0.28 mmHg; 95% CI, 0.06, 0.51; P = 0.01; I2 = 94%), diastolic blood pressure (WMD: 0.38 mmHg; 95% CI, 0.16, 0.60; P = 0.0006; I2 = 90%), and PWV (WMD: 0.38; 95% CI, 0.13, 0.63; P = 0.003; I2 = 100%) were also observed. Augmentation index increased significantly (SMD: 0.39; 95% CI, 0.11, 0.67; P = 0.007; I2 = 90%), whereas reduction in flow-mediated dilation (WMD: -1.48; 95% CI, -2.49, -0.47; P = 0.004; I2 = 45%) was observed. Moreover, significant rise in both soluble P-selectin (WMD: 4.73; 95% CI, 0.80, 8.66; P = 0.02; I2 = 98%) and CD40L (WMD: 1.14; 95% CI, 0.41, 1.87; P = 0.002; I2 = 79%) was observed. Our results demonstrate that smoking EC is associated with a significant increase in cardiovascular hemodynamic measures and biomarkers. Our findings can aid policymakers in making informed decisions regarding the regulation of EC to ensure public safety.

High-Intensity Interval Training Versus Moderate Continuous Training in Patients With Heart Failure With Preserved Ejection Fraction: A Systematic Review and Meta-analysis.

High-intensity interval training (HIIT) is a novel training approach that improves cardiopulmonary fitness and functional capacity in numerous chronic conditions, however its impact in patients with heart failure (HF) with preserved ejection fraction (HFpEF) is uncertain. We evaluated data from prior studies reporting the effects of HIIT versus moderate continuous training (MCT), on cardiopulmonary exercise outcomes in patients with HFpEF. PubMed and SCOPUS were queried from inception till February 1st, 2022 for all randomized controlled trials (RCT) comparing the effect of HIIT versus MCT in patients with HFpEF on peak oxygen consumption (peak VO2), left atrial volume index (LAVI), respiratory exchange ratio (RER), and ventilatory efficiency (VE/CO2 slope). A random-effects model was applied, and the weighted mean difference (WMD) of each outcome was reported with 95% confidence intervals (CI). Three RCTs (total N = 150 patients with HFpEF), with a follow-up of 4 to 52 weeks were included in our analysis. Our pooled analysis demonstrated that HIIT significantly improved peak VO2 (WMD = 1.46 mL/kg/min (0.88, 2.05); P < 0.00001; I2 = 0%), as compared to MCT. However, no statistically significant change was demonstrated for LAVI (WMD = -1.71 mL/m2 (-5.58, 2.17); P = 0.39; I2 = 22%), RER (WMD = -0.10 (-0.32, 0.12); P = 0.38; I2 = 0%), and VE/CO2 slope (WMD = 0.62 (-1.99, 3.24); P = 0.64; I2 = 67%) in patients with HFpEF. Across current RCT data, HIIT, compared to MCT, had a significant impact on improving peak VO2. Conversely, there was no significant change in LAVI, RER, and VE/CO2 slope between HFpEF patients undertaking HIIT as opposed to MCT.

Trajectory of Decongestion and Mortality in Young Adults with Acute Heart Failure.

Although the prevalence of HF in young adults (age <50 years) is increasing, there are limited data on the trajectory of decongestion and short-term outcomes in young adults with acute heart failure (AHF). We pooled patients from 3 randomized trials of AHF conducted within the Heart Failure Network (the Diuretic Optimization Strategies trial, the Renal Optimization Strategies Trial, and the Cardiorenal Rescue Study in Acute Decompensated Heart Failure). The association between young age (<50 years and >50 years) and in-hospital changes in various measures of decongestion as well as short-term outcomes including risk for rehospitalization, and all-cause mortality was evaluated. Of 762 patients, 72 (10.3%) patients were young. Young adults were more likely to be African American (53.8% vs 19.3%), to have a lower rate of ischemic HF etiology (25.6% vs 60.4%, P <0.001), and a lower burden of hypertension, chronic kidney disease and atrial fibrillation. Young adults had a lower left ventricular ejection fraction (median 20% vs 33%, P < 0.001); they had a higher admission weight (median 242.7 lbs vs 201.5 lbs, P < 0.001), but lower NT-pro BNP levels (median 3622 pg/mL vs 4676 pg/mL, P = 0.003). After covariate adjustment, there was no difference in the change in NT-pro BNP (P = 0.25), net fluid loss (P = 0.42), or renal function (P = 0.56) between young and older adults by 72 or 96 hours of randomization. There was no difference in orthodema congestion score or the composite clinical endpoint during the follow-up (all-cause mortality or any rehospitalization) (adjusted odds ratios (95% confidence intervals): 2.51 (0.78-8.01), P = 0.12). In this pooled analysis of 3 clinical trial cohorts, compared with older adults, younger adults had a unique demographic and clinical profile. Despite these differences, there was no difference by age group in in-hospital decongestion or post-discharge readmission or mortality.

Effect of novel glucose lowering agents on non-alcoholic fatty liver disease: A systematic review and meta-analysis.

BACKGROUND: The efficacy of novel glucose-lowering drugs in treating non-alcoholic fatty liver disease (NAFLD) in patients with and without type-2 diabetic patients (T2DM) remains unclear. AIM: To conduct a meta-analysis to evaluate the efficacy of 3 novel glucose-lowering drug classes, namely glucagon-like peptide-1 receptor agonists (GLP-1RA), sodium-glucose co-transporter 2 (SGLT2) inhibitors, and dipeptidyl-peptidase-4 (DPP4) inhibitors on hepatic parameters: Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Gamma-Glutamyl Transferase (GGT), Bilirubin, and FIB-4 (Fibrosis). METHODS: MEDLINE was searched from inception through October 2021 for randomized placebo or active glucose-lowering drug-controlled trials. A random-effects model was used to pool the results. A p-value of less than or equal to 0.05 was considered significant. Results were presented as weighted mean differences (WMD) and corresponding 95% confidence intervals (CIs). RESULTS: Our pooled analysis consisted of 40 studies. A significant reduction was seen in AST with SGLT2 inhibitors (WMD = -2.31 IU/L, 95%CI: -3.16 to -1.47 IU/L, P < 0.00001) and GLP-1RA (WMD = -3.29 IU/L, 95%CI: -5.98 to -0.61 IU/L, P = 0.02). Similarly, significant reduction was seen in ALT with SGLT2 inhibitors (WMD = -5.93 IU/L, 95%CI: -7.70 to -4.16 IU/L, P < 0.00001) and GLP-1RAs (WMD = -9.92 IU/L, 95%CI: -19.89 to 0.05 IU/L, P = 0.05). In contrast, DPP-4 inhibitors showed no significant reduction in AST (WMD = -3.20 IU/L, 95%CI: -11.13 to 4.73 IU/L, P = 0.43) or ALT (WMD = -4.81 IU/L, 95%CI: -15.83 to 6.21 IU/L, P = 0.39). A significant reduction in GGT was seen with SGLT2 inhibitors (WMD = -6.49 IU/L, 95%CI: -11.09 to -1.89 IU/L, P = 0.006) and GLP-1RAs (WMD = -12.38 IU/L, 95%CI: -15.69 to -9.07 IU/L, P < 0.00001). However, significant results were not observed with DPP-4 inhibitors (WMD = -0.92 IU/L, 95%CI: -5.80 to 3.96 IU/L, P = 0.71). There was a statistically significant reduction in FIB-4 index with SGLT2 inhibitors (WMD = -0.21, 95%CI: -0.40 to -0.03, P = 0.02) and GLP-1 RA (WMD = -0.15, 95%CI: -0.29 to 0.00, P = 0.05). Lastly, SGLT2 inhibitors led to a significant change in bilirubin levels (WMD = 2.03, 95%CI: 0.76 to 3.30, P = 0.002) while the change in bilirubin was not significant with GLP-1 agonists (WMD = -0.21, 95%CI: -1.09 to 0.66, P = 0.63) and DPP-4 inhibitors (WMD = 0.14, 95%CI: -1.55 to 1.83, P = 0.87). CONCLUSION: SGLT2 inhibitors and GLP-1 agonists have a beneficial effect on hepatic parameters in patients with NAFLD. However, further research is needed to evaluate the effect of DPP-4 inhibitors on hepatic function properly.

Effects of novel glucose-lowering drugs on the lipid parameters: A systematic review and meta-analysis.

Aim: We aim to evaluate the impacts of sodium-glucose co-transporter 2 inhibitors (SGLT-2), glucagon-like peptide 1 agonist (GLP-1RAs), and dipeptidyl peptidase-four (DPP4) inhibitors on the levels of high-density lipoprotein, low-density lipoprotein, triglyceride and total cholesterol. Methods: The MEDLINE database was searched from inception till October 2021, for randomized controlled trials assessing the effects of sodium-glucose co-transporter two inhibitors (SGLT-2), glucagon-like peptide 1 agonist (GLP-1RAs), and dipeptidyl peptidase-four (DPP4) inhibitors on lipid levels. Results: A total of 57 trials were included in the analysis. Our pooled analysis demonstrates that SGLT-2 inhibitors significantly increase the levels of HDL (WMD = 0.07 mg/dL [0.06 to 0.08], P < 0.00001). SGLT-2 inhibitors were also found to be significantly associated with an increase in the levels of LDL (WMD = 0.11 mg/dL, [0.09-0.13 mg/dL, P < 0.00001). Pooled analysis also demonstrates that SGLT-2 inhibitors significantly reduce the levels of triglyceride (WMD = -0.10 mg/dL, [-0.13 to -0.06], P < 0.00001). Our pooled analysis demonstrates that SGLT-2 inhibitors significantly increased the levels of total cholesterol (WMD = 0.10 mg/dL, [0.06 to 0.15], P < 0.0001), whereas, GLP-1RAs significantly reduced the levels of total cholestrol (WMD = -0.18 mg/dL, [-0.34 to -0.02], P = 0.03). Conclusion: This is the first head-to-head study comparing the effects of 3-novel glucose-lowering agents to lipid parameters. However, more trials are crucial to better understand the impact of glucose-lowering drugs on lipid parameters.

Effectiveness of Autologous Fat Transfer in the Treatment of Scar-Related Conditions: A Systematic Review and Meta-analysis.

BACKGROUND AND AIM: Autologous fat transfer (AFT) has been introduced as a potential treatment option for scar-tissue and its related symptoms. However, the scientific evidence for its effectiveness remains unclear. This meta-analysis aims to evaluate the available evidence regarding the effectiveness of autologous fat transfer for the treatment of scar-tissue and its related conditions. METHODS: PubMed/Medline database was queried from its inception till the end of November 2021. All the relevant studies assessing the effect of autologous fat transfer in the treatment of scar-related conditions were pooled in using a random-effects model. RESULTS: 9 studies (n=179) were included in the meta-analysis. Pooled analysis demonstrates significant improvement in all subscales of the POSAS patient score with most prominent in color 2.4 points (95% CI 1.78-3.041), stiffness 2.9 points (95% CI 2.33-3.45), irregularity 2.2 points (95% CI 1.093-3.297) and thickness 1.8 points (95% CI 0.804-2.719), respectively. Pain and itch improved relatively lesser, 1.3 points (95% CI 0.958-1.674) and 0.6 points (95% CI 0.169-1.215), respectively. The POSAS observer scale showed a relatively lower improvement with the least in vascularity 0.5 points (95% CI 0.098-0.96), pigmentation 0.8 points (95% CI 0.391-1.276) and surface area 0.8 points (95% CI 0.34-1.25). Thickness improved by 1.4 points (95% CI 0.582-2.3), relief 1.0 points (95% CI 0.461-1.545) and pliability 1.5 points (95% CI 1.039-2.036). CONCLUSION: Our findings demonstrate that autologous fat transfer (AFT) is a promising treatment for scar-related conditions as it provides beneficial results in the scar quality. Future research should focus on the long-term effects of AFT and high-level evidence studies such as, randomized controlled trials (RCTs) and cohort studies are required. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .