Safety and efficacy of Withania somnifera for anxiety and insomnia: Systematic review and meta-analysis.

OBJECTIVE: Despite the historical neurological use of Withania somnifera, limited evidence supports its efficacy for conditions like anxiety and insomnia. Given its known anti-stress properties, this review evaluated its safety and efficacy for anxiety and insomnia. METHODS: We searched Medline, Cochrane Library, and Google Scholar until August 2023 for randomized controlled trials (RCTs) comparing W. somnifera to placebo in patients with anxiety and/or insomnia. Outcome measures included changes in anxiety levels via the Hamilton Anxiety Scale (HAM-A), Sleep Onset Latency (SOL), Total Sleep Time (TST), Wake After Sleep Onset (WASO), Total Time in Bed (TIB), Sleep Efficiency (SE), and Pittsburgh Sleep Quality Index (PSQI) score. We utilized a random-effect model for pooling Mean Differences (MD) with a 95% Confidence Interval (CI). Heterogeneity was assessed through sensitivity and subgroup analysis, and the quality of RCTs was evaluated using the Cochrane revised risk of bias tool. RESULTS: Pooled results from five RCTs (n = 254) demonstrated that W. somnifera significantly reduced HAM-A scores (MD = -5.96; [95% CI -10.34, -1.59]; P = 0.008; I2 = 98%), as well as sleep parameters such as SOL, TST, PSQI, and SE, but not WASO and TIB. CONCLUSION: While W. somnifera extracts yielded promising results, further research with larger sample sizes is needed to confirm its effects on anxiety and insomnia.

The potential impact of renin-angiotensin system inhibitors on cancer survival and recurrence: A systemic review and meta-analysis.

Renin-angiotensin-system inhibitors (RASi), specifically angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARBs), are widely used anti-hypertensives. Their impact on the prognostic outcomes among cancer patients has been subject to scrutiny and debate. The aim of this study is to evaluate the effect of RASi on survival in cancer patients. We systematically searched PubMed, Web of Science, Embase and Cochrane Library for relevant studies published until April 1st, 2022. All the studies, interventional or observational, which examined effects of ARBs and ACEi on cancer prognosis compared to a control group and reported the survival outcomes and Hazards Ratios were included in the analysis. From each study, pooled hazard ratios (HR) with corresponding 95% confidence intervals (95% CI) were identified and collected. Subgroup analysis was conducted to investigate heterogeneity. Sixty-one studies were included in this meta-analysis. Data of 343,283 participants were used in the study. It was found that RASi improved overall survival (OS) (HR=0.88; 95% CI: 0.82-0.93; P<0.0001), progression free survival (PFS) (HR=0.72; 95% CI: 0.65-0.79; P<0.00001), disease specific survival (DSS) (HR=0.86; 95% CI: 0.71-1.04; P=0.03), and recurrence free survival (RFS) (HR=0.74; 95% CI: 0.58-0.93; P=0.01) in cancer patients. The effect of RASi on OS varied depending on the type of cancer or type of RASi (ACEi or ARBs), according to subgroup analysis. The usage of RAS inhibitors has a positive impact on survival outcomes and recurrence among cancer patients.

Trends in mortality related to kidney failure and diabetes mellitus in the United States: a 1999-2020 analysis.

BACKGROUND: Kidney failure ranks as the tenth leading cause of mortality in the United States (US), frequently arising as a complication associated with diabetes mellitus (DM). METHODS: Trends in DM and kidney failure mortality were assessed using a cross-sectional analysis of death certificates from the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) database. Crude and age-adjusted mortality rates (AAMR) per 100,000 people and annual percent change (APC) in age-adjusted mortality rate with 95% CI were obtained and measured across different demographic and geographic subgroups. RESULTS: Between 1999 and 2020, a total of 325,515 deaths occurred related to kidney failure and DM. The overall age-adjusted mortality rate showed no significant change between 1999 and 2012, after which it declined until 2015 - 64.8 (95% CI - 75.6 to - 44.8) and has been steadily increasing since. Men had consistently higher age-adjusted mortality rates than women throughout the study duration (overall age-adjusted mortality rate men: 8.1 vs. women: 5.9). Non-Hispanic (NH) Black or African American individuals had the highest overall age-adjusted mortality rate (13.9), followed by non-Hispanic American Indian or Alaskan Native (13.7), Hispanic or Latino (10.3), non-Hispanic Asian or Pacific Islander (6.1), and non-Hispanic White (6.0). Age-adjusted mortality rate also varied by region (overall age-adjusted mortality rate: West:7.5; Midwest: 7.1; South: 6.8; Northeast: 5.8), and non metropolitan areas had higher overall age-adjusted mortality rate (7.5) than small/medium (7.2) and large metropolitan areas (6.4). CONCLUSION: After an initial decline, mortality rose across all the demographic groups from 2015 to 2020, revealing notable disparities in gender, race, and region.

Management of Heart Failure With Reduced Ejection Fraction in Patients With Diabetes Mellitus and Chronic Kidney Disease.

Heart failure (HF), diabetes, and chronic kidney disease (CKD) frequently coexist, with one comorbidity worsening the prognosis of another. ß-blockers, angiotensin-receptor-neprilysin inhibitors, renin-angiotensin-aldosterone system inhibitors, mineralocorticoid-receptor antagonists, and sodium-glucose cotransporter-2 inhibitors all have been shown to reduce mortality in patients with HF with reduced ejection fraction. However, their uptake in real-world clinical practice remains low, especially among patients who have multiple other comorbidities such as CKD and diabetes. The management of HF in patients with diabetes and CKD can be especially challenging because these patients typically are older, frail, and have multiple other comorbidities, and guideline-directed medical therapy used in HF potentially can affect renal function acutely and chronically. In this article, we discuss the available evidence for each of the foundational HF therapies in patients with diabetes and CKD, emphasizing the current challenges and outlining future directions to optimize the management of HF among these high-risk patients.

Clinical Outcomes in Hypertensive Emergency: A Systematic Review and Meta-Analysis.

Background To study the prevalence and types of hypertension-mediated organ damage and the prognosis of patients presenting to the emergency department (ED) with hypertensive emergencies. Methods and Results PubMed was queried from inception through November 30, 2021. Studies were included if they reported the prevalence or prognosis of hypertensive emergencies in patients presenting to the ED. Studies reporting data on hypertensive emergencies in other departments were excluded. The extracted data were arcsine transformed and pooled using a random-effects model. Fifteen studies (n=4370 patients) were included. Pooled analysis demonstrates that the prevalence of hypertensive emergencies was 0.5% (95% CI, 0.40%-0.70%) in all patients presenting to ED and 35.9% (95% CI, 26.7%-45.5%) among patients presenting in ED with hypertensive crisis. Ischemic stroke (28.1% [95% CI, 18.7%-38.6%]) was the most prevalent hypertension-mediated organ damage, followed by pulmonary edema/acute heart failure (24.1% [95% CI, 19.0%-29.7%]), hemorrhagic stroke (14.6% [95% CI, 9.9%-20.0%]), acute coronary syndrome (10.8% [95% CI, 7.3%-14.8%]), renal failure (8.0% [95% CI, 2.9%-15.5%]), subarachnoid hemorrhage (6.9% [95% CI, 3.9%-10.7%]), encephalopathy (6.1% [95% CI, 1.9%-12.4%]), and the least prevalent was aortic dissection (1.8% [95% CI, 1.1%-2.8%]). Prevalence of in-hospital mortality among patients with hypertensive emergency was 9.9% (95% CI, 1.4%-24.6%). Conclusions Our findings demonstrate a pattern of hypertension-mediated organ damage primarily affecting the brain and heart, substantial cardiovascular renal morbidity and mortality, as well as subsequent hospitalization in patients with hypertensive emergencies presenting to the ED.

A Systematic Review and Meta-Analysis on Effectiveness of Mineralocorticoid Receptor Antagonists in Reducing the Risk of Atrial Fibrillation.

Mineralocorticoid receptor antagonists (MRAs) are known to improve clinical outcomes in heart failure, particularly heart failure with reduced ejection fraction. However, the effect of MRAs on the incidence of and recurrence of atrial fibrillation (AF) is not well established. Therefore, databases, such as PubMed, EMBASE, and Cochrane Central, were searched from inception to September 2021 for randomized controlled trials of MRAs with AF as an outcome. Risk ratios (RRs) with 95% confidence interval (CIs) were combined using the random-effects model. A total of 10 randomized controlled trials (n = 11,356) were included. Our pooled analysis demonstrates that MRAs reduce the risk of AF occurrence by 23% compared with the control therapy (RR 0.77, 95% CI 0.65 to 0.91, p = 0.003, I2 = 40%). Subgroup analysis demonstrated that MRAs reduced the risk of both new-onset AF (RR 0.84, 95% CI 0.61 to 1.16, p = 0.28, I2 = 43%) and recurrent AF (RR 0.73, 95% CI 0.59 to 0.90, p = 0.004, I2 = 26%) similarly; p interaction = 0.48. Our meta-analysis concludes that MRAs reduce the risk of development of AF overall, with consistent effects in new-onset and recurrent AF.

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.

Incidence and Comparison of Suicide in Various Phases of the Menstrual Cycle: a Systematic Review and Meta-analysis.

Background: Suicide is a global health concern. There are reproductive health-related factors that are responsible for increasing the risk of female suicide. There are a number of studies examining the association between suicide and the menstrual cycle, but still, there are no conclusive findings. Aim: We aimed to pool data from all the studies reporting data on suicides and the menstrual cycle phase to report the following outcomes: incidence of suicidal deaths in the menstrual, secretory, and proliferative phases, and to find out whether the burden of suicide in the menstrual phase in particular, was more at a young age (18-35 years) or middle age (36-50years). Methods: The PubMed database was extensively searched from inception till 12th April 2022. The data for the number of events occurring for each outcome were pooled using random-effects model and forest plots were created. Results: Five articles were shortlisted for inclusion in our analysis. Incidence of suicide in the secretory phase was highest at 45.2% [95% CI, 0.367-0.537]. The incidence of suicide, when occurring in the menstrual phase, was reported to be 68.4% (95 CI, 0.317-1.052) and 31.6% (95 CI, -0.052.3-0.68) for young-aged and middle-aged victims, respectively. Conclusion: Our results demonstrate that the menstrual phase has a lower risk of mortality due to suicide when compared to the other two phases of the menstrual cycle. Nevertheless, when suicide occurred in the menstrual phase, the incidence of suicide among the younger age-group was higher than for those in the middle age-group.

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.

Bibliometric analysis of the literature on von Willebrand disease: Research status and trends.

BACKGROUND AND AIM: Von Willebrand disease (VWD) is considered the most prevalent inherited bleeding disorder. The current study aims to demonstrate the research status and trends on VWD worldwide. METHODS: Bibliometric analysis was used to investigate the global research productivity and trends on VWD. The publications on VWD from 1956 to 2021 were extracted using the Web of Science database. In the VWD domain, a total of 3,643 records were analyzed for authorship and collaboration patterns, yearly productivity, highly cited documents, relevant source of publication, most prolific scholars, productive countries, and organizations. RESULTS: The most productive journal, author, organization, and country were 'Haemophilia' with 439 publications, 'Favaloro EJ' with 119 publications, the 'University of Milan' with 192 publications, and the United States of America (USA) with 1,048 publications, respectively. The document with the highest citations was 'Srivastava A, 2013, Haemophilia,' which received 1,154 citations in total. In 2016, the highest number of publications shared by two author patterns was 28. With 199 publications, the year 2021 remained on the top, while the citation-wise analysis identified 2006 as the top year with 5,379 citations. CONCLUSIONS: Research productivity and publication trends on VWD revealed that the USA emerged as the most significant contributing country. The 'University of Milan' was the most significant contributing organization, while 'Favaloro EJ' was the most significant author. 'Hemophilia' was found to be the most significant journal in the field of VWD. It is recommended that researchers from countries with significant contributions to the field should collaborate with researchers from Asian countries and other countries that lack behind in research in the domain of VWD.(www.actabiomedica.it).

The Safety and Efficacy of GLP-1 Receptor Agonists in Heart Failure Patients: A Systematic Review and Meta-Analysis.

Evaluation of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) usage in heart failure (HF) patients with or without type 2 diabetes mellitus (T2DM) could be proven to be a critical breakthrough in treatment options available for these patients. Our study focuses on understanding the safety and efficacy of GLP-1 RAs in this patient population by pooling the data from 9 randomized controlled trials (RCTs) comprising 871 subjects. As compared with the placebo, GLP-1 RAs did not improve major adverse cardiovascular events (MACE) which include cardiovascular (CV) mortality and heart failure (HF) hospitalizations, our primary outcome. CV mortality (RR = 1.03, 95% CI = 0.56-1.88, P = 0.92) and HF hospitalizations (RR = 1.18, 95%CI = 0.93-1.51, P = 0.18). Similarly, GLP-1 RAs did not improve our secondary findings of left ventricular ejection fraction (LVEF) and 6-minute walk test (6MWT). LVEF (RR = 1.96, 95%CI = -0.16-4.07, P = 0.07) or 6 MWT (RR = 8.43, 95% CI = -2.69-19.56, P = 0.14). This meta-analysis shows that GLP-1 RAs do not improve cardiovascular outcomes in HF patients with or without T2DM.

Management of Heart Failure With Reduced Ejection Fraction.

Heart failure with reduced ejection fraction (HFrEF) is a complex and progressive clinical condition characterized by dyspnea and functional impairment. HFrEF has a high burden of mortality and readmission rate making it one of the most significant public health challenges. Basic treatment strategies include diuretics for symptom relief and use of quadruple therapy (Angiotensin receptor blocker/neprilysin inhibitors, evidence-based beta-blockers, mineralocorticoid receptor antagonists, and sodium-glucose co-transporter 2 inhibitors) for reduction in hospitalizations, all-cause mortality, and cardiovascular mortality. Despite compelling evidence of clinical benefit, guideline directed medical therapy is vastly underutilized in the real-world clinical practice. Other medications such as intravenous iron, ivabradine, hydralazine/nitrates and vericiguat may also have a role in certain subgroup of HFrEF patients. Specific groups of patients with HFrEF may also be candidates for various device therapies such as implanted cardioverter defibrillators, cardiac resynchronization therapy and trans catheter mitral valve repair. This review provides a comprehensive overview of drug and device management approaches for patients with HFrEF, recommendations for initiation and titrations of therapies, and challenges associated with guideline directed medical therapy in the management of patients with HFrEF (Graphical abstract).

Mediterranean Diet and its Effect on Endothelial Function: A Meta-analysis and Systematic Review.

BACKGROUND: Endothelial dysfunction serves as an early marker for the risk of cardiovascular disease (CVD); therefore, it is a site of therapeutic interventions to reduce the risk of CVD. AIMS: To examine the effect of the Mediterranean diet (MedDiet), as an intervention, on structural and functional parameters of endothelial function, and how it may reduce the risk of CVD and associated mortality. METHODS: Medline database was searched for randomized controlled trials. Random-effects meta-analysis was conducted on 21 independent datasets. Meta-regression and subgroup analysis were performed to assess whether the effect of MedDiet was modified by health status (healthy subjects or with increased CVD risk), type of MedDiet intervention (alone or combined), type of parameter (functional or structural), study design (cross-over or parallel), BMI, age, and study duration. Our study used sample size, mean, and standard deviation of endothelial function measurements for both MedDiet intervention and control in the analyses. RESULTS: Inverse relationship between endothelial function and intake of MedDiet was observed (SMD: 0.34; 95% CI: 0.16, 0.52; P = 0.0001). Overall, MedDiet increased FMD by 1.39% (95% CI: 0.47, 2.19; P < 0.001). There was a significant improvement in endothelial function in both healthy patients and in those with an increased risk of CVD. No significant variation was observed in the effects of MedDiet on endothelial function, due to study design or type of intervention. CONCLUSIONS: These findings support that MedDiet can reduce the risk of CVD by improving endothelial function.

Temporal Trends and Outcomes of Implantable Cardioverter Defibrillators in Heart Failure and Chronic Kidney Disease in the United States.

Chronic kidney disease (CKD) and hemodialysis increase the risk of sudden cardiac death (SCD) in heart failure (HF); however, national trends in utilization and outcomes of implantable cardioverter-defibrillator (ICD) in this population remain unknown. We sought to evaluate the utilization and outcomes of ICD therapy in HF patients with CKD and end-stage renal disease (ESRD) using the National Inpatient Sample from 2009 to 2018. Hospitalizations with a discharge diagnosis of systolic HF and ICD implantation were identified and stratified by stages of kidney disease. A total of 281,219 systolic HF hospitalizations who underwent ICD implantation were included. A significant decrease in inpatient ICD implantation was observed over the past decade (3.7% in 2009 to 1.1% in 2018) regardless of renal impairment. In-hospital mortality was highest in ESRD, followed by CKD compared with patients with no CKD. Length of hospital stay and hospitalization costs were also significantly higher in patients with CKD and ESRD. The overall utilization of inpatient ICD implantation has decreased in systolic HF patients and inpatient ICD placement in CKD is associated with an increased risk of mortality and adverse clinical outcomes. This indicates that patients with renal impairment and HF represent a sicker cohort than the general HF population.

Survey of knowledge and attitude towards fibromyalgia among physicians in Karachi, Pakistan.

Objectives: Our study aims to assess knowledge and understanding of FM among doctors employed at a tertiary care hospital in Karachi, Pakistan with a focus on its diagnostic criteria, treatment modalities, and general knowledge of symptoms. Study Design: Cross-sectional Study. Methods: Our cross-sectional study recruited participants through convenience sampling. A total of 104 participants responded, which included (a) House Officers, (b) Medical Officers, and (c) Residents. A structured questionnaire was used, and an electronic form was generated which was then emailed to the participants to acquire their responses. Results: The majority (66.3%) of our respondents were female and the median age was 26 years. A majority (93.3%) accepted FM as a separate and distinct clinical identity, and 79.8% were confident in recognizing its general symptoms. Widespread pain (95.2%) and fatigue (80.8%) were correctly identified as most commonly observed symptoms. Moreover, 68.3% of respondents possessed no knowledge of both ACR 1990 and 2010 diagnostic criteria for FM. Of those aware, majority favored using the most recent ACR 2010 criteria (72.7%). Majority of our respondents (75%) preferred using pharmaceutical and non-pharmaceutical interventions simultaneously in the treatment. Conclusions: Our study indicates that while physicians have satisfactory knowledge of the symptoms and treatment modalities of FM, a knowledge gap concerning its diagnostic criteria exists. Proper treatment can only be successful when physicians successfully diagnose FM, therefore, future training programs should use this fact as a stepping stone for advances in its healthcare.

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 .