Evaluating the efficacy and safety of weekly Insulin Icodec vs. Daily Insulin Glargine in type 2 Diabetes Mellitus: a systematic review and meta-analysis.

Introduction: Various insulin therapies for Diabetes Mellitus offer different benefits while having potential risks. We aim to compare Insulin Icodec, a novel Insulin analogue with the ease of once-weekly administration, to the once-daily Insulin Glargine U100 regarding glycemic control and safety profile. Methods: We performed a systematic literature search of electronic databases for peer-reviewed articles from inception until September 1 2023. Results: A total of 2215 type 2 diabetic patients were included, of which 1209 received Insulin Icodec and1048 recieved Insulin Glargine U100. In terms of glycemic control, Insulin Icodec showed a significantly longer time in the target glucose range (MD: 0.304, CI: 0.069, P = 0.000) and a more significant reduction in HbA1c (MD: -0.154, CI: 0.003, P = 0.005) compared to Insulin Glargine U100. Fasting Plasma Glucose did not differ significantly. Insulin Icodec led to a more significant increase in body weight (MD: 0.161 kg, P = 0.029), while Insulin Glargine required a higher insulin dose (MD: 1.920 IU, P = 0.000). Regarding safety, the two groups had no significant differences in hypoglycemic events or adverse outcomes. Conclusion: Once-weekly Insulin Icodec demonstrates superior glycemic control with a reduced HbA1c compared to Once-Daily Insulin Glargine U100 while maintaining similar safety profiles. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-024-01431-5.

Evaluating the effectiveness and safety of various Tirzepatide dosages in the management of Type 2 diabetes mellitus: a network meta-analysis of randomized controlled trials.

Purpose: Excess body fat, insulin resistance, and abnormal lipid levels signal type 2 diabetes mellitus (DM2). Globally, 536.6 million people suffer from DM2, projected to rise to 783.2 million by 2045. Obesity fuels insulin resistance and DM2 development, with weight loss significantly improving glycemic control. Titrzepatide (TZP), a dual GIP and GLP-1 receptor agonist, proves highly effective in controlling hyperglycemia, stimulating insulin secretion, and promoting weight loss. TZP, holds promise as a treatment for DM2, surpassing insulin and GLP-1. The study aimed to meticulously assess the safety and efficacy of various doses, offering insights into optimal therapeutic strategies for managing DM2. Methods: This study aimed to comprehensively evaluate the safety and efficacy of TZP in treating DM2. The primary focus of the inclusion criteria was on trials comparing TZP with a placebo until November 23, 2023, excluding patients with certain comorbidities. Data extraction included key parameters, and outcomes were assessed for HbA1c levels, weight changes, fasting serum glucose levels, and various adverse events. Quality assessment utilized the Cochrane Collaboration's risk-of-bias tool, and a network meta-analysis explored outcomes across different TZP dosages. Results: This meta-analysis systematically reviewed ten studies on TZP for DM2. Results revealed significant reductions in HbA1c with TZP 10 mg (19%) and TZP 15 mg (31%) compared to TZP 5 mg (MD: -0.19 and MD: -0.32, respectively). Additionally, weight reduction was notable for TZP 10 mg (MD: -1.96) and TZP 15 mg (MD: -3.31). Fasting serum glucose showed improvement with TZP 15 mg (MD:-6.71). Gastrointestinal events increased with higher doses, yet without statistical significance. Death, nausea, diarrhea, vomiting, dyspepsia, decreased appetite, injection site reaction, hypoglycemia, treatment discontinuation, and serious adverse events showed no significant differences across doses. Conclusion: TZP effectively lowers HbA1c and induces weight loss across its three doses for type 2 diabetes management. The higher dose (15 mg) significantly reduces fasting serum glucose, with increased adverse events observed at higher doses. Dose-specific patterns for adverse effects emphasize the need to balance therapeutic benefits and risks. Further research is crucial for refining clinical applications and understanding TZP's role in DM2 management across doses. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-024-01412-8.

Evaluating the Effectiveness and Safety of Evinacumab in Treating Hypercholesterolemia and Hypertriglyceridemia: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Cardiovascular disease remains a significant global health concern, with high low-density lipoprotein cholesterol (LDL-C) levels contributing to an increased risk. Familial hypercholesterolemia (FH) further complicates its management, necessitating additional lipid-lowering therapies. Evinacumab, an angiopoietin-like protein 3 monoclonal antibody, has emerged as a potential treatment, particularly for patients with FH, by effectively reducing LDL-C and triglyceride levels. This meta-analysis aimed to evaluate the efficacy and safety of evinacumab across diverse patient populations. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria, relevant randomized controlled trials (RCTs) were systematically retrieved from multiple databases until November 24, 2023. The inclusion criteria were studies comparing evinacumab (at doses of 5 and 15 mg) to placebo, with outcomes focusing on lipid levels and adverse events. Standardized protocols were employed for data extraction and quality assessment, and statistical analysis was conducted using RevMan software. RESULTS: Four RCTs, involving 270 patients, were included in the analysis. The analysis revealed significant reductions in lipid markers, particularly with the 15-mg dose of evinacumab, including triacylglycerols (standard mean difference [SMD] = -6.09, 95% confidence interval [CI] - 14.53 to 2.36, P = 0.16), total cholesterol (SMD = - 6.20, 95% CI - 11.53 to - 0.88, P = 0.02), high-density lipoprotein cholesterol (SMD = - 0.79, 95% CI - 1.27 to - 0.31, P = 0.001), LDL-C (SMD = - 4.58, 95% CI - 9.13 to - 0.03, P = 0.05), apolipoprotein (Apo) B (SMD = - 4.01, 95% CI - 7.53 to - 0.46, P = 0.03), and Apo C3 (SMD = - 7.67, 95% CI - 12.94 to - 2.41, P = 0.004). Adverse event analysis revealed no significant association, indicating good tolerability. CONCLUSION: High-dose evinacumab (15 mg) consistently demonstrated efficacy in reducing cholesterol and other lipid markers, with favorable tolerability. Further research is warranted to comprehensively assess its safety and clinical effectiveness, emphasizing the need for additional data to support its use in managing cardiovascular disease.

Comparing equiosmolar hypertonic saline and mannitol for achieving brain relaxation in elective craniotomy patients: A systematic review and meta-analysis.

Background: This study strives to provide a current and thorough assessment of the comparative efficacy and safety between equiosmolar quantities of hypertonic saline (HS) and mannitol in facilitating brain relaxation for patients undergoing elective craniotomies. Methods: This systematic review and meta-analysis, following preferred reporting items for systematic reviews and meta-analyses guidelines, compared the efficacy and safety of equiosmolar concentrations of mannitol and HS in elective craniotomies. PubMed, Scopus, Cochrane Library, ScienceDirect, and Proquest databases were searched using keywords related to mannitol, HS, and craniotomy. Results were analyzed through a random-effects model using Mantel-Haenszel risk ratio and standard mean difference. P < 0.05 was considered significant. Results: Thirteen randomized controlled trials encompassing 965 patients (516 in the HS group and 448 in the mannitol group) were analyzed. The quality of studies was moderate-to-high, and no significant publication bias was observed. The primary outcome, brain relaxation, favored HS over mannitol without significant heterogeneity. Mannitol was associated with increased urine output compared to HS, irrespective of dose, with high heterogeneity. HS was linked to significantly reduced fluid input, confirmed by subgroup analysis with lower heterogeneity. No significant difference was found in serum osmolality between the two agents. Serum sodium (Na+) levels favored HS, whereas arterial blood Na+ levels also favored HS despite considerable heterogeneity. Maximum mean arterial pressure was higher with HS, but it displayed significant heterogeneity. Maximum central venous pressure showed no significant difference between the two agents, with moderate heterogeneity. Conclusion: HS appears more effective than mannitol in achieving brain relaxation, and it may offer advantages in fluid management and Na+ balance. Clinicians should consider these findings when selecting hyperosmotic agents for neurosurgical procedures. Further research is needed to address heterogeneity in certain outcomes and guide clinical practice.

Evaluating the efficacy and safety of nivolumab and ipilimumab combination therapy compared to nivolumab monotherapy in advanced cancers (excluding melanoma): a systemic review and meta-analysis.

BACKGROUND: Nivolumab (Nivo) and ipilimumab (Ipi) have revolutionized cancer treatment by targeting different pathways. Their combination shows promising results in various cancers, including melanoma, but not all studies have demonstrated significant benefits. A meta-analysis was performed to assess the effectiveness and safety of Nivo-Ipi compared to Nivo alone in advanced cancer types (excluding melanoma). METHODS: Following PRISMA guidelines, we conducted a meta-analysis up to September 30, 2023, searching databases for randomized controlled trials (RCTs). We focused on advanced solid malignancies (excluding melanoma) with specific Nivo and Ipi dosing. Primary outcomes were overall survival (OS), progression-free survival (PFS), grades 3-4 adverse events (AEs), and treatment-related discontinuations. Secondary outcomes included specific adverse events. Statistical analysis in Review Manager included hazard ratio (HR) and risk ratio (RR), assessing heterogeneity (Higgins I2). RESULTS: Nine RCTs, involving 2152 patients covering various malignancies, were analyzed. The Nivo plus Ipi group exhibited a median OS of 12.3 months and a median PFS of 3.73 months, compared to monotherapy with 11.67 months and 3.98 months, respectively. OS showed no significant difference between Nivo and Ipi combination and Nivo alone (HR = 0.97, 95% CI: 0.88 to 1.08, p = 0.61). PFS had a slight improvement with combination therapy (HR = 0.91, 95% CI: 0.82 to 1.00, p = 0.04). Treatment-related cumulative grades 3-4 adverse events were higher with Nivo and Ipi (RR = 1.52, 95% CI: 1.30 to 1.78, p < 0.00001), as were treatment-related discontinuations (RR = 1.99, 95% CI: 1.46 to 2.70, p < 0.0001). Hepatotoxicity (RR = 2.42, 95% CI: 1.39 to 4.24, p = 0.002), GI toxicity (RR = 2.84, 95% CI: 1.44 to 5.59, p = 0.002), pneumonitis (RR = 2.29, 95% CI: 1.24 to 2.23, p = 0.008), dermatitis (RR = 2.96, 95% CI: 1.08 to 8.14, p = 0.04), and endocrine dysfunction (RR = 6.22, 95% CI: 2.31 to 16.71, p = 0.0003) were more frequent with Nivo and Ipi. CONCLUSIONS: Combining nivolumab and ipilimumab did not significantly improve overall survival compared to nivolumab alone in advanced cancers (except melanoma). However, it did show slightly better PFS at the cost of increased toxicity, particularly grades 3-4 adverse events. Specific AEs occurred more frequently in the combination group. Further trials are needed to fully assess this combination in treating advanced cancers.

Letter to the editor: "A nomogram based on radiomics and clinical information to predict prognosis in percutaneous balloon compression for the treatment of trigeminal neuralgia: a retrospective cohort study of published cases".

This critique evaluates a recent study on a nomogram based on radiomics and clinical data to predict the prognosis of percutaneous balloon compression (PBC) for trigeminal neuralgia (TN), focusing on its strengths, weaknesses, and suggestions for future research. It acknowledges the innovative approach's potential to personalize treatment and improve outcomes, but raises concerns about the study's retrospective nature, sample size limitations, and challenges in implementing radiomics in clinical practice. Overall, although the nomogram offers promise, further validation in larger cohorts is essential to confirm its utility and reliability. Future research should prioritize prospective multicenter studies with standardized protocols, collaborative efforts among institutions, and innovative techniques to advance our understanding and management.

Breakthroughs in Alzheimer's Research: A Path to a More Promising Future?

Background: Alzheimer's disease (AD) is a widespread neurodegenerative disorder with a significant global impact, affecting approximately 50 million individuals, and projections estimate that up to 152 million people will be affected by 2050. AD is characterized by beta-amyloid plaques and tau tangles in the brain, leading to cognitive decline. Summary: Recent research on AD has made significant strides, including the development of an "amyloid clock" biomarker that tracks AD progression through positron emission tomography (PET) scans. Surf4 and other genes have been discovered to play a role in regulating beta-amyloid toxicity, while inhibiting the enzyme hexokinase-2 has shown positive results in preclinical studies. New brain mapping techniques have identified early brain-based causes of cognitive changes in AD, and biomarkers such as neuronal pentraxin protein Nptx2 and astrocytic 7-subunit of the nicotinic acetylcholine receptors (7nAChRs) show potential for early detection. Other approaches, such as replenishing the enzyme Tip60, selectively degrading the modified protein p-p38 with PRZ-18002, and targeting the protein voltage-dependent anion channel-1 (VDAC1), have shown promise in enhancing cognitive function and preventing pathophysiological alterations linked to AD. Baseline blood samples and other biomarkers such as urine formic acid, p-tau 198, microRNAs, and glial fibrillary acidic protein (GFAP) have also been discovered for early detection and intervention of AD. Additionally, recent FDA approvals for medications such as aducanumab and lecanemab provide options for reducing AD symptoms and improving function, while clinical trials for dementia vaccines show promise for the nasal and beta-amyloid 40 vaccines as well as vaccinations targeting tau. Key Messages: These advancements in AD research, including biomarker discovery and the development of disease-modifying treatments, are crucial steps towards improving the lives of those affected by AD and finding a cure for this debilitating disease.

Pesticides impacts on human health and the environment with their mechanisms of action and possible countermeasures.

Pesticides are chemical constituents used to prevent or control pests, including insects, rodents, fungi, weeds, and other unwanted organisms. Despite their advantages in crop production and disease management, the use of pesticides poses significant hazards to the environment and public health. Pesticide elements have now perpetually entered our atmosphere and subsequently contaminated water, food, and soil, leading to health threats ranging from acute to chronic toxicities. Pesticides can cause acute toxicity if a high dose is inhaled, ingested, or comes into contact with the skin or eyes, while prolonged or recurrent exposure to pesticides leads to chronic toxicity. Pesticides produce different types of toxicity, for instance, neurotoxicity, mutagenicity, carcinogenicity, teratogenicity, and endocrine disruption. The toxicity of a pesticide formulation may depend on the specific active ingredient and the presence of synergistic or inert compounds that can enhance or modify its toxicity. Safety concerns are the need of the hour to control contemporary pesticide-induced health hazards. The effectiveness and implementation of the current legislature in providing ample protection for human health and the environment are key concerns. This review explored a comprehensive summary of pesticides regarding their updated impacts on human health and advanced safety concerns with legislation. Implementing regulations, proper training, and education can help mitigate the negative impacts of pesticide use and promote safer and more sustainable agricultural practices.

Comment on, "Systematic literature review and critical analysis of RDW in patients with aortic pathologies".

Recent medical research has explored Red Cell Distribution Width (RDW) as a potential biomarker for predicting adverse clinical outcomes in patients with aortic pathologies. The study "Systematic literature review and critical analysis of RDW in patients with aortic pathologies" conducted a pooled analysis of 704 patients, revealing a consistent association between elevated RDW levels and adverse clinical progression. While the study provides valuable insights into RDW's diagnostic and prognostic potential, limitations include the inclusion of a limited number of articles and the lack of direct comparison with established biomarkers or imaging techniques. Further research is needed to validate RDW's clinical utility and elucidate underlying biological mechanisms. RDW shows promise as a cost-effective marker for risk stratification and monitoring in clinical practice, but further validation and refinement are necessary for its full clinical impact in aortic diseases.

Preoperative anxiety management in pediatric patients: a systemic review and meta-analysis of randomized controlled trials on the efficacy of distraction techniques.

Background: This study addresses the pervasive issue of heightened preoperative anxiety in healthcare, particularly among pediatric patients. Recognizing the various sources of anxiety, we explored both pharmacological and nonpharmacological interventions. Focusing on distraction techniques, including active and passive forms, our meta-analysis aimed to provide comprehensive insights into their impact on preoperative anxiety in pediatric patients. Methods: Following the PRISMA and Cochrane guidelines, this meta-analysis and systematic review assessed the efficacy of pharmaceutical and distraction interventions in reducing pain and anxiety in pediatric surgery. This study was registered on PROSPERO (CRD42023449979). Results: This meta-analysis, comprising 45 studies, investigated pharmaceutical interventions and distraction tactics in pediatric surgery. Risk of bias assessment revealed undisclosed risks in performance and detection bias. Distraction interventions significantly reduced preoperative anxiety compared to control groups, with notable heterogeneity. Comparison with Midazolam favored distraction techniques. Subgroup analysis highlighted varied efficacies among distraction methods, with a notable reduction in anxiety levels. Sensitivity analysis indicated stable results. However, publication bias was observed, suggesting a potential reporting bias. Conclusion: Our study confirms distraction techniques as safe and effective for reducing pediatric preoperative anxiety, offering a valuable alternative to pharmacological interventions. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=449979, PROSPERO [CRD42023449979].