Evaluating the Efficacy of Immune Checkpoint Inhibitors in Elderly Patients: A Systematic Review and Meta-analysis.

In this chapter, we outline the steps for designing and conducting a rigorous systematic review and meta-analysis, focusing on the efficacy of immune checkpoint inhibitors (ICIs) in elderly patients. ICIs have improved survival rates in advanced cancers, yet their effectiveness in older populations remains unclear. We detail the essential processes involved in both systematic reviews and meta-analyses. We can evaluate the efficacy of ICIs in elderly patients with advanced cancer, examining outcomes such as overall survival and progression-free survival.

Assessing the Predictive Accuracy of the aMAP Risk Score for Hepatocellular Carcinoma (HCC): Diagnostic Test Accuracy and Meta-analysis.

Purpose: We aimed to perform a meta-analysis with the intention of evaluating the reliability and test accuracy of the aMAP risk score in the identification of HCC. Methods: A systematic search was performed in PubMed, Scopus, Cochrane, Embase, and Web of Science databases from inception to September 2023, to identify studies measuring the aMAP score in patients for the purpose of predicting the occurrence or recurrence of HCC. The meta-analysis was performed using the meta package in R version 4.1.0. The diagnostic accuracy meta-analysis was conducted using Meta-DiSc software. Results: Thirty-five studies 102,959 participants were included in the review. The aMAP score was significantly higher in the HCC group than in the non-HCC group, with a mean difference of 6.15. When the aMAP score is at 50, the pooled sensitivity, specificity, negative likelihood ratio, and positive likelihood ratio with 95% CI was 0.961 (95% CI 0.936, 0.976), 0.344 (95% CI 0.227, 0.483), 0.114 (95% CI 0.087, 0.15), and 1.464 (95% CI 1.22, 1.756), respectively. At a cutoff value of 60, the pooled sensitivity, specificity, negative likelihood ratio, and positive likelihood ratio with 95% CI was 0.594 (95% CI 0.492, 0.689), 0.816 (95% CI 0.714, 0.888), 0.497 (95% CI 0.418, 0.591), and 3.235 (95% CI 2.284, 4.582), respectively. Conclusion: The aMAP score is a reliable, accurate, and easy-to-use tool for predicting HCC patients of all stages, including early-stage HCC. Therefore, the aMAP score can be a valuable tool for surveillance of HCC patients and can help to improve early detection and reduce mortality.

Diagnostic Value of Chest Computed Tomography Scan for Identification of Foreign Body Aspiration in Children: A Systematic Review and Meta-analysis.

Introduction: Foreign body aspiration (FBA) is a common, life-threatening pediatric emergency and was shown to be associated with high risk of morbidity and mortality. This systematic review and meta-analysis aimed to investigate the diagnostic value of chest computed tomography (CT) scan for identification of FBA in children. Methods: From inception to May 2024, a systematic search was carried out across multiple databases including Medline, Scopus, and Web of Science, considering published papers in English language. Quality assessment of the included studies was performed using seven domains of Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). Results: The systematic literature search yielded 7203 articles. The pooled sensitivity and specificity of chest CT scan for identification of FBA were 0.99 (95% CI: 0.98-0.99) and 0.97 (95% CI: 0.96-0.98), respectively. The pooled positive likelihood ratio was 10.12 (95% CI: 4.59-22.20), and pooled negative likelihood ratio was 0.05 (95% CI: 0.02-0.1). Furthermore, the area under the summarized receiver operating characteristic (SROC) curve was 0.98. Conclusion: Our meta-analysis revealed that despite high heterogeneity, in the diagnostic characteristics of chest CT scan among studies, it has high diagnostic value in identifying FBA in suspected pediatric cases.

Meta Analysis of the Correlation between Periodontal Health and Cognitive Impairment in the Older Population.

OBJECTIVE: To explore the correlation between periodontal health and cognitive impairment in the older population to provide the evidence for preventing cognitive impairment from the perspective of oral health care in older adults. METHODS: A comprehensive search was conducted in PubMed, Embase, the Cochrane Library, the Web of Science, the China National Knowledge Infrastructure, Wanfang Data, the China Science and Technology Journal Database, and the China Biomedical Literature Database, to include both cross-sectional and longitudinal cohort studies on the association between periodontal health and cognitive impairment in older adults. The search was completed in April 2023. Following quality assessment and data organization of the included studies, meta-analysis was performed using Review Manager 5.4. RESULTS: Twenty-two studies involving a total of 4,246,608 patients were included to comprehensively assess periodontal health from four dimensions (periodontitis, tooth loss, occlusal support, and masticatory ability), with the outcome variable of cognitive impairment (including mild cognitive impairment, Alzheimer's disease and all-cause dementia). Meta-analysis showed that, compared to those of periodontally healthy older adults, the risk of cognitive impairment in older adults with poor periodontal health, after adjusting for confounders, was significantly greater for those with periodontitis (OR=1.45, 95% CI: 1.20-1.76, P<0.001), tooth loss (OR=1.80, 95% CI: 1.50-2.15, P<0.001), compromised occlusal support (OR=1.87, 95% CI: 1.29-2.70, P=0.001), and reduced masticatory ability (OR=1.39, 95% CI: 1.11-1.75, P=0.005). The risk of cognitive impairment was higher in older adults with low-dentition than in those with high-dentition. Subgroup analysis revealed older individuals with fewer remaining teeth were at a higher risk of developing cognitive impairment compared to those with more remaining teeth, as shown by the comparison of number of teeth lost (7-17 teeth compared to 0-6 teeth) (OR=1.64, 95% CI: 1.13-2.39, P=0.01), (9-28 teeth compared to 0-8 teeth) (OR=1.13, 95% CI: 1.06-1.20, P<0.001), (19-28 teeth compared to 0-18 teeth) (OR=2.52, 95% CI: 1.32-4.80, P=0.005), and (28 teeth compared to 0-27 teeth) (OR=2.07, 95% CI: 1.54-2.77, P<0.001). In addition, tooth loss in older adults led to a significantly increased risk of mild cognitive impairment (OR=1.66, 95% CI: 1.43-1.91, P<0.001) and all-cause dementia (OR=1.35, 95% CI: 1.11-1.65, P=0.003), although the correlation between tooth loss and the risk of Alzheimer's disease was not significant (OR=3.89, 95% CI: 0.68-22.31, P=0.13). CONCLUSION: Poor periodontal health, assessed across four dimensions (periodontitis, tooth loss, occlusal support, and masticatory ability), represents a significant risk factor for cognitive impairment in older adults. The more missing teeth in older adults, the higher risk of developing cognitive impairment, with edentulous individuals particularly susceptible to cognitive impairment. While a certain degree of increased risk of Alzheimer's disease was observed, no significant association was found between tooth loss and the risk of developing Alzheimer's disease. Enhancing periodontal health management and delivering high-quality oral health care services to older adults can help prevent cognitive impairment.

Efficacy and safety of vancomycin compared with those of alternative treatments for methicillin-resistant Staphylococcus aureus infections: An umbrella review.

OBJECTIVE: To summarize the evidence on the efficacy and safety of vancomycin compared with those of alternative treatments in adult patients with methicillin-resistant Staphylococcus aureus (MRSA) infection. METHODS: PubMed, Embase, and Web of Science were searched up to December 15, 2023, for systematic reviews and meta-analyses comparing vancomycin with alternative MRSA treatments. Primary outcomes included clinical cure and microbiological eradication rates. Organ-specific safety outcomes were assessed. Summary estimates were recalculated using a random-effects model. Evidence was graded using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) tool. This study was registered in PROSPERO (CRD42022340359). RESULTS: This umbrella review included 19 studies and 71 meta-analyses (46 efficacy and 25 safety) comparing vancomycin with 10 alternative treatments across different MRSA infection types and populations. GRADE assessment showed that 29.58% of the meta-analyses were of high quality. Linezolid and daptomycin showed higher efficacy in MRSA-induced skin and soft tissue infections and pneumonia (moderate evidence quality) and bacteremia (very low evidence quality), respectively, compared with that of vancomycin. Cephalosporins had a higher risk of nausea, whereas linezolid had a higher risk of nausea, diarrhea, and thrombocytopenia than that of vancomycin. Vancomycin posed a higher risk of rash, pruritus, red man syndrome, and nephrotoxicity than that of alternatives. CONCLUSIONS: The quality of evidence supporting the higher efficacy of alternative treatment over vancomycin for MRSA infection was not high. Given varying safety profiles and advancements in therapeutic monitoring, careful consideration of patient-specific factors and pharmacokinetics is crucial when selecting treatment alternatives to vancomycin.

[Utilizing ChatGPT in Systematic Reviews and Meta-Analyses].

The current uses, potential risks, and practical recommendations for using chat generative pre-trained transformers (ChatGPT) in systematic reviews (SRs) and meta-analyses (MAs) are reviewed in this article. The findings of prior research suggest that, for tasks such as literature screening and information extraction, ChatGPT can match or exceed the performance of human experts. However, for complex tasks such as risk of bias assessment, its performance remains significantly limited, underscoring the critical role of human expertise. The use of ChatGPT as an adjunct tool in SRs and MAs requires careful planning and the implementation of strict quality control and validation mechanisms to mitigate potential errors such as those arising from artificial intelligence (AI) 'hallucinations'. This paper also provides specific recommendations for optimizing human-AI collaboration in SRs and MAs. Assessing the specific context of each task and implementing the most appropriate strategies are critical when using ChatGPT in support of research goals. Furthermore, transparency regarding the use of ChatGPT in research reports is essential to maintaining research integrity. Close attention to ethical norms, including issues of privacy, bias, and fairness, is also imperative. Finally, from a human-centered perspective, this paper emphasizes the importance of researchers cultivating continuous self-iteration, prompt engineering skills, critical thinking, cross-disciplinary collaboration, and ethical awareness skills with the goals of: continuously optimizing human-AI collaboration models within reasonable and compliant norms, enhancing the complex-task performance of AI tools such as ChatGPT, and, ultimately, achieving greater efficiency through technological innovative while upholding scientific rigor.

[A Guide to Network Meta-Analysis Using Generative AI and No-Code Tools].

Network meta-analysis (NMA), an increasingly appealing method of statistical analysis, is superior to traditional analysis methods in terms of being able to compare multiple medical treatment methods in one analysis run. In recent years, the prevalence of NMA in the medical literature has increased significantly, while advances in NMA-related statistical methods and software tools continue to improve the effectiveness of this approach. Various commercial and free statistical software packages, some of which employ generative artificial intelligence (GAI) to generate code, have been developed for NMA, leading to numerous innovative developments. In this paper, the use of generative AI for writing R programming language scripts and the netmeta package for performing NMA are introduced. Also, the web-based tool ShinyNMA is introduced. ShinyNMA allows users to conduct NMA using an intuitive "clickable" interface accessible via a standard web browser, with visual charts employed to present results. In the first section, we detail the netmeta package documentation and use ChatGPT (chat generative pre-trained transformer) to write the R scripts necessary to perform NMA with the netmeta package. In the second section, a user interface is developed using the Shiny package to create a ShinyNMA tool. This tool provides a no-code option for users unfamiliar with programming to conduct NMA statistical analysis and plotting. With appropriate prompts, ChatGPT can produce R scripts capable of performing NMA. Using this approach, an NMA analysis tool is developed that meets the research objectives, and potential applications are demonstrated using sample data. Using generative AI and existing statistical packages or no-code tools is expected to make conducting NMA analysis significantly easier for researchers. Moreover, greater access to results generated by NMA analyses will enable decision-makers to review analysis results intuitively in real-time, enhancing the importance of statistical analysis in medical decision-making. Furthermore, enabling non-specialists to conduct clinically meaningful systematic reviews may be expected to sustainably improve analytical capabilities and produce higher-quality evidence.

Short- versus standard-course antibiotic therapy for urinary tract infection in children: a systematic review and meta-analysis.

BACKGROUND: Urinary tract infections are prevalent among children and are responsible for a significant healthcare burden. Antibiotic therapy is the cornerstone of treatment, but the optimal treatment duration remains elusive. OBJECTIVES: This systematic review and meta-analysis aimed to explore the optimal duration of antibiotic therapy for urinary tract infection (UTI) in pediatric patients. DATA SOURCES: A comprehensive search was performed, including MEDLINE, Embase, and Cochrane Library databases. STUDY ELIGIBILITY CRITERIA: We included only randomized controlled trials (RCTs) comparing short-course (2 to 5 days) and standard-course (≥ 7 days) antibiotic treatment in patients < 18 years of age. STUDY APPRAISAL AND SYNTHESIS METHODS: We performed this systematic review and meta-analysis following Cochrane Collaboration recommendations using a random-effects model. Effect estimate was calculated using the risk ratio (RR) with 95% confidence interval (95% CI) for dichotomous and mean difference (MD) with 95% CI for continuous endpoints. Significance was regarded at p-value < 0.05. Statistical analysis was performed using Review Manager 5.4.1. RESULTS: Data from 12 RCTs, encompassing 1442 children, were included. Follow-up ranged from 1 to 12 months. The mean age was 5.9 years, with approximately 87% female patients. E. coli was the most common pathogen isolated from urine cultures. There was a significant difference in cure rates (RR 0.97; 95% CI 0.95-0.99; p = 0.01) between the groups when only studies that included febrile UTI were analyzed together, favoring 7 days or more of treatment, but with high heterogeneity. Otherwise, there was no significant difference in cure rates (RR 0.99; 95% CI 0.91-1.08; p = 0.80) in children with afebrile UTI or recurrence of UTI at any time in children with afebrile (RR 0.98; 95% CI 0.84-1.15; p = 0.80) or febrile UTI (RR 0.52; 95% CI 0.10-2.83; p = 0.45). Also, there was no significant difference in failure rates in children with urinary tract abnormalities and afebrile UTI (RR 0.79; 95% CI 0.47-1.32; p = 0.36), between the short- and the standard-course treatment groups. LIMITATIONS: This analysis was limited by the moderate heterogeneity and the small subgroup of children with urinary tract abnormalities, which could have underpowered our results. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: The primary outcome of this analysis suggests that a short course of antibiotic therapy is feasible in children with afebrile UTI, but more studies are warranted to safely establish an optimal treatment duration for children with febrile UTI. SYSTEMATIC REVIEW REGISTRATION NUMBER: The study protocol was registered in the PROSPERO platform under the number CRD42023489094.

Cardiovascular Outcomes of Uric Acid Lowering Medications: A Meta-Analysis.

BACKGROUND: Although hyperuricemia is a recognized risk factor for cardiovascular diseases, mixed results have been reported regarding the associations between uric acid-lowering medications and cardiovascular events. This meta-analysis compared the cardiovascular outcomes of different uric acid-lowering medications and placebo. METHODS: Following PRISMA guidelines, we searched OVID Medline, Embase, Web of Science, and Cochrane databases to identify potentially relevant articles until December 2023. Studies must be randomized or observational, report cardiovascular and mortality outcomes, and compare uric acid-lowering medications to placebo or each other. Data was analyzed using Revman (version 5.4) software. RESULTS: A total of 3,393 studies were searched, after which 47 studies were included, totaling 3,803,509 patients (28 studies comparing xanthine oxidase inhibitors (XOI) versus placebo, 17 studies comparing allopurinol and febuxostat, and 2 studies comparing XOI and uricosuric agents). Overall mean age was 57.3 years, and females comprised 20.8% of all studies. There were no significant differences between XOI and placebo for cardiovascular outcomes (mortality, myocardial infarction, major adverse cardiovascular events, heart failure, or arrhythmia). There was significant heterogeneity in all these pooled analyses. Comparing Allopurinol to Febuxostat, there was a lower risk of heart failure in febuxostat than allopurinol in 3 RCTs (OR 0.66, 95% CI 0.50-0.89, p = 0.006). Other cardiovascular outcomes were not different. Lastly, when comparing XOI and uricosuric agents, no significant differences in MI rates were evident. CONCLUSION: XOI was not associated with reduced cardiovascular events compared to placebo. When comparing XOI agents, Febuxostat might reduce the risk of HF, but future studies are required to confirm the findings from the current study.

Gastrointestinal adverse events of metformin treatment in patients with type 2 diabetes mellitus: a systematic review and meta-analysis with meta-regression of observational studies.

INTRODUCTION: Metformin is the most prescribed medication for type 2 diabetes mellitus (T2DM); there is a well-established link with the elevated incidence of gastrointestinal (GI) adverse events (AE) limiting its administration or intensification. OBJECTIVES: The objective of this systematic review and meta-analysis of observational studies was to evaluate the pooled incidence of GI AE related to metformin use in patients with T2DM. MATERIALS AND METHODS: PUB MED/CINAHL/Web of Science/Scopus were searched from database inception until 29.07.2024 for observational studies in English describing the frequency of GI AE in patients with T2DM treated with metformin. Random-effects meta-analyses were used to derive effect sizes: event rates. RESULTS: From 7019 publications, we identified 211 potentially eligible full-text articles. Ultimately, 21 observational studies were included in the meta-analysis. The prevalence of GI AE was as follows: diarrhea 6.9% (95% CI: 0.038-0.123), bloating 6,2% (95% CI: 0.020-0.177), abdominal pain 5,3% (95% CI: 0.003-0.529), vomiting 2.4% (95%: CI 0.007-0.075), constipation 1.1% (95%: CI 0.001-0.100). The incidence of bloating (coefficient -4.46; p < 0.001), diarrhea (coefficient -1.17; p = 0.0951) abdominal pain (coefficient -2.80; p = 0.001), constipation (coefficient -5.78; p = 0.0014) and vomiting (coefficient -2.47; p < 0.001) were lower for extended release (XR) metformin than metformin immediate release (IR) formulation. CONCLUSIONS: This study highlights the prevalence of GI AE in patients receiving metformin, with a diarrhea predominance, followed by bloating, diarrhea, abdominal pain, constipation, and vomiting. The incidence is lower in patients administered with XR metformin. TRIAL REGISTRATION: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021289975 , identifier CRD42021289975.

Therapeutic effects of different acupuncture methods on chronic nonspecific low back pain: A network meta-analysis.

BACKGROUND: Low back pain has become a globally challenging health problem, and about 90% of cases are nonspecific. Due to the risks associated with opioid use and the limited effectiveness of drug treatment, acupuncture and other non-drug methods have become the first-line treatment for this disease. However, the best acupuncture method has not yet been determined. In this study, the effects of different acupuncture methods on chronic nonspecific low back pain (CNLBP) were compared by network meta-analysis, aiming at identifying the best option and providing a basis for precise treatment of CNLBP. METHODS: Clinical randomized controlled trials (RCTs) on acupuncture in the treatment of NSLBP were searched in eight databases including PubMed, Embase, Cochrane Library, Web of Science, Sinomed, CNKI, Wanfang Data and VIP from the inception of databases to January 21, 2024. The Cochrane risk-of-bias tool 2.0 (RoB 2.0) and Stata 15.0 (Stata Corp, College Station, Texas, USA) were used to evaluate the literature quality and meta-analysis, and the evidence quality was assessed based on GRADE guidelines. This systematic review was registered at the International Prospective Register of Systematic Reviews. RESULTS: A total of 27 articles were included, involving 2579 patients. The results of the network meta-analysis showed that the top three treatment schemes were warm needle acupuncture, intensive silver needle therapy and meridian-sinew theory-based treatment. In terms of relieving pain, the top three treatments were electrical warm needling, intensive silver needle therapy and warm needle acupuncture. In improving mobility, the top three were meridian-sinew theory-based treatment, routine acupuncture and electroacupuncture. CONCLUSION: For CNLBP patients, warm needle acupuncture, electrical warm needling and meridian-sinew theory-based treatment are mainly recommended. If patients have significant pain, electroacupuncture is strongly suggested. On the contrary, for patients with decreased joint mobility, meridian-sinew theory-based treatment is advocated.

The efficacy of simulation-based learning versus non-simulation-based learning in endocrinology education: a systematic review and meta-analysis.

BACKGROUND: Simulation-Based Learning (SBL) is increasingly adopted in medical education across various specialties, employing realistic simulations to significantly enhance learning experiences. However, a comprehensive evaluation of its effectiveness specifically in endocrinology has not yet been conducted. The study aims to systematically review and meta-analyze the impact of SBL versus Non-Simulation-Based Learning (NSBL) on knowledge acquisition, skills, satisfaction, and interest in learning among endocrinology trainees. METHODS: This systematic review and meta-analysis adhered to the PRISMA guidelines, searching PubMed, Web of Science, Embase, Cochrane library, China National Knowledge Infrastructure (CNKI), Wanfang Data, Weipu, and Chinese Biomedical Database (CBM) until March 2024. We included randomized controlled trials comparing SBL to NSBL in endocrinology education. The quality evaluation relied on the Cochrane risk-of-bias assessment tool. The main results included evaluations from both theoretical and practical assessments. Additional measures consisted of assessing satisfaction and interest in learning. RESULTS: We identified 22 studies suitable for systematic review and 21 for meta-analysis, involving a total of 2517 participants. SBL greatly enhanced theoretical knowledge [standardized mean difference (SMD) = 1.00, 95% confidence interval (CI): 0.68-1.32, P < 0.00001, I2 = 89%] and practical skills (SMD = 1.56, 95% CI: 1.11-2.01, P < 0.00001, I2 = 93%) compared to NSBL. Additionally, SBL was associated with higher satisfaction and greater interest in learning. No significant publication bias was detected, and sensitivity analysis confirmed the stability of these findings. CONCLUSIONS: SBL significantly enhances knowledge, skills, satisfaction, and interest in learning within endocrinology education compared to NSBL. These findings support the integration of high-quality SBL into endocrinology curricula to improve educational outcomes. Future research should explore the lasting effects of SBL on knowledge retention and clinical practice, as well as to evaluate its cost-effectiveness and compatibility with various educational tools in diverse settings.

Effect of vitamin D supplementation on clinical outcomes in adult patients with COVID-19: A GRADE-assessed systematic review and meta-analysis of randomized controlled trials.

The COVID-19 pandemic has emerged as a major global health crisis. Vitamin D, a crucial fat-soluble vitamin, has been recommended for COVID-19 patients, though evidence of its effectiveness is inconsistent. This systematic literature review and meta-analysis aimed to evaluate the impact of vitamin D supplementation on COVID-19-related outcomes. A comprehensive search was conducted across PubMed, Scopus, Web of Science, Embase, and Cochrane databases. Primary outcomes included mortality and hospital length of stay, while secondary outcomes encompassed C-reactive protein (CRP), ferritin, D-dimer, hemoglobin (Hb) concentrations, and lymphocyte, neutrophil, and platelet counts. Data analysis was performed using Stata™ Version 14. A total of 16 trials were analyzed. The meta-analysis revealed that vitamin D supplementation significantly reduced hospital length of stay (mean difference = -1.16; 95% confidence interval [CI]: -2.23, -0.09; p = .033) with significant heterogeneity (I2 = 69.2%, p = .002). Subgroup analysis showed a more pronounced reduction in studies with vitamin D dosages ≤10 000 international units (IU) (mean difference = -1.27; 95% CI: -1.96, -0.57; p < .001) and in patients over 60 years old (mean difference = -1.84; 95% CI: -2.53, -1.14; p < .001). Additionally, vitamin D significantly reduced CRP concentrations in older adults (>60 years) (mean difference = -1.13; 95% CI: -2.07, -0.18; p = .019). No significant changes were found in ferritin, D-dimer, Hb concentrations, or in lymphocyte, neutrophil, and platelet counts (p > .05). In conclusion, while vitamin D supplementation did not significantly affect most COVID-19-related biomarkers, however, it reduces the length of hospital stay.

Transcriptome meta-analysis of Kawasaki disease in humans and mice.

Kawasaki Disease (KD) affects young children less than five years old with severe blood vessel inflammation. Despite being treatable, the causes and mechanisms remain elusive. This study conducted a meta-analysis of RNA sequencing (RNA-seq) data from human and animal models to explore KD's transcriptomic profile and evaluate animal models. We retrieved bulk and single-cell RNA-seq data from Gene Expression Omnibus, with blood and coronary artery samples from KD patients, aorta samples from KD mouse models (Lactobacillus casei cell wall extract-injected mice), and their controls. Upon consistent quality control, we applied Fisher's exact test to assess differential gene expression, followed by an enrichment analysis of overlapping genes. These studies identified 400 differentially expressed genes in blood samples of KD patients compared to controls and 413 genes in coronary artery samples. The data from KD blood and KD coronary artery samples shared only 16 differentially expressed genes. Eighty-one genes overlapped between KD human coronary arteries and KD mouse aortas, and 67 of these 81 genes were regulated in parallel in both humans and mice: 30 genes were up-regulated, and 37 were down-regulated. These included previously identified KD-upregulated genes: CD74, SFRP4, ITGA4, and IKZF1. Gene enrichment analysis revealed significant alterations in the cardiomyopathy pathway. Single-cell RNAseq showed a few significant markers, with known KD markers like S100A9, S100A8, CD74, CD14, IFITM2, and IFITM3, being overexpressed in KD cohorts. Gene profiles obtained from KD human coronary artery are more compatible with data from aorta samples of KD mice than blood samples of KD humans, validating KD animal models for identifying therapeutic targets. Although blood samples can be utilized to discover novel biomarkers, more comprehensive single-cell sequencing is required to detail gene expression in different blood cell populations. This study identifies critical genes from human and mouse tissues to help develop new treatment strategies for KD.

Lisdexamfetamine's Efficacy in Treating Attention Deficit Hyperactivity Disorder (ADHD): A Meta-Analysis and Review.

Lisdexamfetamine dimesylate, a prodrug stimulant, appears to effectively treat Attention-Deficit/Hyperactivity Disorder (ADHD) in children and adults. However, an analysis of the treatment effects of the two subscales (inattentiveness and hyperactivity) within the ADHD Rating Scale-IV (ADHD-RS-IV) has not yet been done to determine if clinical significance may be attributed to either one. Nor has there been a meta-analysis of the individual doses of lisdexamfetamine dimesylate. The current meta-analysis utilizes MEDLINE, Embase, Cochrane, PubMed, and clinicaltrials.gov to identify peer-reviewed studies. Selected studies were eligible if they met the following criteria: English language, randomized-controlled trials, and utilized the ADHD-RS-IV scale to assess the efficacy of lisdexamfetamine on treating ADHD in either children or adults. The primary studies utilized were published between January 2007 and April 2024. Many of these studies calculate effect sizes based on several dosages pooled together rather than by individual dosages. We conducted a random-effects meta-analysis to estimate the effect sizes for these pooled dosages on the full ADHD-RS-IV scale and its subscales, as well as to calculate effect sizes on the same scales based on the individual dosages. Our main outcome measures are the ADHD-RS-IV scale and its subscales in individual doses and pooled results in both children and adults. Adverse events during treatment were also analyzed based on stratified dosages. Eleven publications met our inclusion criteria. The analyses indicate that compared to placebo, lisdexamfetamine effectively alleviates the symptoms outlined by the ADHD-RS-IV. Moreover, there are no differences in the individual subscales or in the safety profile. Lisdexamfetamine demonstrates efficacy in treating the symptoms of ADHD, but we report that differing dosages did not yield significant differences in ADHD symptom management.

Cupping Therapy for the Treatment of Migraine Headache: a systematic review and meta-analysis of clinical trials.

Objectives: Cupping therapy is a widely used complementary medicine for the treatment of migraine headaches globally. However, conflicting evidence exists on its effectiveness. To evaluate the safety and efficacy of cupping therapy in treating migraine headache disorder. Methods: Seven databases were systematically searched PubMed/MEDLINE, Clinicaltrials.gov, Cochrane CENTRAL, ScienceDirect, ProQuest, SinoMed, and the National Science and Technology Library. The primary endpoints are the treatment success and the pain intensity reduction. The secondary endpoints were adverse events (AEs) risk and improvement in quality of life (QoL), which was based on the Migraine Disability Scale (MIDAS). Subgroup analyses were performed based on the cupping techniques (wet and dry cupping) and adjunctive complementary treatments (i.e. acupuncture and/or collateral pricking). Results: Eighteen trials out of 348 records were included, pooling 1,446 participants (n = 797 received cupping therapy). Treatment success was significantly higher among those with cupping therapy (risk ratio [RR] [95% CI] = 1.83 [1.52-2.21]); with significant improvement observed only with wet cupping (RR [95% CI] = 1.88 [1.53-2.30]). The adjunctive complementary therapy did not achieve a greater amplitude of treatment success compared to cupping therapy alone. Furthermore, cupping therapy showed significant pain reduction compared to baseline (standardized mean difference [SMD] [95% CI] = 0.55 [0.39-0.70]) and achieved fewer risks of AEs (RR [95% CI] = 1.88 [1.53-2.30]). However, cupping did not improve the overall QoL (MIDAS SMD [95% CI] = -0.79 [-3.55-1.98]). Conclusion: Cupping therapy was an effective complementary modality to treat migraine headaches. However, it did not demonstrate improvement in QoL (PROSPERO CRD42024514509).

Cognitive potency and safety of tDCS treatment for major depressive disorder: a systematic review and meta-analysis.

Background: The benefits of transcranial direct current stimulation (tDCS) for patients with major depression disorders are well-established, however, there is a notable research gap concerning its comprehensive effects on both depressive symptoms and cognitive functions. Existing research is inconclusive regarding the cognitive enhancement effects of tDCS specifically in MDD patients. The present study aims to fill this knowledge gap by scrutinizing the most updated evidence on the effectiveness of tDCS in anti-depressive treatment and its influence on cognitive function. Methods: A systematic review was performed from the first date available in PubMed, EMBASE, Cochrane Library, and additional sources published in English from 1 January 2001 to 31 May 2023. We examined cognitive outcomes from randomized, sham-controlled trials of tDCS treatment for major depression. The evaluation process strictly followed the Cochrane bias risk assessment tool into the literature, and meta-analysis was performed according to the Cochrane System Reviewer's Manual. Results: In this quantitative synthesis, we incorporated data from a total of 371 patients across 12 studies. Results showed significant benefits following active tDCS compared to sham for the antidepressant effect [SMD: -0.77 (-1.44, -0.11)]. Furthermore, active relative to sham tDCS treatment was associated with increased performance gains on a measure of verbal memory [SMD: 0.30 (-0.02, 0.62)]. These results did not indicate any cognitive enhancement after active tDCS relative to sham for global cognitive function, whereas there was a noticeable trend toward statistical significance specifically in the effect of verbal memory. Conclusions: Our study offers crucial evidence-based medical support for tDCS in antidepressant and dimension-specific cognitive benefits. Further well-designed, large-scale randomized sham-controlled trials are warranted to further validate these findings. Systematic Review Registration: https://inplasy.com/, identifier: INPLASY202360008.

Efficacy and safety of the first-line systemic treatments in patients with advanced-stage urothelial carcinoma: a systematic review and network meta-analysis.

Introduction: In recent years, some clinical studies of first-line treatment for advanced-stage urothelial carcinoma (aUC) have reached the main endpoint, showing inconsistent clinical efficacy. We hope to explore the efficacy and safety of first-line treatment for aUC. Methods: The relevant literature from January 2000 to February 2024 was searched, and the R language (version 4.3.1) was used to perform a network meta-analysis based on the JAGS package and GEMTC package under the Bayesian framework. The main indicators included OS, PFS, ORR and adverse events of grade 3 or higher. This study has been registered in PROSPERO (CRD42024525372). Results: A total of 8 RCTs involving 5539 patients and 12 treatments were included. Pembrolizumab plus Enfortumab Vedotin (PEM+EV) was significantly better than other groups in OS, PFS and ORR. In terms of OS, PEM+EV was significantly better than nivolumab plus platinum-based chemotherapy (NIVO+platinumCT) (HR=0.60; 95% CI: 0.45-0.81), PEM+platinumCT (HR=0.55; 95%CI: 0.42-0.72), atezolizumab (ATE) + platinumCT (HR=0.57; 95%CI: 0.43-0.75) and platinumCT (HR=0.47; 95%CI: 0.38-0.58). In terms of PFS, PEM+EV was also significantly better than NIVO+platinumCT (HR=0.62; 95%CI: 0.48-0.82), PEM+platinumCT (HR=0.58; 95%CI: 0.45-0.74), ATE+platinumCT (HR=0.55; 95%CI: 0.43-0.69) and platinumCT (HR=0.45; 95%CI: 0.38-0.54). In terms of ORR, PEM+EV had a significant be nefit compared with other treatment measures, which was 2.63 times that of platinumCT (OR=2.63; 95%CI: 2.00-3.45). The adverse events of grade 3 or higher in immunotherapy (ATE, PEM, durvalumab) was significantly lower than other treatment measures. Conclusions: PEM+EV can significantly prolong OS and PFS compared with other treatments, and has a higher ORR. The adverse events of grade 3 or higher of ATE was the lowest. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024525372, identifier CRD42024525372.