BACKGROUND: Resveratrol is a non-flavonoid polyphenol that shows promise in reducing pro-inflammatory factors and maintaining endothelial function, which hints at its potential role in slowing atherosclerosis and preventing acute coronary events.
OBJECTIVE: To study the cardioprotective effects of resveratrol on inflammatory mediators and endothelial function in patients with coronary artery disease (CAD).
METHODS: A thorough search was conducted in databases (Cochrane Library, ProQuest, PubMed, LILACS, ScienceDirect, Springer, Taylor&Francis, CNKI, Wanfang, and Weipu) until September 24, 2023. The vasopro-inflammatory mediators, endothelial function and outcomes related to cardiovascular events were observed. Titles and abstracts were assessed, and bias was evaluated with Cochrane RoB 2.0. Heterogeneity of results was explored by meta-regression, certainty of evidence was assessed by the GRADE system, and conclusive evidence was enhanced by trial sequence analysis.
RESULTS: Ten randomized controlled trials and 3 animal studies investigated resveratrol\'s impact on inflammatory mediators and endothelial function. In primary prevention studies, meta-analysis showed a significant reduction (95% CI: -0.73 to -0.20; P=0.0005) in tumor necrosis factor-α (TNF-α) expression with resveratrol, demonstrating a dose-dependent relationship. No significant difference was observed in interleukin-6 (IL-6) expression with P=0.58 for primary prevention and P=0.57 for secondary prevention. Vascular endothelial nitric oxide synthase (eNOS) expression was significantly increased after resveratrol pre-treatment following CAD events. Secondary prevention studies yielded no significant results; however, meta-regression identified associations between age, hypertension, and lower doses with the extent of TNF-α alterations. High certainty of evidence supported TNF-α reduction, while evidence for IL-6 reduction and eNOS elevation was deemed low.
CONCLUSIONS: Resveratrol reduces TNF-α in individuals at risk for CAD, specifically 15 mg per day. However, its usefulness in patients with confirmed CAD is limited due to factors such as age, high blood pressure, and insufficient dosage. Due to the small sample size, the reduction of IL-6 is inconclusive. Animal studies suggest that resveratrol enhances endothelial function by increasing eNOS. (PROSPERO registration No. CRD42023465234).

Nowadays, it has become clear that extracellular vesicles (EVs) are not a cellular waste disposal vesicle but are an essential part of an intercellular communication system. Besides the use of EVs in biomarker studies and diagnostics, the potential of EV-therapeutics has been seen by many. They provide unique properties for disease therapy, including strong immune-modulatory actions, the possibility of engineering, low immunogenicity, and the capability of crossing biological barriers. Proof-of-concept of EV-therapeutics for various pathologies has been achieved in preclinical studies. However, clinical trials with EVs have only been emerging slowly. Here, we aim to provide a comprehensive overview of the current state-of-the-art concerning clinical studies using EVs in human therapy. By approaching the current knowledge in a systematic manner, we were able to include 21 reports for meta-analysis of safety and evaluation of efficacy outcomes. Overall, we have shown that EV-based therapy is safe with a low incidence of serious adverse events (SAE; 0.7% (95%-CI: 0.1-5.2%), and adverse events (AE; 4.4% (95%-CI: 0.7-22.2%). Subgroup analysis showed no significant difference in SAE when comparing autologous versus allogeneic administration, as well as engineered versus non-engineered EV products. A significantly higher number of AE was seen in autologous versus allogeneic administration. However, the clinical relevance remains questionable. Evaluation of the clinical outcomes of immunostimulatory, immunosuppressive or regenerative EV-therapies indicated improvement in the majority of treated patients. Despite these promising results, data need to be approached with caution due to a high heterogeneity in the EVs manufacturing methods, study design, and reporting of (S)AE. Overall, we conclude that EV-based therapy is safe and presents a promising opportunity in therapy. More efforts are needed in the standardization and harmonization of reporting of EV isolation and characterization data as well as in the reporting of (S)AE to allow inter-study comparison.

OBJECTIVE: This systematic review aimed to summarise and synthesise research conducted in psychiatric mother-baby units (MBUs) in relation to patients, their families, or staff, published from 1st January 2016 to 1st May 2024.
METHODS: Quantitative, qualitative, and mixed-method studies were included for review if they were published in peer-review journals in English and reported research on MBUs between January 2016 and May 2024. From the initial yield of 10,007 unique studies, 53 studies were included for review.
RESULTS: MBU research was found to more frequently investigate maternal characteristics rather than the benefits of MBU treatment compared to studies conducted prior to 2016. Most studies that did investigate impact of admission showed favourable results, however few follow-up studies and studies comparing MBU outcomes to other clinical settings were undertaken. Little research has been conducted to investigate the differential impacts of MBU admission on different diagnoses and long-term (>1 year) patient outcomes. There was a dearth of research investigating partners of women in MBUs and few studies conducted on infant outcomes.
CONCLUSIONS: MBUs were consistently found to improve mental health systems and mother-infant attachment in patients after admission. More research investigating patient support networks and child health, impact of diagnosis on outcomes, and studies with adequate follow-up are required.

OBJECTIVE: This systematic review aimed to investigate the occurrence of moderate and severe adverse drug reactions (ADRs) to antimicrobials among hospitalized children.
METHODS: The PubMed/Medline, Cochrane Library, Embase, Web of Science, Scopus, Lilacs and CINAHL databases were searched in April 2023 to systematically review the published data describing the characteristics of moderate and severe ADRs to antimicrobials among hospitalized children. The search was carried out without date restrictions, up to the search date (April, 2023).
RESULTS: At the end of the selection process, 30 articles met the inclusion criteria. Cutaneous reactions were the primary serious clinical manifestations in most articles (19/30), followed by erythema multiforme (71 cases), Stevens-Johnson syndrome (72 cases), and toxic epidermal necrolysis (22 cases). The main antimicrobials involved in moderate and severe ADRs were penicillins, cephalosporins and sulfonamides. Regarding the primary outcomes, 30% (9/30) of the articles reported deaths, and 46.7% (14/30) of studies reported increased lengths of hospital stay, need for intensive care, and transfer to another hospital. Regarding the main interventions, 10% (3/30) of the articles mentioned greater monitoring, suspension, medication substitution or prescription of specific medications for the symptomatology.
CONCLUSIONS: The findings of this review could be used to identify areas for improvement and help health professionals and policymakers develop strategies. In addition, we emphasize the importance of knowing about ADRs so that there is adequate management to avoid undesirable consequences.

Asthma and chronic obstructive pulmonary disease are chronic respiratory disorders characterized by airways obstruction and chronic inflammation. Exacerbations lead to worsening of symptoms and increased airflow obstruction in both airways diseases, and they are associated with increase in local and systemic inflammation. Exosomes are cell-derived membrane vesicles containing proteins, lipids, and nucleic acids that reflect their cellular origin. Through the transfer of these molecules, exosomes act as mediators of intercellular communication. Via selective delivery of their contents to target cells, exosomes have been proved to be involved in regulation of immunity and inflammation. Although, exosomes have been extensively investigated in different diseases, little is currently known about their role in asthma and COPD pathogenesis, and particularly in exacerbations. This review aims to systemically assess the potential role of exosomes in asthma and COPD exacerbations.

UNASSIGNED: Diabetic gastroparesis is a common complication in patient with diabetes. Dietary intervention has been widely used in the treatment of diabetic gastroparesis. The aim of this study is to evaluate the role of diet in the treatment of diabetic gastroparesis.
UNASSIGNED: This systematic review was conducted a comprehensive search of randomized controlled trials using dietary interventions for the treatment of diabetic gastroparesis up to 9 November 2023. The primary outcomes were gastric emptying time and clinical effect, while fasting blood glucose, 2-hour postprandial blood glucose and glycosylated hemoglobin were secondary outcomes. Data analysis was performed using RevMan 5.4 software, and publication bias test was performed using Stata 15.1 software.
UNASSIGNED: A total of 15 randomized controlled trials involving 1106 participants were included in this review. The results showed that patients with diabetic gastroparesis benefit from dietary interventions (whether personalized dietary care alone or personalized dietary care+routine dietary care). Compared with routine dietary care, personalized dietary care and personalized dietary care+routine dietary care can shorten the gastric emptying time, improve clinical efficacy, and reduce the level of fasting blood glucose, 2-hour postprandial blood glucose and glycosylated hemoglobin.
UNASSIGNED: Limited evidence suggests that dietary intervention can promote gastric emptying and stabilize blood glucose control in patients with diabetic gastroparesis. Dietary intervention has unique potential in the treatment of diabetic gastroparesis, and more high-quality randomized controlled trials are needed to further validate our research results.
UNASSIGNED: https://www.crd.york.ac.uk/prospero/, identifier CRD42023481621.

Background: Natural products are widely used for primary insomnia (PI). This systematic review with trial sequential analysis (TSA) aimed to summarize evidence pertaining to the effectiveness and safety of Zao Ren An Shen (ZRAS) prescription, a commercial Chinese polyherbal preparation, for treating PI. Methods: Controlled clinical trials appraising ZRAS compared to controls or as an add-on treatment were systematically searched across seven databases until January 2024. Cochrane ROB 2.0 and ROBINS-I tools were adopted to determine risk of bias. Quality of evidence was assessed using the GRADE framework. Results: We analyzed 22 studies, involving 2,142 participants. The effect of ZRAS in reducing Pittsburgh Sleep Quality Index scores was found to be comparable to benzodiazepines [MD = 0.39, 95%CI (-0.12, 0.91), p = 0.13] and superior to Z-drugs [MD = -1.31, 95%CI (-2.37, -0.24), p = 0.02]. The addition of ZRAS to hypnotics more significantly reduced polysomnographically-recorded sleep onset latency [MD = -4.44 min, 95%CI (-7.98, -0.91), p = 0.01] and number of awakenings [MD = -0.89 times, 95%CI (-1.67, -0.10), p = 0.03], and increased total sleep time [MD = 40.72 min, 95%CI (25.14, 56.30), p < 0.01], with fewer adverse events than hypnotics alone. TSA validated the robustness of these quantitative synthesis results. However, the quality of evidence ranged from very low to low. The limited data available for follow-up did not support meta-synthesis. Conclusion: While ZRAS prescription shows promising effectiveness in treating PI, the overall quality of evidence is limited. Rigorously-designed randomized control trials are warranted to confirm the short-term efficacy of ZRAS and explore its medium-to-long-term efficacy. Systematic Review Registration: (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=471497), identifier (CRD42023471497).

UNASSIGNED: To systematically review existing literature regarding the ankle ligament reconstruction-return to sport after injury (ALR-RSI) scale and to assess its correlation with Return to sport and functional outcomes as well as feasibility, reliability and consistency.
UNASSIGNED: A systematic review of the literature based on the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) was conducted using PubMed, Embase and Cochrane Library. Studies that evaluated psychological readiness to return to sport after ankle ligament reconstruction or repair for the treatment of chronic lateral ankle instability using the ALR-RSI scale were included. The results from each study were pooled, and weighted means and overall rates were calculated.
UNASSIGNED: In total, 157 patients (53.2% male, mean age: 34.2 years) from three articles were included. Overall, 85.0% of patients reported successful return to sport, but only 48.9% of patients returned to the preoperative sporting level. All studies reported a significant difference in psychological scores between patients who returned to sport and those who did not. Pooled mean patient-reported outcome measures, reported as the American Orthopaedic Foot and Ankle Society Ankle-Hindfoot (AOFAS, three studies) Score and Karlsson-Peterson Score (three studies), were 82.7 (range: 29-100) and 81.7 (range: 25-100), respectively. The ALR-RSI scale demonstrated strong correlations with the AOFAS Score and Karlsson-Peterson Score.
UNASSIGNED: Patients who returned to sport after ankle ligament reconstruction or repair exhibited higher psychological readiness compared to those who did not. The ALR-RSI scale showed strong correlations with ankle function. Evaluation of psychological readiness using the ALR-RSI scale may provide an additional tool in the assessment of patients who underwent ankle ligament reconstruction or repair.
UNASSIGNED: Level III, systematic review.

Patients with monogenic obesity display numerous medical features on top of hyperphagic obesity, but no study to date has provided an exhaustive description of their semiology. Two reviewers independently conducted a systematic review of MEDLINE, Embase, and Web of Science Core Collection databases from inception to January 2022 to identify studies that described symptoms of patients carrying pathogenic mutations in at least one of eight monogenic obesity genes (ADCY3, LEP, LEPR, MC3R, MC4R, MRAP2, PCSK1, and POMC). Of 5207 identified references, 269 were deemed eligible after title and abstract screening, full-text reading, and risk of bias and quality assessment. Data extraction included mutation spectrum and mode of inheritance, clinical presentation (e.g., anthropometry, energy intake and eating behaviors, digestive function, puberty and fertility, cognitive features, infectious diseases, morphological characteristics, chronic respiratory disease, and cardiovascular disease), biological characteristics (metabolic profile, endocrinology, hematology), radiological features, and treatments. The review provides an exhaustive description of mandatory, non-mandatory, and unique symptoms in heterozygous and homozygous carriers of mutation in eight monogenic obesity genes. This information is critical to help clinicians to orient genetic testing in subsets of patients with suspected monogenic obesity and provide actionable treatments (e.g., recombinant leptin and MC4R agonist).

BACKGROUND: Ventilator-associated pneumonia (VAP) is a prevalent and grave hospital-acquired infection that affects mechanically ventilated patients. Diverse diagnostic criteria can significantly affect VAP research by complicating the identification and management of the condition, which may also impact clinical management.
OBJECTIVE: We conducted this review to assess the diagnostic criteria and the definitions of the term \"ventilator-associated\" used in randomised controlled trials (RCTs) of VAP management.
METHODS: Based on the protocol (PROSPERO 2019 CRD42019147411), we conducted a systematic search on MEDLINE/PubMed and Cochrane CENTRAL for RCTs, published or registered between 2010 and 2024.
METHODS: We included completed and ongoing RCTs that assessed pharmacological or non-pharmacological interventions in adults with VAP.
METHODS: Data were collected using a tested extraction sheet, as endorsed by the Cochrane Collaboration. After cross-checking, data were summarised in a narrative and tabular form.
RESULTS: In total, 7,173 records were identified through the literature search. Following the exclusion of records that did not meet the eligibility criteria, 119 studies were included. Diagnostic criteria were provided in 51.2% of studies, and the term \"ventilator-associated\" was defined in 52.1% of studies. The most frequently included diagnostic criteria were pulmonary infiltrates (96.7%), fever (86.9%), hypothermia (49.1%), sputum (70.5%), and hypoxia (32.8%). The different criteria were used in 38 combinations across studies. The term \"ventilator-associated\" was defined in nine different ways.
CONCLUSIONS: When provided, diagnostic criteria and definitions of VAP in RCTs display notable variability. Continuous efforts to harmonise VAP diagnostic criteria in future clinical trials are crucial to improve quality of care, enable accurate epidemiological assessments, and guide effective antimicrobial stewardship.