Search Results (1,906)

Background/Objectives: Cannabinoid use is rising among patients undergoing spinal fusion, yet its influence on bone healing is poorly defined. The endocannabinoid system (ECS)—through cannabinoid receptors 1 (CB1) and 2 (CB2)—modulates skeletal metabolism. We reviewed preclinical, mechanistic and clinical evidence to clarify how individual cannabinoids affect fracture repair and spinal arthrodesis. Methods: PubMed, Web of Science and Scopus were searched from inception to 31 May 2025 with the terms “cannabinoid”, “CB1”, “CB2”, “spinal fusion”, “fracture”, “osteoblast” and “osteoclast”. Animal studies, in vitro experiments and clinical reports that reported bone outcomes were eligible. Results: CB2 signaling was uniformly osteogenic. CB2-knockout mice developed high-turnover osteoporosis, whereas CB2 agonists (HU-308, JWH-133, HU-433, JWH-015) restored trabecular volume, enhanced osteoblast activity and strengthened fracture callus. Cannabidiol (CBD), a non-psychoactive phytocannabinoid with CB2 bias, accelerated early posterolateral fusion in rats and reduced the RANKL/OPG ratio without compromising final union. In contrast, sustained or high-dose Δ⁹-tetrahydrocannabinol (THC) activation of CB1 slowed chondrocyte hypertrophy, decreased mesenchymal-stromal-cell mineralization and correlated clinically with 6–10% lower bone-mineral density and a 1.8–3.6-fold higher pseudarthrosis or revision risk. Short-course or low-dose THC appeared skeletal neutral. Responses varied with sex, age and genetic background; no prospective trials defined safe perioperative dosing thresholds. Conclusions: CB2 activation and CBD consistently favor bone repair, whereas chronic high-THC exposure poses a modifiable risk for nonunion in spine surgery. Prospective, receptor-specific trials stratified by THC/CBD ratio, patient sex and ECS genotype are needed to establish evidence-based cannabinoid use in spinal fusion. Full article

Background: Mobile health applications have emerged as a novel tool to support secondary prevention after myocardial infarction (MI) or percutaneous coronary intervention (PCI). However, the impact of app-based interventions on clinically meaningful outcomes such as hospital readmissions remains uncertain. Objective: To systematically evaluate the effectiveness of smartphone app-based interventions in reducing unplanned hospital readmissions among post-MI/PCI patients. Methods: A systematic search of PubMed was conducted for randomized controlled trials published between January 2020 and April 2025. Eligible studies evaluated smartphone apps designed for secondary cardiovascular prevention and reported on unplanned hospital readmissions. Risk ratios (RRs) and 95% confidence intervals (CIs) were pooled using a random-effects model. Subgroup analyses were performed based on follow-up duration and user adherence. Results: Four trials encompassing 827 patients met inclusion criteria. App-based interventions were associated with a significant reduction in unplanned hospital readmissions compared to standard care (RR 0.45; 95% CI: 0.23–0.89; p = 0.0219). Greater benefits were observed in studies with longer follow-up durations and higher adherence rates. Improvements in patient-reported outcomes, including health-related quality of life, were also documented. Heterogeneity was moderate. Major adverse cardiovascular events (MACEs) were reported in only two studies and were not analyzed due to inconsistent definitions and low event rates. Conclusions: Smartphone applications for post-MI/PCI care are associated with reduced unplanned hospital readmissions and improved patient-reported outcomes. These tools may play a meaningful role in future cardiovascular care models, especially when sustained engagement and personalized features are prioritized. Full article

Background: Ingestion of dietary fibers (DFs) is a safe and accessible intervention associated with reductions in blood pressure (BP) and cardiovascular mortality. However, the mechanisms underlying the antihypertensive effects of DFs remain poorly defined. This systematic review and meta-analysis evaluates how DFs influence BP regulation by modulating gut microbial composition and enhancing short-chain fatty acid (SCFA) production. Methods: MEDLINE and EMBASE were systematically searched for interventional studies published between January 2014 and December 2024. Eligible studies assessed the effects of DFs or other prebiotics on systolic BP (SBP) and diastolic BP (DBP) in addition to changes in gut microbial or SCFA composition. Results: Of the 3010 records screened, nineteen studies met the inclusion criteria (seven human, twelve animal). A random-effects meta-analysis was conducted on six human trials reporting post-intervention BP values. Prebiotics were the primary intervention. In hypertensive cohorts, prebiotics significantly reduced SBP (−8.5 mmHg; 95% CI: −13.9, −3.1) and DBP (−5.2 mmHg; 95% CI: −8.5, −2.0). A pooled analysis of hypertensive and non-hypertensive patients showed non-significant reductions in SBP (−4.5 mmHg; 95% CI: −9.3, 0.3) and DBP (−2.5 mmHg; 95% CI: −5.4, 0.4). Animal studies consistently showed BP-lowering effects across diverse etiologies. Prebiotic interventions restored bacterial genera known to metabolize DFs to SCFAs (e.g., Bifidobacteria, Akkermansia, and Coprococcus) and increased SCFA levels. Mechanistically, SCFAs act along gut–organ axes to modulate immune, vascular, and neurohormonal pathways involved in BP regulation. Conclusions: Prebiotic supplementation is a promising strategy to reestablish BP homeostasis in hypertensive patients. Benefits are likely mediated through modulation of the gut microbiota and enhanced SCFA production. Full article

Background: Immunization is a highly effective intervention for controlling over 20 life-threatening infectious diseases, significantly reducing both morbidity and mortality rates. One notable achievement in vaccination efforts was the global eradication of smallpox, which the World Health Assembly declared on 8 May 1980. Additionally, there has been a remarkable 99.9% reduction in wild poliovirus cases since 1988, decreasing from more than 350,000 cases that year to just 30 cases in 2022. Objectives: The objective of this review was to assess the effects of various interventions designed to increase vaccination uptake among adults. Search Methods: A thorough search was conducted in the CENTRAL, Embase Ovid, Medline Ovid, PubMed, Web of Science, and Global Index Medicus databases for primary studies. This search was conducted in August 2021 and updated in November 2024. Selection Criteria: Randomized trials were eligible for inclusion in this review, regardless of publication status or language. Data Analysis: Two authors independently screened the search outputs to select potentially eligible studies. Risk ratios (RR) with 95% confidence intervals (CI) were calculated for each randomized controlled trial (RCT). A meta-analysis was conducted using a random-effects model, and the quality of the evidence was assessed using the GRADE approach. Main Results: A total of 35 randomized controlled trials met the inclusion criteria and were included in this review, with the majority conducted in the United States. The interventions targeted adults aged 18 and older who were eligible for vaccination, involving a total of 403,709 participants. The overall pooled results for interventions aimed at increasing influenza vaccination showed a risk ratio of 1.41 (95% CI: 1.15, 1.73). Most studies focused on influenza vaccination (18 studies), while the remaining studies examined various other vaccines, including those for hepatitis A, COVID-19, hepatitis B, pneumococcal disease, tetanus, diphtheria, pertussis (Tdap), herpes zoster, and human papillomavirus (HPV). The results indicate that letter reminders were slightly effective in increasing influenza vaccination uptake compared to the control group (RR: 1.75, 95% CI: 0.97, 1.16; 6 studies; 161,495 participants; low-certainty evidence). Additionally, participants who received education interventions showed increased levels of influenza vaccination uptake compared to those in the control group (RR: 1.88, 95% CI: 0.61, 5.76; 3 studies; 1318 participants; low-certainty evidence). Furthermore, tracking and outreach interventions also led to an increase in influenza vaccination uptake (RR: 1.87, 95% CI: 0.78, 4.46; 2 studies; 33,752 participants; low-certainty evidence). Conclusions: Letter reminders and educational interventions targeted at recipients are effective in increasing vaccination uptake compared to control groups. Full article

Background: Mesenchymal stem cells (MSCs), multipotent and immune-regulatory cells derived from tissues such as bone marrow, dental pulp, and periodontal ligament, emerged as promising agents in regenerative dentistry. Their clinical applications include endodontic tissue regeneration, periodontal healing, and alveolar bone repair, addressing critical challenges in dental tissue restoration. Methods: A systematic review was conducted following PRISMA guidelines and registered in PROSPERO. We searched PubMed, Scopus, and Web of Science databases for open-access, English-language clinical trials and observational studies published from 2015 to 2025. Studies focusing on the application of MSCs in dental tissue regeneration were included based on predefined eligibility criteria. Results: Out of 2400 initial records, 13 studies met the inclusion criteria after screening and eligibility assessment. Most studies investigated MSCs derived from dental pulp and periodontal ligament for regenerating periodontal tissues and alveolar bone defects. The majority reported improved clinical outcomes; however, variations in MSC sources, delivery methods, sample sizes, and follow-up periods introduced methodological heterogeneity. Conclusions: MSCs show significant potential in enhancing bone and periodontal regeneration in dental practice. Nonetheless, the current evidence is limited by small sample sizes, short follow-up, and inconsistent methodologies. Future large-scale, standardized clinical trials are required to validate MSC-based regenerative therapies and optimize treatment protocols. Full article

Background/Objectives: Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest solid tumors, with a five-year overall survival rate below 10%. While the introduction of multi-agent chemotherapy regimens has improved outcomes marginally, most patients with advanced disease continue to have limited therapeutic options. Molecular profiling has uncovered actionable genomic alterations in select subgroups of PDAC, yet the clinical impact of targeted therapies remains modest. This review aims to provide a clinically oriented synthesis of emerging molecular targets in PDAC, their therapeutic relevance, and practical considerations for biomarker testing, including current FDA and EMA indications. Methods: A narrative review was conducted using data from PubMed, Embase, Scopus, and international guidelines (NCCN, ESMO, ASCO). The selection focused on evidence published between 2020 and 2025, highlighting molecularly defined PDAC subsets and the current status of targeted therapies. Results: Actionable genomic alterations in PDAC include KRAS G12C mutations, BRCA1/2 and PALB2-associated homologous recombination deficiency, MSI-H/dMMR status, and rare gene fusions involving NTRK, RET, and NRG1. While only a minority of patients are eligible for targeted treatments, early-phase trials and real-world data have shown promising results in these subgroups. Testing molecular profiling is increasingly standard in advanced PDAC. Conclusions: Despite the rarity of targetable mutations, systematic molecular profiling is critical in advanced PDAC to guide off-label therapy or clinical trial enrollment. A practical framework for identifying and acting on molecular targets is essential to bridge the gap between precision oncology and clinical management. Full article

Current research reported that the number of clinical studies found for botulinum toxin (BoNT) key effects on biochemical biomarkers in head and neck chronic conditions linked to inflammation was very low. There are no systematic reviews of animal studies on this topic, and hence our review aimed to evaluate the quality of the preclinical evidence. We searched PubMed, Scopus, and Web of Science databases, and registries up to 29 January 2024. There were 22 eligible records, and data were available for 11 randomised controlled trials. There were concerns about the risk of bias and great variations of data obtained regarding chronic conditions, which included mostly trigeminal neuralgia. The leading biomarkers were proinflammatory cytokines (IL-1β, TNF-α) and synaptosomal-associated protein-25 (SNAP25), followed by neuron activation marker c-Fos and calcitonin gene-related peptide (CGRP). Overall, data found that BoNT significantly altered the under/over-expression of biomarkers evoked by the investigated disease models and had no effect when the levels of these biomarkers were not changed by the induced chronic conditions in animals. However, there were some mixed results and exceptions, and the certainty evidence found was very low to low. Although the sample sizes detected significant effect size (p < 0.05), most studies are based on male inferior animals, which may limit the recommendations for clinical trials. This study is registered on PROSPERO (CRD42023432411). Full article

Background/Objectives: Tacrolimus, an immunosuppressant, is increasingly used topically in ophthalmology, particularly for conditions like vernal keratoconjunctivitis and post-keratoplasty rejection prophylaxis. This systematic review aims to evaluate the efficacy and safety of topical tacrolimus in these ocular conditions. Methods: A thorough search was conducted in PubMed and Cochrane Library for relevant studies published up to 16 March 2025. Studies were eligible for inclusion if they were randomized controlled trials investigating topical tacrolimus in human ocular disease, were published in English, and reported clearly defined outcomes. Exclusion criteria included non-randomized studies, animal studies, systemic treatments, non-English publications, and studies lacking clearly reported outcomes. Data regarding study design, patient demographics, intervention details, and outcomes were extracted and analyzed. The Cochrane risk-of-bias tool (RoB 2.0) was used to assess the risk of bias. Results: A total of 10 studies met the inclusion criteria, were retrieved, and were categorized as not highly biased after the risk-of-bias assessment. These studies were included in the systematic review, where a qualitative analysis took place. Our analysis revealed that the topical use of tacrolimus showed promising results, as it improved clinical signs and symptoms in most patients. In half of the studies, tacrolimus demonstrated superior efficacy compared to the control group, while in the remaining studies, it showed equivalent efficacy. Adverse effects, such as a burning sensation, were noted in 7/10 studies but were generally mild. The methodologies were somewhat heterogeneous, and some studies had small sample sizes. Conclusions: Topical tacrolimus shows promising effects in managing various ocular surface diseases. While randomized controlled trials provide evidence, further research with larger sample sizes is necessary to solidify its efficacy and safety profile compared to other immunosuppressants. Full article

Background/Objectives: Being overweight and obesity are major public health concerns that demand effective nutritional strategies for weight and body composition management. Beyond excess weight, these conditions are closely linked to chronic inflammation, oxidative stress, and gut dysbiosis, all of which contribute to cardiometabolic risk. Polyphenols—bioactive compounds in plant-based foods—may support improvements in body composition and metabolic health by modulating gut microbiota, reducing oxidative stress, and suppressing inflammation. This systematic review and meta-analysis aimed to evaluate the effects of polyphenol-rich interventions on gut microbiota composition, in combination with either oxidative stress or inflammatory biomarkers, and their potential impact on body composition in overweight or obese adults. Methods: A systematic search of PubMed, Scopus, Cochrane, and Web of Science was conducted through May 2025. Eligible randomized controlled trials included adults (BMI ≥ 25 kg/m²) receiving polyphenol-rich interventions, with reported outcomes on gut microbiota and at least one inflammatory or oxidative stress biomarker. Standardized mean differences (SMDs) were pooled using a random-effects model. Results: Thirteen trials (n = 670) met inclusion criteria. Polyphenol supplementation significantly reduced circulating lipopolysaccharides (LPSs; SMD = −0.56; 95% CI: −1.10 to −0.02; p < 0.04), indicating improved gut barrier function. Effects on cytokines (IL-6, TNF-α) and CRP were inconsistent. Catalase activity improved significantly (SMD = 0.79; 95% CI: 0.30 to 1.28; p < 0.001), indicating enhanced antioxidant defense. Gut microbiota analysis revealed increased butyrate (SMD = 0.57; 95% CI: 0.18 to 0.96; p < 0.001) and acetate (SMD = 0.42; 95% CI: 0.09 to 0.75; p < 0.01), supporting prebiotic effects. However, no significant changes were observed in BMI or body weight. Conclusions: Polyphenol supplementation in overweight or obese adults may reduce metabolic endotoxemia, boost antioxidant activity, and promote SCFAs production. Effects on inflammation and body weight remain unclear. Further long-term trials are needed. Full article

Time-restricted eating (TRE), a dietary strategy that aligns food intake with circadian rhythms, has emerged as a promising non-pharmacological approach for improving glycemic control in patients with type 2 diabetes. This systematic review and meta-analysis evaluated the effects of TRE on glycemic outcomes by analyzing eight randomized controlled trials involving 312 participants with type 2 diabetes or impaired fasting glucose. Meta-analyses of six eligible studies demonstrated that TRE significantly reduced fasting glucose (mean difference [MD]: −0.74 mmol/L; 95% CI: −1.13 to −0.36) and glycated hemoglobin (ΔHbA1c) (MD: −0.11%; 95% CI: −0.15 to −0.07) and increased time in range (TIR) for blood glucose (MD: +10.51%; 95% CI: 6.81 to 14.21). Improvements in fasting glucose and HbA1c were modest but consistent, while the increase in TIR showed no between-study heterogeneity, suggesting a robust and reproducible benefit of TRE on glycemic stability. These findings support the clinical feasibility and effectiveness of TRE as a dietary intervention in diabetes management. However, further high-quality trials with standardized protocols and longer follow-up are needed to confirm long-term efficacy and inform guidelines. Full article

Research results suggest the potential of topical adenosine as a hair-promoting agent. The aim of this study was to examine the available clinical evidence of the efficacy of topical adenosine products in hair loss. This systematic review was conducted in accordance with PRISMA and PICO guidelines and included articles indexed in PubMed, Scopus, and Web of Science. The strength of evidence was assessed according to the GRADE system. Wherever feasible, data were extracted for a meta-analysis. Among 8625 articles returned by the query, 7 clinical trials were identified of topical adenosine (lotion, shampoo) in hair loss. They unanimously reported on a reduction in hair loss and increase in hair density (strength of evidence very low to moderate). A meta-analysis of three eligible trials showed a tendency to increased hair density (OR = 1.03, 95% CI: 0.89–1.20, p = 0.68), an increase in thick hair (OR = 1.4, 95% CI: 0.82–2.38, p = 0.21) and a decrease in thin hairs (OR = 0.93, 95% CI: 0.61–1.43, p = 0.75) after 6 months of alopecia treatment with a 0.75% adenosine lotion. The results from clinical trials published until now suggest that topical adenosine increases hair thickness, reduces excessive hair loss, stimulates hair regrowth, and increases hair density. The overall strength of evidence remains low due to flawed design and small sample sizes in most trials. Nevertheless, topical adenosine products seem worth trying, especially in the case of contraindications or adverse effects to approved medicinal products for hair loss. Further, better designed trials of adenosine in hair loss are warranted. Full article

Ergogenic supplements are becoming increasingly popular in the diet of trained individuals, due to their potential benefits. Ashwagandha (Withania somnifera) is one of the supplements that has recently grown in popularity. Despite growing interest, its scientific background remains limited and sometimes inconsistent. Objective: This overview of systematic reviews aimed to evaluate the effects of Ashwagandha supplementation on sports performance and health-related outcomes. Methods: A systematic literature search was carried out on the following electronic databases: PUBMed, Scopus, Academic Search Complete, SPORTDiscus, Web of Science, and Google Scholar, using the search terms “ashwagandha” and “systematic review” in the title or abstract of the publication in July 2024. The eligibility of the articles was assessed using the PICOS (Population, Intervention, Comparator, Outcomes, and Study Design) approach, and risk of bias was assessed using the AMSTAR-2 checklist. Results: Of the 2388 systematic reviews found, 11 met the inclusion criteria, which included 151 original studies representing 9005 individuals. Findings suggest that Ashwagandha supplementation may improve various aspects of sports performance, such as endurance and muscular strength, as well as health-related outcomes, including anxiety reduction, improved sleep quality, and enhanced sexual function. The most commonly used doses of Ashwagandha supplementation are between 500 mg and 1000 mg a day. Conclusion: While current evidence indicates promising effects of Ashwagandha on physical and psychological parameters, further high-quality randomized controlled trials are needed. Therefore, its use in athletes or healthy individuals should be considered with caution and based on individual needs. Full article

Deep margin elevation (DME) is a widely adopted technique for managing subgingival cervical proximal margins by repositioning them to a supragingival location. This approach enhances access, visibility, and control in these anatomically challenging areas. This narrative review aimed to evaluate current evidence on the indications, materials, clinical protocols, and outcomes of DME. A structured search was conducted in PubMed, the Cochrane Library and Scopus up to February 2025, using keywords such as “deep margin elevation”, “proximal box elevation” and “subgingival margin.” Clinical studies, in vitro investigations, relevant reviews and reports in English were included. A total of 59 articles were selected based on eligibility criteria. The hypothesis was that DME can serve as a reliable alternative to surgical crown lengthening in appropriate cases. A variety of materials have been investigated for use as the intermediate layer, with composite resins of varying viscosities and filler compositions being preferred due to their favorable long-term mechanical properties. DME may reduce the need for surgical intervention while maintaining periodontal health; however further randomized clinical trials are needed to clarify the material selection, establish long-term outcomes, and standardize clinical protocols. Understanding the indications, limitations, and protocol of DME is critical for achieving biologically sound and predictably functional restorations. Full article

Background and Objectives: Peptide receptor radionuclide therapy (PRRT) using radiopharmaceuticals labelled with Lutetium-177 is currently a therapeutic option for patients with advanced neuroendocrine neoplasms overexpressing somatostatin receptors (SSTRs). One promising option that has gained interest for PRRT is using alpha-emitting radioisotopes such as Actinium-225. The aim of this study was to perform a systematic review and meta-analysis on the efficacy and safety of radioligand therapy with Actinium-225 DOTATATE in advanced, metastatic or inoperable neuroendocrine neoplasms. Materials and Methods: A comprehensive literature search of studies on radioligand therapy with Actinium-225 DOTATATE in neuroendocrine neoplasms was carried out. Three different bibliographic databases (Cochrane Library, Embase, and PubMed/MEDLINE) were screened up to May 2025. Eligible articles were selected, relevant data were extracted, and the main findings on efficacy and safety are summarized through a systematic review. Furthermore, proportional meta-analyses on the disease response rate and disease control rate were performed. Results: Five studies (153 patients) published from 2020 were included in the systematic review. The pooled disease response rate and disease control rate of radioligand therapy using Actinium-225 DOTATATE were 51.6% and 88%, respectively. This treatment was well-tolerated in most patients with advanced, metastatic or inoperable neuroendocrine neoplasms. Conclusions: Radioligand therapy with Actinium-225 DOTATATE in advanced, metastatic or inoperable neuroendocrine neoplasms is effective with an acceptable toxicity profile and potential advantages compared with SSTR-ligands labelled with Lutetium-177. Currently, the number of published studies on this treatment is still limited, and results from multicenter randomized controlled trials are needed to translate this therapeutic option into clinical practice. Full article

Background/Objectives: Parkinson’s disease (PD) is a neurodegenerative disorder that impairs mobility. Treadmill training (TT) is a common rehabilitation strategy for improving gait parameters in individuals with PD. This systematic review evaluated the effectiveness of TT in improving motor function, walking ability, and overall functional mobility in PD patients. Methods: We compared TT to other forms of gait and motor rehabilitation, including conventional and robotic gait training. Trials that compared a treadmill training group with a non-intervention group were excluded from this review. We searched multiple databases for RCTs involving Parkinson’s patients until January 2025. The primary outcomes were motor function (UPDRS-III) and walking ability (6 MWT and TUG test). Results: We identified 285 articles; 199 were excluded after screening. We assessed the full text of 86 articles for eligibility, and 13 RCTs met the inclusion criteria. Some of them were included in the meta-analysis. The TT group showed a significant improvement in UPDRS-III scores [mean difference (MD): −1.36 (95% CI: −2.60 to −0.11)] and greater improvement in TUG performance [MD, −1.75 (95% CI: −2.69 to −0.81)]. No significant difference in walking capacity as assessed through the 6 MWT was observed [MD: 26.03 (95% CI: −6.72 to 58.77). Conclusions: The current study suggests that TT is effective in improving the motor symptoms and functional mobility associated with PD. Further studies are needed to develop protocols that consider the patients’ clinical characteristics, disease stage, exercise tolerance, and respiratory function. Full article