Search Results (198)

Background/Objectives: Anterior cruciate ligament (ACL) injuries continue to present significant clinical and rehabilitative challenges. Despite advances in surgical techniques and rehabilitation protocols, persistent reinjury rates and increased pressure for early return to sport require a critical reassessment of current practices. This narrative review provides a comprehensive overview of the evolution, current standards, and future directions of ACL surgery and rehabilitation. Content: The literature search was conducted primarily in PubMed/MEDLINE and Web of Science using ACLRelated keywords, with emphasis on systematic reviews, randomized controlled trials, registry data, and consensus guidelines published within the past two decades. The evolution of ACL treatment is shaped by the transition from open to arthroscopic and anatomic reconstructions, as well as the refinement of fixation and augmentation techniques. In parallel, rehabilitation concepts shifted from rigid, time-based schedules to criteria-driven, individualized approaches. Key aspects include early mobilization, prehabilitation, and the integration of innovative tools such as anti-gravity treadmill and blood flow restriction training. Evidence on bracing suggests no routine benefit, while structured prevention programs have proven effective. Return-to-play strategies now emphasize objective functional criteria and psychological readiness. Conclusions: ACL therapy has evolved toward personalized, function-oriented rehabilitation. Future developments—including markerless motion analysis, AI-supported rehabilitation, and digital health applications promise for further individualization of care and optimization of long-term outcomes. Full article

Background: Preoperative clear fluid fasting is intended to reduce aspiration risk, but prolonged abstinence may impair hydration, comfort, and cardiovascular stability. Arterial hypotension during anesthesia induction is a common perioperative complication, and its association with fasting duration has become an important concern. The objective of this review was to evaluate the relationship between the duration of preoperative clear fluid fasting and the risk of arterial hypotension during anesthesia induction in both adult and pediatric populations. Methods: A structured PubMed search identified 17 studies, including randomized controlled trials, prospective cohorts, registry-based analyses, and interventional imaging investigations. Data were extracted on patient age, fasting duration, hypotension definitions, and monitoring modalities. Subgroups included adults, pediatric patients, and studies employing echocardiography or ultrasound to evaluate preload. Results: A total of 96,017 patients were included (77,978 adults; 17,685 children). In adults, fasting beyond two hours was associated with hypovolemia and a greater incidence of post-induction hypotension, while fasting of ≤2 h improved hemodynamic stability without increasing aspiration risk. Pediatric studies demonstrated fasting durations often exceeding 6–10 h, correlating with higher odds of hypotension and metabolic derangements. Liberalized regimens, including carbohydrate-containing fluids, were consistently safe. Ultrasound-based studies revealed increased inferior vena cava collapsibility and reduced ventricular filling after prolonged fasting, providing a mechanistic explanation for blood pressure instability. Conclusions: Prolonged preoperative fasting was not consistently an independent predictor of peri-induction hypotension in all populations; however, data from large adult and pediatric studies demonstrate that extended fasting increases hypotension risk through volume and metabolic depletion. These findings support the importance of liberalized fasting policies and proactive fluid optimization to reduce early hemodynamic instability during anesthesia induction. Full article

Objectives: The rapid aging of the U.S. population has raised concerns about age-related cognitive decline and Alzheimer’s disease. Therefore, we aimed to characterize diet quality, nutrient intake, and to examine the associations between specific dietary components and cognitive performance in older adults. Design: Cross-sectional observational study. Setting: Community-based recruitment. Participants: Data from 72 community-dwelling adults aged 65 years and older was analyzed. Measurements: Cognitive performance was assessed using subtests from the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) battery, evaluating episodic memory (Word List Memory/Recall/Recognition), visuospatial skills (Constructional Praxis), and executive function (Verbal Fluency). A composite cognitive score was calculated from memory and visuospatial subtests. Habitual dietary intake was evaluated using structured 24-h recalls to calculate nutrient intake and the Healthy Eating Index score, supplemented by the Short HEI questionnaire. Demographics, health history, depressive symptoms (Patient Health Questionnaire-9), and sleep quality (Pittsburgh Sleep Quality Index) were also collected. Results: Participants demonstrated suboptimal diet quality (mean HEI score 62.9 ± 10.69; recommended >80), with only 9.7% meeting fiber recommendations, 11% meeting calcium or vitamin A recommendations, and 1.4% meeting vitamin D requirements. In bivariate comparisons, higher cognitive performance was observed in younger participants (75.5 vs. 79.5 years; p < 0.01) and females (78% vs. 50%; p = 0.024). Regression models identified significant positive associations between cognitive scores and intakes of dietary fiber (p = 0.007), unsaturated fats (mono- and polyunsaturated; p = 0.012–0.033), protein (p = 0.018), carotenoids (α-carotene, p = 0.001; β-carotene, p = 0.026; lutein + zeaxanthin, p = 0.016), vitamins A (p = 0.044) and E (p = 0.034), and minerals including magnesium (p = 0.006), potassium (p = 0.004), copper (p = 0.008), zinc (p = 0.024), and calcium (p = 0.035). Refined grain intake was inversely associated with cognition (p = 0.011). Conclusions: In this population, dietary components like fiber and micronutrients were positively associated with better cognitive function, and the overall nutrient intake shortfalls observed highlight the need for targeted dietary interventions to support healthy brain aging. Therefore, this work advances our understanding by highlighting potential modifiable nutritional targets for clinical trials focused on delaying or preventing cognitive decline. Full article

Recurrence of the original glomerular disease (GN) poses a significant threat to kidney transplant function and longevity. The probability and severity of this recurrence vary, with C3 glomerulopathy and certain forms of FSGS exhibiting particularly high rates. Kidney transplant GN recurrence risk hinges on the characteristics of the initial GN, recipient/donor genetics, recipient age, donor type, end-stage kidney disease (ESRD) progression rate, and proteinuria levels. Standard immunosuppression has limited efficacy in preventing primary disease recurrence; however, agent selection and induction therapy can influence the risk for specific GNs. Diagnosing recurrent GN involves a comprehensive approach, including clinical evaluation, laboratory tests (such as proteinuria, hematuria, and specific biomarkers like anti-PLA2R for membranous nephropathy or complement for C3G), and, critically, an allograft biopsy analyzed with light, immunofluorescence, and electron microscopy. Treatment strategies are evolving towards targeted therapies, such as rituximab for antibody-mediated GN and complement inhibitors for C3G, moving away from broad immunosuppression. This narrative literature review provides practical monitoring algorithms for post-transplant settings, synthesizing information on the incidence, predictors, diagnostic strategies, and therapeutic options for various glomerular disease subtypes. The methodology involved searching MEDLINE, Embase, and Cochrane databases from 1996 to 2025, prioritizing systematic reviews, cohort studies, registries, and interventional reports. Eligibility criteria included adult transplant recipients and English-language reports on recurrent glomerular disease outcomes, excluding most single-patient case reports. Limitations include potential selection bias, omission of relevant studies, and the absence of a formal risk-of-bias assessment or meta-analysis. The evidence base is heterogeneous, with inconsistent outcome reporting and scarce randomized controlled trials. Future efforts should focus on developing predictive biomarkers, standardizing diagnostic and response criteria, conducting multicenter prospective cohorts and pragmatic trials, and creating shared registries with harmonized data. Full article

Background/Objectives:  Pneumocystis jirovecii pneumonia (PJP) remains a major cause of morbidity and mortality in immunocompromised patients. Bronchoalveolar lavage (BAL) is the diagnostic gold standard but is invasive and often impractical in critically ill patients. Oropharyngeal wash (OW) polymerase chain reaction (PCR) offers a rapid, non-invasive alternative. We performed a systematic review focusing on this respiratory sample’s diagnostic accuracy and clinical utility. Methods: We searched PubMed, Scopus, Web of Science, Cochrane Library, and clinical trial registries including ClinicalTrials.gov and MedRxiv for studies of PCR-based P. jirovecii detection in OW samples from immunocompromised adults, using BAL or induced sputum as reference standards. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology was followed. Quality was assessed with Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2), and pooled sensitivity/specificity were estimated using a bivariate random-effects model. Results: Twelve studies (n = 633; 346 confirmed PJP cases) met the inclusion criteria. Most cohorts were human immunodeficiency virus (HIV)-positive. Pooled sensitivity was 68.3% (95% CI: 59.2–75.9) and specificity 91.8% (95% CI: 85.9–95.3); the area under the summary receiver operating characteristic curve (AUC) was 0.887. Diagnostic yield improved with pre-sample cough induction, 60-s gargling, early sampling before extended therapy, and higher fungal loads. Risk of bias was low, and no significant publication bias was detected. Conclusions: OW-based PCR delivers high specificity and moderate sensitivity for PJP diagnosis, offering a safe, scalable, and patient-friendly alternative when invasive testing is unfeasible. Optimizing collection protocols and expanding evaluation to non-HIV immunosuppressed populations could enhance its role as an early screening tool, enabling faster treatment decisions and reducing unnecessary antimicrobial exposure. Full article

Background: Radiation exposure in the cardiac catheterization laboratory remains a critical occupational hazard for interventional cardiologists and staff, contributing to orthopedic injuries, cataracts, and malignancy. In parallel, procedural complexity continues to increase, demanding both precision and safety. Robotic-assisted percutaneous coronary intervention (R-PCI), alongside advanced shielding systems and imaging integration, has emerged as a transformative strategy to minimize radiation and enhance operator ergonomics. Objective: This state-of-the-art review synthesizes the current clinical evidence and technological advances that support a radiation-reduction paradigm in percutaneous coronary intervention (PCI), with a particular focus on the role of R-PCI platforms, procedural modifications, and emerging shielding technologies. Methods: We reviewed published clinical trials, registries, and experimental studies evaluating robotic PCI platforms, contrast and radiation dose metrics, ergonomic implications, procedural efficiency, and radiation shielding systems. Emphasis was given to the integration of CT-based imaging (coronary computed tomography angiography—CCTA, fractional flow reserve computed tomography—FFR-CT) and low-dose acquisition protocols. Results: R-PCI demonstrated technical success rates of 81–100% and clinical success rates up to 100% in both standard and complex lesions, with significant reductions in operator radiation exposure (up to 95%) and procedural ergonomic burden. Advanced shielding technologies offer radiation dose reductions ranging from 86% to nearly 100%, while integration of (CCTA), (FFR-CT), and Artificial Intelligence (AI) -assisted procedural mapping facilitates further fluoroscopy minimization. Robotic workflows, however, remain limited by lack of device compatibility, absence of haptic feedback, and incomplete integration of physiology and imaging tools. Conclusions: R-PCI, in combination with shielding technologies and imaging integration, marks a shift towards safer, radiation-minimizing interventional strategies. This transition reflects not only a technical evolution but a philosophical redefinition of safety, precision, and sustainability in modern interventional cardiology. Full article

Optic pathway glioma (OPG) is a rare pediatric low-grade glioma, frequently associated with neurofibromatosis type 1 (NF–1), that presents unique therapeutic challenges due to its anatomical location and its potential to impair vision, endocrine function, and developmental trajectories. Current clinical management prioritizes a multidisciplinary, patient-specific approach aimed at tumor control while preserving long-term quality of life. Strategies vary based on clinical presentation, ranging from observation in asymptomatic cases to chemotherapy for progressive or symptomatic tumors. Surgical and radiation options are limited due to potential risks and complications. In recent years, advances in molecular characterization have guided the development of targeted therapies, particularly MEK inhibitors, which demonstrate encouraging efficacy and reduced toxicity profiles. In parallel, investigational therapies including immunotherapy and precision medicine-based approaches are under clinical evaluation. This review provides a synthesis of current standard practices, emerging targeted treatments, and ongoing clinical trials, drawing on relevant literature and expert consensus to inform clinicians and families about available therapeutic options. Literature discussed in this review was identified through a non-systematic search of published articles, clinical trial registries, and authoritative guidelines, with selection based on relevance, clinical significance, and contribution to understanding current and emerging management strategies for OPG. Full article

Background/Objectives: SMARCA4-deficient or SMARCA4-mutated cancers are rare but highly aggressive tumors with poor differentiation, resistance to conventional treatments, and limited clinical guidance. While thoracic SMARCA4-deficient undifferentiated tumors are relatively well described, the full spectrum of SMARCA4-altered cancers across different organs and their therapeutic responses remains poorly understood. This study aimed to systematically review published case reports and case series to clarify the clinical characteristics, molecular features, treatment patterns, and survival outcomes of SMARCA4-altered malignancies. Methods: We conducted a systematic review of case reports and case series published between 2015 and 2025 using PubMed, Embase, and Web of Science. Eligible studies included adult patients with immunohistochemically or genetically confirmed SMARCA4-deficient or SMARCA4-mutated tumors. Key clinical, pathological, molecular, therapeutic, and outcome-related data were extracted. Descriptive statistics were used, and exploratory subgroup analyses were performed based on tumor type and treatment modality. The review protocol was registered in PROSPERO (CRD420251088805). Results: A total of 109 studies reporting 160 individual patients were included. Most tumors arose in the thorax (40.0%), followed by gastrointestinal (17.5%) and gynecologic sites (15.6%). The median age was 58 years, with a male predominance (70.0%) and frequent smoking history (44.4%). Platinum-based chemotherapy was administered in 62.5% of cases, and immune checkpoint inhibitors (ICIs) were used in 25.6%. Among ICI-treated patients, partial responses or stable disease were observed in 80.5%. The median progression-free survival (PFS) was 4.0 months, and the median overall survival (OS) was 5.0 months. Conclusions: SMARCA4-altered cancers are clinically and molecularly diverse but uniformly aggressive, with limited therapeutic benefit from conventional chemotherapy. Immune checkpoint inhibitors may offer improved outcomes in select patients, particularly those with thoracic tumors. Early molecular profiling, rare tumor registries, and biomarker-driven trials are crucial for guiding future treatment strategies. Full article

Background/Objectives: While the integration of artificial intelligence (AI) into clinical research is rapidly accelerating, a comprehensive analysis of the global AI clinical trial landscape has been limited. This study presents the first systematic characterization of AI-related clinical trials registered in the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). It aims to map global trends, identify patterns of concentration, and analyze the structure of international collaboration. Methods: A search of the WHO ICTRP was conducted on 20 June 2025. Following a two-stage screening process, the dataset was analyzed for temporal trends, geographic distribution, disease and technology categories, and international collaboration patterns using descriptive statistics and network analysis. Results: We identified 596 AI clinical trials across 62 countries, with registrations growing exponentially since 2020. The landscape is defined by extreme geographic concentration, with China accounting for the largest share of trial participations (35.6%), followed by the USA (8.5%). Research is thematically concentrated in Gastroenterology (22.8%) and Oncology (20.1%), with Diagnostic Support (45.6%) being the most common technology application. Formal international collaboration is critically low, with only 8.7% of trials involving multiple countries, revealing a fragmented collaboration landscape. Conclusions: The global AI clinical trial landscape is characterized by rapid but deeply imbalanced growth. This concentration and minimal international collaboration undermine global health equity and the generalizability of AI technologies. Our findings underscore the urgent need for a fundamental shift toward more inclusive, transparent, and collaborative research models to ensure the benefits of AI are realized equitably for all of humanity. Full article

Background: Thyroid eye disease (TED) is a rare autoimmune orbital disorder predominantly associated with Graves’ disease. It is characterized by orbital inflammation, tissue remodeling, and potential visual morbidity. Conventional therapies, particularly systemic glucocorticoids, offer only partial symptomatic relief, failing to reverse chronic structural changes such as proptosis and diplopia, and are associated with substantial adverse effects. This review aims to synthesize recent developments in understandings of TED pathogenesis and to critically evaluate emerging therapeutic strategies. Methods: A systematic literature review was conducted using MEDLINE, Embase, and international clinical trial registries focusing on pivotal clinical trials and investigational therapies targeting core molecular pathways involved in TED. Results: Current evidence suggests that TED pathogenesis is primarily driven by the autoimmune activation of orbital fibroblasts (OFs) through thyrotropin receptor (TSH-R) and insulin-like growth factor-1 receptor (IGF-1R) signaling. Teprotumumab, a monoclonal IGF-1R inhibitor and the first therapy approved by the U.S. Food and Drug Administration for TED, has demonstrated substantial clinical benefit, including improvements in proptosis, diplopia, and quality of life. However, concerns remain regarding relapse rates and treatment-associated adverse events, particularly hearing impairment. Investigational therapies, including next-generation IGF-1R inhibitors, small-molecule antagonists, TSH-R inhibitors, neonatal Fc receptor (FcRn) blockers, cytokine-targeting agents, and gene-based interventions, are under development. These novel approaches aim to address both inflammatory and fibrotic components of TED. Conclusions: Teprotumumab has changed TED management but sustained control and toxicity reduction remain challenges. Future therapies should focus on targeted, mechanism-based, personalized approaches to improve long-term outcomes and patient quality of life. Full article

Autologous therapies are currently being studied to determine if they can modulate the course of knee osteoarthritis symptoms and/or disease progression. One potential therapeutic target is the polarization of pro-inflammatory M1 macrophages to pro-healing M2 macrophages. The autologous therapy, Autologous Protein Solution (APS), was incubated with donor-matched human peripheral-derived macrophages for 10 days. M1 pro-inflammatory macrophages were determined by the percentage of CD80+ and M2 pro-healing macrophages were determined by CD68+ and CD163+ by epifluorescent microscopy. To determine clinical effectiveness, an APS-specific minimal clinically important improvement (MCII) using an anchor-based method was calculated in a randomized controlled trial of APS (n = 46) and then applied to a real-world registry study (n = 78) to determine the percentage of pain responders. Compared to control media, APS statistically increased the percentage of M2 macrophages and decreased the percentage of M1 macrophages, while platelet-poor plasma had no effect on polarization. In the randomized controlled trial (RCT), the MCII at the 12-month follow-up visit was calculated as 2.0 points on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scale and 7.5 points on the WOMAC function scale. Applying this MCII to the real-world registry data, 62.5% of patients met the MCII with an average of 4.7 ± 2.5 points of improvement in pain. Autologous therapies can influence macrophage polarization and have demonstrated clinical effectiveness in a real-world patient setting. 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: Perioperative care is an integral part of the procedure of a surgical operation, with strictly defined rules. The need to upgrade and improve some individual long-term processes aims at optimal patient care and the provision of high-level health services. Therefore, preoperative care is drawn up with new data resulting from the evolution of technology to upgrade the procedures that need improvement. According to the international literature, a factor considered to be of major importance is high preoperative anxiety and its effects on the patient’s postoperative course. High preoperative anxiety is postoperatively responsible for prolonged hospital stays, increased postoperative pain, decreased effect of anesthetic agents, increased amounts of analgesics, delayed healing of surgical wounds, and increased risk of infections. The use of Virtual Reality technology appears as a new method of managing preoperative anxiety. Objective: This study investigates the effect and effectiveness of Virtual Reality (VR) technology in managing preoperative anxiety in adult patients. Methods: A literature review was performed on 193 articles, published between 2017 and 2024, sourced from the scientific databases PubMed and Cochrane, as well as the trial registry ClinicalTrials, with a screening and exclusion process to meet the criterion of investigating VR technology’s effectiveness in managing preoperative anxiety in adult patients. This systematic review was conducted under the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020) guidelines. Results: Out of the 193 articles, 29 were selected. All articles examined the efficacy of VR in adult patients (≥18) undergoing various types of surgery. The studies represent a total of 2.354 participants from 15 countries. There are two types of VR applications: distraction therapy and patient education. From the studies, 14 (48%) used the distraction VR intervention, 14 (48%) used the training VR intervention, and 1 (4%) used both VR interventions, using a range of validated anxiety scales such as the STAI, VAS-A, APAIS, and HADS. Among the 29 studies reviewed, 25 (86%) demonstrated statistically significant reductions in preoperative anxiety levels following the implementation of VR interventions. VR technology appears to manage preoperative anxiety effectively. It is a non-invasive and non-pharmacological intervention with minimal side effects. Conclusions: Based on the review, the management of preoperative anxiety with VR technology shows good levels of effectiveness. Further investigation of the efficacy by more studies and randomized controlled trials, with a larger patient population, is recommended to establish and universally apply VR technology in the preoperative care process as an effective method of managing preoperative anxiety. Full article

Background/Objectives: There is a need for randomized clinical trials with higher quality, especially for older people at high risk of falls, with interventions that consider individual needs, comprehensiveness of care, and connection with primary health care. We designed a randomized controlled trial to examine the effects of a case management intervention combined with a physical exercise protocol on risk factors for falls, falls data, adherence, satisfaction, costs, and implementation in community-dwelling older adults with high risk of falls. Methods: A minimum of 60 community-dwelling older people with high falls risk will participate in the randomized controlled assessor-blinded trial (MAGIC—v. 2). The trial will be conducted in a regional health department of São Paulo state (Brazil), which includes 6 cities. Participants will be randomized to the Intervention Group (case management intervention based on all individual risk factors for falls identified by a multidimensional assessment, over 16 weeks, once a week, by telephone calls). Both groups will perform a physical exercise protocol based on falls prevention for 16 weeks (twice a week) in Health Units. The assessment will be performed at baseline, after 16 weeks of intervention, after 6-month follow-up, and after 12-month follow-up. Primary outcome measures include falls data and potentially modifiable risk factors for falls. Discussion: This study has the potential to facilitate the future implementation of the intervention based on case management with a focus on fall prevention in the health sectors. Trial registration: Brazilian Registry of Clinical Trials (ReBEC). Full article

Drug-induced nephrotoxicity is a common and serious problem in clinical practice. We conducted a systematic review of studies reporting nephrotoxicity events associated with antibiotics approved since 2018. The agents assessed included aztreonam/avibactam, cefepime/enmetazobactam, cefiderocol, ceftobiprole, contezolid, gepotidacin, imipenem/cilastatin/relebactam, lascufloxacin, lefamulin, levonadifloxacin, plazomicin, and sulbactam/durlobactam. Literature searches were conducted in PubMed, Scopus, Web of Science, and major pharmacovigilance databases (Vigibase, FAERS, EudraVigilance, EMA, FDA, NMPA, PMDA, and CDSCO) in May 2025, along with reference citation tracking. Studies were included if they reported safety or adverse event data. The risk of bias was assessed using validated tools in accordance with the study design. Out of 2105 potentially relevant records, 74 studies met inclusion criteria, comprising 52 clinical trials, 17 observational studies, 1 registry-based study, 3 case series, and 1 case report. Nephrotoxicity was rarely reported for any of the newly approved antibiotics. No renal adverse events were found in the available studies for aztreonam/avibactam, levonadifloxacin, and contezolid. Most studies were of moderate to high quality; two were classified as low quality. However, nephrotoxicity was inconsistently assessed, with variable definitions and methodologies used. Although current data suggest a low frequency of nephrotoxicity, limitations in study design and reporting preclude firm conclusions. There is a need for post-marketing studies to better characterize renal safety. Clinicians should remain vigilant and continue to monitor for and report renal-related adverse events. Full article