Search Results (5,204)

Background and Objectives: Parkinson’s disease (PD) is a progressive neurodegenerative disorder in which gait and balance disturbances substantially increase the risk of falls and loss of independence. Pharmacological treatment alleviates several motor symptoms but has limited effects on postural instability. Backward walking (BW), a demanding locomotor task, has recently been investigated as both an assessment tool and a rehabilitation strategy in PD. The purpose of this focused systematic review is to analyse the benefits and limitations of retro walking in relation to the gait parameters and balance control of PD patients. Materials and Methods: A structured literature search (2015–2025) was conducted across multiple databases in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines. Eligibility criteria, screening procedures, and qualitative synthesis methods were predefined. Nine studies (including two randomized controlled trials) met the inclusion criteria. Methodological quality was assessed using PEDro and ROBINS-I tools, and the certainty of evidence was evaluated using GRADE. Results: The research results indicate within-group improvements in balance and gait parameters following BW training. Some of the included studies also suggest that BW may be a sensitive marker of balance deficits and fall risk. However, the evidence is limited by small sample sizes, heterogeneity of interventions, and a predominance of non-randomized designs. Conclusions: Current evidence regarding BW in PD remains preliminary. While BW may be considered as a supplementary component of rehabilitation, its specific efficacy cannot be clearly distinguished from general exercise effects. Further high-quality randomized controlled trials with standardized protocols and long-term follow-up are required. Full article

Background/Objectives: Celiac disease (CD) is a chronic immune-mediated enteropathy triggered by gluten ingestion in genetically predisposed individuals, with a highly heterogeneous clinical presentation encompassing both intestinal and extraintestinal manifestations. Despite growing clinical awareness, diagnostic delay remains a significant challenge, and the evolution of clinical and histopathological features following gluten-free diet (GFD) initiation remains incompletely characterized. This study aimed to compare the clinical, serological, and histopathological profile of adults with newly diagnosed CD and those maintained on a long-term GFD. Methods: This prospective observational study enrolled 50 adult patients with biopsy-confirmed CD: 16 at the time of diagnosis (gluten-consuming) and 34 on a GFD for at least one year. All participants underwent standardized clinical assessment, serological testing (IgA anti-tissue transglutaminase [tTG] and/or IgA anti-endomysial antibodies [EMAs]), upper digestive endoscopy with duodenal biopsies graded according to the Marsh–Oberhuber classification, and evaluation for Helicobacter pylori co-infection. Between-group comparisons were performed using the Mann–Whitney U test, Fisher's exact test, and chi-square test, as appropriate. Results: Newly diagnosed patients exhibited a significantly longer median duration from symptom onset to diagnosis compared to the GFD group (p = 0.03). Histopathological severity was greater in the newly diagnosed group, with more advanced Marsh–Oberhuber grades (p = 0.03). Among individual symptoms, bloating was significantly more frequent in newly diagnosed patients (p = 0.02). Notably, thrombocytosis was identified significantly more often in the newly diagnosed group compared to GFD patients (p = 0.02), representing a potentially underrecognized extraintestinal marker of active CD. Overall rates of intestinal and extraintestinal manifestations and CD-specific seropositivity did not differ significantly between groups. Conclusions: The clinical and histopathological profile of adults with celiac disease differs meaningfully between the time of diagnosis and during GFD adherence. Bloating and thrombocytosis were significantly more prevalent at diagnosis, with thrombocytosis emerging as a potentially underrecognized marker of active disease. Conversely, several manifestations persisted despite dietary treatment, underscoring the heterogeneous nature of CD across its clinical course. These findings may support earlier disease recognition and more individualized follow-up strategies in routine clinical practice. Full article

Background: High infectious disease burden and uncontrolled antibiotic usage across human, animal, and environmental contaminants make antimicrobial resistance (AMR) a growing public health problem in Africa. Mobile genetic elements (MGEs) such plasmids, transposons, integrons, conjugative elements, and phages help spread AMR via horizontal gene transfer (HGT) across human, animal, food, and environmental sources. Despite growing evidence for antibiotic resistance genes (ARGs), Africa lacks a one-health-focused synthesis of mobile genetic element-mediated AMR. Objective: This systematic review and meta-analysis aimed to consolidate information on MGEs and ARGs in AMR dissemination throughout Africa’s one health interface. Methods: The literature was searched using PubMed, Scopus, and ScienceDirect. Observational. molecular epidemiology, whole genome sequencing (WGS), and metagenomic investigations of MGE-associated AMR in Africa were eligible. The study selection, data extraction, and quality assessment were performed by two independent reviewer and quality was graded using ROBVIS 2 utilizing Rayyan software. Narrative synthesis, random-effect meta-analysis, subgroup analysis, and meta-regression were utilized. Results: A total of 109 studies were included, with 91 studies contributing to the meta-analysis. MGEs reported were plasmids (71.7%) and integrons (54.8%). ARGs carried by MGEs were blaCTMX-M-15 (78.6%), Sul2 (69.6%), blaTEM (59.1%), and tetA (49.9%). Horizontal gene transfer was seen in 259 instances; however, transmission was unclear. In 442 observations, transmission pathways across human, animal, and environmental interfaces showed AMR prevalence of 75.1% in human, 98.0% in human–animal, and 61.3% in one health interface. Whole-genome sequencing was the most frequently used method for detecting MGEsThe pooled pathogen and AMR prevalence rates were 73.3% (95% CI: 60.5–83.7%) and 94% (95% CI: 85–98%), with significant heterogeneity (I² = 97.8% and 97.4%, respectively). The prevalence of Escherichia coli was 93% and Salmonella enterica 85% in subgroup analysis. Fluoroquinolones, aminoglycosides, and beta-lactams were prevalent in humans (89.7%) and human–animal interactions (98.0%) according to AMR Class. Conclusions: Horizontal gene transfer has propagated MGE-mediated antimicrobial resistance across human, animal, and environmental interfaces in Africa. To combat AMR in Africa, coordinated, genomics-informed One Health surveillance and antibiotic stewardship are needed. Due to variability and publication bias, these data should be considered cautiously. Pooled data may only show descriptive patterns, and not necessarily precise continent-wide prevalence estimates. Full article

Background/Objectives: Acute cholecystitis is associated with an increased risk of morbidity and mortality. Thus, early diagnosis and detection of complications are essential. Neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein (CRP) are inflammatory biomarkers that could predict the diagnosis and complications of acute cholecystitis. Yet, the results of which biomarker has higher accuracy are inconsistent. Objective: To compare the accuracy of NLR and CRP in the diagnosis and prediction of complications in patients with acute cholecystitis. Methods: We searched PubMed, Scopus, and Web of Science in January 2026 for studies that compared both biomarkers (NLR and CRP) for the diagnosis and detection of complications or severity in patients with acute cholecystitis. We assessed the quality of the included studies using the QUADAS 2 tool. A bivariate meta-analysis was performed using R to compare the pooled diagnostic odds ratio (DOR) and the difference in sensitivity and specificity between both biomarkers. We used RevMan software to generate forest plots and summary receiver operating characteristic (SROC) curves using parameters calculated through R. Results: We included 15 studies in the systematic review, and 12 of them were included in the meta-analysis. The pooled data showed that NLR had higher accuracy in the diagnosis of acute cholecystitis compared to CRP, DOR 2.257 (95% CI 1.1, 4.633); however, there was no significant difference in sensitivity or specificity. There was no significant difference between NLR and CRP in detecting complications, including perforation, gangrene, and suppurative cholecystitis, DOR 1.100 (95% CI 0.817, 1.481). Meanwhile, NLR had similar sensitivity but lower specificity −0.050 (95% CI −0.090, −0.010) compared to CRP. NLR had lower overall accuracy in the detection of disease severity grades according to the Tokyo guidelines compared to CRP, DOR 0.170 (95% CI 0.081, 0.359), but higher specificity 0.230 (0.182, 0.279) compared to CRP. Conclusions: This systematic review and meta-analysis showed that NLR had higher diagnostic accuracy than CRP in patients with acute cholecystitis. However, both biomarkers had comparable sensitivity and specificity. Additionally, both biomarkers had comparable accuracy in detecting complications such as perforation, gangrene, or suppurative cholecystitis. CRP had higher overall accuracy in detecting disease severity according to the Tokyo guidelines. Thus, while NLR may be useful in diagnosing acute cholecystitis, CRP could be more effective in assessing disease severity. However, owing to the limited number of included studies, these findings should be interpreted with caution, and further studies are needed to confirm these results. Full article

Muscle vulnerability occurs at both extremes of the human lifespan, although its biological significance differs substantially between developmental growth and late-life decline. During childhood and adolescence, insufficient muscle accretion reflects disruption of physiological anabolic trajectories driven by inadequate energy availability, inflammatory burden, endocrine imbalance, or disease-associated catabolism. In older adults, muscle deterioration is characterized by anabolic resistance, neuromuscular remodeling, chronic low-grade inflammation, and hormonal decline, culminating in sarcopenia and loss of functional independence. The absence of harmonized diagnostic frameworks across age groups limits direct translational extrapolation. A lifespan-informed perspective distinguishing growth-supportive from function-preserving nutritional approaches is, therefore, required. This narrative review examines how major classes of nutritional bioactive interact with molecular pathways regulating skeletal muscle homeostasis in fragile populations across the lifespan. The analysis encompasses energy adequacy, protein quantity and quality, amino acid-dependent anabolic signaling, vitamin D status, lipid-derived mediators, redox-modulating phytochemicals, and micronutrients supporting mitochondrial bioenergetics. In pediatric contexts, nutritional interventions primarily aim to restore anabolic permissiveness within a structurally intact growth environment. In aging individuals, strategies focus on mitigating anabolic resistance through optimized protein intake, correction of micronutrient insufficiencies, and integration with resistance exercise to preserve functional capacity. This narrative review emphasizes the need to distinguish mechanistic rationale from clinically validated interventions, as improvements in molecular pathways do not consistently translate into meaningful functional outcomes. Full article

Background/objectives: Current treatments for advanced hepatocellular carcinoma (HCC) are tyrosine kinase inhibitors (TKI) and immune checkpoint inhibitors (ICI). When HCC is resistant to TKI or ICI, subsequent available treatments are limited. Dendritic cells (DC) can activate antigen-specific cytotoxic T-cells and may be employed as a subsequent treatment when HCC is resistant to TKI or ICI treatments. Methods: Fifty advanced HCC patients with resistance to ICI or TKI treatment were invited to have autologous DC therapy. DCs were propagated from peripheral blood monocytes and pulsed with tumor lysate. All the patients received ≥3 courses of DC intravenously. For the outcome analysis, 17 patients who were resistant to TKI or other traditional treatments were grouped into A, and 33 patients who were resistant to ICI treatment were grouped into B. Results: For group A patients, the median (interquartile) progression-free and overall survivals were 6 (3–16.3) and 19 (8–24) months, respectively. The 1-, 2- and 3-year overall survivals after DC therapy were 58.2%, 21.8%, and 14.6%, respectively. For group B patients, the median (interquartile) progression-free and overall survivals were 5.0 (4–8) and 9 (5–14.5) months, respectively. The 1-, 2- and 3-year overall survivals after DC therapy were 27.6%, 8.6% and 4.3%, respectively. Taking together 50 patients, the objective response rate was 6.0% and disease control rate was 72.0%. Only three patients (6.0%) had grade I-II hepatitis. Conclusions: DC therapy is a safe treatment for advanced HCC patients. DC can serve as a subsequent therapy to extend the patients’ lives when TKI or ICI treatments are ineffective as advanced HCC treatments. Full article

Background and Objectives: Sentinel lymph node biopsy (SLNB) is increasingly used for high-risk, clinically node-negative cutaneous squamous cell carcinoma (cSCC), yet pathological reporting remains binary, lacking morphological stratification. The prognostic relevance of nodal tumor burden subtypes—isolated tumor cells (ITC), micrometastases, and macrometastases—is well established in melanoma and breast cancer but remains uncharacterized in cSCC. We aimed to describe the morphological spectrum of sentinel lymph node involvement in a consecutive institutional cohort and determine whether primary tumor characteristics predict the extent of nodal colonization. Materials and Methods: We conducted a retrospective-observational study at Clinical Center Niš (Serbia) including 35 consecutive clinically N0 high-risk cSCC patients who underwent SLNB using a dual-tracer protocol (⁹⁹mTc-labeled albumin and methylene blue). Sentinel nodes were processed by serial sectioning with hematoxylin-eosin and pancytokeratin (AE1/AE3) immunohistochemistry. Deposits were classified as ITC (≤0.2 mm), micrometastases (>0.2–2.0 mm), or macrometastases (>2.0 mm). Clinicopathologic predictors were evaluated using the Mann–Whitney U test, Fisher’s exact test, the Kruskal–Wallis test, and the Spearman rank correlation test. Results: SLN involvement was identified in 12 of 35 patients (34.3%). Among positive cases, ITC accounted for 6 patients (50.0%), micrometastases for 5 (41.7%), and macrometastasis for 1 (8.3%)—minimal nodal disease constituting 91.7% of positive findings. No primary tumor feature—including diameter, thickness, grade, perineural invasion, or lesion multiplicity—significantly distinguished ITC from overt metastatic deposits. Patients with ITC showed numerically higher median tumor thickness (8.0 mm) than those with micrometastases (4.0 mm), though this did not reach significance (Kruskal–Wallis p = 0.065). Conclusions: SLN positivity in high-risk cSCC is morphologically heterogeneous, with minimal nodal disease predominating. Primary tumor features do not reliably stratify the extent of nodal colonization. Structured tumor-burden reporting—distinguishing ITC, micrometastases, and macrometastases—should be adopted as standard practice to enable meaningful prognostic comparisons and inform individualized management. Full article

Micro- and nanoplastics (MNPs) have now been detected in human blood, placenta, and arterial tissue, yet the oral cavity has received strikingly little mechanistic attention despite serving as a primary portal of environmental exposure and a local site of polymer generation from dental and oral-care materials. This narrative review addresses that gap from an environmental microbiology perspective, synthesizing recent literature on periodontal disease, chronic low-grade inflammation, oral biofilms, dental materials, microbial–plastic interactions, and systemic chronic disease risk. Unlike prior reviews, we apply an explicit three-tier evidentiary framework (established, plausible, unproven) that distinguishes what is directly demonstrated from what is biologically plausible but unproven, and we situate the periodontal environment specifically as a particle-retention and inflammatory-amplification niche. The strongest direct oral evidence shows that human dental calculus harbors at least 26 microplastic types, dominated by polyamide (41.4%), polyethylene (32.7%), and polyurethane (7.0%). Polyethylene isolated from calculus induces cytotoxicity, apoptosis, impaired migration, NF-κB activation, and upregulation of IL-1β and IL-6 in human gingival fibroblasts. From a microbiological standpoint, oral organisms actively degrade methacrylate dental polymers, and the degradation products of these polymers reciprocally modulate oral bacterial virulence gene expression. Across experimental systems, MNPs activate oxidative stress, inflammasome signaling, macrophage polarization, and barrier dysfunction, pathways that overlap extensively with periodontal pathobiology. Adjacent environmental microbiology demonstrates that plastic-associated biofilms enhance extracellular polymeric substance production, quorum sensing, pathogen persistence, and antibiotic resistance gene transfer, supporting a plausible but not yet validated oral plastisphere within plaque and calculus. We argue that periodontitis should be reconceptualized as a chronically inflamed particle-processing interface that may increase local MNP retention, cellular reactivity, and systemic inflammatory spillover, with implications for cardiovascular, metabolic, and other chronic disease risk pathways. Current evidence does not yet prove that environmental MNP exposure causes human periodontitis, and that evidentiary boundary is maintained throughout. A priority research agenda is proposed, centered on contamination-controlled subgingival biomonitoring stratified by periodontal status, spatially resolved multi-species biofilm models, polymer source attribution, and longitudinal clinical studies linking oral plastic burden to inflammatory and systemic outcomes. Full article

Background and Methods: Sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) is a severe complication of allogeneic stem cell transplant (allo-SCT). Given the increased use of allo-SCT and variability of SOS/VOD incidence in published reports, cases of allo-SCT from two major transplant centers in Ontario, Canada (2019–2021), were reviewed to identify risk factors prognostic for SOS/VOD onset and to assess outcomes. Results: This study included 536 allo-SCT cases, with a mean age of 53.4 years [min–max: 17–76], including 322 male recipients and 214 female recipients. There were 17 SOS/VOD cases diagnosed during the first 100 days, representing 3% of allo-SCT cases, with a median age of 48 years [18–72] and equally distributed between genders. All cases were classical SOS/VOD, with onset prior to day 21 [1–20]. These cases were graded as one mild, six moderate, six severe, and four very severe cases. The mild case of SOS/VOD recovered after treatment with diuretics. In respect to the 16 cases graded as ≥moderate SOS/VOD, the average inpatient stay was 56 days [24–178], and eight patients were in the ICU for an average of 6 days [0–42], with a median of zero days. Five of the sixteen ≥moderate SOS/VOD patients died within 100 days [9–59]—four from SOS/VOD. After day +100, five remained alive, and six died between days 125 and 419. Treatments for ≥moderate SOS/VOD included diuretics [n = 15], steroids [n = 3], and defibrotide [n = 9]. The nine patients treated with defibrotide were graded as moderate [n = 2], severe [n = 4], and very severe [n = 3]. Three of the nine patients treated with defibrotide died before day 100, and the other six survived beyond day 100. None of the six surviving patients died from SOS/VOD. Univariable regression analysis identified a higher baseline absolute neutrophil count (ANC) of 4.2 × 10⁹/L compared to 2.6 × 10⁹/L [p = 0.035] and lower baseline platelet count of 104 × 10⁹/L compared to 140 × 10⁹/L [p = 0.034] in SOS/VOD and non-SOS/VOD cases, respectively, as independent risks for ≥moderate SOS/VOD. Treatment with inotuzumab ozogamicin was also identified as a risk factor for ≥moderate SOS/VOD (p = 0.016). The absence of late-onset SOS/VOD in the cohort of 536 patients prompted a retrospective analysis of the data to identify potentially missed cases. Seven cases were identified as meeting the diagnostic criteria for SOS/VOD: four classical and three late-onset. One case would have been graded as severe, and the remaining six would have been graded as very severe. Six patients were reported to have died between days 11 and 107, with four deaths before day 100. The clinical diagnoses of patients meeting diagnostic criteria for SOS/VOD included infection (n = 3), graft-versus-host disease (GVHD) (n = 3), and pulmonary hemorrhage (n = 1). The inclusion of potentially missed cases in the analysis again suggested a lower baseline platelet count (p = 0.002) and prior treatment with inotuzumab ozogamicin (p = 0.003) as potential risk factors for SOS/VOD. The baseline ANC was lower in this combined cohort but did not reach statistical significance (p = 0.089) as it did in the confirmed SOS/VOD cohort (p = 0.035). Additional clinical features that were identified as statistically significant for the onset of SOS/VOD (potential and confirmed cases) included a lower Karnofsky Performance Status (p = 0.01), the presence of pulmonary hypertension (p = 0.012), lower baseline hemoglobin (p = 0.017), and higher baseline serum ferritin (p = 0.01). Conclusions: The incidence of classical SOS/VOD in this cohort was consistent with recent published reports and carried a high fatality rate. A higher ANC, lower platelet count at the start of the preparative regimen, and prior treatment with inotuzumab ozogamicin were identified as potential risk factors for diagnosed SOS/VOD. Hospital and intensive care unit stays were longer in SOS/VOD patients. There were no cases of late-onset VOD diagnosed within the first 100 days of allo-SCT transplant, which is inconsistent with recently reported incidence rates. Potentially missed cases of SOS/VOD were identified, suggesting that this disease may be under-diagnosed and underscoring the need for ongoing education and resources to allow for early intervention. Full article

Prior research suggests a connection between osteoarthritis and gout at sites commonly affected by gouty attacks. Whether this connection exists at sites with known monosodium urate crystal deposition but less commonly affected by gouty attacks, such as the lumbosacral spine, has not been previously investigated. We assessed whether lumbosacral osteoarthritis is more prevalent and more severe in subjects with gout compared with controls, and whether lumbosacral osteoarthritis is associated with higher levels of spinal monosodium urate deposition. Fifty gout subjects and 25 controls underwent dual-energy computed tomography imaging of the lumbosacral spine. We assessed lumbosacral osteoarthritis using a modification of a validated computed tomography scoring system, incorporating grade of intervertebral disc narrowing and facet joint osteoarthritis, and presence of spondylolysis and spondylolisthesis. We quantified spinal monosodium urate deposition using the default post-processing algorithm, plus a maximally specific algorithm to exclude potential artefacts. Forty-six gout subjects and 25 controls, average age 62 years, were included in the final analysis. Both gout and control subjects exhibited high rates of facet joint osteoarthritis and degenerative disc disease, with no difference in prevalence or severity between groups. Gout subjects did not have differing prevalence of spondylolysis and spondylolisthesis vs. controls. Subjects with lumbosacral osteoarthritis did not have higher levels of spinal monosodium urate deposition. Overall, lumbosacral osteoarthritis was not more prevalent or more severe in gout patients compared with controls, and spinal monosodium urate crystal deposition did not differ between patients with and without lumbosacral osteoarthritis. Full article

Background: Amyloid-related pathways are well studied in neurodegenerative diseases but remain poorly characterized in gliomas. Amyloid-related transcriptional programs in low-grade gliomas (astrocytoma grade II-III) and oligodendrogliomas, and their association with patient survival, were analyzed in this study. Methods: Transcriptomic data from 193 grade II-III astrocytomas and 191 oligodendrogliomas were analyzed to evaluate histology-specific expression patterns and prognostic significance. Differential and single-sample gene set enrichment analyses (ssGSEA) were used to calculate per-sample enrichment scores for 30 amyloid-related Gene Ontology biological process gene sets across the combined cohort. These scores were used to compare pathway activity between grade II-III astrocytoma and oligodendroglioma samples. Pathway-level survival analyses were performed for each tumor type using ssGSEA enrichment scores to evaluate associations with overall survival. Results: Distinct amyloid-related transcriptional programs were identified between glioma subtypes. Grade II-III astrocytomas showed enrichment of pathways related to amyloid precursor protein (APP) processing and amyloid-β clearance, whereas oligodendrogliomas were enriched in lipid transport and negative regulation of amyloid formation. Survival analyses revealed that higher activity of the positive regulation of APP biosynthetic process and amyloid-β clearance by transcytosis was significantly associated with worse overall survival in grade II-III astrocytoma, but not in oligodendroglioma. Gene-level analyses in astrocytoma demonstrated consistent survival associations across multiple genes within these pathways, supporting coordinated pathway-level effects rather than isolated single-gene prognostic markers. Conclusions: Amyloid-related transcriptional programs differ substantially between diffuse glioma subtypes. Increased APP biosynthesis and amyloid-β transcytosis pathways are associated with poorer survival specifically in grade II-III astrocytoma, suggesting a potential role for amyloid metabolism in tumor progression. These findings identify APP-related pathways as candidates for further mechanistic investigation and potential therapeutic targeting in grade II-III astrocytoma. Full article

Background/Objectives: Anthocyanins are dietary pigments associated with reduced risk of chronic diseases, yet their low systemic bioavailability challenges the traditional direct antioxidant hypothesis. This review aims to reconceptualize anthocyanin bioactivity by proposing the gut microbiome as a key mediator that biotransforms these compounds into bioactive metabolites responsible for systemic health effects. Methods: This review synthesizes evidence on the microbial metabolism of anthocyanins and includes a structured appraisal of the literature using an evidence evaluation framework analogous to GRADE, focusing on their transit to the colon, enzymatic biotransformation by gut microbiota, and resulting production of phenolic metabolites such as protocatechuic acid (PCA). It also examines the role of specific bacterial taxa (e.g., Bifidobacterium and Lactobacillus) in enhancing bioavailability and explores the downstream cellular pathways modulated by these metabolites. Results: Gut microbiota convert anthocyanins into smaller phenolic metabolites such as PCA, syringic acid, gallic acid, and other respective metabolites, which achieve plasma concentrations up to 100-fold higher than parent compounds and can cross the blood–brain barrier. These metabolites exert systemic effects by modulating key signaling pathways (NF-κB and Nrf2) and restoring redox homeostasis. Additionally, beneficial gut bacteria enhance anthocyanin bioavailability and support the production of short-chain fatty acids (SCFAs). Conclusions: Systemic health benefits of anthocyanins are largely mediated by gut microbiota through the generation of bioactive metabolites. This microbiota-driven process redefines the mechanistic understanding of anthocyanin action and highlights the microbiome as a critical determinant of their efficacy in preventing cardiometabolic and neurodegenerative diseases. Full article

Background: Anterior cruciate ligament (ACL) injuries are increasing in young athletes and many are related to non-contact, spontaneous mechanical fatigue-related ruptures. The objective of this narrative review is to identify and synthesize the anatomical, histological, physiological, and biomechanical basis of extracellular matrix (ECM) factors that contribute to ACL injuries and suggest ways to decrease their occurrence. Methods: The primary investigator searched PubMed, Web of Science, and Google Scholar database titles and abstracts using search phrases with Boolean operators: “anterior cruciate ligament” OR “ACL”, OR “cranial cruciate ligament” AND “disease”; “anterior cruciate ligament” OR “ACL”, OR “cranial cruciate ligament” AND “spontaneous rupture” OR “non-contact injury”; and “anterior cruciate ligament” OR ACL, OR cranial cruciate ligament” AND “crosslink”, “collagen” OR “extracellular matrix”; and “anterior cruciate ligament” OR “ACL”, OR “cranial cruciate ligament” AND “microtrauma”, OR “sudden” OR “fatigue failure”. The primary investigator and a sports orthopedic surgeon reviewed titles and abstracts of diverse evidence sources. From these identified sources, the study team performed full text reviews, selected contributing articles, performed Strength of Recommendation Taxonomy (SORT) grading, and synthesized the following themes: A Hostile Environment, ACL Strain, and Poor Nutrient Delivery; Accumulative ACL Microtrauma and Mechanical Failure; The ACL Differs From Other Ligaments; Collagen, the ECM, and ACL Mechanobiology; Crimps and ACL ECM Stretch; Crosslinks Improve ECM Mechanical Properties; The Delicate Collagen Synthesis and Degradation Balance; Exercise Training and the ACL; Can Nutraceuticals Help Restore the Balance?; Training Induced ACL Hypoxia; Estrogen and the Female Athlete; Counting Pitches or Counting Collagen Fiber Ruptures; and Restoring A Positive Anabolic–Catabolic Collagen Balance. Results: Regular exercise training within a physiologically safe loading range is vital to ACL ECM health. However, low or moderate evidence suggested that poor blood supply, slow metabolism, and a hypoxic environment may unbalance anabolic and catabolic homeostasis. Active rest and recovery concepts that prevent youth baseball shoulder and elbow injuries may help prevent non-contact ACL injuries. Conclusions: More prescriptive active rest and recovery intervals and neuromuscular control training may restore the anabolic–catabolic balance that increases mature crosslink density and improves ACL ECM strength. Confirmatory studies are needed to better establish therapeutic intervention mode(s), timing, dosage, and frequency optimization. Full article

Background/Objectives: High-grade serous ovarian carcinoma (HGSOC) is associated with high relapse rates despite aggressive multimodal treatment. BRCA mutations, present in a substantial subset of patients, confer homologous recombination deficiency and increased sensitivity to platinum-based chemotherapy. This study evaluated the association between BRCA mutation status and clinical outcomes, focusing on dissemination patterns, treatment allocation, perioperative parameters, and progression-free survival (PFS). Methods: This prospective single-center cohort included 133 consecutive patients with newly diagnosed HGSOC treated between January 2020 and December 2025. Primary treatment strategy (primary debulking surgery [PDS] or neoadjuvant chemotherapy [NACT]) was determined by multidisciplinary assessment. BRCA testing was performed using tumor tissue or germline analysis. Patients were followed for 24 months. PFS was analyzed using Kaplan–Meier estimates and Cox regression models. Results: Pathogenic BRCA mutations were identified in 39.1% of patients. BRCA-mutated tumors demonstrated significantly lower rates of peritoneal carcinomatosis (50% vs. 77.77%, p = 0.001) and were more frequently managed with PDS (59.6% vs. 41.8%, p = 0.048). Perioperative outcomes were comparable between groups. Disease progression occurred less frequently in BRCA-mutated patients (32.69% vs. 51.85%, p = 0.017). In univariate analysis, BRCA mutation was associated with a 48% reduction in progression risk (HR 0.52, 95% CI 0.27–0.99, p = 0.048). After adjustment for age, FIGO stage, and residual disease, BRCA mutation was not independently associated with progression (HR 0.57, p = 0.124), although a protective trend was observed, while residual disease remained a significant predictor. Conclusions: In this prospective cohort, BRCA mutation status was associated with distinct dissemination patterns and a significant reduction in progression risk in HGSOC. Although residual disease remained the strongest independent prognostic factor after multivariable adjustment, a trend toward improved PFS observed among BRCA-mutated patients supports the role of homologous recombination deficiency as a meaningful modifier of disease trajectory. These findings reinforce the clinical relevance of molecular stratification in the contemporary management of HGSOC. Full article

The growing participation in competitive and recreational sports has increased the clinical relevance of Sports Cardiology, particularly for athletes with borderline or ambiguous findings during cardiovascular screening. Advanced imaging is essential to differentiate physiological cardiac remodeling from early or subclinical cardiomyopathy. Cardiovascular magnetic resonance (CMR) has emerged as the reference standard for comprehensive assessment of cardiac morphology, function, and myocardial tissue characterization. Beyond conventional cine imaging and late gadolinium enhancement (LGE), parametric mapping techniques (including native T1, T2, and extracellular volume (ECV) quantification) enable quantitative and reproducible evaluation of diffuse fibrosis, edema, and low-grade inflammation that may precede overt structural disease. In athletes, physiological remodeling may overlap with pathologic phenotypes, posing diagnostic and prognostic challenges. Accurate interpretation requires integration of volumetric and functional measurements with the athlete’s training profile and electrocardiographic features, using population-specific reference values to avoid misclassification of adaptive changes as pathological. This narrative review provides a clinically oriented overview of CMR in athletes, focusing on typical findings, advanced tissue characterization, and emerging techniques such as myocardial strain analysis, right ventricular-focused imaging, and 4D flow. Technical challenges, standardization issues, and future directions are discussed. Multiparametric CMR is increasingly recognized as a key tool for improving diagnostic accuracy, refining risk stratification, and supporting clinical decision-making in athletes with suspected cardiomyopathy or ventricular arrhythmias. Full article