Search Results (8,750)

Background: Large language models (LLMs) show considerable promise for medical question answering and reasoning. Their use in medical microbiology, however, remains constrained by limited domain-specific knowledge and the risk of hallucinated outputs. Objective: To develop and evaluate Smart Medical Microbiology (SmartMM), a specialized LLM for accurate, reliable, and context-aware responses in medical microbiology. Methods: SmartMM integrates domain-adaptive continual pretraining, supervised fine-tuning (SFT), reinforcement learning from human feedback (RLHF), knowledge distillation, and retrieval-augmented generation (RAG). We constructed a high-quality microbiology corpus from textbooks, clinical guidelines, the scientific literature, case reports, and other authoritative sources. Model performance was assessed using objective examinations, subjective generation tasks, expert review, and real-world user preference evaluation. Results: SmartMM achieved accuracies of 0.897 and 0.563 on true-or-false and fill-in-the-blank questions, respectively. In subjective generation tasks, it obtained the highest ROUGE-L score (0.265) and BERTScore F1 score (0.771) among all compared models. Expert assessment showed excellent inter-rater reliability, with all ICC(C,3) values exceeding 0.970. In a user evaluation involving 20 participants and 100 real-world questions, SmartMM received the largest number of first-place rankings (33), placing it among the top-performing systems overall. Conclusions: SmartMM showed strong domain adaptability in medical microbiology knowledge organization, semantic generation, and retrieval-augmented reasoning. These findings support its potential use in educational support, infectious disease knowledge assistance, and retrieval-enhanced medical question answering. Full article

Clinical image publications represent an important educational resource across healthcare disciplines, providing concise visual demonstrations of diseases, diagnostic findings, and therapeutic outcomes. Despite their widespread use, reporting practices remain highly heterogeneous, with substantial variability in the description of clinical context, image acquisition, ethical considerations, and educational content. Existing reporting guidelines, including the CARE Guidelines, do not specifically address the unique methodological and technical aspects of image-based publications. The aim of this study was to develop the IMAGE Statement (Improving Clinical Image Reporting Standards), a reporting guideline specifically designed for clinical image publications as an extension of the CARE Guidelines. The development process was informed by recommendations from the EQUATOR Network and included a literature review, analysis of journal instructions for authors, generation of candidate reporting items, and expert consensus. The resulting IMAGE Statement comprises 15 essential reporting items covering the title, patient information, clinical context, diagnostic assessment, image acquisition, image quality, image selection, image annotation, image description, diagnostic interpretation, final diagnosis, educational message, ethics and consent, artificial intelligence use disclosure, and figure legend. The IMAGE Statement provides a structured framework intended to improve completeness, transparency, reproducibility, educational value, and ethical reporting of clinical image publications across healthcare disciplines. Full article

Background: Diverticular disease (DD) represents an important clinical and healthcare burden, particularly in ageing populations. The relationship between the Diverticular Inflammation and Complication Assessment (DICA) classification and overall healthcare utilisation remains insufficiently defined. The aim of our study was to assess predictors and causes of all-cause hospitalisation during follow-up in patients with DD evaluated using the DICA classification. Methods: This prospective observational study included consecutive ambulatory patients with DD evaluated endoscopically in a tertiary gastroenterology centre during a 6-month period. Patients were prospectively followed for 3 years. Demographic and clinical characteristics, DICA classification, treatment, diverticulitis episodes and hospital admissions were recorded. The primary endpoint was any all-cause hospitalisation during follow-up. Results: Among 243 patients, all-cause hospitalisation occurred in 101 patients (41.6%), while recurrent hospitalisation occurred in 37 (15.2%). The cumulative hospitalisation burden reached 1607 hospital days. Acute diverticulitis occurred in 15 patients (6.2%), with only one diverticulitis-related hospitalisation, and no diverticular disease-related surgery was recorded. In multivariable analysis, age (OR 1.49; 95% CI 1.06–2.11; p = 0.023) and respiratory comorbidity (OR 5.31; 95% CI 1.49–18.88; p = 0.010) were independently associated with hospitalisation, whereas DICA ≥ 2 was not. However, the estimate for respiratory comorbidity should be interpreted cautiously because it was based on only 14 affected patients and had a wide confidence interval. Conclusions: Although all-cause hospitalisation was common and driven predominantly by age and comorbidity rather than diverticular disease severity, diverticular disease-specific outcomes were generally favourable in this stable ambulatory cohort. Full article

Background/Objectives: Internet Gaming Disorder (IGD) is included in ICD-11 and poses a substantial risk to Saudi university students, yet no structured nursing intervention framework exists within Saudi higher education health services. This paper presents the Resilience-Based Nursing Intervention Framework (RBNIF), a three-tiered, theory-driven nursing architecture translating evidence on impulsivity, resilience, and IGD into practice specifications for this setting. Methods: Using secondary analysis of a dataset of 207 gaming students from four King Saud University colleges, framework development followed a four-phase Medical Research Council (MRC) process: theoretical identification (I-PACE, Dual Process Theory, COM-B), evidence synthesis, Behavior Change Wheel/Intervention Mapping, and cultural adaptation via Bernal et al.’s Ecological Validity Framework. Results: The sample (58.9% male; 20–25 years, 61.4%; bachelor’s level, 73.9%) yielded three tiers differentiated by a dual-domain screening rule (elevated impulsivity and/or low resilience, rather than a single combined score): Tier 1 (universal psychoeducation); Tier 2 (six-session group program, S-UPPS-P ≥ 52 and/or CD-RISC-10 ≤ 20; 63 of 207 participants [30.4%]); and Tier 3 (10-session RIRDH clinical program, IGDS9-SF ≥ 36, met by 38 of 207 participants [18.4%]). Fifty-two participants (25.1%) met the elevated-impulsivity criterion, and 51 (24.6%) met the low-resilience criterion. Each tier specifies nursing competencies and behavior change techniques, with cultural adaptation integrating Islamic values concepts (sabr, mizan, tawakkul), family protocols, and single-sex delivery. Conclusions: To our knowledge, the RBNIF is the first theory-driven, culturally adapted nursing intervention architecture for IGD in Saudi university health services; a focused, non-systematic search of PubMed, Scopus, and CINAHL identified no directly comparable published framework. It is pre-implementation and requires feasibility testing, pilot evaluation, and a cluster-randomized controlled trial (c-RCT). Full article

In 1909, Paul Ehrlich first suggested that the immune system is critical for suppressing carcinogenesis and cancer growth, which led to the introduction of cancer immunosurveillance by Sir MacFarlane Burnet in 1960. Burnet’s cancer immunosurveillance was further supported and elaborated by Thomas Lewis in 1982, who noted, for example, the limitations of investigating cancer immunosurveillance in available experimental models, except for virus-induced cancers. The concept of cancer immunosurveillance in 2001 was revised to cancer immunoediting (the immunoediting term was introduced by Dr. Rober Schreiber), based on findings that the immune system not only controls tumorigenesis and tumor growth but also tumor quality/grade or immunogenicity. Advances in immunology, including the identification of target organs and the local immune system, and the identification of novel innate immune cells regulating the adaptive immune response, have further advanced the understanding of cancer immunosurveillance and immunoediting. The current article discusses the evolution of the cancer immunosurveillance hypothesis into cancer immunoediting. At the time of the introduction of cancer immunoediting, the direct role of dendritic cells (DCs) in tumor immunity and immunoediting was not much explored. Similarly, the concept of tumor-associated macrophages (TAMs) and their role in cancer immunosurveillance and immunoediting was not much studied. The current article discusses the evolution of DCs and TAMs in the context of tumor immunity, cancer immunoediting, and immunotherapies specifically targeting these innate immune cells. Full article

Antimicrobial resistance (AMR) is usually addressed through surveillance, prescribing policy, stewardship programs, infection prevention, and drug development. Less attention is given to an earlier educational question: how future doctors first learn to connect microorganisms, antibiotics, and resistance. In some preclinical medical curricula, microbiology provides essential knowledge of microbial structure, virulence, antimicrobial mechanisms, laboratory diagnosis, and resistance pathways, but opportunities to use this knowledge for antimicrobial reasoning may be limited. Students may therefore recall resistance mechanisms yet remain less prepared to interpret culture and susceptibility reports, consider local resistance patterns, or explain when therapy should be escalated, narrowed, optimized, or discontinued. This Perspective argues that AMR education should begin before students prescribe. Preclinical microbiology should preserve its scientific foundation while more deliberately linking microbial mechanisms to clinical scenarios, stewardship principles, microbiology report interpretation, and assessment design. Implementation should be adapted to local standards, supported by faculty development, and evaluated prospectively. Full article

Background/Objectives: Diabetes mellitus is associated with cognitive impairment, but evidence from southern Morocco remains limited. This study examined the associations of diabetes status, HbA1c, and diabetes duration with Mini-Mental State Examination (MMSE) performance among adults aged 45 years or older in Dakhla. Methods: This hospital-based comparative cross-sectional study included 100 participants (50 with diabetes and 50 without diabetes). Data were collected through a structured bilingual questionnaire and medical records. MMSE scores below 27 defined MMSE-based cognitive impairment. Crude and age-, sex-, and education-adjusted linear regression models with HC3 robust standard errors were complemented by correlation, subgroup, chi-square, and odds-ratio analyses. Results: Mean MMSE scores were lower in participants with diabetes than in those without diabetes (24.4 ± 5.39 vs. 28.8 ± 2.08). After adjustment, diabetes remained associated with a 4.13-point lower score (β = −4.13; 95% CI: −5.57 to −2.69; p < 0.001). MMSE-defined impairment occurred in 54% and 14% of the diabetic and non-diabetic groups, respectively (OR = 7.21; 95% CI: 2.72–19.05; p < 0.001). Within the diabetic group, MMSE scores correlated inversely with diabetes duration (r = −0.523; p < 0.001) and HbA1c (r = −0.393; p = 0.005), but neither remained independently associated after adjustment. Participants with type 1 diabetes had lower median MMSE scores and longer disease duration than those with type 2 diabetes, although this subgroup comparison was exploratory. Conclusions: Diabetes was strongly associated with lower MMSE performance and a higher prevalence of MMSE-defined impairment in this hospital-based sample. The cross-sectional design precludes causal interpretation, and the findings require confirmation in larger prospective studies. Full article

Background: The adoption of restrictive diets without medical indication is increasing, but the cognitive factors associated with this dietary behavior remain insufficiently understood. The aim of this study was to examine the proportion of participants following restrictive diets in a self-selected online sample of adults living in Romania and to analyze the associations of nutrition knowledge, beliefs regarding the relationship between diet and health, food vigilance, and social media use with the adoption of restrictive diets without medical indication. Methods: This cross-sectional observational study was conducted online in a self-selected sample of 766 adults living in Romania. Participants were classified into three groups: no restrictive diet, medically indicated restrictive diet, and restrictive diet without medical indication. Three composite scores were constructed: Restrictive Health Beliefs, Food Vigilance, and Nutrition Knowledge. Differences between groups were assessed using non-parametric tests and χ² tests, and factors associated with the adoption of restrictive diets were analyzed using multinomial logistic regression and multiple linear regression. Results: Among the participants, 30.9% reported following a restrictive diet, and 13.1% adopted one without medical indication. Participants who followed restrictive diets scored higher for Restrictive Health Beliefs and Food Vigilance but not Nutrition Knowledge. In the multivariate analysis, Restrictive Health Beliefs showed the strongest independent association with restrictive diets without medical indication. Food Vigilance was only associated with medically indicated restrictive diets (p < 0.001), suggesting an adaptive role in a therapeutic context. Nutrition knowledge and social media use were not independently associated with restrictive diets without medical indication, although social media use was associated with higher levels of Restrictive Health Beliefs. Conclusions: The results suggest that the adoption of restrictive diets without medical indication is more closely associated with beliefs regarding the relationship between diet and health than with the level of nutrition knowledge. These findings support the development of nutrition education interventions that, in addition to conveying evidence-based information, promote the development of critical thinking and the correction of insufficiently scientifically substantiated dietary beliefs. Full article

Background and Objectives: This study investigated the association between periodontal procedure intensity, serving as an indirect proxy for periodontal disease burden, and incident tinnitus in Korean adults. Materials and Methods: Using the Korean National Health Insurance Service–National Health Screening Cohort (2002–2019), we included adults aged ≥40 years who had a diagnosis of periodontal disease (International Classification of Diseases, 10th Revision [ICD-10] code K05), had undergone relevant periodontal treatment, and had available health-screening data. Because direct clinical periodontal measures were unavailable, participants were classified according to treatment intensity into: a mild procedure group (scaling or root planing only) and a moderate-to-severe procedure group (subgingival curettage, extraction, periodontal flap surgery, bone grafting, or guided tissue regeneration). Incident tinnitus was defined as an ICD-10 H93.1 diagnosis recorded during two or more outpatient visits to a neurology or otolaryngology department to improve diagnostic specificity. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models adjusted for demographic, socioeconomic, cardiometabolic, and behavioral factors. Results: Among 132,808 participants (76,844 mild; 55,964 moderate-to-severe), the incidence rate of tinnitus was higher in the moderate-to-severe group than in the mild group (4.38 vs. 3.87 per 1000 person-years). After adjustment, the moderate-to-severe group showed a significantly higher risk of tinnitus (HR 1.24, 95% CI 1.17–1.30). These associations were consistent across sex- and age-stratified analyses and in sensitivity analyses using stricter tinnitus definitions. Conclusions: Greater periodontal procedure intensity was associated with a modestly higher incidence of tinnitus in this nationwide cohort. Because procedure intensity serves only as an indirect surrogate for periodontal disease burden, and because auditory confounders and short-term procedure-related factors were unavailable, causality and a specific inflammatory mechanism cannot be established. Further studies incorporating direct periodontal measurements, audiological data, and prespecified lag-time analyses are warranted to confirm these findings. Full article

Background: Nosocomial infections, or healthcare-associated infections (HAIs), represent a significant global health challenge frequently associated with invasive medical procedures and extended hospitalizations. This study was designed to evaluate the current level of knowledge and the perceptions of inpatients regarding HAIs within a high-risk tertiary hospital in the Qassim region of Saudi Arabia. Method: A descriptive cross-sectional study was conducted from August 2024 to February 2025 at a tertiary facility in the Qassim region. The study population included 500 inpatients aged 18 years and older who consented to participate. Data were collected via individual interviews using a closed-ended questionnaire, which assessed demographics, knowledge and perceptions of HAIs on a 4-point Likert scale. Results: Among 500 study participants, good knowledge, fair knowledge and poor knowledge regarding HAIs were demonstrated by 57%, 38.4% and 4.6%, respectively. More than 98% of participants achieved a perception score of above 70%, indicating a profoundly positive perception level. Knowledge was significantly associated with age (p = 0.018), educational status (p < 0.01), and nationality (p < 0.01). Participants most commonly recognized contaminated hospital beds (95.6%), airborne transmission (91.2%), and unsterilized equipment (90%) as the potential modes of infection transmission. Conclusions: Sustaining ongoing infection prevention efforts and fostering improved awareness among inpatients regarding HAIs are of paramount importance in implementing effective public health prevention measures. Full article

Background: Gestational diabetes mellitus (GDM) is a major opportunity for type 2 diabetes mellitus (T2DM) prevention, yet gaps remain in the transition from postpartum care to long-term diabetes prevention despite clear management guidelines. This study evaluated awareness of future T2DM risk among parous women in Riyadh, Saudi Arabia, comparing women with and without a self-reported history of GDM, and identified sociodemographic and clinical determinants of risk awareness and adherence to follow-up and preventive measures. Methods: This observational, questionnaire-based cross-sectional survey included 316 parous women in Riyadh (n = 88 with self-reported prior GDM; n = 228 without), recruited non-probabilistically via a self-administered Google Forms questionnaire distributed through WhatsApp. GDM status, risk awareness, sociodemographic parameters, and postpartum screening and lifestyle-modification outcomes were all self-reported and not verified against medical records. Full awareness was defined a priori as selecting the highest of three ordered response options (“Yes, I am fully aware”) on a single item assessing whether GDM increases future T2DM risk; the remaining two options were combined as low/moderate awareness. Analyses used Pearson’s Chi-square tests and multivariable logistic regression to compute adjusted Odds Ratios (aOR). The primary between-group comparison was adjusted for age and educational attainment, with equivalence assessed by two one-sided tests (TOST) and subgroup differences by likelihood-ratio interaction tests. Results: A prior self-reported history of GDM was not associated with significantly elevated long-term risk awareness when compared with parous women without self-reported prior GDM (71.6% vs. 66.2% full awareness; p = 0.361, phi coefficient, φ = 0.06); this remained the case after adjustment for current age and education (aOR = 1.02, 95% CI 0.57–1.82, p = 0.936), and formal equivalence could not be established at a ±10 percentage-point margin (TOST p = 0.209). Older current age (≥45 years) was associated with higher awareness (78.0% vs. 60.3%; OR = 2.34, 95% CI 1.41–3.88, p = 0.0009). Within the GDM subset, structured postpartum counseling was associated with higher awareness levels (89.5% for scheduled appointments vs. 50.0% for no counseling; p = 0.002). In the whole sample of 316 parous women, multivariable analysis identified high awareness as the strongest independent correlate of self-reported adherence to postpartum glucose screening (aOR = 3.57, 95% CI 2.04–6.23, p < 0.001), with prior GDM diagnosis also independently associated with screening (aOR = 2.18, 95% CI 1.27–3.74, p = 0.005). Because postpartum glucose screening is specifically indicated only after GDM, a corresponding analysis was restricted to the 88 women with self-reported prior GDM, in whom 66.7% of those with full awareness reported having been screened compared with 16.0% of those with low/moderate awareness (OR = 10.50, p < 0.001). Conclusions: A prior history of GDM did not translate into higher self-reported awareness of future T2DM risk. Within the prior-GDM subgroup, structured postpartum counselling was associated with higher risk awareness, which was in turn associated with greater self-reported adherence to postpartum screening. Given the cross-sectional design and self-reported exposures and outcomes, these findings represent associations only and cannot establish causality or direction of effect. Full article

The progressive integration of Whole Slide Imaging (WSI) technology and Artificial Intelligence (AI) architectures is driving a structural transformation in pathology and precision oncology. This structured critical review analyzes and systematizes the impact of this technological transition along two fundamental operational dimensions of the modern biopharmaceutical industry: pre-registration Clinical Research and post-launch strategies governed by Medical Affairs. The first section explores how computational pathology is improving efficiency and reducing risk in drug development. Replacing analog visual assessment—intrinsically subject to inter-observer and intra-observer variability—with quantitative algorithms for cellular classification and segmentation enables optimization of patient recruitment in clinical trials, reducing screening failure rates. This review also examines the emerging role of Spatial Biology in extracting complex topological metrics from the Tumor Microenvironment (TME) and the use of AI for the objective and auditable quantification of critical surrogate endpoints, such as Pathological Complete Response (pCR), while acknowledging that algorithmic precision remains sensitive to pre-analytical variables and dataset biases. In the second section, the study investigates the strategic evolution of Medical Affairs, acting as a vital scientific communication and translational bridge between the complexity of Data Science and clinical hospital practice. Challenges related to AI adoption by clinicians are examined, emphasizing the importance of educational programs based on Explainable AI (XAI) to overcome the cognitive limitations of the black-box paradigm and the complex regulatory validation pathway for Software as a Medical Device (SaMD) under the stringent European IVDR framework—supported by an analysis of historical regulatory benchmarks such as the Paige Prostate case. The paper also explores the potential of AI in the large-scale generation of Real-World Evidence (RWE), applied to the creation of synthetic control arms in pharmacoeconomic settings. In conclusion, the study highlights that the diagnostic algorithm has ceased to be merely a laboratory support tool and has become a strategic asset and an integral adjunct to therapeutic decision-making. Overcoming current challenges related to data privacy through Federated Learning architectures, together with the imminent transition toward Foundation Models, foreshadows a fully data-driven healthcare ecosystem, making continuous skills development (digital upskilling) an essential requirement for professionals in the biopharmaceutical sector. Full article

Background: Patients with inflammatory bowel disease (IBD) often follow restrictive diets. Data on dietary habits and beliefs in pediatric IBD are scarce. Our aim was to assess dietary habits, beliefs, and knowledge regarding nutrition and IBD among children with IBD. Method: In this single-center, cross-sectional study, pediatric patients aged 12–18 years with IBD completed a non-scoring, 25-item questionnaire assessing general dietary habits, beliefs about diet’s role in IBD pathogenesis and treatment, food avoidance, and food-related experiences since diagnosis. Results: We included 72 IBD patients (mean age [SD]: 15.2 [2.3] years; 41 (57%) were male, 32 (45%) had Crohn’s disease (CD)). Almost half of the participants did not believe that eating habits contributed to the pathogenesis of IBD. One-third of patients considered diet to be more important than medication. Approximately two-thirds changed their eating habits after diagnosis, regardless of disease type (χ²: 0.70, p = 0.40), or induction therapy (nutritional vs. non-nutritional, χ²: 0.02, p = 0.88). At least one food was avoided by 65% of the participants. Conclusions: Most children have changed their dietary habits and avoided one or more food groups. The type of induction therapy did not relate to the knowledge and dietary beliefs after induction. Our findings suggest that repeated education and dietary counseling should be an integral part of the management of pediatric IBD. Full article

Background and Objectives: Digital tools are now embedded in anesthesia and intensive care, but access to them, and in particular to digital educational resources, is distributed unevenly across professional groups. This study describes how nurses, residents, and specialist physicians in one department appraise the contribution of digital technologies to continuing education, patient safety, and clinical and managerial decision-making, and how they report using the digital educational resources available to them. The study is descriptive and exploratory. It does not evaluate an educational intervention and does not measure learning. Methods: We conducted an anonymous, paper-based cross-sectional survey of all 198 clinical staff of a tertiary anesthesia and intensive care department between 2 June and 31 July 2025; 161 questionnaires were analyzable (81.3%). The instrument was investigator-developed and has not been validated, and it is therefore treated as a set of individual items rather than as a scale. Four trichotomous items (Yes/No/Cannot appraise) covering continuing education, patient safety, clinical decision-making, and managerial decision-making were designated primary outcomes and are reported as proportions with Wilson 95% confidence intervals, together with between-group differences and their confidence intervals; overall comparisons used the chi-square or Fisher exact test with Cramér’s V as the effect size. Reporting follows STROBE and the CROSS checklist for survey research. Composite indices, regression models, and correlation analyses were devised after data inspection, are labelled exploratory, and are not reported in this manuscript. Results: Daily use of at least one digital tool was reported by 98.1% of respondents. An educational contribution was affirmed by 56.4% of nurses (95% CI 43.3–68.6), 91.9% of residents (82.5–96.5), and 93.2% of specialists (81.8–97.7); the difference was 35.5 percentage points between residents and nurses (95% CI 20.1–49.4) and 36.8 points between specialists and nurses (20.1–50.7). Response distributions differed by professional category on all four items (p < 0.001 for education, patient safety, and clinical decisions; p = 0.005 for managerial decisions; Cramér’s V 0.22–0.31). Explicit disagreement was very rare (1 to 4 respondents per item), so the differences consist almost entirely of the “Cannot appraise” category, which is reported descriptively because the reason for that response was not measured. Reported use of digital educational resources followed the same ordering: e-learning 50.9% of nurses, 98.4% of residents, 93.2% of specialists; simulators 18.2%, 72.6%, 50.0%; webinars 65.5%, 67.7%, 86.4%. These proportions correspond to documented differences in institutional access, since simulation rotations were mandatory for residents only and the e-learning platform was opened to physicians in 2021 but to nursing staff only in October 2023. Conclusions: In this single department, response distributions on all four appraisal items differed by professional category, and reported use of digital educational resources was lowest in the group with the latest and most restricted institutional access. Because the groups used different technologies under different access conditions, these differences cannot be attributed to professional role itself, and because no learning outcome was measured they are not evidence of educational benefit. The findings are exploratory and support the hypothesis that equalizing access to digital educational resources deserves prospective evaluation. Full article

Fracture healing depends on coordinated osteogenesis and restoration of the vascular microenvironment. Endothelial cells support skeletal repair through angiogenesis, tissue perfusion and angiocrine signaling that regulates osteoprogenitor recruitment and differentiation. This narrative review examines endothelial dysfunction (ED) as a potential systemic contributor to impaired fracture healing by integrating evidence from vascular biology, experimental models and clinical studies. ED is characterized by reduced nitric oxide (NO) bioavailability, oxidative stress, inflammation and impaired vascular repair. These changes may disrupt angiogenic–osteogenic coupling through altered hypoxia-inducible factor 1-alpha subunit (HIF-1α)/vascular endothelial growth factor (VEGF) signaling, endothelial Notch activity, platelet-derived growth factor (PDGF)-mediated vascular remodeling and endothelial progenitor cell (EPC) mobilization. Conditions associated with endothelial dysfunction, including diabetes, aging, chronic kidney disease (CKD), smoking, obesity and chronic inflammatory disease, are also linked to delayed union, nonunion and poorer orthopedic outcomes. Cardiovascular disease and perioperative cardiovascular instability may further impair perfusion and physiological reserve during repair. However, the available evidence is predominantly experimental or observational, and direct causal evidence in fracture patients remains limited. Prospective studies combining standardized endothelial assessments with fracture-healing outcomes are needed to clarify clinical relevance and identify potential therapeutic targets. Full article