Search Results (17,447)

Background: Diabetes mellitus (DM) is associated with an increased susceptibility to lower respiratory tract infections (LRTIs) and more severe clinical courses, including prolonged hospitalization and increased mortality. During LRTI-related hospitalizations, clinical management often prioritizes the acute respiratory condition, potentially under-recognizing DM-related multimorbidity. We evaluated whether inpatient diabetes specialist consultation is associated with improved outcomes in this high-risk population. Methods: We conducted a retrospective cohort study of 677 adults with DM admitted for LRTI. Specialist consultation was defined as involvement of an endocrinology and/or diabetes nurse specialist during index hospitalization. Outcomes included length of hospital stay (LOHS) and 90-day mortality. Multivariable zero-truncated negative binomial regression (LOHS) and logistic regression (mortality) were adjusted for age, sex, Charlson Comorbidity Index (CCI), National Early Warning Score (NEWS), and pre-admission insulin use, hypoglycemic events, and admission laboratory parameters. Inverse probability of treatment weighting (IPTW) based on propensity scores was performed as a sensitivity analysis. Results: Among 677 patients, 84 (12.4%) received diabetes specialist consultation. Patients receiving consultation had lower unadjusted 90-day mortality (4.8% vs. 17.5%, p = 0.001) but longer median LOHS (9 vs. 7 days, p < 0.001). After multivariable adjustment, diabetes specialist consultation was associated with lower 90-day mortality (OR 0.23, 95% CI 0.08–0.68, p = 0.008) and longer LOHS (IRR 1.27, 95% CI 1.12–1.44, p < 0.001). The results were consistent in IPTW sensitivity analyses. Conclusions: In this retrospective cohort of patients with DM hospitalized for LRTIs, inpatient diabetes specialist consultation was associated with lower 90-day mortality, but longer hospital stay. These findings suggest that structured inpatient diabetes specialist involvement may contribute to improved medium-term outcomes in high-risk multimorbid patients. Prospective studies are required to determine causality and evaluate the impact of consultation timing and referral strategies. Full article

Background/Objectives: Inpatient falls are an important patient-safety concern in rehabilitation hospitals; however, factors determining whether a fall results in fracture remain poorly understood. This study investigated clinical factors associated with radiographically confirmed fracture after inpatient falls, evaluated the fracture-discrimination performance of the Morse Fall Scale and Hendrich II Fall Risk Model, and characterized the resulting orthopaedic burden. Methods: This single-center retrospective cohort study included adults who experienced a documented fall while hospitalized in a tertiary physical medicine and rehabilitation hospital. Patients with and without radiographically confirmed fractures were compared regarding demographic characteristics, comorbidity burden, bone health, continence, mobility, medication exposure, laboratory findings, and fall circumstances. Factors associated with fracture were evaluated using univariable analyses and a parsimonious Firth penalized logistic regression model. Discrimination of the Morse and Hendrich II scores was assessed using receiver operating characteristic analysis. Results: Among 91 adult inpatient fall events, 51 (56.0%) resulted in fracture. In unadjusted analyses, patients with fractures had lower lumbar spine T-scores and higher frequencies of urinary and fecal incontinence, whereas age, sex, femoral T-score, mobility status, fall location, and fall mechanism did not differ significantly between groups. In the adjusted Firth model comprising 87 complete cases and 49 fracture events, no variable reached independent statistical significance; lower lumbar T-score (adjusted odds ratio [aOR], 0.74; 95% confidence interval [CI], 0.52–1.05; p = 0.073) and urinary incontinence (aOR, 2.30; 95% CI, 0.87–6.12; p = 0.082) showed the strongest associations. The Morse and Hendrich II scores demonstrated poor fracture discrimination, with AUCs of 0.372 (95% CI, 0.255–0.489) and 0.411 (95% CI, 0.295–0.526), respectively, without a significant difference between them (p = 0.500). Among patients with fractures, 41.2% sustained major fractures, 27.5% underwent surgery, and 11.8% developed complications. Conclusions: Among documented inpatient falls in this rehabilitation cohort, fractures were common and imposed a clinically important orthopaedic burden. Conventional fall-risk scores did not distinguish falls resulting in fracture, suggesting that prediction of fall occurrence and prediction of orthopaedic injury represent distinct clinical objectives. Fracture-prevention strategies in rehabilitation settings should therefore complement general fall-risk assessment with targeted evaluation of skeletal and functional vulnerability. Full article

Background: Systemic inflammatory indices derived from routine complete blood counts have been proposed as inexpensive biomarkers in gynecological malignancies. Their ability to discriminate tumor grade in endometrial cancer, however, has rarely been evaluated against routinely available clinical variables under rigorous validation. Methods: We retrospectively analyzed 225 women with endometrial cancer (166 low-grade, G1–G2; 59 high-grade, G3). Nine inflammatory indices were computed. Four feature sets were compared using a prespecified elastic-net logistic regression under repeated nested cross-validation (5 outer × 5 inner folds, 20 repetitions) with 5000 stratified bootstrap confidence intervals: a collinearity-reduced inflammatory panel, the full inflammatory panel, preoperative clinical variables (age, CA-125 and preoperative albumin), and their combination. Selection among nine classifiers was retained as an exploratory analysis. Because 66% of high-grade events were non-endometrioid, every analysis was repeated in three cohorts: the full cohort, endometrioid tumors only, and the subgroup with assessed hormone receptor status. Histologic subtype was deliberately excluded because non-endometrioid carcinomas are high-grade by definition. Model behavior was interpreted with TreeSHAP and cross-checked against permutation importance. Results: Of nine inflammatory indices, only the eosinophil-to-lymphocyte ratio remained statistically associated with grade after false discovery rate correction (AUC 0.626, 95% CI 0.543–0.705; q = 0.036), with all others showing negligible effect sizes (|r| < 0.08); its discrimination was nonetheless modest and insufficient for individual-level prediction. The inflammatory panel achieved AUC 0.533 (95% CI 0.443–0.621), within the range attainable by chance in this design (permutation p = 0.254). Preoperative clinical variables reached AUC 0.687 (95% CI 0.590–0.772) in the full cohort but 0.390 (0.257–0.524) in endometrioid tumors alone and 0.627 (0.485–0.765) in the receptor-assessed subgroup. Adding inflammatory indices to clinical variables did not improve discrimination (ΔAUC = −0.025, 95% CI −0.062 to +0.012; one-sided upper bound +0.007 against a prespecified margin of +0.05). The results were unchanged under an alternative grade dichotomization and after excluding patients with inconsistent blood-count entries. Conclusions: Most inflammatory indices did not demonstrate clinically useful discrimination between G3 and G1–G2 disease in this cohort, and did not add incremental discriminative value beyond the prespecified margin over routinely available preoperative clinical variables. The apparent discrimination of the clinical variables in the full cohort did not survive restriction to endometrioid histology, indicating that it reflected histologic composition rather than grade. Decision curve analysis on recalibrated probabilities showed that no model exceeded the treat-all strategy at thresholds below the prevalence of high-grade disease, and that, above it, any advantage over treating no one was small in the full cohort and absent within endometrioid tumors. Full article

Background/Objectives: Musculoskeletal pain is a common condition that negatively affects quality of life and functional capacity. Integrative nursing emphasizes patient-centered and non-pharmacological approaches; however, variability in clinical decision-making persists due to reliance on clinician experience. This study aimed to design, retrospectively train, and evaluate the preliminary feasibility of a machine learning-based clinical decision support framework for personalized pain management within an integrative nursing approach in a Traditional and Complementary Medicine setting. Methods: This study included a retrospective cohort of 487 patients (mean age: 48.2 ± 14.7 years; 63.0% women) for machine learning model development and evaluation. The classification model predicted binary clinical improvement, defined as a ≥3-point reduction in VAS pain score, whereas the regression model predicted post-treatment VAS score. The resulting models were incorporated into the GETAIA prototype to generate modality-specific predicted post-treatment VAS scores and probabilities of clinically meaningful improvement for the three available T&CM modalities; these predicted profiles were compared to provide a model-derived treatment recommendation for clinical review. In addition, a prospective, non-randomized pilot involving 42 patients (21 AI-assisted and 21 standard care) was conducted to assess preliminary point-of-care workflow feasibility. Results: Significant reductions in pain intensity were observed across all treatment groups (p < 0.001). Clinically meaningful improvement rates were 76.2% for cupping therapy, 68.3% for acupuncture, and 58.8% for mesotherapy (p = 0.007). The prototype demonstrated 78.3% concordance with historical clinician treatment decisions, which was interpreted as an internal model-fidelity measure reflecting the reproduction of historical clinical decision patterns rather than evidence of improved decision-making, clinical effectiveness, or external validity. During a preliminary prospective feasibility implementation, clinically favorable numerical trends were observed in the AI-assisted group compared with standard care, including clinically meaningful improvement in 85.7% (18/21) versus 71.4% (15/21) of patients (p = 0.449) and mean VAS reductions of 3.9 ± 1.2 versus 3.2 ± 1.4 (p = 0.092). These exploratory differences were not statistically significant and were not intended to establish comparative clinical effectiveness. On the held-out test set, the primary XGBoost classification model achieved an accuracy of 82.6% and an AUC-ROC of 0.87 (95% CI: 0.82–0.92), while the regression model predicting post-treatment VAS achieved an MAE of 0.87. Key predictors of improvement included diagnosis, baseline pain intensity, and age. Conclusions: The findings support the preliminary development and evaluation of a machine learning-based decision-support framework and GETAIA prototype for individualized pain management within an integrative nursing context. The retrospective analysis demonstrated predictive performance of the evaluated models, while the small, non-randomized prospective pilot provided preliminary information on point-of-care workflow integration. These findings do not establish the clinical effectiveness, superiority, routine-care readiness, or external validity of a fully implemented clinical decision support system. Larger, prospective, multicenter studies are required to evaluate clinical effectiveness, generalizability, usability, and implementation readiness. Full article

Population aging is reshaping later-life well-being, yet whether the tie–satisfaction association is itself stable over time is seldom researched. This study compares the 2011 (n = 10,899) and 2023 (n = 9951) waves of the Korean National Survey of Older Persons, a nationally representative repeated cross-section of Koreans aged 65+. Social contact was decomposed into total contact volume and non-face-to-face orientation, retaining socially isolated respondents via structural dummy variables. Models were estimated by year and pooled with year interactions. Mean life satisfaction rose from 3.04 to 3.36 even as the proportion reporting no friends rose from 0.2% to 10.1%. Total contact volume predicted life satisfaction in both years, but the association weakened significantly (interaction B = −0.042, p < 0.001), and this held under sampling weights. The old-old’s relative advantage reversed in the unweighted model (p = 0.001) but not under weights (p = 0.341) and is reported descriptively. Non-face-to-face orientation became a significant positive predictor by 2023, though its between-year change was not confirmed. Because the waves are independent samples, all between-year differences confound cohort and period and are not causal effects. Sustaining later-life satisfaction may depend on the mode, target, and quality of contact, not volume alone. Full article

Background/Objectives: Femoroacetabular impingement (FAI) is a common cause of hip pain and functional limitation in young and active patients. Conventional hip arthroscopy commonly requires traction and central-compartment access, which may contribute to traction-related neuropraxia and access-related chondrolabral injury. This study evaluated clinical outcomes after traction-free only peripheral hip arthroscopy (OPHA) for cam-type FAI with associated labral pathology. Methods: This retrospective cohort study included consecutive patients who underwent OPHA between November 2016 and May 2022 and had complete paired preoperative and postoperative outcome data. Outcomes included the visual analog scale (VAS) pain score, Hip Outcome Score activities of daily living subscale (HOS-ADL), Hip Outcome Score sport subscale (HOS-Sport), International Hip Outcome Tool-12 (iHOT-12), and Tegner activity score. Labral status was categorized as intact, repaired, or debrided. Paired outcomes were analyzed with the Wilcoxon signed-rank test. Results: Sixty-six patients were included (mean age, 38.9 ± 10.8 years; 34 female). The mean postoperative follow-up was 5.7 years (range, 3.7–9.2 years). Labral status was intact in 32 patients, repaired in 23, and debrided in 11. Secondary intervention occurred in eight patients. In the overall cohort, VAS improved from 7.0 ± 0.6 to 3.2 ± 2.5 (p < 0.001), HOS-ADL from 59.1 ± 1.9 to 79.2 ± 17.5 (p < 0.001), HOS-Sport from 45.1 ± 2.1 to 67.6 ± 21.3 (p < 0.001), and iHOT-12 from 48.3 ± 1.8 to 72.2 ± 19.4 (p < 0.001). The Tegner activity score decreased from 5.2 ± 0.7 to 4.3 ± 1.4 (p < 0.001). Conclusions: Traction-free OPHA was associated with improvements in pain and hip-specific functional outcomes in selected patients with cam-type FAI and allowed individualized labral management without routine central-compartment distraction. The retrospective design and retrospective reconstruction of baseline PROMs in a subset of patients should be considered when interpreting the magnitude of the observed improvement. Full article

Background: Fumarate hydratase (FH)-deficient uterine leiomyomas are rare tumors that may be associated with germline FH variants and FH tumor predisposition syndrome. This study aimed to evaluate the clinical characteristics, germline genetic findings, and follow-up outcomes of patients with FH-deficient uterine leiomyomas, and to determine the frequency of germline pathogenic/likely pathogenic (P/LP) FH variants. Methods: This ambispective single-center cohort study included 19 patients diagnosed with FH-deficient uterine leiomyomas at a center between February 2021 and February 2026. Clinical characteristics, surgical data, FH and S-(2-succino) cysteine (2SC) immunohistochemical findings, germline FH analyses, renal imaging, dermatologic evaluation, and follow-up outcomes were reviewed. Results: Mean age was 44.9 ± 7.2 years, and the median largest leiomyoma diameter was 6.5 cm. Loss of FH expression was observed in 17/19 cases, while diffuse 2SC positivity was present in all cases. Among 17 patients who underwent germline testing, two (11.8%) harbored P/LP FH variants, [c.434C>G, p.(Ser145Ter) and c.1256C>G, p.(Ser419Ter)], and one (5.9%) had a variant of uncertain significance (VUS) [c.1090G>A, p.(Gly364Arg)]. Dermatologic evaluation was completed, with no cutaneous leiomyomas identified; no renal malignancy was detected on imaging in the two P/LP variant carriers. Among nine patients who underwent myomectomy, three developed recurrence; the patient carrying the likely pathogenic variant conceived after myomectomy. Conclusions: Identification of an FH-deficient uterine leiomyoma on pathologic examination is an important finding that should prompt evaluation for germline FH variants. These patients require integrated genetic, renal, dermatologic, and gynecologic follow-up. Obstetricians and gynecologists have an important role in initiating genetic evaluation and long-term surveillance after surgery. Full article

Background: HHLA2 (human endogenous retrovirus-H long terminal repeat-associating protein 2) is a B7 family immune checkpoint molecule that delivers costimulatory or coinhibitory signals depending on the receptor engaged. Although it has been implicated in various cancers, its clinical significance in hormone receptor (HR)-positive breast cancer remains unclear. Methods: Ninety-three patients with HR-positive breast cancer who underwent surgical resection were analyzed using tissue microarrays. HHLA2 expression was assessed by immunohistochemistry using a combined intensity and proportion score (0–8), analyzed as a continuous variable by Cox regression, with dichotomized comparisons (score >5 vs. ≤5) as sensitivity analyses. Associations with clinicopathologic variables were evaluated using Fisher’s exact test and Spearman correlation. A complementary analysis was performed using RNA-sequencing data from the TCGA-BRCA cohort. Results: HHLA2 immunoreactivity was detected in 86 tumors (92.5%). No significant associations were identified between HHLA2 expression and age, tumor size, nodal status, grade, or HER2 status. The HHLA2 score was not associated with overall, disease-specific, or relapse-free survival (hazard ratio per 1-point increase 1.17, 1.86, and 1.19, respectively; all p > 0.1), and no cutoff reached significance after correction for multiple comparisons. In TCGA-BRCA, HHLA2 transcript levels were low overall and higher in triple-negative than in HR-positive tumors (p < 0.001), but were not associated with survival in either group. Conclusions: HHLA2 immunoreactivity was detected in most HR-positive breast cancers, but no association with clinicopathologic features or survival was detected in this small exploratory cohort. Larger studies are needed to exclude modest prognostic effects. Full article

Background and Objectives: Pulsed radiofrequency (PRF) of the cervical medial branches is a non-destructive neuromodulatory option for chronic cervical facet joint pain, yet evidence regarding the durability of clinical response and factors associated with sustained benefit remains limited. This study aimed to characterize the 6-month trajectory of pain and disability after fluoroscopy-guided cervical medial branch PRF and to explore baseline factors associated with meaningful pain relief (MPR). Materials and Methods: In this retrospective single-center cohort study, 75 patients with chronic cervical facet joint pain who achieved ≥50% temporary pain relief following a diagnostic medial branch block underwent fluoroscopy-guided cervical medial branch PRF, followed by injection of local anesthetic and corticosteroid at the treated levels. Numeric Rating Scale (NRS) and Neck Disability Index (NDI) scores were evaluated at baseline and at 1, 3, and 6 months. MPR was defined as ≥50% reduction in NRS from baseline. Global Perceived Effect (GPE) and changes in analgesic medication use were assessed as complementary clinical outcomes. An exploratory multivariable logistic regression analysis was performed to examine factors independently associated with MPR at 6 months. Results: Median NRS scores decreased from 7.0 at baseline to 4.0, 4.0, and 5.0 at 1, 3, and 6 months, respectively, while median NDI scores decreased from 30.0 to 14.0, 16.0, and 20.0 (both overall p < 0.001). Despite sustained improvement relative to baseline, MPR progressively declined from 57.3% at 1 month to 49.3% at 3 months and 36.0% at 6 months (overall p < 0.001). Favorable GPE and reduced analgesic medication use showed parallel declines, supporting attenuation of overall clinical benefit over time. In the exploratory multivariable model, fibromyalgia was independently associated with 75% lower odds of 6-month MPR (OR = 0.25, 95% CI: 0.088–0.709; p = 0.009). Age, sex, and baseline NRS were not significantly associated with 6-month MPR. No serious acute periprocedural adverse events were documented during the 2 h observation period. Conclusions: Fluoroscopy-guided cervical medial branch PRF, combined with post-procedural corticosteroid and local anesthetic administration, was associated with clinically meaningful improvements in both pain and neck-related disability, with the greatest benefit during the first 3 months and partial attenuation by 6 months. The progressive decline across pain response, patient-reported global improvement, and analgesic-use outcomes highlights the time-dependent nature of the benefit associated with the combined intervention. Fibromyalgia was independently associated with substantially lower odds of 6-month MPR in this exploratory analysis; this association should be interpreted cautiously and requires prospective validation before it can inform patient selection, although it may be relevant when counseling patients regarding the durability of response. Full article

Hospitalized COVID-19 frequently involves several organ systems at once, yet neuropsychiatric manifestations are often examined in isolation. In a retrospective single-center cohort study, a five-axis phenotype atlas was constructed (respiratory, cardiovascular, neuropsychiatric, hepato-gastrointestinal, and renal-urinary) from ICD-linked hospital records of 1361 adults hospitalized with confirmed SARS-CoV-2 infection at a Romanian county emergency hospital between March 2020 and January 2025. Candidate neuropsychiatric associations were evaluated under prespecified cross-axis adjustment, treatment- and indication-bias gates, penalized outcome models, and pandemic-era comparison. Multi-organ involvement was almost universal: 91.0% of admissions carried at least two axes. Neuropsychiatric positivity reached 22.9% but was dominant in 0.8%, while 98.1% of these patients carried another chronic organ axis. Of the 42 initial laboratory candidates, three correlated electrolyte associations remained after adjudication, suggesting that these associations were more consistent with shared renal-metabolic burden than with neuropsychiatric-specific biology. Renal-urinary involvement was independently associated with intensive care admission (OR 1.97) and in-hospital death (OR 2.58); neuropsychiatric positivity was not. The previously reported Late Omicron enrichment of severe neurological presentations remained evident after age and sex adjustment (adjusted OR 3.35) and was the only one of 35 prespecified claims retained as neuropsychiatric-specific. Renal-urinary rather than neuropsychiatric involvement carries the adjusted prognostic weight in hospitalized COVID-19, and, given the dependence of retrospective record-derived phenotypes on clinical documentation, multi-organ adjudication should precede organ-specific inference from hospital records. Full article

Background: Respiratory syncytial virus (RSV) and influenza can both cause severe viral pneumonia requiring intensive care. Influenza is supported by established vaccination programs and antiviral therapy, whereas outcomes of RSV infection among critically ill adults remain less well characterized. This study compared clinical presentation, treatment, and outcomes between ICU admissions classified as RSV pneumonia and those classified as influenza pneumonia. Methods: A retrospective cohort was assembled from MIMIC-IV data covering 2008–2019. The analytical cohort comprised 201 infection-specific ICU observations classified as RSV pneumonia (n = 40) or influenza pneumonia (n = 161). Demographic characteristics, clinical measurements, treatments, and hospital outcomes were compared. Multivariable logistic regression was used to examine the association between infection type and in-hospital mortality, with adjustment for age, sex, and serum lactate. Internal model validation used 300 bootstrap resamples. Results: The RSV group was older than the influenza group (66.7 vs. 59.1 years; p = 0.009), had a longer ICU stay (median 3.0 [IQR 2.0–7.0] vs. 2.0 [IQR 1.0–4.0] days; p = 0.003), and had a higher admission heart rate (p = 0.009). Oseltamivir was recorded in 89.4% of influenza observations and 2.5% of RSV observations (p < 0.001). In-hospital mortality was 30.0% in the RSV group and 11.8% in the influenza group (p = 0.0091). In the primary adjusted model, RSV pneumonia was associated with higher odds of in-hospital death (adjusted OR 6.03, 95% CI 2.08–17.49; p = 0.001), as was increasing serum lactate (adjusted OR 1.46, 95% CI 1.24–1.74; p < 0.001). The apparent AUC was 0.864, and the optimism-corrected AUC after bootstrap validation was 0.845. Sensitivity analyses indicated that the magnitude of the RSV association varied with covariate adjustment. Conclusions: RSV pneumonia was associated with higher in-hospital mortality and a longer ICU stay than influenza pneumonia in this ICU cohort. The mortality association remained after adjustment for the variables included in the primary model, although its magnitude was sensitive to model specification. Given the observational design, these findings should not be interpreted as causal. They underscore the clinical burden of severe RSV infection in adults and support further investigation in larger cohorts with standardized virological testing and measures of acute illness severity. Full article

Background: Gastric carcinoma with coexisting exocrine and neuroendocrine components (GC-EN) is rare and clinically aggressive, but its temporal pattern and prognostic impact remain poorly characterized. Materials and Methods: We retrospectively analyzed 1043 patients who underwent curative gastrectomy at our center between 2008 and 2024. Following tumor–node–metastasis staging and 1:2 pTNM stage matching, 882 patients were included; 294 had GC-EN, of which 175 had GNEC, and 588 had GC. Clinicopathological characteristics were compared, survival outcomes were assessed using Kaplan–Meier estimates and multivariate Cox regression, and the proportion of GNEC cases in our center and the U.S. surveillance, epidemiology, and end results (SEER) database were evaluated. Survival patterns of GNEC were further compared with published international cohorts using Engauge Digitizer software. Results: Among the patients with gastric cancer admitted for treatment, the proportion of NEC fluctuated between 4.01% and 4.38% (2008–2013) and finally dropped to 1.6% (2020–2021), whereas the SEER database showed a modest rise with a late dip (1.67% → 2.72% → 2.44%). The overall survival (OS) of patients with NEC appeared to improve at our center (1-/2-/3-year OS: 85.1%/59.6%/34% in 2008–2012 to 94.1%/87.5%/76.2% in 2021–2024), whereas that in the SEER database declined over the same periods. The 5-year OS of the two databases remained similar (42.7% vs. 41.0%). The 1, 2 and 5-year survival rates of NEC in the external cohorts were higher than those in the SEER and Berlin series; however, the 3-year survival rates were similar, with the Italian multicenter cohort performing the worst. The Kaplan–Meier analysis demonstrated significantly worse OS for GC-EN versus GC (p < 0.001); within GC-EN, the NEC subgroup (NEC ≥ 70%) had the poorest outcomes (p < 0.001), whereas mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) and adenocarcinoma-dominant (AC-dominant) cases had similar outcomes as GC (p = 0.52, p = 0.81). In the multivariable Cox model, GC-EN histology remained independently associated with worse OS (HR = 1.49, 95% CI 1.15–1.92; p < 0.01). Metastatic lymph node burden and higher pTNM stage were associated with worse survival, whereas greater lymph node retrieval and age 40–65 years were protective. After adjustment, vascular invasion, tumor size, and location were not independently significant. Conclusions: Over the past 16 years at the National Cancer Center of China, the proportion of NEC cases decreased, and survival appeared to improve. NEC-dominant disease appeared to be the main driver of poor prognosis within GC-EN, whereas MiNEN and AC-dominant tumors showed survival patterns similar to GC in this cohort. These findings emphasize the need for GC-EN-specific risk stratification and tailored treatment strategies. Full article

Background: This retrospective study evaluated pretreatment masseter muscle index (MMI), masseter radiodensity (HUAC), and Global Immune–Nutrition–Inflammation Index (GINI) as prognostic markers in patients with laryngeal squamous cell carcinoma treated with definitive radiotherapy. Methods: MMI and HUAC were measured on simulation computed tomography, and GINI was calculated from pretreatment laboratory values. Biomarkers were analyzed continuously using Firth penalized Cox models adjusted for age, performance status, tumor site, and T and N categories. Nonlinearity was assessed using restricted cubic splines. Joint models and multiple imputation assessed robustness. HUAC associations were assessed over time. Exploratory cutoffs were derived using censoring-aware three-year time-dependent receiver operating characteristic analysis, with radiotherapy initiation as time zero. Results: Among 146 patients, 30 died and 48 experienced progression or death; GINI was available in 116. Each standard-deviation decrease in MMI was associated with worse overall survival (OS; adjusted hazard ratio 1.92, 95% confidence interval 1.21–3.05; p = 0.002) and progression-free survival (PFS; 1.91, 1.35–2.71; p < 0.001). These associations weakened after further adjustment for body mass index and concurrent systemic therapy. GINI findings were not robust in adjusted, joint, and missing-data analyses. Lower HUAC showed an exploratory association with poorer outcomes later in follow-up, based on few late events. Three-year OS/PFS estimates were 92.5%/81.1% versus 68.9%/59.5% for MMI > 2.830 versus ≤2.830 cm²/m², and 90.2%/81.9% versus 45.1%/38.0% for GINI < 139.67 versus ≥139.67. The GINI cutoff was unstable, with a 95% bootstrap interval of 20.104–180.985. Conclusions: Lower MMI showed the most consistent prognostic association. This initial evaluation of GINI in laryngeal cancer supports further investigation of its prognostic potential. HUAC findings and cohort-derived cutoffs remain exploratory and require external validation. Full article

Background/Objectives: Repetitive head impacts (RHI) from contact and collision sports have been associated with later-life cognitive and neurobehavioral impairments, as well as neurodegenerative conditions such as chronic traumatic encephalopathy (CTE). RHI-associated clinical sequelae among female former soccer players, specifically, are not well understood. This cross-sectional study aimed to examine the relationship of RHI exposure proxies (e.g., total years of soccer play, concussion history, highest level of play, and estimated cumulative heading frequency) with clinical measures (e.g., subjective cognitive complaints, objective cognitive performance, behavioral dysregulation, and depressive symptoms) among 2732 women, aged 40 years or above, enrolled in the Head Impact and Trauma Surveillance Study (HITSS), all of whom formerly played organized soccer. Methods: HITSS participants completed an online battery that elicited self-reported cognitive and behavioral complaints and depressive symptoms and that assessed cognitive performance via computerized tests. Multivariable linear regression models estimated associations between soccer-related RHI proxies and outcome measures, adjusting for age and education. Results: Among the former soccer players, longer duration of soccer play, higher level of play, greater estimated cumulative heading frequency, and concussion history were significantly associated with worse self-reported cognitive functioning, greater behavioral dysregulation, and elevated depressive symptom severity. Apart from a single association between concussion history and visual learning and episodic memory performance, we found no other associations between RHI proxies and objective cognitive test performance. Conclusions: Among middle-aged women who played organized soccer, cumulative RHI exposure corresponded to a higher degree of subjective cognitive complaints, worse behavioral functioning, and more severe depressive symptoms. Continued monitoring of this large cohort of female former soccer players offers a more comprehensive understanding of long-term health consequences of soccer play. Full article

Background: Perioperative blood loss represents a major challenge in elderly patients undergoing hip fracture surgery. Although tranexamic acid (TXA) has been shown to reduce bleeding complications, evidence from large registry-based cohorts remains limited. This study assessed the efficacy and safety of perioperative TXA administration in geriatric proximal femoral fracture surgery and evaluated in a subgroup analysis whether repeated TXA administration provides additional benefit compared with a single intraoperative dose. Methods: Data were derived from the Registry for Geriatric Trauma of the German Trauma Society (ATR-DGU), a prospective multicenter registry of patients aged ≥70 years undergoing surgery for proximal femoral fractures. From a total cohort of 23,830 patients, 1:1 nearest-neighbor matching based on age, sex, America Society of Anesthesiologists (ASA) classification, fracture type, and pre-fracture mobility yielded 3697 patients receiving intraoperative TXA and 3697 controls without TXA. Outcomes included transfusion requirements, thromboembolic events, mortality, reoperation rate, and length of stay. A subgroup analysis compared single-dose intraoperative TXA with combined pre- and intraoperative administration. Results: Intraoperative TXA significantly reduced packed red blood cell transfusion rates compared with controls (44.6% vs. 52.2%; p < 0.001). No significant differences were observed in thromboembolic events, mortality, overall complication rates, or length of hospital stay. Subgroup analysis showed no additional benefit of repeated pre- and intraoperative TXA administration compared with a single intraoperative dose but was associated with a significantly higher incidence of thromboembolic risks in the multiple-dose cohort (3.56% vs. 1.1%; p = 0.038). Conclusions: Intraoperative TXA administration significantly reduces transfusion requirements in geriatric patients undergoing surgery for proximal femoral fractures without increasing thromboembolic complications or mortality. TXA should therefore be considered a safe and effective adjunct in the perioperative management of geriatric hip fracture patients. Full article