Treatment of classical Hodgkin lymphoma (cHL) can be eventually complicated by avascular necrosis of the femoral head (AVN FH). Stages 1 and 2 of AVN FH can be treated conservatively, but stages 3 and 4 are indicated for surgery. In adults, total hip replacement (THR) is the preferred method. The goal of our study was to analyze the risk factors for AVN FH and functional results after THR.

This is a single-center retrospective observational longitudinal study. Patients with AVN FH after previous cHL treatment were included. Basic epidemiological data, time to AVN FH and THR, and complications of hemato-oncological treatment and THRs were recorded. Risk ratios, derived from 2×2 tables and from univariate Cox regression and Kaplan-Meier graphs, were analyzed. Categorical data were evaluated using the Fisher exact test and quantitative data using the Mann-Whitney-Wilcoxon test. Outcomes were measured using the modified Harris Hip Score (MHHS).

The mean incidence of AVN HF was 1.7 per year (95% CI 1.1-2.2). Patients with THRs tended to be older (p = 0.0424), the highest risk was ≥ 50 years. Mixed cellularity (MC) cHL had a higher risk of THR (log-rank test p = 0.0249) compared to nodular sclerosis (NS) cHL. Clinical stage IIB with massive mediastinal tumor was associated with the lowest risk of THR, p = 0.0348. The mean modified Harris Hip Score (MHHS) was higher in NS compared to MC subtype (85.1 (82.7-87.6) vs. only 75.4 (66.6-84.2), p = 0.0311). Periarticular calcification grade 1 was diagnosed in 84.6% of patients (95% CI 54.6-98.1). Revision surgery with cup and stem replantation was performed in one patient. No infections or cases of deep venous thrombosis were recorded.

THR is a causal treatment of symptomatic AVN FH following cHL treatment. Age ≥ 50 years, MC subtype cHL, and AVN FH stages 3 and 4 were associated with a higher risk of THR. The mean MHHS was fully comparable with THRs for other indications. Higher calcification rates had no impact on the clinical outcome.

Background: Upper-limb lymphedema after breast cancer treatment is associated with pain, functional limitations, and impaired quality of life. Although complex decongestive therapy (CDT) is standard conservative care, prospective evidence regarding factors associated with clinically meaningful response remains limited. We evaluated the short-term outcomes following Phase-I CDT and identified factors associated with clinically meaningful pain reduction. Methods: A prospective observational study was conducted in 94 women with breast cancer-related lymphedema undergoing a standardized 14-day Phase-I CDT program. Outcomes included limb circumference, pain intensity measured using the Visual Analogue Scale (VAS), and quality of life assessed with LYMQOL-Arm. Clinically meaningful improvement was defined a priori as a reduction of at least 2 points on the VAS (ΔVAS ≥ 2). Analyses included paired t-tests, Cohen's d, multivariable logistic regression, analysis of covariance (ANCOVA), and receiver operating characteristic (ROC) analysis. Results: Significant reductions in limb circumference were observed across all measurement levels (3.08-5.83%; all p < 0.001). Pain intensity decreased from 5.53 ± 2.15 to 2.82 ± 1.41, with a mean reduction of 2.71 points (95% CI 2.32-3.11; p < 0.001) and a very large effect size (Cohen's d = 1.40). All LYMQOL domains improved significantly. Higher baseline pain intensity was associated with a greater likelihood of achieving the predefined criterion for clinically meaningful improvement (OR 3.03; 95% CI 1.91-4.80), while older age was associated with reduced odds of response (OR 0.90; 95% CI 0.85-0.96). Baseline pain intensity demonstrated good discriminative performance (AUC 0.85). Circumference changes were not correlated with subjective improvement. Conclusions: Following the 14-day Phase-I CDT program, statistically significant reductions in total limb circumference, clinically meaningful pain reduction, and significant improvements in quality of life were observed. Exploratory analyses demonstrated an association between baseline pain intensity and the predefined responder outcome; however, this association is structurally influenced by the mathematical relationship between baseline VAS and the responder definition, baseline-dependent opportunity for improvement, and regression to the mean. Therefore, it should not be interpreted as evidence of an independent predictive effect and requires external validation before being considered for patient stratification or clinical decision-making. Because of the observational pre-post design without a control group, the observed changes cannot be attributed specifically to Phase-I CDT.

Objectives: Assessment of the impact on survival of endometrial carcinoma according to the 2009 FIGO (International Federation of Gynecology and Obstetrics) classification and the new FIGO 2023 classification highlighting the worse prognosis of the aggressive subtypes. Methods: This multicenter retrospective study included 1181 patients with endometrial cancer. Comprehensive clinical, pathological and treatment-related variables were collected. Primary outcomes included overall survival assessed through five-year follow-ups. Statistical analysis included comparative tests, Kaplan-Meier survival estimation, Cox proportional hazards models and ROC curves analysis to review prognostic accuracy. Results: Aggressive endometrial carcinoma (n = 353) showed significant worse overall survival compared with non-aggressive cases (35.7 versus 60 months). A novel classification based on FIGO 2023 was developed, integrating histological aggressiveness into a different stage and combining early non-aggressive stages in only one stage. While FIGO 2009 and 2023 classifications showed prognostic value, the new model improved risk stratification, clearly distinguishing high-risk groups. Multivariate analysis identified aggressive subtype, stage, age, diabetes, myometrial invasion and lymphovascular invasion as independent predictors. Conclusions: Aggressive histological subtype in endometrial cancer should carry greater prognostic weight in terms of survival and clinical management. Our findings support a potential shift in the current paradigm for these relatively rare but high-risk cases.

Inpatient falls are among the most common adverse events in acute-care hospitals and may result in functional decline, prolonged hospitalization, and increased healthcare costs. However, the characteristics of fall-related fractures and recurrent falls in university hospitals have not been fully investigated.

We retrospectively reviewed all inpatient fall events reported to the Department of Patient Safety at Niigata University Medical and Dental Hospital between January 2021 and December 2025. Patients younger than 20 years were excluded. Data regarding patient characteristics, mobility status, fracture occurrence, recurrent falls, medication use, and clinical departments were collected from medical records. Univariate and multivariable logistic regression analyses were performed to identify factors associated with fall-related fractures and recurrent falls.

A total of 2571 fall events were identified, yielding an incidence of 2.306 falls per 1000 inpatient-days. Malignant neoplasms were the most common primary diagnosis (36.9%). The incidence of falls was highest in the Departments of Neurology and Neurosurgery. Fall-related fractures occurred in 54 cases (2.1%), most commonly involving the lower extremities, including 17 proximal femoral fractures. Multivariable analysis identified mobility status as the only independent factor associated with fractures (odds ratio [OR], 1.821; 95% confidence interval [CI], 1.263-2.627; p = 0.001). Receiver operating characteristic analysis demonstrated a mobility cutoff value of 2.5, indicating an increased fracture risk among patients who were ambulatory with assistive devices or had higher mobility levels. Recurrent falls were observed in 439 patients (24.2%). Reduced mobility (OR, 0.837; 95% CI, 0.713-0.981; p = 0.028), polypharmacy (≥5 medications) (OR, 1.634; 95% CI, 1.254-2.016; p < 0.001), and use of central nervous system depressants (OR, 1.363; 95% CI, 1.124-1.653; p = 0.002) were independently associated with recurrent falls.

Patients with fall-related fractures tended to have relatively high mobility, whereas recurrent falls were associated with reduced mobility, polypharmacy, and central nervous system depressant use. Different characteristics of falls were observed across clinical departments. These findings may help identify patients at high risk for adverse fall-related outcomes and support the development of targeted fall-prevention strategies in university hospitals.

Background: Total neoadjuvant therapy is becoming a preferred option for locally advanced rectal cancer, particularly in patients with high-risk baseline features. However, real-world evidence comparing tumor response, MRI-defined high-risk feature clearance, surgical outcomes, and survival after total neoadjuvant therapy versus conventional long-course chemoradiotherapy remains limited. This study aimed to compare outcomes between total neoadjuvant therapy and long-course chemoradiotherapy in patients with locally advanced rectal cancer treated in routine clinical practice. Methods: This is a retrospective, single-centre cohort study focused on patients with stage II-III locally advanced rectal adenocarcinoma treated with curative-intent neoadjuvant therapy using either total neoadjuvant therapy or long-course chemoradiotherapy. Tumor response was assessed using restaging MRI, clinical complete response, and pathological complete response. Surgical outcomes and overall survival were evaluated. Results: A total of 110 patients were included. Patients treated with total neoadjuvant therapy had a higher baseline disease burden reflected by a greater proportion of cT4 tumors (40.6% vs. 19.2%; p = 0.014). Radiologic tumor-length response and clearance of MRI-defined high-risk features were comparable between treatment strategies. Clinical and pathological complete response rates were numerically higher in the total neoadjuvant therapy group, but the differences were not significant (cCR: 15.6% vs. 6.4%, p = 0.151; pCR: 18.5% vs. 9.7%, p = 0.301). Conclusions: In this real-world cohort, TNT was preferentially used in patients with more advanced baseline disease and showed numerically higher complete response rates, although differences were not statistically significant. Radiologic response, surgical outcomes, and short-term survival were comparable between treatment strategies. These findings support the feasibility of TNT in routine clinical practice but should be interpreted as exploratory and hypothesis-generating rather than evidence of treatment superiority.

Background: Conventional axillary ultrasound (US) is least reliable in lymph nodes with diffusely thickened cortex. We evaluated whether contrast-enhanced ultrasound with ultra-resolution microvascular imaging (CEUS-URM) improves discrimination of metastatic nodes in this subgroup. Materials and methods: This was a prospective single-center study of patients with histologically confirmed breast cancer; one index (most suspicious) node per patient (unit of analysis = index node). Two separately recruited consecutive cohorts were analyzed: a US-only cohort (n = 181; diffuse-thickening subgroup with histology, n = 52) and a subsequent CEUS-URM cohort (n = 42; 15 metastatic). Surgical histopathology (SLNB/ALND) was the reference standard. A CEUS-URM score was built from data-driven, Youden-optimized cut-offs (URM vessel count ≥8; DV mean density ≥ 13.05) and internally validated by bootstrap with optimism correction. As the cohorts were separate, the US-versus-CEUS comparison is cross-cohort and exploratory. Results: Within the diagnostically challenging subgroup of lymph nodes with diffusely thickened cortex, conventional axillary US alone demonstrated limited discriminatory performance for metastatic involvement (AUC 0.43). CEUS-derived quantitative parameters significantly improved diagnostic accuracy, with the best individual parameter achieving an AUC of 0.68. A simple CEUS score combining hypervascular vessel count and vascular density provided the highest diagnostic performance (AUC 0.81, 95% CI 0.68-0.92). At a low threshold, the CEUS score showed high sensitivity (93%), suitable for screening and exclusion of nodal metastases, while at a higher threshold it achieved high specificity (96%), allowing reliable confirmation of metastatic disease. Conclusions: In this exploratory study, a simple CEUS-URM score improved discrimination of diffusely thickened axillary nodes and may serve as an adjunct to conventional US. The findings are preliminary-derived and tested in the same small cohort-and require external, within-patient paired validation.

Background: Retinoblastoma (RB) is a rare pediatric malignancy characterized by small sample sizes and low event rates, where conventional association-driven feature selection may lead to unstable models, overadjustment, and limited generalizability. However, existing survival prediction studies lack a careful treatment of feature selection that accounts for underlying causal structure. Objectives: To develop and validate a causality-guided machine learning model for RB survival prediction by jointly incorporating survival time and survival status as outcome variables. Methods: We analyzed 1015 RB patients from the SEER database (1975-2020). A causality-informed feature selection framework was developed to address the challenges of rare-disease data. Specifically, candidate variables were evaluated through a three-step evidence-integration process: (1) univariate Cox proportional hazards (CPH) analysis for initial statistical screening; (2) causal structure learning using the PC algorithm on the variables retained from Step 1 to construct a directed acyclic graph (DAG) and exclude structurally inappropriate variables (colliders or descendants of the outcome); and (3) LASSO-based feature screening performed independently on the full set of candidate variables. The final features were obtained by taking the intersection of the variables retained from Step 2 and Step 3. Survival models were then trained using the selected features, with model comparison performed as a secondary step. Results: The proposed framework consistently identified four structurally and prognostically robust predictors-laterality, "SEER historic stage A", "RX Summ", and sequence number-through this evidence-integration process. Compared with conventional approaches, the causality-informed framework reduced the feature set while improving model stability and interpretability. Notably, compared with LASSO-only selection, which retained a larger set of variables, the causality-informed approach yielded a more parsimonious feature set with improved predictive performance, suggesting reduced overfitting in a low-event setting. Survival models trained on this refined feature set demonstrated reliable predictive performance, with the random survival forest achieving the highest discrimination (C-index = 0.739). Importantly, the selected predictors aligned with clinically plausible pathways in the learned DAG, supporting their causal relevance. Conclusions: This study demonstrates that incorporating causal structure into feature selection provides a more reliable and interpretable foundation for survival modeling in retinoblastoma. Rather than focusing on algorithmic comparison alone, our findings highlight that careful, causality-informed feature selection is critical for improving robustness in rare-disease prediction tasks. This framework may serve as a generalizable methodological template for other rare clinical settings prone to spurious associations.

Low skeletal muscle index (SMI) has been linked to adverse outcomes in colorectal cancer, but its association with local pathological tumor extent is less clear. This study examined whether preoperative CT-derived SMI was associated with pathological T4 disease in patients undergoing colorectal cancer resection.

This retrospective single-center observational study included 147 consecutive adults who underwent colorectal resection for histologically confirmed adenocarcinoma between January 2022 and November 2025 and had suitable preoperative abdominal or abdomino-pelvic CT imaging within 90 days before surgery. Skeletal muscle area was measured on a single axial CT image at the L3 level, and SMI was calculated as muscle area/height². Patients were classified as having pathological T1-3 or T4 disease. Logistic regression assessed the association between SMI, expressed per 5 cm²/m² increase, and pathological T4 stage.

Patients with pathological T4 tumors had lower SMI than those with T1-3 disease (37.22 vs. 42.85 cm²/m², p = 0.016). Higher SMI was associated with lower odds of T4 disease in univariable analysis (OR 0.79, 95% CI 0.66-0.94; p = 0.008) and after adjustment for age and sex (OR 0.77, 95% CI 0.63-0.94; p = 0.009).

Lower preoperative SMI was associated with pathological T4 colorectal cancer in this cohort. Because of the retrospective observational design, causality cannot be inferred. The association should be interpreted as hypothesis-generating and may reflect reverse causality, shared inflammatory-nutritional pathways, or residual confounding.

Background/Objectives: Celiac disease (CD) is common, but its cancer-risk profile remains incompletely defined. Estimates vary because of referral patterns, diagnostic era, outcome definitions, and surveillance around diagnosis. We evaluated cancer-category-specific associations in a matched cohort of clinically recognized CD. Methods: We used longitudinal electronic health record (EHR) data from Clalit Health Services for a propensity-matched cohort. Adults with EHR-coded CD were matched to controls on demographic, socioeconomic, comorbidity, and inflammatory variables. Pre-index invasive malignancies and non-invasive neoplasms were excluded. Dated EHR-coded invasive oncology outcomes were analyzed using Cox models. A restricted dated-event cohort, lag analyses, competing-risk modeling, hemoglobin adjustment, and age-at-index strata assessed robustness. Results: The primary matched cohort included 8143 individuals: 1006 with CD and 7137 controls, contributing 49,330.5 person-years. CD was associated with increased hazard of an EHR-coded invasive oncology outcome (hazard ratio [HR] 1.61, 95% confidence interval [CI] 1.47-1.77; p<0.001). Strongest signals were hematological malignancy codes (HR 1.99), lymphoma codes (HR 1.90), and gastrointestinal (GI) cancer codes (HR 2.71). Associations persisted after one-year and two-year lags. In the dated-event sensitivity cohort (161 CD; 1610 controls), CD remained associated with invasive cancer (HR 1.68, 95% CI 1.31-2.14), with the strongest signals for lymphoma (HR 2.81) and GI cancer (HR 2.25). The association was essentially unchanged under competing-risk modeling (Fine-Gray subdistribution HR 1.69) and after hemoglobin adjustment (HR 1.61), and was present in both age strata. Neither breast nor lung cancer was associated. Lymphoma codes included peripheral T-cell lymphomas recorded at intra-abdominal and extranodal sites, the pattern most consistent with enteropathy-associated T-cell lymphoma (EATL). Conclusions: In clinically recognized CD, cancer hazard was elevated and category-specific, concentrated in hematological, lymphoid, and GI codes with a gut-oriented T-cell lymphoma signal. The findings support targeted clinical vigilance, not expanded screening, and describe relative associations that require registry-linked confirmation.

Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy and is associated with profound metabolic reprogramming. This exploratory study aimed to characterize the metabolomic profiles of plasma and cerebrospinal fluid (CSF) in children with newly diagnosed pre-B-cell acute lymphoblastic leukemia (pre-B ALL) prior to therapy. Metabolomic analyses were performed using mass spectrometry-based platforms combined with multivariate statistical approaches (PCA, OPLS-DA, SVM-RFE, EBAM). In plasma, we identified 41 significantly altered metabolites (FDR < 0.011), revealing a distinct signature that differentiated pre-B ALL patients from healthy controls. Specifically, patients exhibited elevated levels of hypoxanthine, xanthine, and phosphatidylcholine derivatives, alongside reduced concentrations of L-cysteine and prasterone sulfate, indicating systemic dysregulation of purine, lipid, and amino acid metabolism. In CSF, we observed a distinct metabolic profile characterized by coordinated disturbances in purine degradation, phospholipid metabolism, and sphingolipid pathways. Notably, correlation analysis between the two matrices suggested that systemic metabolic shifts, particularly in purine metabolism (e.g., hypoxanthine and xanthine levels), are mirrored within the central nervous system microenvironment. These findings indicate that children with pre-B ALL exhibit specific metabolic alterations in both compartments before treatment. This work serves as a proof-of-concept for applying metabolomics in pediatric oncology, highlighting the necessity for further validation in larger, prospective cohorts to assess the clinical utility of these profiles.