Diabetic foot syndrome (DFS) is characterized by chronic inflammation, thrombotic imbalance, and impaired wound healing, yet systemic molecular alterations underlying this complication remain incompletely defined. In this study, we combined clinical plasma proteomics with experimental pharmacological modulation to characterize a circulating damage-associated molecular pattern (DAMP)-related signature linked to systemic inflammatory signaling in DFS.

Plasma samples from patients with type 2 diabetes with and without DFS, including individuals with varying degrees of limb ischemia, were analyzed using liquid chromatography-tandem mass spectrometry. Differentially abundant proteins were evaluated in relation to inflammatory, hematological, and metabolic parameters. Pharmacological responsiveness was assessed in a murine diabetic ischemic wound model treated with a selective Toll-like receptor 4 (TLR4) inhibitor.

Proteomic analysis identified coordinated differences in the abundance of multiple acute-phase and stress-associated proteins, including serum amyloid A1, serum amyloid A2, serum amyloid P component, S100A8, defensin alpha 1B, fibrinogen chains, heat shock protein family A member 5, thymosin beta 4, fibronectin 1, and tenascins. These proteins exhibited differences between DFS patients and diabetic controls and were explored in relation to systemic inflammatory variables. Several DAMPs demonstrated reproducible patterns across the studied groups, suggesting the presence of a coordinated circulating molecular pattern rather than isolated changes in individual proteins. In diabetic ischemic mice, TLR4 inhibition was associated with altered abundance of several circulating proteins, including reductions in selected amyloid-associated proteins. These observations suggest an association between modulation of innate immune signaling pathways and circulating protein profiles.

Overall, these findings support a systemic alteration in circulating DAMP abundance in DFS and provide exploratory clinical and experimental evidence to guide future investigations into DAMP-mediated inflammatory pathways in diabetic ischemic complications. Proteomics data are available via ProteomeXchange with identifier PXD073507.

Some patients with breast cancer show low adherence to endocrine therapy (ETs). The Temporal self-regulation theory (TST) can explain adherence to medication behavior. Using TST to demonstrate medication adherence in patients with cancer has not been previously investigated. This study aimed to describe the behavior of ET adherence in women with breast cancer and examine the factors affecting health behaviors by applying the TST model.

A cross-sectional study design was used to collect data on connectedness beliefs, temporal valuations, intentions, self-regulatory capacity, behavioral prepotency, and ET adherence among 222 women with breast cancer.

Approximately one in seven women with breast cancer had low ET adherence. Under the guidance of the TST, it was found that factors directly influencing ET adherence included connectedness beliefs-barriers, intention, self-regulatory capacity, and behavioral prepotency. Both self-regulatory capacity and behavioral prepotency partially mediated the relationship between intention and medication adherence. Benefits and barriers to connectedness beliefs indirectly affected medication adherence through intentions. There were no significant moderators.

This finding indicated that connectedness beliefs, intention, self-regulatory capacity, and behavioral prepotency are important factors of ET adherence. Future clinical interventions may target these specific psychological and behavioral mechanisms to effectively promote ET adherence in women with breast cancer.

Anti-nuclear matrix protein 2 (NXP2) antibodies are increasingly recognized in adult idiopathic inflammatory myopathies (IIM) and have been associated with an elevated risk of malignancy. However, the spectrum of associated malignancies remains incompletely characterized. We report a case of anti-NXP2-positive myositis associated with bladder carcinoma in a 56-year-old man who presented with severe proximal muscle weakness, early dysphagia, and subcutaneous edema. Evaluation confirmed inflammatory myopathy, and myositis-specific antibody testing demonstrated anti-NXP2 positivity. Given the recognized association between anti-NXP2 antibodies and cancer-associated myositis, a malignancy workup identified urothelial carcinoma of the bladder. The patient received immunomodulatory therapy and transurethral resection of the bladder tumor. We performed a structured literature search in PubMed/MEDLINE, Scopus, Embase and reference-list screening from inception to May 2026. Search terms included combinations of "Myositis", "Dermatomyositis," "Polymyositis," "Autoantibodies," "Neoplasms", "Paraneoplastic Syndromes" and "Urinary Bladder neoplasms". Data extracted from eligible studies included patient demographics, inflammatory myopathy phenotype, anti-NXP2 antibody status, associated malignancies, and clinical characteristics. Forty-one relevant studies, including 20 observational cohorts or case series and 21 individual case reports, encompassing 411 patients were identified. Malignancy was reported in 63 patients, with the most common cancer types including prostate, lung, renal, thyroid, hematologic, gynecologic, and hepatocellular malignancies. To our knowledge, no previously published case of anti-NXP2-positive myositis associated with bladder carcinoma has been identified through our structured literature search. This case highlights a possible association and reinforces the importance of guideline-directed malignancy screening in adults with anti-NXP2 antibodies.

Genomic instability is common in cancer, driven by different mechanisms and often linked to disease stage and progression. Optical genome mapping (OGM) enables the detection of genome-wide balanced and unbalanced structural rearrangements (SRs), providing an overview of genomic complexity.

To explore the utility of OGM in brain tumour characterisation, we conducted a pilot study on a well-characterised series of 43, mostly paediatric, cases encompassing different histotypes and enriched for gene fusion-positive neoplasms (30 cases).

SRs were observed in 37/43 samples and defined three genomic patterns based on their number and distribution across the chromosomes: SR-chromothripsis (11 cases), high SR-complexity (11 cases) and low SR-complexity (21 cases). Genomic complexity was also assessed according to the number of copy number alterations (CNA) and, to this end, in SR-chromothripsis samples, only CNAs affecting chromosomes not involved in chromothripsis were considered: absence of CNAs was found in 15 cases, 1-9 CNAs in 19 cases, 10-49 CNAs in three cases and ≥ 50 CNAs in six cases. When examining the relationship between SR and CNA, a positive correlation emerged between CNA burden and the number of chromosomes harbouring SR (Spearman's r = 0.588, p = 0.0001), while breakpoint number was weakly associated; chromothripsis occurred exclusively within low CNA-complexity groups (p = 0.0836). Genome complexity patterns correlated with tumour types, with diffuse high-grade gliomas exhibiting high complexity, whereas infant-type hemispheric gliomas, most low-grade gliomas and embryonal tumours showed low complexity profiles. Importantly, SR-chromothripsis cases corresponded to low/intermediate-grade fusion-driven tumours, with balanced/nearly balanced CNA profiles. OGM allowed the detection of gene fusions in 24/30 cases, failing in six. When integrated with RNA sequencing, OGM unveiled the mechanisms underlying gene fusion formation in all cases: chromothripsis (11 cases), isolated chromosomal abnormalities (12 cases) and genome-wide alterations (seven cases).

OGM reveals distinct genomic complexity patterns and refines the definition of chromothripsis, improving insights into tumourigenic mechanisms.

To identify biomarkers for sudden death in leukemia through common genes across leukemia subtypes using bioinformatics technology, and to validate them in a specific case repository of sudden death in leukemia, thereby providing reference for cause of death determination in leukemia-related sudden death and cause of death analysis in medical malpractice cases.

Differentially expressed genes (DEGs) common across different types of leukemia were identified using the GEO database (GSE13159 dataset). Enrichment analyses were performed using the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, and enriched pathways were mapped to routine clinical laboratory parameters. Case data from patients who died suddenly due to stroke, respiratory failure, sudden cardiac death, and infectious shock, were collected and divided into the case group(leukemia sudden death group) and the control group(non-leukemia sudden death group) for validation. The Wilcoxon rank sum test and univariate logistic regression were used to screen biomarkers. A multivariate logistic regression model was constructed based on univariate logistic regression results to predict whether a sudden death patient had leukemia. Model performance was evaluated using receiver operator characteristic (ROC) curves and area under the curve (AUC).

A total of 540 DEGs shared across four leukemia subtypes were significantly enriched in pathways related to cell cycle, inflammatory immunity, and coagulation. The pathway enrichment results showed clear correspondence with routine clinical laboratory parameters. Compared with the control group, the case group exhibited overall characteristics of low white blood cell counts (mean: 2.42×10⁹/L), low platelet counts (mean: 23×10⁹/L), and low interleukin-6 (IL-6) levels (mean: 386.0 pg/mL). Based on the univariate logistic regression results, IL-6 and platelet count were included in a multivariate logistic regression model. The model yielded an AUC of 0.828.

The enrichment pattern of DEGs in leukemia sudden death biomarkers is consistent with the shared molecular mechanisms of uncontrolled leukemia cell proliferation, immune evasion, and hypercoagulable state. The combination of blood routine test parameters and IL-6 can be used for the differential diagnosis of sudden death in leukemia, providing objective evidence for auxiliary determination of cause of death in leukemia sudden death cases and offering a quantitative reference for cause of death analysis in medical malpractice identification.

To assess gender-related differences in patient-reported experiences across the cancer care pathway in Switzerland among patients with non-sex-specific cancers.

Multicentre cross-sectional survey study.

Secondary and tertiary oncology care across 21 public and private hospitals in Switzerland, covering all linguistic regions.

Adult patients (≥18 years) with a confirmed diagnosis of cancer who received oncological care in participating centres and completed a standardised patient experience questionnaire. Of 4408 respondents included in the analysis, both men and women with non-sex-specific cancers were analysed. Patients with sex-specific cancers were excluded.

None PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was the overall rating of cancer care (0-10 scale). The secondary outcomes were specific patient experiences in the pretreatment phase (consultations before the diagnosis, diagnosis and decision-making), during treatment (inpatient and outpatient care, specific treatments and nurse consultations) and in the post-treatment phase (follow-up, home care and psychosocial support).

Women rated their overall care lower than men (8.9 vs 9.1 on a 0-10 scale, p<0.001). After adjustment, women had lower odds of reporting a high rating (9 or 10) of their care (OR=0.74, 95% CI 0.62 to 0.87, p<0.001), of having received a written care plan (0.69, 0.59 to 0.82, p=0.001) and of receiving adequate information before surgery (0.42, 0.27 to 0.67, p=0.006) compared with men. Across the pathway, women consistently reported poorer experiences regarding communication, information and support compared with men. Conversely, men more often perceived unnecessary repetition of tests (1.42, 1.14 to 1.77, p=0.017).

Persistent gender inequities in cancer care experiences were identified, pointing to systemic gaps in communication, information and support. Addressing these disparities through gender-sensitive care is crucial to ensuring equitable, patient-centred oncological care for all.

Squamous cell carcinoma antigen (SCC-Ag) and carcinoembryonic antigen (CEA) are routinely monitored after definitive chemoradiotherapy (dCRT) for esophageal squamous cell carcinoma (ESCC) in Japan, but their clinical significance remains unclear.

We analyzed data from patients with resectable ESCC treated with dCRT in the JCOG0502 and JCOG0909 trials, who underwent intensive protocolized surveillance with computed tomography (CT), esophagogastroduodenoscopy (EGD), SCC-Ag, and CEA. Tumor marker positivity was defined as exceeding the cut-off value at least once, at two consecutive measurements, or at three consecutive measurements during follow-up. Sensitivity and specificity were calculated for SCC-Ag and CEA at 0.1-ng/mL increments to determine whether any cut-off met the predefined performance criteria (sensitivity ≥60% and specificity ≥70%).

This study included 239 patients (stage I/II/III = 147/58/34 [UICC 6th edition]), among whom 38% (91/239) experienced disease progression or recurrence. The median baseline SCC-Ag and CEA levels were 1.0 ng/mL (interquartile range [IQR], 0.8-1.5) and 2.3 ng/mL (IQR, 1.6-3.6), respectively, with a median of 16 measurements each (IQR, 8-19 for SCC-Ag; 8-20 for CEA). The highest specificities with sensitivity ≥60% were 19.6% for SCC-Ag (cut-off, 1.5 ng/mL) and 20.3% for CEA (cut-off, 2.2 ng/mL), but neither met the predefined criteria.

In this pooled cohort of patients with resectable ESCC who underwent dCRT and intensive protocolized CT and EGD surveillance, routine SCC-Ag and CEA monitoring showed limited incremental diagnostic value. The relevance of these findings to higher-risk cohorts and less intensive surveillance settings warrants further study.

Fear of cancer recurrence is one of the most frequent concerns among breast cancer survivors and can significantly affect health-related quality of life. However, it remains insufficiently explored in routine clinical practice. The aim of this study is to describe the frequency of fear of cancer recurrence and quality of life in patients with early breast cancer, to analyze their association with clinical and sociodemographic characteristics. As a complementary descriptive exploration, communication between patients and the healthcare team regarding fear of cancer recurrence was also assessed.

Cross-sectional observational study conducted in two public centers. A total of 301 women with stage I-III breast cancer, disease-free and at least 12 months post-treatment, were included. Fear of cancer recurrence was assessed using the Cancer Worry Scale, and quality of life was evaluated using the PROMIS Global 10 questionnaire.

High fear of cancer recurrence was observed in 34.9% of participants, and moderate fear of cancer recurrence in 20.9%. This concern was significantly associated with ≤5 years since diagnosis, age <50 years, education level, chemotherapy, and endocrine therapy. No associations were found with tumor stage, type of breast surgery, axillary surgery, or radiotherapy. Nearly half of the patients had not discussed fear of cancer recurrence with their medical team, mainly because they did not consider it a serious issue or were unaware that it could be addressed during consultations. PROMIS scores showed median values of 37.4 for physical health and 43.5 for mental health. Quality of life did not vary according to clinical characteristics or treatments but was associated with age and education. Patients with higher fear of cancer recurrence consistently showed poorer quality of life across all domains (p < 0.001).

Fear of cancer recurrence is highly frequent and strongly associated with poorer quality of life, independently of clinical variables. Its identification and management should be systematically integrated into survivorship care for women with breast cancer.

Interpretation of recurrence following resection of intraductal papillary mucinous neoplasms (IPMNs) is hindered by inconsistent terminology and outcome reporting. A distinction between metachronous/de novo IPMN development, progression of residual disease, and true recurrence of invasive entities is rarely considered.

A systematic review and meta-analysis were conducted following PRISMA and Cochrane guidelines (PROSPERO-ID: 1009399). The primary endpoint was postoperative recurrence of non-invasive IPMN and IPMN-derived pancreatic cancer (PC). Recurrence following resection of non-invasive IPMN was reclassified as progression of persistent cysts or de novo metachronous IPMN. Secondary endpoints comprised risk-factors for recurrence.

Sixty-six articles with 11 464 patients were included. After a median follow-up of 26 (interquartile range (i.q.r.) 18.0-53.0) to 72 (i.q.r. 5-318) months, the recurrence rate of IPMN-derived PC was 41.9% (1646/3925 patients), with a 5-year pooled recurrence-free survival of 46.6%. Systemic recurrence was most common (1034/1646; 62.8%), followed by locoregional (430/1646; 26.1%). Secondary treatments were administered in 655/1646 patients (39.8%) presenting with recurrence and included chemotherapy (65.5%), surgery (22.1%) and radiation (5.8%). Lymph node involvement (hazard ratio 2.87, 95% confidence interval 1.51 to 5.43) and tubular subtype (hazard ratio 1.68, 1.16 to 2.43) were identified as independent predictors of recurrence-free survival. The overall recurrence rate following pancreatic resection of non-invasive IPMN was 11.2% (831/7446), after median follow-up of 28 (i.q.r. 1-153) to 114 (i.q.r. 12-204) months. Among these, 408 (49.1%) developed as de novo lesions in the remnant pancreas and 174 (20.9%) as progression of pre-existing cyst detected at the time of index surgery; the remaining 249 patients (30.0%) could not be reclassified. Non-invasive recurrence was more common (308; 37.1%) than IPMN-derived PC (118; 14.2%), whereas the type of recurrence was unspecified in 405 patients (48.7%). Secondary treatment data were available for 265 patients, of whom 131 (49.4%) underwent reoperation.

The recurrence rate of IPMN-derived PC is high and warrants close surveillance policies. The majority of 'recurring' non-invasive IPMNs are de novo lesions. Standardized reporting, distinguishing true recurrence from de novo development and progression of residual disease, is essential to stratify recurrence risk and optimize surveillance protocols accurately.

To develop a large language model (LLM) (Truveta Language Model Oncology [TLM-Oncology]) to extract real-world oncology staging data across multiple cancer types from clinical documentation with high precision.

We selected patients from a large integrated health system with a bladder, cervical, colorectal, breast, or prostate cancer diagnosis in their structured data. We identified relevant notes using note metadata and keywords and annotated overall stage; T, N, and M; associated timeframe; and cancer diagnosis on a sample of 700 notes as ground truth. Of the 700 notes, 450 were divided equally between training, validation, and test sets for bladder, cervical, and colorectal cancers; 150 were used for targeted error-pattern training on these cancers; and the remaining 100 were split equally between breast and prostate cancer test sets. We started with a pretrained LLM and applied supervised fine-tuning to adapt the model to structured clinical information extraction. Model performance was measured using precision, recall, and F1 scores at the relation level and individual attribute level.

We extracted over 2.5 million staging records for 217,768 patients from over two million notes. Relation-level precision across the six attributes ranged from 0.77 to 1.0 for the first three cancers and, without further training, 0.83 to 1.0 for two additional cancers.

TLM-Oncology extracted detailed cancer staging information for five cancers from a variety of clinical documentation within a single integrated health system with high precision and turned data that were previously inaccessible into a valuable resource for downstream use. We are currently evaluating TLM-Oncology on other solid tumors within three additional health systems to assess its generalizability.