OBJECTIVES: Cefuroxime ocular administration is widely used to reduce the incidence of endophthalmitis after ocular surgery. However, due to ocular administration not being the recommended route in the prescribing information for cefuroxime, there is still a lack of systematic research on the adverse events of cefuroxime ocular administration. This study evaluated the adverse events following cefuroxime ocular administration using the FDA Adverse Event Reporting System database, with particular focus on the potential heterogeneity of reporting adverse events across different populations and dosing regimens. METHODS: The clinical characteristics of cefuroxime ocular administration-associated adverse event reports were analyzed and significant adverse event signals were identified using four disproportionality methods. Then, the potential demographic and dose-dependent differences in reporting adverse events were studied using the reporting odds ratio algorithm and Fisher's exact test. RESULTS: 88.7% of the adverse event cases resulted in severe outcomes. Sixteen signals for "eye disorders" and three signals for "injury, poisoning and procedural complications" were identified. There may be potential difference in reporting cefuroxime ocular administration-associated adverse events across continents, sexes and doses. CONCLUSION: This study emphasizes the need for careful attention to eye disorders and stringent quality control measures for off-label use when cefuroxime was administered ocular. The findings underscore the need for future confirmatory studies into the potential demographic and dose differences in adverse events associated with cefuroxime ocular administration. The findings represent hypothesis-generating associations which require further validation.What is already known on this topicCefuroxime ocular administration during ocular surgeries significantly reduces postoperative intraocular inflammation.Previous research highlighted a significant disproportionality of eye disorders after post-marketing of cefuroxime.Due to ocular administration not being the recommended route, there is still a lack of systematic research on the adverse events of cefuroxime ocular administration. What this study addsThis represents a pharmacovigilance study to evaluate cefuroxime ocular administration-associated adverse events.88.7% of the cases resulted in severe outcomes.There may be potential difference in reporting cefuroxime ocular administration-associated adverse events across continents, sexes and doses. How this study might affect research, practice or policyThis study emphasizes the need for careful attention to ocular adverse events when cefuroxime was administered ocular.The findings underscore the need for future confirmatory studies into the potential demographic and dose differences in adverse events associated with cefuroxime ocular administration.

BACKGROUND: Accurate assessment of volume status in dialysis patients remains challenging, and no single method is universally accepted. This study aimed to evaluate the combined diagnostic performance of lung ultrasonography and physical examination for predicting bioimpedance spectroscopy (BIS)-defined volume overload. METHODS: In this cross-sectional study, 44 dialysis patients underwent clinical evaluation, lung ultrasonography, inferior vena cava assessment, and BIS measurement. Clinically significant volume overload was defined as BIS-derived overhydration ≥ 2500 mL. The diagnostic performance of B-line count and pretibial edema was assessed using logistic regression and receiver-operating characteristic (ROC) analysis. RESULTS: Volume overload was significantly associated with B-line count and pretibial edema. In multivariable analysis, both parameters remained independent predictors of volume status, with B-line count demonstrating the strongest individual predictive performance. The addition of pretibial edema significantly improved overall model fit and provided incremental diagnostic value beyond B-line count alone. The combined model showed good discriminative ability for identifying hypervolemic dialysis patients, with an area under the curve (AUC) of 0.941 (95% CI 0.879-1.000). CONCLUSION: The combined use of bedside lung ultrasound-derived B-lines with pretibial edema assessment demonstrates good discriminatory performance for identifying clinically relevant overhydration in dialysis patients and may serve as a practical, noninvasive adjunct to bioimpedance analysis, particularly in settings where BIS is not readily available.

BACKGROUND: Multi-cancer early detection (MCED) tests present a paradigm transform in cancer screening by detecting multiple cancer types from one blood sample. While studies have shown high levels of public interest in MCED screening, little is known about factors shaping individuals' perception of the emerging technology. Guided by the PRECEDE-PROCEED framework, we aimed to identify factors associated with the perception of value of MCED testing among American adults. METHODS: We conducted a cross-sectional secondary analysis of the Health Information National Trends Survey cycle 7 (HINTS 7) to identify factors associated with the perceived value of MCED screening. After removing respondents with missing outcome data, our final sample size was 6,728. Using the PRECEDE-PROCEED framework, candidate predictors were grouped into predisposing, reinforcing, and enabling factors. We used descriptive, survey-weighted analyses, spearman correlation analyses, survey-weighted multivariable logistic regression, and supervised machine learning analyses (logistic regression and random forest) to explore the associations. RESULTS: Overall, 74.9% of the sample perceived MCED testing as very valuable. Trust-related domains showed the strongest associations with the outcome, including trust in physicians (OR = 1.89), trust in science (OR = 1.80), and trust in the healthcare system (OR = 1.64). Cancer information seeking (OR = 1.59), online health information use (OR = 1.63), smartphone access (OR = 1.54), cancer fatalistic beliefs (OR = 1.52), trust in government (OR = 1.50), knowledge of hepatitis B as a cancer risk factor (OR = 1.48), and family history of cancer (OR = 1.45) were also significantly associated with higher perceived value. Machine learning analyses demonstrated consistent predictor rankings, highlighting trust and health information engagement as the most influential determinants. CONCLUSIONS: The value of MCED screening was largely driven by trust, cancer information seeking, and access to healthcare and health information resources. Our study highlights the efficacy of the PRECEDE-PROCEED approach to studying factors associated with complex health outcomes. Future implementation strategies should prioritize equitable communication, strengthen public trust, and improve access to reliable health information to facilitate informed decision-making regarding MCED testing.

BACKGROUND: Stroke is the second most common neurological complication in cancer patients after metastases. Cancer-associated coagulopathy (CAC) is an important mechanism of ischemic stroke in this population. We systematically reviewed the epidemiological, clinical, radiological, and pathophysiological features of CAC-related stroke, as well as associated biomarkers and treatment strategies. METHODS: A systematic search of PubMed/MEDLINE, Scopus, Cochrane Library, and Embase (2000-2025) was performed according to PRISMA 2020 guidelines. Search terms included "stroke", "cancer", "hypercoagulability", "coagulopathy", "disseminated intravascular coagulation", and "non-bacterial or marantic thrombotic endocarditis". Studies published in English or Spanish were included, whereas case reports and review articles were excluded. Data were synthesized qualitatively. RESULTS: Eighty-two studies met inclusion criteria. CAC-related stroke occurs predominantly within six months of cancer diagnosis and is strongly associated with advanced or metastatic disease and a high risk of early recurrence. Adenocarcinoma, particularly lung and pancreatic cancer, is the most frequently associated histological subtype. Proposed mechanisms include mucin-mediated platelet aggregation, tissue factor-driven coagulation, extracellular vesicles, and neutrophil extracellular trap formation, leading to thromboinflammation and platelet-rich thrombi. D-dimer is the biomarker most consistently associated with recurrence and mortality, while C-reactive protein, fibrinogen, CA-125, and transcranial Doppler microembolic signals show limited specificity. Characteristic imaging findings include multiple infarcts involving more than two vascular territories, particularly the 'three territories sign'. Low-molecular-weight heparin and direct oral anticoagulants are the most commonly used secondary prevention strategies. Thirty-day mortality rates range from 25 to 50%. CONCLUSIONS: CAC-related stroke is a distinct and underrecognized entity characterized by specific biological and radiological features and poor outcomes. Earlier recognition and optimized antithrombotic strategies may improve prognosis.

PURPOSE: Real-world oncology data are essential for clinical research and precision cancer care. However, genomic biomarkers are often embedded in scanned, unstructured clinical documents requiring manual abstraction before becoming available in cancer registries, delaying real-world evidence generation. This study evaluated and compared three open-source optical character recognition (OCR) approaches, Tesseract, EasyOCR, and a hybrid implementation, to determine which best enables automated extraction of Oncotype DX recurrence scores and improves the timeliness and quality of real-world oncology data. METHODS: We evaluated the feasibility of automated genomic data extraction using 675 Oncotype DX reports from a Midwestern U.S. health system. EasyOCR, Tesseract, and a hybrid OCR approach were used to extract recurrence scores from scanned reports. OCR-derived values were compared with manually abstracted scores and local cancer registry data. Performance was assessed using agreement, precision, recall, F1 score, and processing time. Multivariable logistic regression was performed to identify factors associated with discordance between registry-reported and manually abstracted scores. RESULTS: The hybrid OCR approach demonstrated the highest performance, achieving 97% agreement with manual abstraction, precision of 0.997, recall of 0.972, and an F1 score of 0.984. Registry abstraction demonstrated comparable performance but required greater manual effort. Automated extraction substantially reduced processing time while maintaining high accuracy. Logistic regression showed registry discordance was largely independent of patient and tumor characteristics, with unknown progesterone receptor (PR) status as the only significant predictor. CONCLUSION: Automated extraction of genomic biomarkers represents a scalable approach to reducing delays in cancer data availability. Earlier capture of genomic information may support cancer registry modernization and improve real-world evidence generation in precision oncology.

IQGAP2 gene defects can lead to aberrant cell proliferation and are associated with multiple diseases. Previous studies suggest that IQGAP2 knockdown can activate AKT/mTORC1 and thereby promote aberrant cell proliferation. However, the upstream molecular regulatory mechanisms remain unclear. In our study, we found that IQGAP2 knockdown enhances PI3K activity, leading to accumulation of PI(3,4,5)P, thereby activating downstream AKT and mTORC1 activity. Integrative multi-omics and co-immunoprecipitation analyses revealed that IQGAP2 downregulation promotes PI3K activation within the IQGAP1 complex, while simultaneously activating the Wnt/β-catenin and AREG/EREG-EGFR signaling axes, thereby directly or indirectly enhancing PI3K activity. Furthermore, we found that the IQGAP1/IQGAP2 expression ratio is significantly elevated in tumor tissues and this ratio is associated with poor patient survival prognosis by TCGA pan-cancer analysis. This study provides insights into the signaling mechanisms associated with IQGAP2 downregulation, suggesting that the IQGAP1/IQGAP2 expression ratio may have clinical potential as a pan-cancer prognostic biomarker, and providing a basis for further investigation of targeted interventions for IQGAP2-related diseases.

PURPOSE: Immunotherapy-targeted combination therapy has transformed hepatocellular carcinoma (HCC) treatment, yet longitudinal patient-reported outcome (PRO) trajectories remain poorly characterized. We prospectively examined decision regret, hope, fatigue and quality of life during first-line treatment. METHODS: This convergent mixed-methods study enrolled 33 patients initiating first-line immunotherapy-targeted therapy at a Taiwan medical center (December 2022-October 2023). PROs were assessed across six cycles using validated instruments, and all participants were interviewed. Strands were integrated through joint display analysis. RESULTS: Twenty-one patients (63.6%) completed six cycles; 12 (36.4%) discontinued. Completers maintained stable PROs with low regret, whereas discontinuers declined faster in EQ-5D utility (interaction B =  - 0.169 per cycle, p = .007) and showed a larger, non-significant rise in regret (+ 9.58, p = .051, d = 0.50; between-group p = .042). Hope declined in both groups (- 1.48, p = .003), correlating negatively with regret (r =  - .383, p = .028). Interviews centered on treatment-related discomfort (24/33), sustained hope for disease control (31/33) and financial strain (25/33); where regret was voiced (3/33) it concerned earlier points in the illness course rather than the current treatment decision. Integration yielded four expanded meta-inferences and one discordance, between measured and voiced regret. CONCLUSION: Treatment completers maintain stable PROs, but more than one-third discontinued and experienced worse fatigue and greater regret, supporting pre-treatment counselling that is honest and informative rather than reassuring. Discontinuation marks a psychologically vulnerable transition, while universal hope decline warrants psychosocial monitoring for all patients. Given the sample size, predictors of regret are hypothesis-generating.

Cancer therapy-related cardiovascular toxicity (CTR-CVT) is an umbrella term for myocardial, vascular, electrical, and inflammatory complications of cytotoxic, targeted, immune, and radiation-based therapies. Cancer therapy-related cardiac dysfunction (CTRCD) is used here more narrowly for treatment-related myocardial dysfunction, typically identified by changes in left ventricular ejection fraction, global longitudinal strain, and/or cardiac biomarkers. The pathophysiology of CTR-CVT is multifactorial, but the implicated pathways should not be interpreted as equally causal. The dominant initiating mechanism is therapy-specific - anthracycline injury is best supported by topoisomerase IIβ (TOP2B)-mediated DNA damage with secondary mitochondrial and redox injury; HER2-directed toxicity by disruption of NRG1-ERBB2/ERBB4 survival signalling; fluoropyrimidine toxicity by coronary vasomotor dysfunction; VEGF-pathway inhibition by endothelial dysfunction and hypertension; immune checkpoint inhibitor toxicity by loss of immune tolerance; and radiotherapy injury by endothelial and microvascular damage with progressive fibrosis. Mitochondrial dysfunction, oxidative stress, inflammation, calcium dysregulation, apoptosis, and ferroptosis frequently act as downstream or amplifying pathways, although the clinical relevance of several regulated cell-death mechanisms remains incompletely established. Genetic susceptibility may further modify risk, but the strength of evidence differs among reported loci. Replicated pharmacogenetic associations, rare variants in established cardiomyopathy genes, and preliminary candidate-gene findings should therefore be considered separately. Most available studies remain limited by small cohorts, heterogeneous phenotyping, ancestry imbalance, and incomplete external replication. This review critically evaluates the hierarchy and strength of mechanistic and genetic evidence and discusses the extent to which these findings can currently inform risk stratification, surveillance, prevention, and treatment in precision cardio-oncology.

PURPOSE: Neoadjuvant chemotherapy (NACT) is reserved for tumours with a worse prognosis, introducing confounding by indication. Using sequentially adjusted Cox models to display confounding step by step, we assessed prognostic factors and the role of neoadjuvant therapy in a single-centre breast cancer cohort. METHODS: Retrospective study of 461 women treated at a single Spanish hospital (2016-2018) and followed to March 2026 (median 7.3 years; 456 in survival analyses). Overall (OS) and disease-free survival (DFS) were estimated by the Kaplan-Meier and Cox regression methods; proportional hazards were checked with Schoenfeld residuals and missing data handled by multiple imputation. RESULTS: Five-year OS and DFS were 89.7% and 86.0%. Independent prognostic factors were stage III-IV (HR 3.9), triple-negative subtype (HR 2.4) and adjuvant radiotherapy (HR 0.32). The apparent adverse effect of neoadjuvant therapy (univariable HR 2.35) disappeared after stage adjustment (HR 1.6; p = 0.17), with the same pattern for DFS; treated women differed chiefly in stage III-IV (60% vs. 14%; standardised mean difference 1.09). Recovering missing histological grade from source reports abolished its apparent prognostic effect (HR 1.40, 0.82-2.39). The triple-negative excess risk was concentrated in the first three years (HR 4.8 vs 0.4; interaction p = 0.020). CONCLUSIONS: After adjustment for stage and tumour burden, the apparent adverse effect of neoadjuvant therapy is largely explained by confounding by indication rather than treatment although the small treated subgroup cannot exclude a modest residual effect. Sequentially adjusted Cox models display the confounding pathway explicitly, complementing propensity-score approaches.

Transdermal drug delivery offers a noninvasive alternative to conventional administration by avoiding gastrointestinal degradation and hepatic first-pass metabolism. However, its broader clinical application remains limited by the barrier function of the stratum corneum and insufficient drug accumulation within target tissues. Metal-organic frameworks (MOFs), characterized by their high surface area, tunable pore structures, and versatile surface chemistry, have recently emerged as promising platforms for transdermal drug delivery. This review summarizes the key advantages of MOF-based transdermal systems, including high drug-loading capacity, particularly for hydrophobic compounds and macromolecules, programmable multidrug delivery, favorable biocompatibility, and the integration of diagnostic and therapeutic functions with complementary physical treatment modalities. We further discuss recent advances in the rational design of MOF-based transdermal platforms across major biomedical applications, including diabetic wound management, skin regeneration, skin cancer therapy, and cosmetic delivery. Despite these advances, clinical translation remains challenged by insufficient long-term biosafety evaluation, incomplete understanding of degradation behavior and biodistribution, limited manufacturing scalability, and regulatory requirements for complex multifunctional systems. Recent developments in artificial intelligence (AI) provide new opportunities to address several of these challenges by accelerating MOF design, predicting structure-property relationships, optimizing stimuli-responsive drug release, and supporting the development of personalized transdermal therapies. Overall, this review provides an integrated perspective on the design principles, therapeutic applications, and translational challenges of MOF-based transdermal systems, while outlining future directions for their successful clinical development.

BACKGROUND: Accurate patient-level risk prediction supports treatment decisions in breast cancer. Using the U.S. Surveillance, Epidemiology, and End Results (SEER) registry, we developed and internally validated an interactive web-based survival calculator integrating molecular and anatomical predictors. METHODS: We analysed 1 742 998 women diagnosed with breast cancer in SEER between 2010 and 2020, when human epidermal growth factor receptor 2 (HER2) ascertainment was reliable. Predictors included age at diagnosis, HER2, oestrogen/progesterone receptor (ER/PR) status, and American Joint Committee on Cancer (AJCC) 6th-edition tumour, node, metastasis (TNM) staging. HER2 was recoded to separate equivocal from unknown/untested cases. A multivariable Cox model was fitted and assessed on a held-out 30% sample using discrimination and calibration. Robustness was evaluated using stratified Cox, Royston-Parmar flexible parametric, and restricted mean survival time (RMST) analyses. RESULTS: Discrimination was good (Harrell C-index 0.72; time-dependent area under the time-dependent receiver operating characteristic (ROC) curve 0.76-0.78 at 12-120 months) with close calibration. Older age, distant metastasis, advanced T stage, nodal involvement, and ER/PR-negative status independently increased mortality. HER2-positive disease showed lower risk, whereas equivocal and unknown HER2 had higher risk. Findings remained stable across sensitivity analyses; RMST showed ~ 61 fewer restricted-mean survival months for M1 disease. CONCLUSION: The tool provides individualized survival probabilities from routine clinical and molecular inputs. It is prognostic, not predictive, and should complement rather than replace clinical judgement alone.

BACKGROUND: Malignant melanoma is highly aggressive and prone to therapeutic resistance. Chimeric antigen receptor macrophage (CAR-M) therapy is promising for solid tumors, but conventional ex vivo-engineered CAR-M has limited in vivo persistence, complicating longer-term safety evaluation. This study established a myeloid-specific, endogenously expressed tyrosinase-related protein 1 (TRP1)-CAR mouse model to assess antitumor activity and safety. METHODS: TRP1-CAR was conditionally knocked into the Rosa26 locus and crossed with Lysozyme 2 -Cre mice to generate mice with myeloid-specific TRP1-CAR expression (TRP1-CAR). CAR signals and baseline observations were assessed by flow cytometry, tissue immunofluorescence, histopathology, and hematology. Phagocytosis, cytotoxicity, and inflammation-related gene expression were evaluated in vitro. A syngeneic B16-Fluc-GFP melanoma model was used in two independent cohorts to assess tumor growth, survival, intratumoral CD8 T-cell infiltration, and histopathology. RESULTS: CAR signals were detected in peripheral blood and in F4/80-positive macrophage-containing areas of the lung, liver, and spleen. No overt histopathological abnormalities or hematological changes were observed in the tissues examined under baseline conditions. TRP1-CAR-BMDMs showed enhanced phagocytic and cytotoxic activity against B16-Fluc-GFP cells, accompanied by altered inflammation-related gene expression in the co-culture system. In vivo, TRP1-CAR mice showed delayed tumor growth (P < 0.0001) and prolonged survival (P = 0.0005), with increased intratumoral CD8 T-cell infiltration. CONCLUSION: This myeloid-specific TRP1-CAR knock-in model showed in vitro antitumor activity and delayed melanoma progression in vivo. It provides a proof-of-concept framework for investigating antitumor activity and preliminary safety observations associated with sustained endogenous CAR expression.

Alcohol use in aviation has traditionally been addressed in relation to acute impairment and operational safety. However, the health implications of alcohol extend beyond intoxication and include carcinogenic risk, neurobiological changes associated with alcohol use disorders, and potential effects on cognitive functioning. This narrative review examines these issues within the occupational and aeromedical contexts of professional pilots. It also considers aviation-specific factors that may influence behavioral health and help-seeking, along with the role of the Human Intervention Motivation Study (HIMS) program in treatment, monitoring, recovery, and return to professional flying status. Examining these areas together provides a broader perspective on alcohol and pilot health than an impairment-focused approach. In aerospace medicine, this perspective supports continued attention to prevention, early identification, recovery, and long-term health, while maintaining aviation safety as the primary operational consideration.

INTRODUCTION: Baicalin (BAI) is a natural flavonoid with antitumor potential, but its poor water solubility and low bioavailability limit clinical use. Mesoporous silica nanoparticles are promising drug carriers due to their large surface area and tunable pore structure, yet premature drug leakage remains a key challenge. METHODS: A multifunctional nanoplatform, designated as BPCD@BAI@BMSN, was constructed to enable efficient baicalin loading, pH-responsive gated release, and biotin-mediated active tumor targeting. A novel biotin-ε-polylysine-cyclodextrin (BPCD) conjugate was synthesized via EDCI/NHS coupling and characterized by NMR and GPC. Hollow mesoporous silica nanoparticles (BMSN) were prepared by the Stöber method, surface-modified with benzothiazole. The BPCD conjugate was coated onto the nanoparticle surface via cyclodextrin-benzothiazole host-guest self-assembly. The resulting nanoparticles were characterized by TEM, DLS, zeta potential, FTIR, and TGA. Drug loading, pH-responsive release, cytotoxicity against SMMC-7721 cells, cellular uptake evaluated by confocal microscopy and flow cytometry, and in vivo antitumor efficacy in nude mice were systematically evaluated. RESULTS: BPCD@BAI@BMSN exhibited near-spherical morphology with a particle size of approximately 200 nm, a positive zeta potential of +10 mV, a drug loading of 19.85%, and an encapsulation efficiency of 89.6%. Cumulative baicalin release reached approximately 62% at pH 5.5, whereas only about 6% was released at pH 7.4, confirming acid-triggered gated release. The blank carrier showed no significant cytotoxicity with cell viability above 95%, while drug-loaded nanoparticles exhibited enhanced cytotoxicity at pH 6.8. Biotin-functionalized nanoparticles demonstrated significantly higher cellular uptake and tumor accumulation compared to non-targeted controls. In vivo, BPCD@BAI@BMSN achieved a tumor growth inhibition rate of 72.5% compared to the control group, with no obvious toxicity to major organs observed during the 21-day treatment period. CONCLUSION: BPCD@BAI@BMSN integrates high drug loading, pH-responsive supramolecular gating, and active tumor targeting into a single nanoplatform, offering a promising strategy for baicalin delivery with enhanced antitumor efficacy and favorable short-term biosafety.

PURPOSE: To develop and evaluate a glutathione (GSH)-responsive "Off-On" drug delivery system based on thiol-functionalized N-doped carbon dots (SNCDs) for controlled intracellular release of disulfiram (DSF). MATERIALS AND METHODS: SNCDs were synthesized using a solvothermal technique and subsequently characterized using dynamic laser scattering, high-resolution electron imaging, UV-Vis spectrophotometry, and Fourier-transform infrared spectroscopy (FTIR). DSF was immobilized onto SNCDs through redox-cleavable disulfide linkages, and loading efficiency was determined by UV-Vis analysis. The in vitro drug release kinetics were examined under simulated physiological (pH 7.4) and tumor-relevant acidic (pH 5.4) conditions, evaluating the impact of glutathione (GSH) by performing experiments with and without its inclusion. Cytotoxicity and compatibility studies in MCF-7 breast tumor cells, evaluated via MTT test, were used to investigate SNCD biocompatibility and the anticancer performance of DSF-SNCDs. RESULTS: The FTIR spectra confirmed effective thiol functionalization and revealed oxygenated and nitrogenous groups on the particle surface suitable for disulfide linkage formation. DSF loading efficiency reached approximately 75%. Under non-reducing conditions, DSF-SNCDs exhibited minimal premature release (≤30% over 24 h at pH 7.4 and 5.4), demonstrating an "Off" state. In contrast, the presence of 5% (w/v) GSH at pH 5.4 triggered rapid DSF release, achieving approximately 80% cumulative release within 24 h, corresponding to the "On" state through reductive disulfide bond cleavage. Bare SNCDs showed high biocompatibility (>85% cell viability at 50 µg/mL), whereas DSF-SNCDs produced significantly enhanced cytotoxicity under GSH conditions, confirming redox-activated drug release. CONCLUSION: SNCDs provide an effective GSH-responsive nanoplatform for DSF delivery, combining high drug loading, excellent stability under non-reducing conditions, and efficient intracellular drug release under reductive environments. This strategy minimizes premature drug leakage while enhancing anticancer activity, demonstrating strong potential for cancer therapy.

Ovarian cancer remains one of the most lethal gynecologic malignancies, characterized by early peritoneal dissemination, extensive microenvironmental remodeling, and frequent emergence of chemoresistance. Beyond genetic alterations, dysregulated lipid mediator signaling represents a regulatory layer that links inflammation, invasion, immune evasion, and cellular stress adaptation. The 5-lipoxygenase (5-LOX, encoded by ALOX5) pathway converts arachidonic acid into bioactive leukotrienes through coordinated activity with 5-LOX-activating protein (FLAP, encoded by ALOX5AP), thereby activating G protein-coupled receptors, including BLT1, BLT2, and cysteinyl leukotriene receptors. This narrative review synthesizes preclinical, translational, and clinical-association evidence for 5-LOX signaling in ovarian cancer. Particular attention is given to BLT2-driven invasion and chemoresistance, hypoxia-induced leukotriene production, macrophage recruitment, ALOX5AP-associated immune suppression, and biomarker-guided therapeutic development. The available evidence supports the 5-LOX axis as a biologically relevant but still clinically immature target. Future development should prioritize compartment-resolved pathway mapping, functional validation in patient-derived models and immune-competent experimental systems, and rational combination strategies rather than unselected monotherapy.

OBJECTIVE: This cross-sectional study aimed to examine self-management behaviours in patients with malignant fungating wounds and to explore the structural pathways linking self-efficacy, powerlessness, and social support to self-management behaviours. METHODS: A cross-sectional study was conducted in an outpatient oncology setting. Data were collected between January and October 2024. Mediation analysis was conducted using structural equation modelling, with indirect effects evaluated through bootstrapping with 5000 resamples. RESULTS: 303 participants were included in the analysis. They achieved a mean self-management behaviour score of 97.72 ± 12.67, indicating a moderate level. Self-management behaviour was negatively correlated with powerlessness (r = -0.72) and positively correlated with self-efficacy (r = 0.60) and social support (r = 0.48). Structural equation modelling revealed that powerlessness had a significant direct negative effect on self-management behaviour (β = -1.33). Importantly, both self-efficacy and social support showed significant indirect effects on self-management behaviour through powerlessness (β = 0.69 and 0.69, respectively). The model explained 83.3% of the variance in self-management behaviours. CONCLUSION: Feelings of powerlessness emerged as a potential psychological mediator in the association between psychosocial determinants and self-management behaviours in this population. These findings underscore the critical need for targeted interventions that explicitly address powerlessness. Healthcare providers can strengthen the theoretical foundation for enhancing self-management practices and offering new pathways to improved health outcomes in patients with malignant fungating wounds.

Circulating tumor DNA (ctDNA) is an increasingly important biomarker for molecular residual disease (MRD) after curative-intent treatment of colorectal cancer (CRC), but its prognostic value must be distinguished from proven clinical utility. This structured narrative review synthesizes evidence from PubMed/MEDLINE, Embase, ClinicalTrials.gov, and major oncology conference proceedings, covering stage I-III CRC and selected patients with resected or ablated oligometastatic stage IV disease. We review tumor-informed and tumor-agnostic assay strategies, postoperative sampling, serial versus landmark testing, low-shedding disease, clonal hematopoiesis, and major prospective and randomized studies. Postoperative ctDNA positivity consistently identifies patients at substantially increased risk of recurrence, while serial ctDNA dynamics provide additional prognostic information. In stage II colon cancer, the randomized DYNAMIC trial showed that a ctDNA-guided strategy reduced adjuvant chemotherapy use without compromising long-term recurrence outcomes. By contrast, DYNAMIC-III did not establish non-inferiority for ctDNA-guided de-escalation and showed no recurrence-free survival benefit from conventional chemotherapy escalation in ctDNA-positive stage III disease. The Phase III ALTAIR trial likewise did not meet its pre specified primary disease-free survival endpoint for treatment of molecular relapse with trifluridine/tipiracil. Current professional guidance therefore supports a cautious distinction between clinical validity and clinical utility: ctDNA can inform prognosis, counseling, and clinical-trial eligibility, but should not routinely replace standard surveillance or independently determine treatment escalation or de-escalation outside evidence-based indications or clinical trials. Future progress requires harmonized assays, randomized demonstration of outcome benefit, and prospective validation of integrated ctDNA, pathology, transcriptomic, and AI-derived risk models.

OBJECTIVES: Intraductal oncocytic papillary neoplasm (IOPN) is a digestive system tumor typically found in the head of the pancreas. Most often, they remain confined to the pancreas; it is rare that they develop into an invasive carcinoma or metastasize. METHODS: This paper presents the case of a 63-year-old postmenopausal female with a past medical history notable for BRCA1 mutation and exploratory laparotomy with pancreatoduodenectomy who underwent risk-reducing laparoscopic bilateral salpingo-oophorectomy. RESULTS: Postoperative pathology revealed metastatic oncocytic papillary neoplasm involving the bilateral ovaries. She was ultimately referred to gastrointestinal medical oncology for further management. CONCLUSIONS: This is the first report to our knowledge of pancreatic IOPN metastasizing to the ovaries. It is essential for cases to be reported for guidance of treatment regimens.

Intravascular large B-cell lymphoma (IVLBCL) is a rare malignancy and is a challenging diagnosis to make given its varied clinical presentation. Here, we present the case of a 69-year-old male who presented with multiple cryptogenic strokes. Despite multiple hypercoagulable and malignancy workups, no etiology was identified, with multiple CT scans negative for any masses. Ultimately, a vascular abnormality was noted on a CTA of the head and neck, and IVLBCL was diagnosed on biopsy. The patient was initiated on R-CHOP and had improvement in his neurological status after the initiation of chemotherapy, and his ClonoSeq MRD testing is negative. This case is of interest given the lack of imaging findings for this patient prior to diagnosis as all of his CT scans were negative, making it a challenge to diagnose him as well as monitor his response to treatment. Additionally, his case highlights the importance of ClonoSeq MRD testing, which allows for the detection of even minimal amounts of disease in tracking response to treatment.

Primary cardiac angiosarcoma should be considered in patients with hemorrhagic pericardial effusion and a right-sided infiltrative cardiac mass. Atrioventricular-groove involvement may cause rupture and right coronary artery compromise, requiring multimodality imaging and emergency salvage surgery; early multidisciplinary planning is essential because complete resection may be impossible.

Lifestyle medicine (LM) provides a high-value framework for treating and potentially reversing chronic diseases, such as type 2 diabetes (T2D), obesity, cardiovascular diseases, and some cancers. Yet, the field of LM is still growing, and few examples exist of how to successfully implement LM into clinical care. This paper describes the implementation of 1:1 lifestyle medicine (LM) coaching visits for 45 patients with uncontrolled type 2 diabetes (T2D), (mean HbA1c 10.5%) and on multiple diabetes medications, at Cone Health's Reidsville Endocrinology practice in North Carolina, USA. In brief, during routine endocrinology visits, the lead physician of the LM program at Cone Health, who is trained in LM, identified patients with uncontrolled T2D where scheduling allowed him to fit in some additional time for coaching. Forty-five interested patients selected over a period of several weeks from Spring of 2022 to Fall of 2022 made the first cohort. During a typical LM encounter, immediately after addressing their referral concerns with a routine endocrinology consult, verbally consenting patients were personally invited to learn more about LM. They were provided with a packet of materials focused predominately on prescribing nutrition and exercise as treatment for chronic disease. The physician spent an additional 10-15 minutes with each verbally consenting patient to go through selected materials in the packet, focusing largely on nutrition and physical activity, and successfully billed for the additional time. The patients were encouraged to take the packet home for further learning and return to their next routine visits with questions and to engage in further coaching. Following this brief but intensely focused coaching session which was done in addition to the routine endocrinology visit, lifestyle medicine coaching was able to be incorporated into subsequent, routine endocrinology visits in many of the initially identified patients. The majority of these patients also accepted a referral to a dietitian in the same practice. This experience highlights a model for potentially integrating LM coaching into routine practice and, consistent with previous research, highlights the importance of a site champion for successful LM implementation. Future research is needed to formally assess the success of coaching visits, particularly in terms of assessing health outcomes in patients who engaged in the 1:1 coaching.

[This retracts the article DOI: 10.1155/2021/6868514.].

PD-1/PD-L1 blockade can produce durable tumor control, yet primary, adaptive, and acquired resistance remain common. Existing accounts often catalogue resistance by cellular compartment, obscuring the coordinated nature of tumor adaptation. Here, we introduce immune-pressure redistribution as a treatment-oriented framework that complements cancer immunoediting by asking where therapeutic immune pressure is diverted after checkpoint release. Resistance is organized into three coupled routes: transfer into tumor-intrinsic escape through antigen-presentation loss, interferon-response defects, oncogenic rewiring, and lineage plasticity; weakening through defective priming, terminal T-cell differentiation, compensatory checkpoints, metabolic constraint, and chronic cytokine signaling; and unloading into stromal, vascular, myeloid, regulatory, microbial, and systemic host compartments. We integrate clinically validated mechanisms with emerging evidence, including the temporal duality of interferon-JAK signaling, the role of tumor-draining lymph nodes in sustaining progenitor-exhausted T cells, and the limited translation of TIGIT, IDO1, TGF-β, and CSF-1R targeting. We further propose a biomarker-guided strategy that combines tumor visibility, immune-cell state, spatial architecture, systemic inflammation, and early treatment dynamics to identify the dominant resistance topology. This framework supports topology-matched combinations and adaptive sequencing rather than uniform escalation, with the aim of restoring productive immune pressure while limiting compensatory escape and toxicity.

Relapse remains the leading cause of treatment failure after allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia and myelodysplastic syndromes. Post-transplant treatment may provide a third anti-leukemic effect after conditioning-related cytotoxicity has waned and before graft-versus-leukemia immunity is fully established. Prophylactic maintenance is initiated in high-risk patients despite undetectable measurable residual disease (MRD), whereas pre-emptive treatment is triggered by the detection of MRD or declining donor chimerism. Hypomethylating agents (HMAs) are biologically attractive and feasible with post-transplant-adapted dosing, but prophylactic azacitidine did not improve relapse-free or overall survival in a randomized trial. Newer decitabine-based, oral HMA, and venetoclax-containing strategies require confirmation. FMS-like tyrosine kinase 3 (FLT3) inhibitors have the strongest prospective evidence in a molecularly selected population. The QuANTUM-First trial supports quizartinib throughout induction, consolidation, and continuation, including after transplantation, whereas the MORPHO trial directly evaluated post-transplant gilteritinib and identified its clearest benefit in patients with detectable peri-transplant FLT3-internal tandem duplication (FLT3-ITD) MRD. This review traces the evolution of relapse prevention strategies and proposes a practical framework integrating baseline risk, serial MRD assessment, targetable biology, immune intervention, and post-transplant feasibility.