Post-polypectomy surveillance is a cornerstone of colorectal cancer (CRC) prevention, yet current reliance on colonoscopy poses challenges related to capacity, patient burden, and adherence. Amid growing interest in non-invasive strategies, this review evaluates the diagnostic performance, clinical applicability, and limitations of emerging alternatives, including faecal immunochemical testing (FIT), multitarget stool DNA (mt-sDNA), CT colonography (CTC), circulating tumour DNA (ctDNA), and colon capsule endoscopy (CCE), in the context of post-polypectomy surveillance. While FIT remains widely endorsed for low-risk populations, its limited sensitivity for flat adenomas and serrated lesions constrains its utility. mt-sDNA and CTC offer incremental improvements in detection but face cost-effectiveness, false-positive, and guideline limitations in surveillance. ctDNA holds promise for recurrence monitoring in high-risk CRC but remains investigational for adenoma surveillance. Evidence for CCE as a triage tool is emerging, though concerns persist regarding incomplete examinations, cost, and residual risk. Importantly, substantial heterogeneity in surveillance guidelines and suboptimal real-world adherence complicate evaluation and implementation of these modalities. Integration of molecular biomarkers and risk-adaptive strategies may support more personalised follow-up. However, robust comparative effectiveness studies that account for system-level and behavioural factors are essential to guide appropriate adoption. Non-invasive tools remain complementary, not yet replacements, for colonoscopy in post-polypectomy care.

Gastrointestinal stromal tumors (GISTs), the most common mesenchymal neoplasms of the digestive tract, are primarily driven by gain-of-function mutations in the receptor tyrosine kinases KIT or PDGFRA. The introduction of imatinib, a selective tyrosine kinase inhibitor (TKI), revolutionized the management of advanced GIST. However, the emergence of drug resistance remains a major clinical challenge, limiting long-term efficacy. Resistance mechanisms are multifactorial, predominantly involving secondary mutations in KIT or PDGFRA that impair TKI binding or stabilize the kinase in an active conformation. Beyond genomic alterations, nonmutational adaptive responses-including dysregulation of noncoding RNAs, metabolic reprogramming, epigenetic modifications, and an immunosuppressive tumor microenvironment-significantly contribute to treatment failure. This review comprehensively analyzes these resistance pathways and discusses the evolution of therapeutic strategies toward precision medicine. Current approaches emphasize molecular subtype-guided first-line therapy, ctDNA-driven sequencing of subsequent lines, and the use of novel TKIs (e.g., avapritinib, ripretinib, bezuclastinib) tailored to specific resistance mutations. Furthermore, we explore emerging modalities such as boron neutron capture therapy (BNCT), which offers a kinase-independent mechanism to target resistant disease, and combination strategies that integrate immunotherapy, epigenetic modulators, and pathway-specific inhibitors. Advances in liquid biopsy and molecular profiling are enabling real-time adaptation of therapy, moving GIST management toward a dynamic, personalized paradigm aimed at overcoming resistance and improving patient outcomes.

The 6th Edition of the WHO Classification of Digestive System Tumours represents a significant update to the 5th edition. It integrates pathological, new molecular, and clinical insights to refine the taxonomy of digestive system neoplasms. The revised classification continues to emphasise standardisation in terminology, coding, and diagnostic criteria to facilitate global consistency in diagnosis, treatment, epidemiological reporting and research. Structural reorganisation of book chapters describes epithelial tumours by anatomical site, while separating neuroendocrine, mesenchymal and haematolymphoid tumours into dedicated chapters that are aligned with other WHO tumour volumes. Genetic tumour syndromes are classified by mechanisms, pathways and genes, whereas metastatic disease is comprehensively covered under other tumours and metastases. Key structural and diagnostic refinements include consolidation of gastric dysplasia entities; separation of duodenal/ampullary from jejuno-ileal tumours; clearer categorisation of colorectal serrated polyps and novel carcinoma grading; introduction of small- and large-duct intrahepatic cholangiocarcinoma as separate entities, and redefinition of undifferentiated carcinoma to include 'carcinoma with mesenchymal differentiation'. Several new entities are introduced, including oesophageal epidermoid metaplasia, colorectal intramucosal adenocarcinoma, low-grade tubuloglandular adenocarcinoma and lymphoglandular complex-like adenocarcinoma, intraductal tubulopapillary and intraductal oncocytic papillary neoplasms of the bile ducts and sonic hedgehog hepatocellular adenoma. The concept of amphicrine-like carcinoma (ALC) is distinguished from MiNEN and broadens the understanding of tumours with dual neuroendocrine-non-neuroendocrine differentiation. Grading systems are simplified to two-tier classifications (low/high grade) across precursor lesions, with enhanced criteria for neuroendocrine tumour grading. Anal canal neoplasia terminology is harmonised with human papillomavirus (HPV) related Lower Anogenital Squamous Terminology (LAST) and mass-forming biliary and gallbladder cancer precursors share similar terminology. Finally, carcinoma of unknown primary (CUP) is included in a separate section for the first time, classified by molecular and immunophenotypic profiles to guide therapy. Overall, the 6th edition strengthens tumour diagnostic precision and molecular alignment across the digestive system.

Adrenergic (ADRN) neuroblastoma cells have a paradoxical increase in TET1 expression and 5-hydroxymethylcytosine (5-hmC) deposition in hypoxia. However, the effect of hypoxia on the mesenchymal (MES) lineage remains less well understood. To identify lineage specific hypoxia responses, we evaluated 5-hmC and RNA expression in a panel of ADRN and MES cells cultured in normoxic or hypoxic conditions. In hypoxia, MES cells had only a modestly elevated expression of hypoxia signaling and no phenotypic changes. In contrast, ADRN cells showed increased 5-hmC deposition and decreased mitochondrial function in hypoxia. In hypoxia, only ADRN cells had increased expression of MES signature genes (p < 0.05) and related pathways including TNF-α signaling. Publicly available RNA-Seq data of diagnostic tumors was accessed (GSE62564 and GSE73517). Each tumor was assigned a hypoxia score using a published hypoxia signature. A MES/hypoxia signature comprising 94 MES signature genes that had increased expression in ADRN cells exposed to hypoxia was also generated. This MES/hypoxia signature was significantly correlated with a T cell infiltration signature (r = 0.66, p = 2.3 × 10^-12). Kaplan-Meier analysis and the log rank test assessed overall survival (OS) differences between groups. High-risk patients with hypoxic tumors that had high MES/hypoxia scores had significantly improved 3-year OS compared to those with low MES/hypoxia scores (71% vs. 40%; p = 0.0054). Superior survival was also observed in high-risk patients with hypoxic tumors that had high MES/hypoxia scores in the validation cohort (GSE73517; n = 28; 3-year OS 78% vs. 26%, p = 0.0012). Our results suggest that hypoxia changes expression of genes in ADRN cells towards MES cells.

Immune cell intravasation into the tumor is an absolute requirement for the immune system to exert control on tumor growth. Its regulation directly influences immune surveillance and therapeutic response to immunotherapies and other immune cell-dependent cancer therapies. Despite its significance, investigation of this process remains a major challenge due to technical limitations. Intravital microscopy (IVM) has emerged as an essential tool for visualizing dynamic cellular interactions within the tumor microenvironment. This study presents an optimized IVM-based technique to track immune cell interactions with tumor endothelium in a preclinical model. Our approach combines high-resolution imaging with fluorescent labeling strategies to capture real-time interactions between immune and endothelial cells. By providing an enhanced method for studying immune infiltration in tumors, this technique could contribute to a better understanding of the tumor microenvironment and the development of novel therapeutic strategies.

The Integrated Motivational-Volitional (IMV) Model of Suicidal Behavior places defeat and entrapment central to the development of suicidal ideation. Factors such as loneliness and resilience may moderate risk. This study examines the longitudinal relationship between these variables.

Secondary data from the UK COVID-19 Mental Health and Wellbeing Study (COVID-MH) were analyzed (n = 2518). Defeat, entrapment, loneliness, resilience, and suicidal ideation were measured across 3 waves (March to May 2020). Six longitudinal mediation models were tested, each with wave 2 entrapment (or subscales) as mediator of wave 1 defeat and wave 3 suicidal ideation. Loneliness and resilience (from waves 1 and 2) were included as moderators of the associations between defeat and entrapment with suicidal ideation.

Wave 2 entrapment mediated the relationship between wave 1 defeat and wave 3 suicidal ideation, controlling for wave 1 entrapment and suicidal ideation. Wave 1 loneliness and resilience moderated the pathway from defeat to entrapment, but wave 2 resilience or loneliness did not moderate the pathway from entrapment to suicidal ideation.

Findings provide robust longitudinal support for the motivational phase of the IMV model and highlight the importance of targeting entrapment and loneliness and enhancing resilience.

Adolescence is a critical developmental stage during which environmental, metabolic, and psychosocial factors co-occur and may interact, influencing health and creating a syndemic context that remains insufficiently explored.

We analyzed a syndemic model, considering socioeconomic determinants and metabolic risk associated with asthma and depression in adolescents.

This population-based study (n = 2515) utilized data from the RPS Brazilian Consortium Cohorts at follow-up of 18-19 years in São Luís, Brazil. A theoretical model analyzed the association among socioeconomic determinants, metabolic risk, asthma, and depression using Structural Equation Modeling (SEM). Low Socioeconomic Status was a distal determinant. The metabolic risk included the TG/HDL ratio, as an insulin resistance marker, as well as obesity. Asthma was a latent variable based on wheezing, asthma history, medical diagnosis, and frequency of wheezing. Depression was diagnosed based on major and recurrent episodes using the M.I.N.I.

Low socioeconomic status was associated with higher insulin resistance precursor (TG/HDL ratio) (standardized coefficient, SC = 0.064; p = .027) and with higher levels of depression (SC = 0.084; p = .001). Higher insulin resistance precursor was associated with asthma (SC = 0.069; p = .042). Asthma was associated with depression (SC = 0.078; p < .001). Lower insulin resistance precursor levels were observed in girls (SC = -0.254; p < .001); meanwhile, obesity (SC = 0.124; p < .001) and depression (SC = 0.165; p < .001) had higher values for them.

Our findings underscore interconnected issues of low socioeconomic status, metabolic risk, asthma, and depression in adolescents. Recognizing the syndemic framework can lead to more effective health policies to prevent long-term physical and mental health consequences.

The optimal airway management strategy for critically ill patients requiring prolonged mechanical ventilation is debated. Tracheostomy is often performed to mitigate complications of prolonged endotracheal intubation (ETT), but its comparative impact on outcomes remains unclear due to confounding by indication.

To compare the baseline characteristics and unadjusted clinical outcomes between mechanically ventilated ICU patients managed with an ETT and those who underwent tracheostomy.

A prospective observational cohort study was conducted over 1 year (January to December 2024) in the General, Trauma and Medical Intensive Care Units of a tertiary university hospital in Cairo, Egypt. Baseline severity was assessed using APACHE II scores. Primary outcomes were VAP incidence and in-hospital mortality. Only unadjusted analyses were performed due to significant baseline confounding.

Mechanically ventilated adult patients were grouped based on their airway status into an Endotracheal Tube (ETT) group (n = 89) and a Tracheostomy group (n = 57). Patients in the tracheostomy group had significantly higher baseline illness severity (mean APACHE II: 26.4 ± 5.7 vs. 23.2 ± 5.9; p = 0.001) and a different clinical profile, with a higher prevalence of neurological diagnoses (63.2% vs. 9.0%, p < 0.001). The unadjusted incidence of VAP was higher in the tracheostomy group (80.7% vs. 57.3%; p = 0.004). Mortality was also higher (52.6% vs. 46.1%), but this difference was not statistically significant (p = 0.455). The tracheostomy group had longer durations of mechanical ventilation and ICU stays.

In this observational study, patients selected for tracheostomy were sicker at baseline and had poorer unadjusted outcomes than those managed with ETTs. The findings highlight profound confounding by indication, where tracheostomy is performed on patients with a poorer prognosis. The results underscore that valid comparisons of airway strategies require randomised controlled trials or meticulously adjusted observational studies to account for baseline differences. The high-performance predictive model can serve as a sustainability indicator for quality improvement initiatives, allowing ICUs to track the long-term effectiveness of airway management's protocols.

This study challenges the perception that tracheostomy universally improves outcomes in mechanically ventilated ICU patients. Clinicians should carefully weigh the timing and indication for tracheostomy, recognising that it may not reduce-and could potentially increase-infection risk and mortality, particularly in high-severity patients. Rigorous infection control measures and daily assessment for tracheostomy weaning or decannulation are essential.

Accurate estimates of the burden of vaccine-preventable community-acquired pneumonia (CAP) hospitalisations both overall and due to the most frequent and vaccine-preventable pathogens are needed to inform the use of respiratory vaccines in adults.

This was a prospective, population-based CAP surveillance study at three hospitals in Germany. All patients admitted with clinically suspected CAP were tested for Streptococcus pneumoniae using urine antigen tests and for respiratory syncytial virus (RSV), influenza virus and SARS-CoV-2 using multiplex PCR from nasopharyngeal swabs. Incidence rate calculations for all-cause CAP were based on eligible patients, regardless of enrolment status.

Individuals admitted to study hospitals within the surveillance period with suspected or confirmed diagnosis of pneumonia who provided informed consent.

Radiologically confirmed (RAD) CAP.

Active surveillance between 1 January 2021 and 30 June 2023 identified at the three study sites 4319 adults with RAD-CAP that met eligibility criteria, of which 1479 (34.2%) were enrolled and included in the analysis for pathogen distribution. The main reason for non-enrolment was the inability to provide informed consent. Incidence estimates were based on 1254 study-eligible individuals admitted at the largest study site. SARS-CoV-2, S. pneumoniae, RSV or influenza were identified in 36.5%, 9.1%, 3.7% and 1.8% of patients with RAD-CAP, respectively. Serotypes included in the 20-valent pneumococcal conjugate vaccine were detected in 6.9% of RAD-CAP and 76.0% of pneumococcal CAP. The overall adjusted annual incidence of all-cause RAD-CAP over the study period was 490/100 000 (95% CI 461 to 521). The incidence of pneumococcal and RSV-related RAD-CAP increased 8.6-fold and 10.0-fold over the study period, resulting in an incidence of 60/100 000 (95% CI 45 to 75) and 30/100 000 (95% CI 19 to 41) in 2022/2023, respectively, while SARS-CoV-2 related RAD-CAP declined by 70% to 97/100 000 (95% CI 78 to 116).

Active pneumonia surveillance reported a high burden of RAD-CAP hospitalisations in Germany, especially among older adults. The resurgence of CAP due to RSV, S. pneumoniae or influenza, alongside maintained activity of SARS-CoV-2, was associated with an overall increase of RAD-CAP among adults.

To examine differences in physical health conditions among female veterans compared with male veterans and female civilians.

Cohort analysis using data from the UK Biobank, incorporating self-reported and hospital-derived health information.

Veteran status was identified using Standard Occupational Classification codes. The study included female veterans (n=546), male veterans (n=2722) and female civilians (n=66 305).

Physical health conditions were identified through self-report and hospital records. Multivariable logistic regression models estimated associations between veteran status and selected health conditions, adjusting for age, sociodemographic factors, time in service, body mass index and current smoking status.

Compared with female civilians, female veterans had increased odds of chronic obstructive pulmonary disease (adjusted OR (aOR) 1.79, 95% CI 1.04 to 3.08) and lower odds of hypertension (aOR 0.74, 95% CI 0.59 to 0.93), with no significant difference in musculoskeletal conditions or osteoarthritis. Compared with male veterans, female veterans had significantly higher odds of osteoarthritis (aOR 1.61, 95% CI 1.25 to 2.08), migraine (aOR 2.63, 95% CI 1.66 to 4.19) and thyroid disorders (aOR 4.42, 95% CI 2.83 to 6.89).

Female veterans have distinct physical health profiles, including a greater burden of musculoskeletal and respiratory conditions compared with male veterans and female civilians. These findings highlight the need for targeted prevention and clinical interventions for women with a history of military service.