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PubMed2026

Assessing the public health impact of routinely collected electronic healthcare record data in NICE guidelines: A systematic review of CPRD research.

OBJECTIVES: Evidence used in NICE guidance has traditionally prioritised randomised controlled trials, but increasing availability of electronic health record (EHR) data has expanded opportunities for real-world evidence. The Clinical Practice Research Datalink (CPRD) is a commonly used UK primary care EHR resource, yet the extent to which CPRD studies have informed NICE guidelines in the past decade is unclear. STUDY DESIGN: The systematic review was conducted in accordance with PRISMA guidelines. METHODS: We conducted a systematic review of CPRD studies in PubMed, MEDLINE, and Embase published between 04/16-09/25. For each eligible CPRD study, targeted searches of NICE guidelines were performed to identify explicit citations in NICE guidelines. Two reviewers screened and extracted data independently, resolving disagreements by consensus or third reviewer. Guideline information, number of guidelines over time, type of guidelines, and disease area guidelines (using British National Formulary (BNF) chapters) were described. RESULTS: 7181 records were identified. After de-duplication, 2704 unique CPRD studies were screened against NICE guidelines. Of these, 92 CPRD-based studies met inclusion criteria and were cited across 67 NICE documents. The annual number of NICE guidelines citing CPRD studies increased between 2016 and 2025; 1.5% of identified guidelines published in 2016 and 27.7% in 2025. The guideline citing the most CPRD studies was cancer related. The most common types of guidelines included clinical guidelines (49.3%) and technology appraisals (32.8%). Guidelines made up 12 different BNF categories, most frequently central nervous system related (23.9%; n = 16). CONCLUSION: Observational CPRD studies are increasingly referenced in NICE guidelines across multiple disease areas, supporting the growing role of EHR data in national guideline development.

Clinical studies↗

PubMed2026

ORBIT: Oncogenic Representation Learning via Bi-Prototype Contrastive Learning in Hyperbolic Space for cancer driver gene identification.

Accurate identification of cancer driver genes is crucial for precision oncology but remains challenging due to the complexity of integrating heterogeneous data and modeling dynamic biological systems. To address these limitations, we propose ORBIT (Oncogenic Representation Learning via Bi-Prototype Contrastive Learning in Hyperbolic Space). Our framework synergistically fuses multi-omics profiles with functional network data using a context-adaptive graph reweighting mechanism to capture cancer-specific dynamics. The model employs a bi-prototype contrastive learning strategy within hyperbolic space, which aligns gene representations around distinct driver and non-driver semantic anchors while preserving the intrinsic hierarchy of biological networks. Comprehensive evaluations demonstrate that ORBIT achieves highly competitive stability in pan-cancer analysis while consistently outperforming state-of-the-art methods in cancer-specific predictions. Furthermore, functional enrichment analysis confirms that the model effectively segregates core cancer pathways, and drug sensitivity profiling validates the clinical relevance of the identified drivers. By integrating hyperbolic geometry with context-adaptive learning, ORBIT offers a robust and interpretable paradigm for precision medicine. The source codes and datasets are publicly accessible at https://github.com/spcho-dev/ORBIT.

Humans↗

PubMed2026

Characteristics of p53 and Smad4 immunohistochemistry in pancreatic ductal adenocarcinoma and validation by next-generation sequencing.

BACKGROUND: Mutations in four major driver genes -KRAS, CDKN2A, TP53, and SMAD4- are central to the pathogenesis of pancreatic ductal adenocarcinoma (PDAC) and critically inform diagnosis, therapeutic decision-making, and prognostic assessment. Although next-generation sequencing (NGS) is widely regarded as the gold standard for detecting these mutations, its clinical application is often limited by suboptimal analytical efficiency and substantial economic cost. Among these genes, immunohistochemical (IHC) staining for the proteins encoded by TP53 and SMAD4 has been extensively adopted in routine pathology practice. However, standardized IHC pattern classification schemes and rigorous validation of their predictive accuracy for underlying genomic alterations remain lacking in PDAC. METHODS: We retrospectively enrolled 63 PDAC patients and systematically characterized the typical IHC expression patterns of p53 and Smad4. Targeted NGS was subsequently performed on all available tumor specimens, and the resulting mutational profiles were correlated with corresponding IHC findings. Diagnostic performance including sensitivity, specificity and accuracy of p53 IHC for predicting TP53 mutations and of Smad4 IHC for predicting SMAD4 mutations was rigorously evaluated. RESULTS: Among the four canonical driver genes, co-occurring double- or triple-gene mutations were prevalent; within TP53 and SMAD4, missense mutations constituted the most frequent variant type. Using NGS as the reference standard, we validated the diagnostic utility of a three-tiered p53 IHC classification system, particularly in fine-needle biopsy (FNB) specimens. Furthermore, we proposed a novel, refined Smad4 IHC pattern classification that incorporates an "intermediate" category, thereby expanding upon conventional binary interpretation. This new scheme achieved markedly improved mutation prediction accuracy (0.76) compared with traditional approaches (0.57). CONCLUSION: Our study highlights the complementary diagnostic value of p53 and Smad4 IHC relative to molecular testing in PDAC, especially when tissue is limited, as commonly encountered in FNB specimens. The newly established Smad4 IHC classification system, which integrates an intermediate expression category into the conventional two-tier framework, demonstrates superior clinical utility and enhances predictive accuracy for SMAD4 genomic alterations.

Humans↗

PubMed2026

Prognostic Value of Circulating Tumor DNA-Based Minimal Residual Disease for Recurrence-Free Survival in Resectable Gastric Cancer: A Systematic Review and Meta-Analysis with Serial Monitoring Analysis.

BACKGROUND: Circulating tumor DNA (ctDNA)-based minimal residual disease (MRD) is an emerging biomarker, but its utility in resectable gastric cancer remains incompletely characterized. METHODS: We conducted a systematic review and meta-analysis of eight studies (520 patients) to evaluate the prognostic value of ctDNA-based MRD for recurrence-free survival (RFS) and overall survival (OS) in resectable gastric cancer. RESULTS: In localized resectable gastric cancer (Stage I-III), the setting in which postoperative ctDNA most coherently represents true molecular residual disease after curative-intent surgery, postoperative ctDNA positivity was associated with diminished recurrence-free survival (RFS: HR 12.26, 95% CI 3.30-45.52) and overall survival (OS: HR 8.57, 95% CI 3.06-23.98). The test for subgroup differences between localized and mixed-stage cohorts was not statistically significant (P = 0.57), and the numerically higher HR in the localized subgroup should therefore not be interpreted as evidence of a quantitatively stronger prognostic effect. Postoperative ctDNA detection demonstrated substantially stronger prognostic value (overall RFS: HR 10.00, 95% CI 4.53-22.10) compared to preoperative assessment (HR 2.17, 95% CI 1.10-4.28). Both tumor-informed and tumor-agnostic strategies effectively stratified high-risk patients. However, these effect sizes should be interpreted cautiously given the small number of studies and substantial heterogeneity (I2 = 65-72%). Results from mixed-stage cohorts including Stage IV disease are supportive but should not be considered equivalent to localized-disease findings, as ctDNA in metastatic disease reflects persistent systemic burden rather than minimal residual disease in the postoperative sense. CONCLUSIONS: Postoperative ctDNA-based MRD shows a consistent adverse prognostic association in resectable gastric cancer, with localized disease (Stage I-III) representing the most biologically and clinically coherent setting for interpretation. However, the large pooled hazard ratios (HR 10.00-12.26) should be interpreted as a directionally consistent signal rather than precise quantitative estimates, given the small number of studies, wide confidence intervals, and substantial heterogeneity (I2 = 65-73%). This heterogeneity is largely driven by substantial variation in postoperative sampling timing (4 days to 16 weeks) and ctDNA assay characteristics (platform, sensitivity, coverage, variant filtering, and positivity thresholds), which require standardization in future studies. While ctDNA is prognostically valuable, its clinical utility remains unestablished. Prospective randomized trials are needed to determine whether ctDNA-guided strategies improve patient outcomes before routine clinical implementation can be recommended.

Humans↗

PubMed2026

Antibody-drug conjugates against multidrug-resistant cancers: Biomarker-guided patient selection, payload engineering, linker chemistry, and bystander effects.

Antibody-drug conjugates (ADCs) are one of the most significant advancements in modern cancer therapeutics. Combining the target selectivity of monoclonal antibodies with the cytotoxic potential of payloads, ADCs effectively kill cancer cells and offer hope to patients with even refractory cancer types. Beyond simply increasing the number of therapeutic options available for cancer patients, ADCs have become a powerful frontline agent in overcoming multidrug resistance (MDR). As one of the most challenging obstacles to effective cancer care, MDR is mediated by ATP-binding cassette (ABC) transporter-mediated drug efflux, target-based mutations, and dysregulated apoptosis. The clinical success of ADCs specifically engineered to overcome MDR, including in heterogeneous tumors and cancer cells that exhibit bypass signaling, is well established. This is especially evident with trastuzumab deruxtecan (T-DXd) in HER2-low, HER2-positive, and HER2-mutant cancers; sacituzumab govitecan (SG) in TROP2-expressing triple-negative breast cancer (TNBC) and urothelial carcinoma; and enfortumab vedotin in Nectin-4-positive bladder cancer. By overcoming MDR, ADCs have enabled more effective treatment algorithms across multiple malignancies. Most importantly, the clinical application of ADCs has become inextricably linked to cancer genomics. HER2 testing has evolved from a two-tiered system to a continuous spectrum including HER2-ultralow, HER2-low, HER2-positive, and ERBB2-mutant categories. Each of these categories exhibits different eligibility guidelines for ADC patient selection. As cancer cells continue to evolve and develop resistance to even ADCs through mutations and variants, researchers and clinicians have used pharmacogenomics to predict ADC response and resistance. To define the genomic architecture of ADC-resistant tumor subpopulations, single-cell transcriptomic studies and liquid biopsy approaches are being used to enable real-time examination of the tumor genome during ADC therapy, thereby optimizing treatment and circumventing resistance driven by emerging mutations and variants. This review provides a comprehensive analysis of the molecular structure of ADCs, the pharmacological principles underlying their potent cytotoxic activity against MDR cancer cells, the genomic and transcriptomic biomarkers that guide ADC patient selection, and the emerging resistance mechanisms that will shape the next generation of promising ADC development.

Humans↗

PubMed2026

Utility of hearing aid use on neurocognitive functions and auditory processing: A systematic review.

PURPOSE: Hearing loss not only affects the peripheral auditory system but also leads to changes in central auditory pathways and neurocognitive skills. The use of hearing aids has shown potential benefits in mitigating the adverse effects of hearing loss. Earlier literature showed various studies assessing the impact of hearing aid use on cognitive functions and auditory processing, a comprehensive review of the existing literature is warranted. Existing literature showed heterogeneous outcomes among studies investigated the effect of Hearing aid use in combating the adverse effects of hearing loss on neurocognitive functions and auditory processing. METHOD: Databases including PubMed, SciELO, Cochrane Library, PsycINFO, Web of Science, and Index Copernicus were searched (2005-2025) using English keywords on hearing aid effects on neurocognition and auditory processing in individuals with hearing loss. Studies on effect of hearing aid use on neurocognition and auditory processing were included, while those involving cochlear implant users or other neurological disorders unrelated to hearing loss were excluded. Titles, authors and publication years were examined, and duplicates were removed. RESULTS: Total of 61 research papers were found on specific area and were included in the present review. Findings of these 61 articles have been analysed and are reported in this article. The outcome of the present study showed usefulness of hearing aid use on neurocognitive functions and auditory processing. CONCLUSION: The present literature review emphasized the importance of early rehabilitation through hearing aid use to alleviate the adverse effects of hearing loss on neurocognitive function and auditory processing.

Humans↗

PubMed2026

Improved quality of life and prolonged survival with add-on homeopathic treatment in patients with non-small cell lung cancer: a prospective, randomized, placebo-controlled, double-blind, three-arm, multicenter study.

BACKGROUND: Alongside conventional anticancer treatment, add-on homeopathy might help to alleviate adverse effects of conventional therapy. AIM: The aim of this study was to replicate previous studies on the effect of adjunctive homeopathy on quality of life (QoL) and survival in non-small cell lung cancer (NSCLC) patients. METHOD: In this prospective, randomized, placebo-controlled, double-blind, three-arm multicenter phase III study with quadruple-checked data analysis, we investigated the potential effects of an add-on homeopathic treatment compared to placebo in patients with stage IV NSCLC in terms of QoL. Ninety-eight received either individualized homeopathic medicinal products (HMPs; n = 51) or placebo (n = 47) in a double-blinded fashion. Fifty-two control patients without homeopathic treatment were only observed in terms of their survival rate. The ingredients of the various HMPs were mainly prepared of plant, mineral, or animal origin. The data entry and statistical analysis were subject to an exceptional quadruple-checked data analysis process. The analysis presented in this article was inspired by our earlier report of this trial published in The Oncologist in 2020, which was retracted by that journal in November 2025 after two corrections; a majority of the co-authors disagreed with this decision. The present article is based on the same trial dataset but was deliberately designed to highlight the unique research methodology: design and preparation by a lead statistician, data entry, data clearing and independent statistical evaluation were performed in four mutually independent steps, reporting follows the CONSORT statement, and the interpretation of the findings has been reframed conservatively. RESULTS: Global health status (QoL) was higher in the homeopathy group than in the placebo group after 9 weeks and after 18 weeks (p < 0.001). With the exception of cognitive functioning at 9 weeks and of pain, diarrhea and financial difficulties at 9 weeks, all functional and symptom scales of the EORTC QLQ-C30 favored the homeopathy group (p < 0.001 for the multivariate comparisons), with between-group differences exceeding the threshold of 10 points that is generally regarded as clinically meaningful. Median survival time over the 730-day observation period was 435 days in the homeopathy group, 257 days in the placebo group (p = 0.010), and 228 days in the non-randomized control group (p < 0.001); the corresponding 2-year survival rates were 45.1%, 23.4%, and 13.5% (homeopathy vs. placebo p = 0.020; homeopathy vs. control p < 0.001). The difference between the placebo group and the non-randomized control group was not statistically significant (p = 0.154). CONCLUSION: In this trial, add-on homeopathy was associated with better quality of life across most functional and symptom domains, with clinically meaningful effect sizes congruently to a previous open study. Survival time was significantly longer in the homeopathy group compared to both the placebo and control groups. Independent replication, ideally within contemporary immuno-oncological treatment regimens is required. TRIALS REGISTRATION: ClinicalTrials.gov; No.: NCT01509612; January 7, 2012.

Humans↗

PubMed2026

Perspectives of participating neurologists and study nurses - Mixed-methods process evaluation of a web-based program for relapse management in multiple sclerosis (POWER@M2).

BACKGROUND: Relapsing-remitting multiple sclerosis is a chronic inflammatory disease of the central nervous system and the leading cause of disability in young adults. In Germany, 90% of relapses are treated with high-dose intravenous glucocorticoids, despite limited evidence for long-term benefit and international preference for oral administration. Time constraints often hinder informed decision-making. The multicentre Randomized Controlled Trial (RCT) POWER@MS2 (N = 160, 2020-2023), conducted at 18 German MS-centres, aimed to promote self-determined relapse management through a complex intervention (dialogue-based decision aid, nurse-led webinar, online-chat). OBJECTIVE: While RCTs demonstrate effectiveness, process evaluations are essential to understand implementation, mechanisms of impact and contextual factors. This study explored healthcare professionals' experiences and attitudes toward implementing relapse self-management and self-medication in clinical practice. METHODS: A mixed-methods process evaluation followed the UK Medical Research Council- framework. Quantitative data were collected via validated questionnaires at up to three time points and analysed descriptively. Interview guides were developed based on these results. Qualitative data from neurologist and study nurse interviews were thematically analysed. Results were triangulated using a joint display. RESULTS: Data were collected from 55 neurologists and 17 study nurses (quantitative) and from 7 neurologists and 4 nurses (qualitative) (2020-2024). Most neurologists opposed routine steroid use, reserving it for severe relapses. Some voiced concerns about self-management, but informed patients were generally viewed as capable of safe self-medication. Study nurses gave mixed feedback on the intervention, citing overload and improved guidance. CONCLUSION: Clinicians showed openness toward implementing the intervention. Enhancing accessibility and addressing specific concerns may support broader adoption.

Humans↗

PubMed2026

Pre-treatment polyfunctionality percentage (PFA) of CD8+ T cells is associated with development of immune-related adverse events (irAEs) in patients receiving immune checkpoint inhibitors (ICIs).

INTRODUCTION: Immune checkpoint inhibitors (ICIs) have improved cancer survival, but immune-related adverse events (irAEs) occur frequently and can have devastating consequences. There are no validated methods to evaluate risk of irAEs prior to initiation of ICIs. MATERIALS AND METHODS: We conducted a pilot study evaluating the ability of blood-based, single-cell secretomic analysis to characterize irAEs. A total of 10 patients with thoracic malignancies who were scheduled to receive ICIs were enrolled. Each patient had a pre-ICI blood sample drawn as well as a sample at the time of irAE development or 12 weeks after ICI initiation, whichever came first. Utilizing IsoPlexis's IsoLight system, polyfunctionality percentages (PFAs) and strength indices (PSIs) were analyzed for CD4+ and CD8+ T cells. RESULTS: Five patients developed irAEs and 5 patients did not develop irAEs. Pre- and post-ICI CD8+ T cell PFA was significantly elevated in patients who developed irAEs compared with those who did not (p = 0.017 and p = 0.014, respectively). CONCLUSIONS: In this pilot study, pre-ICI CD8+ T cell PFA was associated with development of irAEs. While this is a pilot study, this is a first step toward developing a blood-based, streamlined assay to assess risk of irAEs prior to initiation of ICIs. Validation in larger cohorts is warranted.

Humans↗

PubMed2026

Identification of molecular subtypes in clear cell renal cell carcinoma based on chromatin regulators and tumor immune microenvironment profiling.

In the histological classification of renal cell carcinoma, clear cell renal cell carcinoma (ccRCC) accounts for the highest proportion and is the most common subtype. Despite advances in management, it continues to be associated with considerable incidence and mortality. Although surgery and systemic therapies are available, their efficacy is constrained by pronounced intratumoral heterogeneity and treatment resistance. Identifying robust biomarkers and clarifying the underlying biological mechanisms are therefore essential to improving diagnosis, risk stratification and therapeutic decision-making. In this work, we identified two ccRCC molecular subtypes displaying divergent chromatin regulator (CR) profiles and different clinical prognoses. Using the genes differentially expressed between these subgroups, we constructed a CR-related score (CRS) that effectively stratified patients according to survival. More analysis concluded that the low expression of CR was more linked with the immune-activated tumors, which encompassed the immune pathway enrichment, as well as the elevation of numerous immune cell subtypes. Moreover, elevated CRS was associated with improved immunotherapy responsiveness. Drug-sensitivity analyses nominated several candidate agents, and SMARCD3 knockdown in 786-O cells inhibited proliferation and migration and reduced sensitivity to masitinib. Collectively, these findings support the prognostic and therapeutic relevance of CR-related states in ccRCC and provide a framework for future experimental validation of chromatin-regulated tumor-immune interactions.

Humans↗

PubMed2026

Corneal Epithelial Alterations Associated With Cyclin-Dependent Kinase 4/6 Inhibitor Therapy in Hormone Receptor-Positive Breast Cancer.

IMPORTANCE: Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors are standard therapy for hormone receptor-positive (HR+), HER2-negative breast cancer. By blocking the G1/S cell-cycle transition, these agents may impair renewal of the corneal epithelium. No controlled study has systematically evaluated corneal epithelial changes in patients receiving CDK4/6 inhibitors. OBJECTIVE: To determine whether CDK4/6 inhibitor-based therapy is associated with cornealepithelial alterations independent of aromatase inhibitor exposure and tear film dysfunction. DESIGN, SETTING, AND PARTICIPANTS: Retrospective comparative cross-sectional study at a tertiary ophthalmology center. A total of 132 women were enrolled: 45 receiving a CDK4/6 inhibitor plus an aromatase inhibitor (CDKAI group), 44 receiving aromatase inhibitor monotherapy (AI group), and 43 age-matched postmenopausal controls without systemic oncologic therapy. EXPOSURES: CDK4/6 inhibitor (ribociclib, palbociclib, or abemaciclib) combined with an aromatase inhibitor; aromatase inhibitor alone; or no systemic oncologic therapy. MAIN OUTCOMES AND MEASURES: Prevalence and severity of punctate epitheliopathy and vortex keratopathy, assessed by a masked ophthalmologist. Secondary outcomes included Schirmer I test, tear film break-up time, and Ocular Surface Disease Index (OSDI). RESULTS: PE was present in 44.4% of eyes in the CDKAI group vs 4.7% in the AI group and 2.3% in controls (χ² = 34.31; P < .001). All moderate (13.3%) and severe/complicated (8.9%) PE cases occurred exclusively in the CDKAI group. Vortex keratopathy was observed in 13.3% of CDKAI patients and in none of the other groups (P = .025). Schirmer values, tear film break-up time, and OSDI scores did not differ among groups (all P > .05). Within the CDKAI group, PE was not associated with treatment duration (P = .963) or tear film parameters. CONCLUSIONS AND RELEVANCE: In this comparative study, CDK4/6 inhibitor-based therapy was associated with significantly higher prevalence and severity of PE and vortex keratopathy, independent of aromatase inhibitor exposure and in the absence of measurable tear film dysfunction. These findings suggest a direct cytostatic effect on the corneal epithelium. Symptom scores were low, although OSDI interpretation was limited by incomplete responses. Proactive corneal surface evaluation with fluorescein staining may be warranted during CDK4/6 inhibitor treatment.

Humans↗

PubMed2026

Diagnostic performance of intraoperative in vivo hyperspectral imaging for meningioma grading and molecular alterations: results from a prospective feasibility study.

OBJECTIVE: Hyperspectral imaging (HSI) is an emerging intraoperative, noninvasive, contrast agent-free imaging modality that enables quantitative assessment of tissue composition. The present study aimed to investigate whether HSI-derived tissue parameters correlate with WHO grade and molecular markers of aggressiveness in cranial meningiomas. METHODS: In this prospective study, intraoperative in vivo HSI was performed using the TIVITA tissue system, capturing spectral signatures between 500 and 1000 nm. Quantitative tissue parameters included tissue oxygen saturation (StO2), near-infrared perfusion index, organ hemoglobin index (OHI), and tissue water index (TWI). HSI parameters were correlated with histopathological WHO grade and molecular alterations, including CDKN2A/B deletion, TERT promoter mutation, and 1p/22q loss. Group differences were analyzed using one-way ANOVA, and diagnostic performance was assessed using receiver operating characteristic (ROC) analysis. RESULTS: Forty-six meningiomas were included, comprising WHO grade 1 (n = 35) and WHO grade 2-3 (n = 11) tumors. TWI was significantly higher in WHO grade 2-3 meningiomas compared with WHO grade 1 tumors (mean 0.49 [SD 0.12] vs 0.38 [SD 0.17], p = 0.048). ROC analysis demonstrated an area under the ROC curve (AUC) of 0.71 (95% CI 0.56-0.86, p = 0.036) for TWI in discriminating higher-grade disease. A TWI cutoff ≥ 0.367 identified all WHO grade 2-3 meningiomas with 100% sensitivity and 100% negative predictive value. In a molecular subgroup (n = 15), OHI appeared higher in tumors with homozygous CDKN2A/B deletion than in nondeleted tumors (mean 0.77 [SD 0.04] vs 0.62 [SD 0.10]). However, only 3 CDKN2A/B-deleted cases were available, and these findings should be considered descriptive. ROC analysis yielded an AUC of 0.89 (95% CI 0.71-1.00). An OHI cutoff ≥ 0.712 identified all three CDKN2A/B-deleted tumors (100% sensitivity), with 83.3% specificity and 86.7% accuracy. CONCLUSIONS: The present investigation demonstrated that HSI-derived tissue water and hemoglobin metrics provide biologically meaningful information in meningiomas. Low tissue water content appeared to rule out higher-grade diseases in this first subset cohort, while elevated hemoglobin showed a potential association with CDKN2A/B deletion in a small exploratory subgroup. These findings support the potential of HSI as a real-time noninvasive tool for intraoperative risk stratification and should be evaluated in large-scale studies. German Clinical Trials Register no. DRKS00036771 (www.drks.de).

Humans↗

PubMed2026

Specific Instruments for Caregiving Competence Among Family Caregivers of Cancer Patients: A COSMIN Systematic Review of Psychometric Properties.

OBJECTIVE: To evaluate and summarize the psychometric properties of specific instruments for caregiving competence among family caregivers of cancer patients. METHODS: Systematically searched eight databases for studies published up to November 2025. The methodological quality and psychometric properties of the instruments were evaluated using COSMIN 2.0. Evidence grades were rated using the modified GRADE system (four grades: "High," "Moderate," "Low," and "Very Low"), and recommendations were formulated (Category A: recommended, Category B: potential with further validation, and Category C: not recommended). RESULTS: Seven studies were included, comprising three specific instruments: the Care Competency Scale for Family Caregivers in Home Palliative Care (CCSHPC) (n = 1), the Caregiver Caregiving Self-Efficacy Scale-Oral Cancer (CSES-OC) (n = 1), and the Caring Ability of Family Caregivers of Patients with Cancer Scale (CAFCPCS) (n = 5). Both the CCSHPC and CAFCPCS received Category B recommendations, demonstrating "adequate" content validity with evidence grades rated "very low" and "low," respectively. The CAFCPCS also shows good structural validity ("moderate") and internal consistency ("low") in some cultural contexts. The CSES-OC is a Category C recommendation, with high-quality evidence indicating "inadequate" criterion validity. CONCLUSION: Few specific instruments exist, and most did not strictly follow COSMIN guidelines. The CAFCPCS is provisionally recommended based on relative evidence superiority rather than complete psychometric validation. Further cross-cultural and localized instrument development is warranted. IMPLICATIONS FOR NURSING PRACTICE: Use well-validated specific instruments to identify strengths and weaknesses in the caregiving competencies of family caregivers of cancer patients, enabling them to deliver high-quality home-based cancer care.

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PubMed2026

Artificial intelligence-assisted detection and optical differentiation of colorectal lesions in Lynch syndrome surveillance (CADLY2): a multicentre, open-label, randomised controlled superiority trial.

BACKGROUND: Artificial intelligence (AI)-based computer-aided detection (CADe) systems improve adenoma detection in average-risk colorectal cancer screening. Meanwhile, evidence in Lynch syndrome surveillance is sparse and inconsistent. We assessed the effect of CADe on adenoma detection during Lynch syndrome surveillance. Computer-aided optical diagnosis (CADx) performance for optical differentiation of colorectal lesions was evaluated as a secondary aim. METHODS: CADLY2 was an international, multicentre, open-label, randomised controlled superiority trial at nine specialised hereditary cancer surveillance centres in Belgium, Germany, the Netherlands, and Spain. Adults aged 18 years or older with genetically confirmed Lynch syndrome scheduled for surveillance colonoscopy were randomly assigned (1:1) to high-definition white-light (HD-WL) colonoscopy alone or to HD-WL colonoscopy with computer-aided assistance from CAD EYE (Fujifilm, Tokyo, Japan). CAD EYE was used for CADe during withdrawal and for CADx after lesion detection. Randomisation was done centrally through a secure web-based system using Pocock's minimisation algorithm with a stochastic component and was stratified by centre, sex, previous colorectal cancer, underlying pathogenic variant, and interval since previous colonoscopy. Allocation concealment was ensured through the centralised web-based system. Patients were masked to group allocation until the start of withdrawal in procedures with mild sedation, or until completion of the procedure in procedures with propofol-based sedation. Endoscopists were not masked. The primary outcome was adenoma detection rate, defined as the proportion of patients with at least one histopathologically confirmed adenoma, analysed in the full analysis set (defined as all randomly allocated patients with available data for the primary outcome). The diagnostic performance of the CADx system was evaluated as a secondary outcome. The safety analysis set comprised all randomly allocated patients who underwent a study colonoscopy. This study is registered with the German Clinical Trials Register, DRKS00030695, and is completed. FINDINGS: Between May 9, 2023, and Oct 30, 2025, 757 patients were randomly allocated to HD-WL colonoscopy (377 patients) or to AI-assisted colonoscopy (380 patients); 733 patients were included in the full analysis set (369 HD-WL and 364 AI-assisted). The median age was 49 years (IQR 38-59) in the HD-WL group and 50 years (38-59) in the AI-assisted group; 213 (58%) were female and 156 (42%) male in the HD-WL group, and 207 (57%) were female and 157 (43%) male in the AI-assisted group. The adenoma detection rate was 30·9% (114 of 369 patients) with HD-WL versus 33·8% (123 of 364 patients) with CADe assistance (odds ratio 1·14 [95% CI 0·83-1·57], p=0·41). For CADx differentiation of neoplastic versus non-neoplastic lesions in the paired lesion-level analysis, with histopathology as the reference standard and sessile serrated lesions and traditional serrated adenomas classified as non-neoplastic, CADx sensitivity was 85·9% (95% CI 82·0-89·1) and specificity was 91·4% (89·4-93·0). Three adverse events occurred in the AI-assisted group: two mild post-polypectomy bleedings and one serious pulmonary embolism or deep venous thrombosis unrelated to the procedure. No adverse events occurred in the HD-WL group. INTERPRETATION: CADe-assisted colonoscopy did not show the absolute improvement in adenoma detection rate that was assumed in the prespecified sample-size calculation. CADx did not clearly improve lesion differentiation beyond expert optical diagnosis in expert Lynch syndrome surveillance settings. FUNDING: Third-party research funding of the National Center for Hereditary Tumor Syndromes, University Hospital Bonn.

Humans↗

PubMed2026

The gut microbiota-obesity axis in the pathogenesis and prognosis of breast cancer.

BACKGROUND: Breast cancer (BC) remains a major global health concern, accounting for 11.7% of all cancer cases and ranking as the second leading cause of female cancer-related deaths worldwide. Increasing evidence highlights the interplay between gut microbiota (GM) dysbiosis and obesity-associated metabolic dysfunction in BC progression. This review aims to elucidate the role of GM in obese patients with BC. METHODS: A systematic literature search was conducted in PubMed and Web of Science databases for publications from July 2015 to January 2025. Search terms combined BC, GM, obesity, dysbiosis, immunity, and microbiome. Article selection prioritized studies investigating microbial alterations in BC patients, mechanistic links between obesity and cancer progression, and GM-targeted interventions. Both original studies and authoritative reviews were included, supplemented by manual reference screening. DISCUSSION: Obesity may trigger systemic inflammation, altered adipokine secretion, and disrupted steroid hormone metabolism via gut-derived β-glucuronidase activity, thereby exacerbating BC occurrence and recurrence. GM dysbiosis-driven metabolites such as branched-chain amino acids (BCAAs) and short-chain fatty acids (SCFAs) can activate oncogenic signaling pathways and immunosuppressive myeloid-derived suppressor cells (MDSCs), fostering tumor immune evasion. Conversely, dietary interventions, probiotics, and fecal microbiota transplantation (FMT) can alleviate dysbiosis, strengthen gut barriers, and restore anti-tumor immunity, improving chemotherapy response and reducing recurrence. However, challenges persist in deciphering BC subtype-related microbial signatures and optimizing microbiota-targeted therapies. CONCLUSION: Future longitudinal studies are needed to clarify causal relationships, validate microbial biomarkers, and translate preclinical findings into clinical applications. Addressing the gut-breast axis may offer transformative potential for precision oncology in obesity-driven BC.

Humans↗

PubMed2026

Germline variants and impact on lung cancer outcomes following chemotherapy: A systematic review.

BACKGROUND: Lung cancer is the primary cause of cancer deaths in the UK and globally, and the main subtypes are non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Many treatment options are available, with platinum-based chemotherapy being a key component for many patients. However, variation in survival outcomes exists among individuals of European ancestry, which makes it important to identify germline genetic variants that help guide decision-making and optimise patient treatment and outcomes. METHOD: A systematic literature search was conducted in PubMed and Web of Science for lung cancer studies investigating the impact of germline genetic variants on systemic anti-cancer therapy (SACT) outcomes in populations of European ancestry. The review was conducted according to the Preferred Reporting Items of Systematic Review and Meta-Analysis (PRISMA) and Synthesis without Meta-Analysis (SWiM) guidelines. RESULTS: A total of 20 studies were included in the review out of 4469 on NSCLC and SCLC, encompassing 3639 patients. The most thoroughly investigated area was NSCLC treated with platinum-based chemotherapy. Genetic variants associated with overall survival and/or progression-free survival included XPD Lys751Gln, XPD Asp312Asn, ERCC1 C118T, and XRCC1 Arg399Gln. For non-platinum-treated NSCLC and SCLC, there was insufficient evidence to conduct a meaningful investigation. CONCLUSION: The XPD Lys751Gln, XPD Asp312Asn, ERCC1 C118T, and XRCC1 Arg399Gln variants showed potential associations with survival outcomes among patients of European ancestry with NSCLC after platinum-based chemotherapy. To support clinical implementation, large real-world pharmacogenomics studies stratified by ancestry are needed to overcome statistical power and heterogeneity limitations.

Humans↗

PubMed2026

Tracking GAD-specific T-cell expansions in Type 1 diabetes by intradermal GAD-Alum challenge.

Identifying and monitoring autoreactive T cells that drive beta cell destruction remains a major obstacle to developing effective immunotherapies for type 1 diabetes (T1D). These cells are extremely rare in peripheral blood and cannot be accessed directly from the pancreas. We used intradermal injection of Glutamic Acid Decarboxylase (GAD)-Alum to recruit GAD-specific T cells to accessible sites in the skin and skin-draining lymph nodes (LNs), sampled by skin suction blisters and ultrasound-guided LN aspiration. Peripheral blood samples obtained before GAD injection were restimulated with GAD in vitro to detect reactive CD4+ T cells. Single-cell RNA sequencing (scRNAseq) followed by re-expression of selected T cell receptors (TCRs) confirmed antigen specificity. Up to 70% of T cells at the skin injection site were clonally-expanded and 4 of 14 (28%) re-expressed TCRs were GAD-reactive. In LNs 1 of 14 (4%) clonally-expanded TCRs was GAD-reactive, representing ~0.08% of all T-cells. GAD-reactive cells across compartments displayed Th1 and Th17-associated transcription signatures. These results demonstrate the intradermal autoantigen challenge and scRNAseq, enable direct identification and molecular profiling of autoreactive T cells in vivo. This minimally invasive approach provides a powerful platform for tracking antigen-specific T cells to monitor disease activity and evaluate immune interventions in T1D.

Autoimmunity↗

PubMed2026

Robust optimisation for photon radiotherapy: A scoping review of models, paradigms, and reporting.

BACKGROUND AND PURPOSE: Robust optimisation offers an alternative to conventional margin-based photon radiotherapy planning by explicitly modelling uncertainty, but practice is variable and not standardised. MATERIALS AND METHODS: A scoping review was conducted to map robust optimisation for photon external beam radiotherapy. Electronic searches of Scopus, PubMed and Google Scholar (2000-2025, English language) identified planning studies that incorporated modelled uncertainties into the optimisation process and reported at least one robustness-related outcome. Data were charted on clinical context, uncertainty models, optimisation paradigms, robustness metrics and evidence for clinical implementation. RESULTS: Seventy-one studies were included. Most investigated prostate, breast or lung cancer and used intensity-modulated radiotherapy or volumetric-modulated arc therapy in commercial or research treatment planning systems. Scenario-based worst-case (minimax) optimisation was the dominant paradigm in clinically oriented work, while chance-constrained, conditional value at-risk, distributionally robust and adaptive formulations were confined to small methodological series. Uncertainty modelling focused mainly on rigid set-up error; fewer studies incorporated respiratory motion, inter-fraction anatomical change, dose-calculation uncertainty or biological variation. Robustness was evaluated with diverse scenario-based dose-volume metrics, probabilistic coverage measures, composite robustness indices and, less often, biological endpoints. Direct clinical implementation reports were scarce. CONCLUSION: Robust photon planning is technically feasible and generally maintains or improves target coverage and organ sparing compared with margin-based planning. However, heterogeneity in uncertainty models, optimisation configuration and robustness reporting limits comparison and synthesis. Pragmatic minimum standards are proposed to support future consensus and wider clinical adoption.

Humans↗