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Background European cancer programmes and policies lack a unified health-related quality of life (HRQoL) assessment tool. The European oncology quality of life toolkit (EUonQoL-Kit) is a novel set of HRQoL questionnaires, co-designed with cancer patients and survivors, translated and culturally adapted into 31 European languages, and with both static and dynamic electronic administration modes. The main aim of this study is the psychometric assessment of the static version. Secondary aims include evaluating the EUonQoL-Kit acceptability, cross-validating the administration modes, exploring individual factors potentially affecting HRQoL and HRQoL inequalities between countries. Methods A sample of 4,500 participants, including three groups (active treatment, survivors, and palliative care) from 45 centres in 25 EU Member States and 7 associated countries, will be enrolled in a multicentre observational cross-sectional study. All participants will complete the static EUonQoL-Kit; three subsamples (each 10% of the total sample) will also respectively complete the following: a) dynamic EUonQoL-Kit, based on Item Response Theory (IRT)/Computer Adaptive Testing (CAT), b) FACT-G and EQ-5L-5D, and c) static EUonQoL-Kit (re-test). Psychometric analyses will encompass exploratory and confirmatory factor analyses (measurement model and structural validity), Cronbach's alpha (internal consistency), intraclass correlation coefficient (test–retest reliability), Pearson/Spearman correlation (concurrent validity), comparison of group scores (construct validity), and Differential Item Functioning (cross-country item equivalence). Secondary analyses will evaluate participant response time and rate, and static/dynamic score differences. Regression models will estimate associations between individual factors and HRQoL. Discussion The EUonQoL-Kit will serve to systematically incorporate patient perspectives into European cancer policies and to address HRQoL inequalities across Europe. Trial registration ClinicalTrials.gov Identifier: NCT05947903, 2023–06-28.

Treatment for a chronic condition can pose a heavy burden on young people and affect their quality of life. The present study examined young people's experiences with treatment burden and their coping strategies. The body mapping method was employed, in which a life-sized outline of someone's body is traced and populated with visual representations, symbols and words. For the present study, a digital tool for body mapping was developed. This is a chat robot which helps young people make a body map by asking questions about their lives, wellbeing and the influence of their treatment on this. In two series of three workshops, ten young people (16 to 25 years) with a chronic, somatic condition created individual body maps using this tool. The body maps were discussed in the group to obtain insight into experiences with treatment burden. The findings were analysed using thematic analysis. In all stages of the study, two adolescents with a chronic condition were involved as co-researchers. The results show that young people with a chronic condition experience considerable treatment burden. Although treatment reduces their symptoms, it also leads to physical and emotional side-effects, restrictions of meaningful activities, issues with future planning, reduced independence, and autonomy and loneliness. Young people apply several strategies to cope with this burden, such as seeking support from others, focusing on the positive, ignoring treatment advice, and seeing a psychologist. Treatment burden is a subjective experience and not merely based on the number or types of treatment. It is therefore vital that young people with a chronic condition discuss their experiences with their care provider. This can help to tailor treatment decisions to their lives and needs.

Abstract Sutureless coronary connectors may enable minimally invasive bypass surgery, but consistent sealing in human vessels remains a key challenge. This ex vivo study evaluates the hydrostatic performance of a titanium connector that employs a novel sealing principle: tissue-to-metal coaptation enabling stepwise distal anastomosis construction. Thirteen anastomoses were created in porcine and human cadaveric vessels using a standardized three-step deployment protocol. Target sites included internal mammary arteries, saphenous veins, and coronary arteries, selected for suitability for hand-suturing. Sealing was assessed by hydrostatic pressure testing up to 300 mmHg. Key anatomical parameters and procedural outcomes were recorded. Twelve of 13 anastomoses were completed without leakage up to 300 mmHg; one case exhibited minor oozing at 260 mmHg. The connector accommodated vessels down to 1.3 mm in diameter and up to 0.8 mm wall thickness. One misdeployment due to an oversized incision was corrected intraoperatively without compromising the hydrostatic result. Visual inspection confirmed wide, unobstructed anastomotic orifices. This ex vivo evaluation demonstrates that the connector achieved consistent hydrostatic sealing through bare-metal vessel coaptation, even in small-diameter human coronary tissue. These findings support further in vivo validation towards minimally invasive coronary bypass applications. Minimally invasive and endoscopic coronary artery bypass grafting (CABG) is gaining renewed momentum.

DNA mismatch repair deficiency (dMMR) in metastatic colorectal cancer (mCRC) is associated with poor survival and a poor response to systemic treatment. However, it is unclear whether dMMR results in a tumor cell-intrinsic state of treatment resistance, or whether alternative mechanisms play a role. To address this, we generated a cohort of MMR-proficient and -deficient Patient-Derived Organoids (PDOs) and tested their response to commonly used drugs in the treatment of mCRC, including 5-fluorouracil (5-FU), oxaliplatin, SN-38, binimetinib, encorafenib, and cetuximab. MMR status did not correlate with the response of PDOs to any of the drugs tested. In contrast, the presence of activating mutations in the KRAS and BRAF oncogenes was significantly associated with resistance to chemotherapy and sensitivity to drugs targeting oncogene-activated pathways. We conclude that mutant KRAS and BRAF impact the intrinsic sensitivity of tumor cells to chemotherapy and targeted therapy. By contrast, tumor cell-extrinsic mechanisms—for instance signals derived from the microenvironment—must underlie the association of MMR status with therapy response. Future drug screens on rationally chosen cohorts of PDOs have great potential in developing tailored therapies for specific CRC subtypes including, but not restricted to, those defined by BRAF/KRAS and MMR status.

Objective The cardiovascular response to a meal is modulated by gastric distension and the interaction of nutrients, particularly carbohydrate, within the small intestine. We tested the hypothesis that the depressor effect of small intestinal glucose is greater in older than in young subjects, because the reflex increase in muscle sympathetic nerve activity (MSNA) is blunted by age. Methods The effects of intraduodenal glucose infusion (IDGI) on blood pressure, heart rate and MSNA were evaluated in eight healthy young subjects (4 women; mean age ± SEM: 28.8 ± 3.4 years), eight healthy elderly (4 women; 75.3 ± 1.6 years) and in two patients with symptomatic postprandial hypotension (PPH), one young (21 years), and one old (90 years). Results In both young and elderly healthy subjects, IDGI decreased blood pressure ( P  < 0.05), but the fall in systolic blood pressure was greater in the older subjects (−17.0 ± 4.1 vs. −6.5 ± 1.6 mmHg, P  < 0.03). MSNA increased similarly, after infusion in both young (9.0 ± 3.4 bursts/min) and elderly (7.8 ± 1.0 bursts/min) subjects. Baroreflex sensitivity for number of sympathetic bursts was attenuated in the elderly ( P  < 0.03). The increase in burst area in the young patient with PPH was attenuated (18 vs. 63% in the healthy young group). Interpretation The fall in BP induced by IDGI was greater in healthy elderly compared to healthy young subjects. The reason for this is unclear, as they have similar increases in MSNA.