Citations

Background: There is growing recognition of the importance of patient-reported tolerability in complementing traditional clinician-reported safety evaluation of cancer therapies. Recent regulatory guidance listed the evaluation of overall side effect impact as a core patient-reported outcome in oncology clinical trials. A single item (‘GP5’) that asks about side effect bother is included in the Functional Assessment of Chronic Illness Therapy and has been used to capture overall side effect impact. This paper sought to expand the evidence base for GP5 by examining its association with clinician-reported treatment-emergent adverse events and patient-reported global health. Methods: We examined six commercial cancer clinical trials that collected GP5. The patient population was drawn from the safety population and the analysis focused on the first on-treatment assessment. Clinician-reported adverse events were classified as symptomatic if such adverse events were considered amenable to patient self-reporting (e.g. nausea). Chi-square tests and Pearson’s correlation were used to examine associations. We considered adverse event grade and frequency, both for symptomatic adverse events and any type of adverse events. Global health was measured using the visual analogue scale of the EuroQol-5 Dimensions-3 Levels measure. ‘Moderate-severe’ bother was characterised as scores of 2–4 on a 0–4 point scale for GP5, and ‘severe’ bother was characterised as scores of 3–4. Analyses were conducted separately for each trial. Results: Data from 3,557 patients were included. Across the trials, most (71.7%–94.2%) patients had an adverse event of some kind, but fewer (17.1%–44.4%) had an adverse event of grade 3 or higher. In general, fewer than 50% of patients (20.6%–44.2%) reported moderate-severe bother and 5.8%–17.% reported severe bother. There were consistent, albeit not always statistically significant, associations between GP5 and adverse events, and GP5/global health correlations ranged from −0.17 to −0.41. Discussion: GP5 is associated with both clinician- and patient-reported symptoms, suggesting its validity and usefulness as part of comprehensive tolerability assessment of cancer trials.

We highlight the complex management considerations in a patient with cerebral amyloid angiopathy who developed venous thromboembolism, explicitly navigating the balance between risks of thromboembolism and bleeding with anticoagulation therapy. This case highlights a man in his 70s who presented to the emergency department with an acute right frontal intracerebral haemorrhage secondary to cerebral amyloid angiopathy with an acute segmental pulmonary embolism managed with an inferior vena cava (IVC) filter. During hospitalisation, the patient developed a large expansile thrombus extending inferior from the IVC filter to the right popliteal vein. This necessitated the initiation of anticoagulation therapy, beginning with unfractionated heparin, transitioning to enoxaparin and ultimately to apixaban. He was treated with 3 months of anticoagulation with no haemorrhagic complications. The patient’s successful outcome underscored the potential for safe and effective anticoagulation management in this complex clinical scenario.

T he simplicity of performing peritoneal dialysis belies the physiologically complex processes that underlie the removal of solutes and water from the bloodstream. The successful removal of solutes and water during a peritoneal dialysis (PD) exchange represents the multiple interactions of a number of properties of the peritoneal exchange surface (something more than merely a “membrane”; this multi-layered, physiologically active surface is in many senses “alive” and may well respond to the process of an exchange, rendering it quite difficult to measure and characterize) and the steps of the PD exchange, such as the nature of the dialysate, the volume instilled, the times of the cycle, etc. Peritoneal equilibration is defined as the tendency of the concentration of solutes in the blood and the dialysate to come into balance. Other similar concepts have been developed or applied to this process, such as clearance, dialysance, and mass transfer, but these in fact represent very different entities. It is important to understand some of the fundamental aspects of the PD process. Once again, the basic contributing factors to the removal of solute and water seem quite simple: blood must get to the membrane and be spread over an area available for exchange. The membrane must allow for the movement of water and solutes, but some selectivity must exist. The dialysate must contain an osmotic agent to drive fluid removal. The access device must allow for free and rapid flow of dialysate. It should be emphasized that the peritoneal exchange process is the sum of two simultaneous and interrelated transport mechanisms: diffusion and convection. Diffusion refers to the movement of solute down a concentration gradient, while convection refers to the movement of solutes that are more or less trapped in a fluid flux.

Abstract Background The incidence of type 2 diabetes mellitus among young adults has been increasing over the past few decades. There are limited data on contemporary national cardiovascular mortality rates in young adults with diabetes mellitus (DM). Methods We queried the Centers for Disease Control and Prevention's Wide‐Ranging Online Data for Epidemiologic Research database for patients aged 15 to 44 years from 1999 to 2019 in the primary analysis. A secondary analysis included data from 2020 to 2022 to examine the effect of the COVID‐19 pandemic. We analysed patients in whom cardiovascular diseases (CVD) were listed as the main cause of death and DM as a contributing cause of death. In calculating age‐adjusted mortality rates (AAMR) per 100 000 individuals, we used CVD mortality in young adults with comorbid diabetes as the numerator and the overall population as the denominator. We determined temporal trends by estimating the average annual percent change (AAPC) using the Joinpoint regression program. Results Among 3 309 079 individuals aged 15–44 years who died, 30 978 deaths were due to CVD with comorbid DM listed as a contributing cause. The overall AAMR increased from 1.08 per 100 000 individuals in 1999 to 1.23 per 100 000 individuals in 2019, with an average APC of 0.75 (95% CI, 0.31–1.20). Compared with 1999, the percentage increase in CVD deaths in 2019 among young adults with comorbid DM was +6.2%, whereas a decrease of 19.9% was observed among those without comorbid DM. Males had a higher AAMR than females (1.60 vs. 0.97). Non‐Hispanic Black individuals and non‐Hispanic American Indian/Alaska Native individuals had the highest AAMRs of 2.99 and 2.89, respectively. The AAMR was higher in rural regions compared to urban areas (1.63 vs. 1.23). The overall AAMR increased markedly from 1.23 in 2019 to 1.60 in 2022, with a similar pattern observed across demographic subgroups. Conclusion Our study reveals a rising trend in CVD mortality in young adults with DM as a contributing cause. Males, non‐Hispanic Black individuals, and individuals from rural regions had higher AAMR than their counterparts. This warrants the development of specific healthcare policies aimed at these at‐risk populations. Lay summary Our study shows that cardiovascular disease (CVD) deaths are increasing in young adults with diabetes mellitus listed as a contributing cause.

The 2025 Annual Congress of the International Liver Transplantation Society (ILTS), themed “ Advancing Liver Transplantation: Embracing Innovation for the Future ,” was held from May 28 to 31 in Singapore. The meeting offered a comprehensive scientific program, featuring 92 sessions and 7 pre-congress workshops spanning living donor liver transplantation, advanced surgery, anesthesia and critical care, transplant oncology and immunology, basic science, pediatrics, and more. The program emphasized collaboration and innovation to advance patient outcomes in liver transplantation. In this report, the ILTS Vanguard Committee summarizes the key proceedings of the congress.

The success of living donor liver transplantation (LDLT) has bridged the growing gap between organ demand and availability in patients with liver failure or liver cancer. Safety of the living liver donor (LLD) is paramount, and astute intraoperative management plays a critical role in ensuring optimal outcomes for them. Given that intraoperative surgical and anesthesia practices vary widely across centers, the International Liver Transplantation Society (ILTS) and the International Living Donor Liver Transplantation Group (iLDLT Group) convened a global consensus conference in Toronto in March 2025 to develop guidelines for intraoperative management of the LLD. This manuscript details the recommendations on intraoperative considerations for the safety of LLD developed by Working Group II of the Consensus Scientific Committee, using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system for assessment of recommendations, and the Danish model of consensus. Working Group II focused on intraoperative monitoring, fluid and ventilation strategies, surgical techniques for vascular and biliary division, surgeon and center-specific experience, and intraoperative crises planning. These guidelines aim to support both established and emerging LDLT teams to ensure high-quality and safe intraoperative care for the LLD.

ABSTARCT BACKGROUND: IRRAflow is a novel active cerebrospinal fluid (CSF) exchange system for the treatment of hemorrhagic strokes and intracranial infections. It is a closed system that irrigates various medications dissolved in irrigation solutions at a speed of up to 180 mL/h, expediting resolution. Disrupting this closed system to withdraw CSF samples or infuse medications is necessary in certain circumstances. We report our novel approach for maintaining the sterility of the closed IRRAflow system using a needleless extension and assess the compatibility and safety of this technology throughout treatment. METHODS: We used a needleless extension to withdraw CSF samples and deliver medications to 5 patients treated with the IRRAflow system. We used 1 stopcock with a 3-way valve, 2 neutral needleless connectors, and 2 antiseptic caps. The stopcock was connected between the irrigation and drainage ports of the catheter. The needleless connectors were mounted at the 12 o’clock position of the attached stopcock and the irrigation port with antiseptic caps covering the distal ends. To initiate fluid exchange, the 2 needleless connectors were separated. The extra stopcock valve was connected between the drainage arm, the cassette, and the irrigation arm. The needleless connectors remained mounted at the 12 o’clock position of the stopcock and irrigation port throughout treatment. RESULTS: The needleless connectors mounted on the 12 o’clock position of the stopcock and irrigation port on the drainage and irrigation arms, respectively, provided efficient management of fluid exchange, CSF fluid sampling, and medication delivery. Our needleless extension was compatible with the IRRAflow device and prevented secondary infections despite repeated CSF sampling and medication delivery. CONCLUSION: The needleless extension facilitated a simple and safe interaction with the closed IRRAflow system without compromising the sterile environment during CSF sampling and medication delivery.

Abstract Secondary central nervous system (CNS) large B-cell lymphoma (SCNSL) occurs in the de novo setting, as a CNS-isolated relapse, or synchronous (concomitant CNS and systemic) relapse. SCNSL is a devastating event without therapeutic consensus. Thus, we aimed to evaluate treatment outcomes in an international cohort. Progression-free survival (PFS), overall survival (OS), and cumulative incidence of relapse (CIR, estimated using competing-risk models) were reported. Prognostic factors were identified in a 6-month landmark multivariate analysis. Outcomes after thiotepa autologous stem cell transplant (ASCT) and chimeric antigen receptor (CAR) T-cell therapy (CAR-T) delivered at relapse were compared after propensity score matching (PSM). A total of 1139 patients were included in the analysis (de novo: 537; relapsed SCNSL: 602). Two-year PFS estimates were 40.4%, 43.9%, and 16.2% for de novo SCNSL, CNS-isolated relapse, and synchronous relapse, respectively. Patients with CNS-isolated relapse demonstrated low rates of systemic recurrence (24-month CIR, 6%). Thiotepa-ASCT correlated with longer survival in de novo SCNSL (PFS: hazard ratio [HR], 0.57; P = .005; and OS: HR, 0.62; P = .023) and CNS-isolated relapses (PFS: HR, 0.55; P = .002; and OS: HR, 0.39; P< .0001). ASCT (thiotepa or no thiotepa) also associated with improved survival in synchronous relapses (PFS: HR, 0.57; P = .023; and OS: HR, 0.48; P = .019). Higher survival with thiotepa-ASCT than CAR-T was observed after PSM (PFS: HR, 0.45; P = .005 and OS: HR, 0.41; P = .014). These data support thiotepa-ASCT in eligible patients, particularly de novo disease and CNS-isolated relapses. CNS-isolated relapse was infrequently associated with systemic recurrence, supporting treatment regimens adopted from primary CNS lymphoma.

Background/Objectives: Mild cognitive impairment (MCI) affects multiple functional and cognitive domains, rendering it challenging to diagnose. Brief mental status exams are insensitive while detailed neuropsychological testing is time-consuming and presents accessibility issues. By contrast, the Oculo-Cognitive Addition Test (OCAT) is a rapid, objective tool that measures oculometric features during mental addition tasks under one minute. This study aims to develop artificial intelligence (AI)-derived predictive models using OCAT eye movement and time-based features for the early detection of those at risk for MCI, requiring more thorough assessment. Methods: The OCAT with integrated eye tracking was completed by 250 patients at the Mayo Clinic Arizona Department of Neurology. Raw gaze data analysis yielded time-related and eye movement features. Random Forest and univariate decision trees were the feature selection methods used to identify predictors of Dementia Rating Scale (DRS) outcomes. Logistic regression (LR) and K-nearest neighbors (KNN) supervised models were trained to classify PMCI using three feature sets: time-only, eye-only, and combined. Results: LR models achieved the highest performance using the combined time and eye movement features, with an accuracy of 0.97, recall of 0.91, and an AUPRC of 0.95. The eye-only and time-only LR models also performed well (accuracy = 0.93), though with slightly lower F1-scores (0.87 and 0.86, respectively). Overall, models leveraging both time and eye movement features consistently outperformed those using individual feature sets. Conclusions: Machine learning models trained on OCAT-derived features can reliably predict DRS outcomes (PASS/FAIL), offering a promising approach for early MCI identification. With further refinement, OCAT has the potential to serve as a practical and scalable cognitive screening tool, suitable for use in clinics, at the bedside, or in remote and resource-limited settings.

ABSTRACT Lymphocytic colitis (LC) is a subtype of microscopic colitis, often associated with chronic watery diarrhea and characterized by an increase in intraepithelial lymphocytes. Although various medications are implicated in drug-induced LC, its incidence as a treatment-related adverse effect of rearrangement during transfection-selective tyrosine kinase inhibitors is not known. We report a case of pralsetinib-induced LC in a patient with stage 3c nonsmall cell lung cancer. This case highlights pralsetinib-induced LC as a cause of persistent diarrhea that is refractory to standard antidiarrheal treatments and prompts gastrointestinal evaluation and histopathological examination to facilitate early diagnosis and management.