Total mesorectal excision (TME) is highly effective for early-stage rectal cancer, but is associated with considerable morbidity, which can substantially impair the quality of life (QoL) of patients. For very early tumours (low-risk cT1), local excision (LE) offers the possibility of organ preservation (OP) with reduced morbidity; however, its application is limited to a selected group. For early tumours where upfront LE is not feasible, primary OP with (chemo)radiotherapy as an alternative to TME surgery has been evaluated in the STARTREC phase II/III studies, which reported promising 1-year OP rates.

The STARTREC-3 trial aims to increase the 2-year OP rate from 60% to 80% in early rectal cancer (cT1–3abN0) and from 30% to 60% in early-intermediate rectal cancer (cT1–3abN1, ≤3 mesorectal nodes measuring ≤8 mm) by intensifying neoadjuvant treatment in different study arms.

STARTREC-3 is embedded in the STARTREC master trial protocol, which uses an adaptive platform study design allowing early termination of inferior treatment arms and the addition of novel arms. The multicentre STARTREC-3 trial investigates three parallel, non-comparative treatment strategies for patients with early and early-intermediate rectal adenocarcinoma who prefer OP over primary TME surgery. All arms start with 5x5 Gy radiotherapy, followed by: an endoluminal boost via contact X-ray brachytherapy (arm 1), an external beam radiotherapy (EBRT) boost by MR-guided EBRT (arm 2) or three cycles of capecitabine oxaliplatin systemic treatment chemotherapy (arm 3). Treatment allocation is predefined and centre-dependent. Response evaluations (MRI and endoscopy) are planned at 14–16 weeks and 26 weeks after onset of radiotherapy. The primary endpoint is the proportion of patients with successful OP at 24 months from onset of therapy. Secondary endpoints include toxicity, QoL, functional and oncological outcomes. Data will be analysed separately for early (cN0) and early-intermediate (cN1) disease. The total planned sample size is 210 patients across the three arms. Interim analyses will be performed for each study arm to determine early failures and discontinue ineffective arms.

The trial was approved by the medical ethics committee NedMec of the Netherlands and is registered in the EU Clinical Trials Information System (CTIS). The results will be published in an international peer-reviewed journal.

CTIS EU 2024-514620-17-00

To develop survey items for a national patient registry on Long COVID using a modified Delphi process.

This study was based on a modified Delphi process involving three rounds of anonymous, online surveys to develop consensus on and prioritise survey elements to be included in a minimum dataset for use in a national patient registry in Canada. Initial Long COVID items were identified through an environmental scan of the literature.

This study focused on healthcare systems in Canada and was conducted online.

A panel of 52 experts (patients, caregivers, clinicians and researchers) participated in all three rounds of the online survey. These participants were recruited through the Long COVID Web network and word of mouth.

In total, 243 survey elements related to care, quality of life and symptoms were included in round 1 of the survey. 200 reached consensus and moved to round 2 with two additional elements being developed based on open-ended responses. In round 2, participants ranked these survey elements and 34 advanced. In round 3, 33 survey elements met the threshold of consensus with one added a priori. The 33 survey elements were then used to develop a Long COVID minimum dataset, which consists of 48 items.

The findings affirm broad consensus for collecting data related to fatigue, post-exertional malaise, cardiovascular issues, respiratory problems and cognitive issues. This highlighted the desire for quality-of-life indicators and information related to care utilisation, quality and access.

The only supportive therapy for patients with severe acute kidney injury (AKI), a common complication among the critically ill, is dialysis. Based on the literature and current guidelines, continuous renal replacement therapy (CRRT) with a total effluent dose of 20–25 mL/kg/hour and adjustments to ensure such dose is delivered despite down time (eg, due to surgical procedures) is recommended. However, experimental and clinical studies suggest that azotaemia, which can be induced by lowering the effluent dose, may accelerate renal recovery. This clinical study investigates whether a lower effluent dose (10–15 mL/kg/hour) for a maximum of 7 days or until successful (>24 hours) liberation of CRRT in critically ill patients with a dialysis-dependent AKI accelerates renal recovery and reduces time on CRRT compared with guideline-directed standard dose (25–30 mL/kg/hour).

The Ketzerei trial is an international, multicentre randomised, controlled trial, designed to investigate if a lower effluent dose (10–15 mL/kg/hour) accelerates renal recovery and reduces the time on CRRT compared with the guideline directed standard effluent dose (25–30 mL/kg/hour). The study aims to enrol 150 critically ill patients with a dialysis-dependent AKI. Eligible patients will be randomised to receive either a standard effluent dose (control group, 25–30 mL/kg/hour) or lower effluent dose (interventional group, 10–15 mL/kg/hour). The primary endpoint is the number of days free from CRRT and alive (from randomisation through day 28). Key secondary endpoints include the number of (serious) adverse events due to potential uremia, the duration of RRT and intensive care unit survival.

The Ketzerei trial has been approved by the Ethics Committee of the Chamber of Physicians Westfalen-Lippe (2023–343 f-s), the University of Muenster and subsequently by the corresponding Ethics Committee of the participating sites. Results will be disseminated widely and published in peer-reviewed journals, presented at conferences and will guide patient care and further research.

clinicaltrials.gov (NCT06021288).

For patients with perihilar cholangiocarcinoma (pCCA), surgical resection remains the sole treatment modality that can potentially result in cure. Unfortunately, the majority of patients present with unresectable tumours or are excluded from surgical treatment due to complications like cholangitis affecting their performance status. In the Netherlands, recommended first-line treatment for patients with unresectable pCCA is palliative chemotherapy with gemcitabine and cisplatin. This regimen yields an estimated median overall survival (OS) of 11.7–15.2 months, highlighting the urgent need for novel treatment options. The STRONG I trial, a phase I study in patients with unresectable pCCA, was completed in 2020. Its aim was to assess the feasibility and toxicity profile of adding stereotactic body radiation therapy (SBRT) to chemotherapy. SBRT, delivered in 15 fractions of 4.0 Gray (Gy), was considered to be feasible and safe, with no dose-limiting toxicity being observed. The 1-year local tumour control rate was 80% and the 1-year OS rate 100%, with maintenance of quality of life (QoL). These results encouraged us to initiate the STRONG II trial, aiming to investigate the efficacy of adding SBRT to chemotherapy in a larger patient cohort.

STRONG II is a single-arm, multicentre phase II study. Patients with non-metastatic unresectable pCCA (T1-4, N0-2) are eligible. A total of 30 patients will be enrolled in six academic centres in the Netherlands and two in Belgium. SBRT will be delivered in 15 fractions of 4.0–4.5 Gy. The primary endpoint is local tumour control, defined by Response Evaluation Criteria in Solid Tumours (RECIST) V.1.1. Secondary endpoints include toxicity, biliary stent-related events, progression-free survival, OS and QoL using the EuroQoL five-dimensional, five-level (EQ-5D-5L) questionnaire, European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) and the EORTC Biliary Module (QLQ-BIL21). In addition, we will explore the predictive value of the peripheral immunological status (immune-related proteins and serum functional immunological status assay) and its dynamics in determining survival outcomes. For this explorative translational study, two blood samples will be collected, one before the start of chemotherapy and another after completing chemotherapy.

Approval of the study was obtained on 5 June 2024 by the Medical Ethics Review Committee of Erasmus Medical Center Rotterdam, the Netherlands (ID: NL86210.078.24). The anticipated time frame for patient enrolment is July 2024 to December 2027. The main study findings will be published in peer-reviewed medical journals, and presented at national and international conferences.

NCT06493734 (ClinicalTrials.gov).

During the COVID-19 pandemic, a substantial decrease was observed in hospital admissions and in-hospital procedures for patients with acute cardiovascular diseases (CVDs). The extent to which measures to prevent COVID-19 transmission, for example, lockdowns, affected the outpatient care of patients at higher cardiovascular risk remains unclear. We aimed to compare outpatient department (OPD) attendance, cardiovascular risk management (CVRM) and cardiovascular health (CVH) of patients at higher cardiovascular risk referred to an OPD of a tertiary care centre between preCOVID-19, during and postCOVID-19 periods.

We included all adult patients at higher cardiovascular risk referred to the cardiology, vascular medicine, diabetology, geriatrics, nephrology or multidisciplinary vascular surgery OPDs of the University Medical Centre Utrecht, the Netherlands, between March 2019 and December 2022, in a prospective cohort study.

We assessed trends in the number of first and follow-up appointments and in the completeness of extractable CVRM indicators from the electronic health record (EHR) as a proxy for CVRM guideline adherence. CVH was determined using the Life’s Essential 8 metric (score 0–100, the higher score, the better). We investigated whether CVH differed between COVID-19 periods compared with the reference period (ie, 2019) and stratified by OPDs, using multivariable linear regression, adjusted for age, gender, CVD history and whether the patient had a previous appointment before the reference period.

Among 15 143 patients, we observed a 33% reduction in the weekly number of first appointments during the COVID-19 pandemic, with the largest reductions in the cardiology and nephrology OPDs, with no differences between women and men. Follow-up appointments conducted remotely, compared with before the COVID-19 pandemic, increased significantly for all OPDs. CVRM indicators were up to 11% less extractable during the first lockdown yet returned to prepandemic levels directly after the first lockdown period. The CVH score of patients visiting the nephrology, vascular medicine and geriatrics OPDs during the first lockdown was 11.23 (95% CI 2.74 to 19.72), 5.68 (95% CI 0.82 to 10.54) and 5.66 (95% CI 0.01 to 11.31) points higher, respectively, compared with the prepandemic period. In between the second and third lockdowns, the CVH score was comparable to the preCOVID reference period, yet for the cardiology OPD it was significantly higher (5.54, 95% CI 2.04 to 9.05).

During the COVID-19 pandemic, weekly numbers of first appointments to OPDs decreased, and a population with a higher CVH score (ie, better CVH) visited certain OPDs, especially during the first lockdown period. These suggest that patients with poorer CVH more often avoided or were unable to visit OPDs, which might have resulted in missed opportunities to control cardiovascular risk factors and potentially may have led to preventable disease outcomes. For future epidemics and pandemics, it seems vital to develop a strategy that includes an emphasis on seeking healthcare when needed, with specific attention to patients at higher CVD risk.