Ziekenhuis Gelderse Vallei

Adequate oral food intake remains a challenge in Intensive Care Unit (ICU) survivors on the general hospital ward, with evidence suggesting that daily energy and protein intake from oral food intake are inadequate during recovery from critical illness. Currently, limited evidence is available regarding meal intake distribution patterns and the impact of prolonged enteral tube feeding on oral intake in survivors of critical illness. This study aimed to: (1) investigate daily distribution of energy and protein intake patterns of oral meals; and (2) evaluate the impact of enteral tube feeding on oral food intake, including potential differences across mealtimes, in post-ICU patients during the first 14 days of recovery after critical illness on the ward. This was a pre-post comparison of two prospective observational cohorts (PROSPECT-I and II) conducted at Hospital Gelderse Vallei (the Netherlands) before and after the implementation of a tailored nutrition protocol in post-ICU patients during recovery on the general hospital ward. Adult ICU survivors who stayed ≥72 h in the ICU and were receiving enteral tube feeding at ICU discharge were included. Daily energy and protein content from oral food consumption during the first 14 days post-ICU were analysed. Ordered and consumed intake data were pooled by mealtime (breakfast, lunch, and dinner) and intake distributions across mealtimes (within-group comparisons) were compared using the Kruskal-Wallis test, with Dunn's post-hoc test applied in case of significant differences. Oral food consumption data from 90 participants (n = 24 pre-implementation and n = 66 post-implementation) with a median hospital stay of 10 days post-ICU discharge were analysed. For all ordered meals, median oral energy content ranged from approximately 481 to 555 kcal across main meals, and median oral protein content ranged from 22.1 g to 28.2 g. However, median energy intake from consumed meals ranged from 302 to 354 kcal, with no differences between specific meal moments (all p > 0.05). Absolute protein intake did not differ across meals (p = 0.423), with median values ranging from 14.5 to 15.0 g per mealtime. Following implementation of the tailored nutrition protocol, patients received enteral tube feeding for a longer duration (median 5 vs. 3 days, p = 0.002). Patients had lower energy and protein intake from oral food intake (both p < 0.001). The tailored nutrition intervention resulted in higher total daily energy (2115 vs. 1816 kcal, p < 0.001) and protein intake levels (108.1 vs. 91.5 g, p < 0.001). Post-ICU patients showed an even distribution of energy and protein intake from oral food consumption throughout the day, suggesting a per-meal intake threshold. The introduction of a tailored nutrition protocol resulted in prolonged enteral tube feeding post-ICU, increased energy and protein adequacy, but reduced oral meal consumption.

Usher syndrome type 2A (USH2a), the most common form of hereditary deaf-blindness, is frequently accompanied by fatigue and poor sleep quality. As these sleep problems occur independently of visual decline, it is hypothesized that the USH2A-encoded protein usherin regulates sleep and circadian rhythmicity via an extra-retinal mechanism. Ush2a knockout zebrafish models were utilized to investigate this hypothesis. Immunohistochemical analysis demonstrated usherin localisation in pineal gland photoreceptor cells in wild-type larvae, alongside the USH2 complex proteins Adgrv1 and Whrna. Cross-species transcriptomic and proteomic analyses confirmed USH2A expression in all mammalian pineal gland tissues studied. Circadian clock gene expression was measured over 24 h and showed preserved oscillatory patterns in wild-type and mutant zebrafish. Ex vivo superfusion of pineal glands revealed sustained circadian melatonin release with comparable phase and period to controls, although potential differences in absolute melatonin levels could not be excluded. Despite intact clock gene expression and melatonin release in ush2a mutants, behavioural classification over 24-h recordings revealed altered sleep-wake behaviour: ush2a mutants displayed elevated daytime sleep and significantly prolonged and more variable sleep latency. The dissociation between intact molecular rhythms and abnormal sleep behaviour likely implicates that usherin plays a role in sleep-wake regulation independent of the circadian pacemaker and melatonin synthesis. These findings suggest a novel role of usherin in the pineal gland and establish a mechanistic link between usherin dysfunction and sleep disturbances, providing a biological basis for the fatigue and sleep problems reported in USH2a patients.

Knowledge of how persistent COVID-19-related chemosensory dysfunction affects quality of life and eating behaviour over time is lacking. The COVORTS cohort included 76 patients with recent (<3 months) COVID-19 infection and persistent self-reported smell dysfunction (>1 month). For one year, patients completed monthly questionnaires on quality of life impairment, appetite and hunger ratings, as well as self-reported and self-assessed chemosensory dysfunction. Psychophysical testing of olfactory and gustatory functioning was performed every 3 months. Our results revealed that quality of life, appetite, and hunger ratings all slowly but significantly improved by around 10% after the one-year follow-up. Dysfunction in all chemosensory modalities (i.e., olfaction, gustation, and trigeminal sensations) was significantly associated with quality of life, appetite and hunger ratings. Self-reported and self-assessed measures of chemosensory dysfunction were more frequently significantly associated with quality of life, appetite and hunger ratings compared to psychophysical measures, especially at the baseline measurement. Patients who presented with low quality of life, appetite or hunger ratings at baseline were likely to still have low ratings at one-year follow-up, regardless of the type of chemosensory dysfunction they experienced. These results highlight that, although patients seem to slowly improve in quality of life, appetite and hunger ratings, there is a need for psychological counselling for patients struggling early on in symptom progression.

Reduced skeletal muscle mass at Intensive Care Unit (ICU) admission is associated with increased mortality. Bedside techniques, including bioelectrical impedance analysis (BIA), ultrasonography (US), and calf circumference (CC), may help to estimate skeletal muscle mass in critically ill patients. This study aimed to investigate the accuracy of these bedside methods in assessing muscle mass compared to lumbar 3 (L3) CT-derived skeletal muscle index (CT-SMI) and determine cut-offs for reduced muscle mass upon ICU admission. A prospective, single-centre, cohort study conducted between May 2023 and April 2025. Patients (≥18 years) with an expected ICU stay ≥3 days were included. Bedside parameters (<48 h of ICU admission) included multifrequency BIA-derived skeletal muscle mass (BIA-SMM) and fat-free mass (BIA-FFM)), US-derived rectus femoris cross-sectional area (US-RFCSA) and quadriceps muscle layer thickness (US-QMLT), and CC (adjusted for BMI). These were compared to L3 CT-SMI and CT-derived skeletal muscle area (CT-SMA) retrieved 7 days before to 24 h after ICU admission. Correlations between CT and bedside methods were assessed. Reduced muscle mass was defined using CT-based SMI cut-offs (females <38 cm2/m2; males <50 cm2/m2) to determine cut-off values of bedside parameters using ROC analyses. Fifty-six ICU patients (70 % male) were included, showing 64 % having reduced skeletal muscle mass. Correlations of CT-SMI with BIA and US parameters were weak to moderate (r = 0.36-0.45, all p < 0.05), while CT-SMA correlated moderately with BIA-FFM (r = 0.57) and BIA-SMM (r = 0.62, both p < 0.001) but not with US-RFCSA, US-QMLT, and CC (p > 0.05). Cut-offs for reduced skeletal muscle mass were BIA-FFMI: 23.8 kg/m2 and 20.0 kg/m2; BIA-SMMI: 13.4 kg/m2 and 10.7 kg/m2; adjusted CC: 36.8 cm and 33.8 cm, in males and females, respectively, and US-RFCSA: 4.3 cm2 and US-QMLT: 2.3 cm (both sexes). At ICU admission, correlations between bedside methods and L3 CT-derived muscle mass were low to moderate. Cut-off values were derived to detect reduced skeletal muscle upon ICU admission. However, further validation is required before clinical implementation.

Prolonging the hang time (HT) of administration sets and enteral feeding containers beyond the recommended 24 h may reduce waste, decrease nursing workload and lower hospital costs. The objective of this pilot study was to explore the safety of extending the HT from 24 to 48 h by investigating its impact on the occurrence of diarrhoea and new-onset pneumonia in intensive care unit (ICU) patients. This monocenter pilot study had a combined retrospective and prospective cohort (24 and 48-h HT, respectively) design and included ICU patients (≥ 18 years) receiving enteral nutrition for at least 48 h. The primary outcome was diarrhoea, defined as (1) ≥ 3 defecations/day with a Bristol Stool Chart score of 6 or 7, or (2) colostomy/ileostomy output ≥1.5 L/24 h. The secondary outcome was new-onset pneumonia ≥48 h after ICU admission. Associations between HT protocol and the onset of outcomes were assessed by Cox regression analyses. Additionally, retrograde bacterial growth was assessed through microbiological analysis in enteral feeding systems. A total of 102 ICU patients were included between December 16, 2023 and October 11, 2024, with 51 in each cohort. Actual median HT was 31 [27-45] hours vs. 56 [37-83] hours in the 24 and 48-h groups, respectively (p < 0.001). In multivariable Cox regression, no significant association was found between prolonged HT and diarrhoea-free survival (HR 0.92, 95 % CI 0.55-1.53, p = 0.746) and new-onset pneumonia (HR 1.33, 95 % CI 0.54-3.24, p = 0.537), respectively. Retrograde bacterial growth did not extend beyond the first 30 cm of the administration set and was not correlated to HT. We observed no association between prolonging the HT of enteral feeding sets from 24 to 48 h and the occurrence of diarrhoea or new-onset pneumonia in ICU patients. However, a substantial, adequately powered, non-inferiority trial must be conducted prior to integrating extended hang times into clinical practice.

ABSTRACTBackgroundColon cancer (CC), the third most common cancer worldwide, is accompanied by cachexia in 30% of patients. Its associated muscle loss directly impairs therapeutic response and survival. Early intervention is crucial, yet the underlying mechanisms of early‐stage muscle dysfunction remain unclear. This study investigates mitochondrial function in skeletal muscle across different CC stages to identify early metabolic alterations.MethodsThe present study investigated mitochondrial function in rectus abdominus muscle biopsies from 30 patients with primary CC (83% male, mean age 67 ± 8 years), 10 patients with colorectal cancer with liver metastases (50% male, mean age 69 ± 6 years), and 17 age‐matched controls (65% male, mean age 66 ± 7 years). Mitochondrial oxygen consumption was assessed using high‐resolution respirometry, and transcriptional profiles were analysed via RNA sequencing.ResultsPatients with primary CC exhibited reduced complex I activity compared to controls (9.02 vs. 12.47 pmol/s/mg, p < 0.001), accompanied by transcriptional upregulation of oxidative phosphorylation (OXPHOS)‐related genes. In contrast, patients with liver metastases showed more severe mitochondrial dysfunction, with reductions in both complex I (7.38 vs. 9.65 pmol/s/mg, p < 0.01) and complex II (8.36 vs. 19.73 pmol/s/mg, p < 0.05), but without the compensatory transcriptional upregulation seen in primary CC. These mitochondrial impairments occurred before detectable declines in physical function or systemic inflammation (C‐reactive protein, albumin).ConclusionsOur findings reveal stage‐specific mitochondrial dysfunction in CC, with early complex I impairment and a transient transcriptional adaptation in primary CC. These alterations precede clinical cachexia, suggesting mitochondrial dysfunction as a potential early biomarker for cancer‐induced muscle loss and a target for early intervention.

While mortality for critically ill patients has decreased, many survivors face persistent physical, cognitive, and psychological impairments, collectively known as post-intensive care syndrome, which significantly reduce health-related quality of life (HRQoL). Nutrition is a crucial component of recovery, yet evidence-based strategies for post-intensive care unit (ICU) nutritional management remain underdeveloped. The Global Research Initiative on Post-ICU Nutrition (GRIP) was established to address this gap by advancing research, education, and clinical practice in post-ICU nutrition. International experts in the field of critical care nutrition were invited to a diagnostic matrix meeting, to develop a definition of post-ICU patients relevant to GRIP, discuss emerging evidence regarding post-ICU nutritional management, and identify core research domains to guide future research. The consortium consensus was achieved. A post-ICU patient is defined as any adult patient who has been admitted to an ICU for more than 48h and is in the post-ICU recovery phase, which begins after the first ICU discharge and continues for up to one year, regardless of hospital length of stay, readmissions, or discharge destination. Ten core nutrition research domains were identified, including: (1) pathophysiology of post-ICU recovery, (2) phenotyping and personalised nutrition strategies, (3) timing and delivery of nutrition, (4) nutritional intake monitoring and optimisation, (5) nutrition interventions and effectiveness, (6) long-term functional and health-related quality of life outcomes, (7) digital tools and remote monitoring, (8) education and healthcare professional engagement, (9) implementation science and system integration, and (10) patient and family involvement. GRIP envisions a future in which patients post-ICU receive personalised, timely, and effective nutritional care to enhance recovery, reduce complications, and improve long-term HRQoL. By identifying knowledge gaps, initiating targeted research projects, and supporting global educational efforts, GRIP aims to generate robust evidence, foster international collaboration, and strengthen clinical capacity to improve global post-ICU nutritional care.

IntroductionSeveral barriers, such as lack of time, knowledge and support, hinder clinicians from providing an individually tailored physical activity (PA) prescription and referral to their patients. As a result, “exercise is medicine” (E = M) is not systematically implemented in clinical care today. Many studies have identified facilitators and barriers to implementation, yet linking these factors to tailored implementation strategies is still an under-researched area. Therefore, this study aimed to apply Implementation Mapping to develop an implementation protocol to support the individually tailored PA prescription in hospital care.MethodsWe used strong stakeholder participation and, we applied the five tasks of the systematic Implementation Mapping approach to match implementation strategies to implementation barriers and facilitators identified through interviews with clinicians working at two university hospitals in the Netherlands.ResultsWe identified clinicians as primary actors. Secondary actors were managers of the departments and stakeholders in the broader context. For each actor group, performance objectives were defined. We matched previously identified facilitators and barriers to theory and evidence-informed implementation strategies from the Effective Practice and Organisation of Care taxonomy using the CFIR Strategy Matching Tool. Next, we translated these implementation strategies (e.g., active learning, audit, and feedback, technical assistance, peer education) into practical activities to support the implementation of the E = M tool, such as training for clinicians, creating overviews of possible local exercise referral options, and appointing role models for clinicians. Lastly, these activities were bundled into an implementation protocol. The implementation protocol consisted of a set of implementation activities to support and guide clinicians during the adoption, implementation, and sustainability process of the prescription of E = M. All activities were supported by implementation tools, practical applications, and materials while allowing tailoring to the specific clinical context.Discussion/conclusionThis study illustrates the application of Implementation Mapping to design an implementation protocol to support and guide the prescription of E = M by clinicians in the hospital environment, using strong stakeholder participation in the development process. The stepwise development of the implementation protocol can serve as an example for researchers or practitioners preparing for E = M implementation.