Decreased antigen-specific T-cell proliferation by moDC among hepatitis B vaccine non-responders on haemodialysis

Patients with end-stage kidney disease, whether or not on renal replacement therapy, have an impaired immune system. This is clinically manifested by a large percentage of patients unresponsive to the standard vaccination procedure for hepatitis B virus (HBV). In this study, the immune response to HBV vaccination is related to the in vitro function of monocyte-derived dendritic cells (moDC). We demonstrate that mature moDC from nonresponders to HBV vaccination have a less mature phenotype, compared to responders and healthy volunteers, although this did not affect their allostimulatory capacity. However, proliferation of autologous T cells in the presence of tetanus toxoid and candida antigen was decreased in non-responders. Also, HLA-matched CD4+ hsp65-specific human T-cell clones showed markedly decreased proliferation in the group of non-responders. Our results indicate that impairment of moDC to stimulate antigen-specific T cells provides an explanation for the clinical immunodeficiency of patients with end-stage kidney disease

Patients suffering from psychological impairments following critical illness are in need of information

Background: Because critical illness survivors frequently experience several long-term psychological impairments altering quality of life after ICU, there is a trend towards increasing follow-up care, mainly via ICU follow-up clinics. Despite these and other initiatives, understanding of patient's post-ICU needs to help them cope with their problems and subsequently improve quality of life is largely lacking. Our aim was therefore to assess the needs, expectations and wishes in ICU survivors to receive information with the purpose to help them better grasp ICU treatment. In addition, we assessed the perceived burden of psychological trauma after ICU treatment and the health-related quality of life (HRQoL) up to 2.5 years after ICU discharge. Methods: In a multicentre, retrospective cross-sectional cohort study, the needs and preferred intervention methods were assessed using a self-composed inventory in adult mechanically ventilated ICU survivors (n = 43). Additionally, the Impact of Event Scale Revised, the Beck Depression Inventory, the EuroQol-5D-5L, and the Short-Form 12 were used to assess psychological burden and HRQoL. Results: A substantial proportion of all ICU survivors (59%, 95% CI 44% to 74%) suffered from psychological impairments after ICU treatment. Seventy-five percent of these patients expressed a wish to receive information, but only 36% desired to receive this information using a commonly used information brochure. In contrast, 71% of these patients had a wish to receive information using a video film/VR. Furthermore, only 33% of these patients was satisfied with the information provided by their treating hospital. Patients with psychological PICS reported a worse HRQoL as compared to a normative Dutch sample (P < 0.001) and as compared to patients without psychological PICS (P < 0.01). Conclusions: In a Dutch cohort of critical illness survivors, a substantial part of ICU survivors suffer from psychological impairments, such as PTSD and depression, which was associated with a worse HRQoL. These patients are in need of information, have no desire using an information brochure, but are willing to receive information using a video film/virtual reality module. These results support the exploration of such an intervention

Cholestase bij pasgeborenen als gevolg van parenterale voeding

Toediening van totale parenterale voeding (TPN) aan pasgeborenen is geassocieerd met het ontstaan van cholestase. Ondanks intensief onderzoek zijn de pathofysiologische mechanismen slechts gedeeltelijk opgehelderd. In dit artikel wordt ingegaan op de huidige inzichten in de risicofactoren die geassocieerd zijn met TPN-cholestase bij pasgeborenen, de specifieke bestanddelen en deficiënties van TPN die cholestase kunnen veroorzaken, de mogelijke relatie met de ‘fysiologische cholestase van de pasgeborene’, die de pasgeborene kwetsbaarder maakt voor potentieel hepatotoxische stoffen, en de transportsystemen in de levercelmembraan die betrokken zijn bij galvorming. De hypothese dat ‘cholestatische galzuren’ een rol spelen in de etiologie van TPN-cholestase en de therapeutische mogelijkheden worden besproken.Administration of total parenteral nutrition (TPN) to neonates is associated with the occurrence of cholestasis. Despite intensive research, the pathophysiological mechanisms have not been elucidated. In this review we describe the present insights into the risk factors for the development of TPN-associated cholestasis, the specific components or lack of components (deficiencies) in TPN that can cause cholestasis, the possible correlation with 'physiologic cholestasis of the neonate', which makes the infant more susceptible for potentially hepatotoxic compounds, and the transport systems in the liver cell membrane which are involved in bile formation. The hypothesis that 'cholestatic bile salts' play a role in the etiology of TPN-related cholestasis and the therapeutic options will be discussed.</p

Glycoengineered antibody, antibody-conjugate and methods for their preparation

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Functional impairment of monocyte-derived dendritic cells in patients with severe chronic kidney disease

Background. Dendritic cells (DCs) are antigen-presenting cells that are pivotal for the initiation of the primary immune response. Patients with chronic kidney disease (CKD) with or without chronic intermittent haemodialysis (CIHD) show an impaired immune response. Dysfunction of DCs may underlie this phenomenon. Methods. In this study, several different functions of monocyte-derived DCs (moDC) of patients with CKD class IV-V (glomerular filtration rate <30 ml/min) and patients on CIHD were studied in vitro and compared with age- and sex-matched healthy volunteers. Results. We demonstrate that, independent of the maturation stimulus used, mature moDC from both groups of patients did not acquire the same level of terminal differentiation as moDC from controls, as shown by analysis of cell surface markers and the relative high macropinocytosis activity of moDC. The stimulation of allogeneic T-cells by immature moDC and mature moDC did not differ between patients and controls. However, in the presence of immature moDC or antigen-loaded maturated moDC from patients, less proliferation of autologous T-cells was observed in response to recall antigens. There was no difference between moDC from controls and patients in their ability to activate naive T-cells and to differentiate them into Th1 and Th2 cells. Conclusions. These results show that the terminal differentiation of moDC in patients with severe CKD is impaired. This impairment is not restricted to one maturation stimulus and is independent of treatment with haemodialysis

Obesity in asylum seekers' children in The Netherlands - the use of national reference charts

Background: Growth assessment can be used to monitor health at individual and population level. For asylum seekers children with different geographic backgrounds, growth reference values are frequently not available. We assessed nutritional condition and growth of asylum seekers children upon arrival and follow-up in The Netherlands, using national growth charts, and related these parameters to geographic origin. Methods: Height and weight of 135 children originating from Africa (n = 47), Central Asia (n = 41), and Eastern Europe (n = 47), were assessed longitudinally (median follow-up 3 years, range 18 years). Body-mass-index (BMI) was calculated, and overweight and obesity were defined according the international BMI cut-off values for age and gender. Results: Upon arrival at a median age of 4.5 years (range 011.5 years), 13 of the children were small for age (below 2 SD of the Dutch height for age reference), which decreased to 5 during follow-up (P <0.05). During follow-up, 90 of the height measurements in boys and 85 in girls were within the normal range (2 SD) of the Dutch references. The proportion of children with overweight including obesity increased from 15 at arrival to 21 during follow-up (P <0.05). Irrespective of age, children originating from Africa were taller than children from Central Asia or Eastern Europe at follow up (P <0.05). Overweight and obesity was most prominent among children of Eastern Europe. Conclusion: Dutch national reference values allow monitoring growth and the development of overweight or obesity in asylum seekers children in The Netherlands. Prevention strategies to reduce the development of overweight and obesity among these children seem warranted

Prevalence and management of delirium in intensive care units in the Netherlands: An observational multicentre study

Contains fulltext : 229294.pdf (Publisher’s version ) (Closed access)OBJECTIVES: This study aimed to determine the prevalence, risk factors of delirium and current practice of delirium management in intensive care units of various levels of care. RESEARCH METHODOLOGY/DESIGN: Prospective multicentre cohort study. SETTING: In all adult patients admitted to one of the participating intensive care units on World Delirium Awareness Day 2018, delirium point and period prevalence rates were measured between ICU admission and seven days after the index day. RESULTS: In total, 28 (33%) Dutch intensive care units participated in this study. Point-prevalence was 23% (range 41), and period-prevalence was 42% (range 70). University intensive care units had a significantly higher delirium point-prevalence compared with non-university units (26% vs.15%, p = 0.02). No significant difference were found in period prevalence (50% vs. 39%, p = 0.09). Precipitating risk factors, infection and mechanical ventilation differed significantly between delirium and non-delirium patients. No differences were observed for predisposing risk factors. A delirium protocol was present in 89% of the ICUs. Mean delirium assessment compliance measured was 84% (±19) in 14 units and estimated 59% (±29) in the other 14. CONCLUSION: Delirium prevalence in Dutch intensive care units is substantial and occurs with a large variation, with the highest prevalence in university units. Precipitating risk factors were more frequent in patients with delirium. In the majority of units a delirium management protocol is in place