Improvement of Thymopoiesis after Hematopoietic Stem Cell Transplantation by Cytokines: Translational studies in experimental animal models

Allogeneic hematopoietic stem cell transplantation (AlloHSCT) is a powerful treatment modality that is frequently applied as part of treatment of hematological malignancies, aplastic anemia and inborn errors of hematopoietic progenitor cells. A major drawback of alloHSCT is the treatment related morbidity and treatment related mortality (TRM), which are largely accounted for by opportunistic infections. Those infections occur during a prolonged period (1-2 years), characterized by an impaired reconstitution of the adaptive immune system. Especially, the recovery of naïve T cells and thymopoiesis are protracted after transplantation, but are considered pivotal for restoration of anti-infectious immunity. This thesis has experimentally addressed new strategies that may improve thymopoiesis, including the post-transplant administration of cytokines that are physiologically involved in the differentiation and proliferation of thymocytes

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

A cross-sectional investigation of communication in Do-Not-Resuscitate orders in Dutch hospitals

Background: The decision to attempt or refrain from resuscitation is preferably based on prognostic factors for outcome and subsequently communicated with patients. Both patients and physicians consider good communication important, however little is known about patient involvement in and understanding of cardiopulmonary resuscitation (CPR) directives. Aim: To determine the prevalence of Do No

Clinically relevant potential drug-drug interactions in intensive care patients: A large retrospective observational multicenter study

Purpose: Potential drug-drug interactions (pDDIs) may harm patients admitted to the Intensive Care Unit (ICU). Due to the patient's critical condition and continuous monitoring on the ICU, not all pDDIs are clinically relevant. Clinical decision support systems (CDSSs) warning for irrelevant pDDIs could result in alert fatigue and overlooking important signals. Therefore, our aim was to describe the frequency of clinically relevant pDDIs (crpDDIs) to enable tailoring of CDSSs to the ICU setting. Materials & methods: In this multicenter retrospective observational study, we used medication administration data to identify pDDIs in ICU admissions from 13 ICUs. Clinical relevance was based on a Delphi study in which intensivists and hospital pharmacists assessed the clinical relevance of pDDIs for the ICU setting. Results: The mean number of pDDIs per 1000 medication administrations was 70.1, dropping to 31.0 when considering only crpDDIs. Of 103,871 ICU patients, 38% was exposed to a crpDDI. The most frequently occurring crpDDIs involve QT-prolonging agents, digoxin, or NSAIDs. Conclusions: Considering clinical relevance of pDDIs in the ICU setting is important, as only half of the detected pDDIs were crpDDIs. Therefore, tailoring CDSSs to the ICU may reduce alert fatigue and improve medication safety in ICU patients

IL-7-mediated protection against minor-antigen-mismatched allograft rejection is associated with enhanced recovery of regulatory T cells

BACKGROUND AND OBJECTIVES: Interleukin-7 (IL-7) has been studied for its possible immunorestorative capacities following stem cell transplantation and has been shown to enhance post-transplant immune recovery predominantly by peripheral T-cell expansion. A major concern of IL-7 is its possible aggravating effect on graft-versus-host and host-versus-graft reactivity. DESIGN AND METHODS: To study the effect of IL-7 on host-versus-graft reactivity, we applied IL-7 in an experimental transplantation model using RAG-1-/- mice supplied with B6 CD45.1 congenic T cells as recipients of T-cell depleted allogeneic bone marrow grafts. RESULTS: Rejection of minor antigen-mismatched bone marrow was significantly reduced in IL-7 treated recipients compared with PBS treated control mice. Rejection was observed in 2 out of 18 IL-7 treated mice compared with 9 out of 17 PBS treated mice (11% vs. 53%; p=0.012). IL-7 administration resulted in enhanced recovery of peripheral blood CD4+CD25+ regulatory T cells (Treg) with a concomitant increase in peripheral blood Foxp3 mRNA expression. IL-7Ra (CD127) was expressed by the vast majority of CD4+Foxp3+ T cells. The incidence of graft rejection following fully MHC mismatched bone marrow transplantation was not reduced nor enhanced by IL-7 administration. INTERPRETATION AND CONCLUSIONS: Post-transplant IL-7 administration protects against minor antigen-mismatched bone marrow rejection, which may be due to enhanced Treg recover

Determining a target SpO2to maintain PaO2within a physiological range

Objective In the context of an ongoing debate on the potential risks of hypoxemia and hyperoxemia, it seems prudent to maintain the partial arterial oxygen pressure (PaO2) in a physiological range during administration of supplemental oxygen. The PaO2 and peripheral oxygen saturation (SpO2) are closely related and both are used to monitor oxygenation status. However, SpO2 values cannot be used as an exact substitute for PaO2. The aim of this study in acutely ill and stable patients was to determine at which SpO2 level PaO2 is more or less certain to be in the physiological range. Methods This is an observational study prospectively collecting data pairs of PaO2 and SpO2 values in patients admitted to the emergency room or intensive care unit (Prospective Inpatient Acutely ill cohort; PIA cohort). A second cohort of retrospective data of patients who underwent pulmonary function testing was also included (Retrospective Outpatient Pulmonary cohort; ROP cohort). Arterial hypoxemia was defined as PaO2 125 mmHg. The SpO2 cut-off values with the lowest risk of hypoxemia and hyperoxemia were determined as the 95th percentile of the observed SpO2 values corresponding with the observed hypoxemic and hyperoxemic PaO2 values. Results 220 data pairs were collected in the PIA cohort. 95% of hypoxemic PaO2 measurements occurred in patients with an SpO2 below 94%, and 95% of hyperoxemic PaO2 measurements occurred in patients with an SpO2 above 96%. Additionally in the 1379 data pairs of the ROP cohort, 95% of hypoxemic PaO2 measurements occurred in patients with an SpO2 below 93%. Conclusion The SpO2 level marking an increased risk of arterial hypoxemia is not substantially different in acutely ill versus stable patients. In acutely ill patients receiving supplemental oxygen an SpO2 target of 95% maximizes the likelihood of maintaining PaO2 in the physiological range

Determining a target SpO2to maintain PaO2within a physiological range

Objective In the context of an ongoing debate on the potential risks of hypoxemia and hyperoxemia, it seems prudent to maintain the partial arterial oxygen pressure (PaO2) in a physiological range during administration of supplemental oxygen. The PaO2 and peripheral oxygen saturation (SpO2) are closely related and both are used to monitor oxygenation status. However, SpO2 values cannot be used as an exact substitute for PaO2. The aim of this study in acutely ill and stable patients was to determine at which SpO2 level PaO2 is more or less certain to be in the physiological range. Methods This is an observational study prospectively collecting data pairs of PaO2 and SpO2 values in patients admitted to the emergency room or intensive care unit (Prospective Inpatient Acutely ill cohort; PIA cohort). A second cohort of retrospective data of patients who underwent pulmonary function testing was also included (Retrospective Outpatient Pulmonary cohort; ROP cohort). Arterial hypoxemia was defined as PaO2 125 mmHg. The SpO2 cut-off values with the lowest risk of hypoxemia and hyperoxemia were determined as the 95th percentile of the observed SpO2 values corresponding with the observed hypoxemic and hyperoxemic PaO2 values. Results 220 data pairs were collected in the PIA cohort. 95% of hypoxemic PaO2 measurements occurred in patients with an SpO2 below 94%, and 95% of hyperoxemic PaO2 measurements occurred in patients with an SpO2 above 96%. Additionally in the 1379 data pairs of the ROP cohort, 95% of hypoxemic PaO2 measurements occurred in patients with an SpO2 below 93%. Conclusion The SpO2 level marking an increased risk of arterial hypoxemia is not substantially different in acutely ill versus stable patients. In acutely ill patients receiving supplemental oxygen an SpO2 target of 95% maximizes the likelihood of maintaining PaO2 in the physiological range

Virtual reality for relatives of ICU patients to improve psychological sequelae

Introduction Intensive care unit (ICU) admission of a relative might lead to psychological distress and complicated grief (post-intensive care syndrome-family; PICS-F). Evidence suggests that increased distress during ICU stay increases risk of PICS-F, resulting in difficulty returning to their normal lives after the ICU experience. Effective interventions to improve PICS-F are currently lacking. In the present trial, we hypothesised that information provision using ICU-specific Virtual Reality for Family members/relatives (ICU-VR-F) may improve understanding of the ICU and subsequently improve psychological well-being and quality of life in relatives of patients admitted to the ICU. Methods and analysis This multicentre, clustered randomised controlled trial will be conducted from January to December 2021 in the mixed medical-surgical ICUs of four hospitals in Rotterdam, the Netherlands. We aim to include adult relatives of 160 ICU patients with an expected ICU length of stay over 72 hours. Participants will be randomised clustered per patient in a 1:1 ratio to either the intervention or control group. Participants allocated to the intervention group will receive ICU-VR-F, an information video that can be watched in VR, while the control group will receive usual care. Initiation of ICU-VR-F will be during their hospital visit unless participants cannot visit the hospital due to COVID-19 regulations, then VR can be watched digitally at home. The primary objective is to study the effect of ICU-VR-F on psychological well-being and quality of life up to 6 months after the patients' ICU discharge. The secondary outcome is the degree of understanding of ICU treatment and ICU modalities. Ethics and dissemination The Medical Ethics Committee of the Erasmus Medical Centre, Rotterdam, the Netherlands, approved the study and local approval was obtained from each participating centre (NL73670.078.20). Our findings will be disseminated by presentation of the results at (inter)national conferences and publication in scientific, peer-reviewed journals. Trial registration number Netherlands Trial Register (TrialRegister.nl, NL9220). </p