A systematic review and meta-analysis of the clinimetric properties of the core outcome measurement instruments for clinical effectiveness trials of nutritional and metabolic interventions in critical illness (CONCISE).

BACKGROUND: CONCISE is an internationally agreed minimum set of outcomes for use in nutritional and metabolic clinical research in critically ill adults. Clinicians and researchers need to be aware of the clinimetric properties of these instruments and understand any limitations to ensure valid and reliable research. This systematic review and meta-analysis were undertaken to evaluate the clinimetric properties of the measurement instruments identified in CONCISE. METHODS: Four electronic databases were searched from inception to December 2022 (MEDLINE via Ovid, EMBASE via Ovid, CINAHL via Healthcare Databases Advanced Search, CENTRAL via Cochrane). Studies were included if they examined at least one clinimetric property of a CONCISE measurement instrument or recognised variation in adults ≥ 18 years with critical illness or recovering from critical illness in any language. The COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist for systematic reviews of Patient-Reported Outcome Measures was used. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses were used in line with COSMIN guidance. The COSMIN checklist was used to evaluate the risk of bias and the quality of clinimetric properties. Overall certainty of the evidence was rated using a modified Grading of Recommendations, Assessment, Development and Evaluation approach. Narrative synthesis was performed and where possible, meta-analysis was conducted. RESULTS: A total of 4316 studies were screened. Forty-seven were included in the review, reporting data for 12308 participants. The Short Form-36 Questionnaire (Physical Component Score and Physical Functioning), sit-to-stand test, 6-m walk test and Barthel Index had the strongest clinimetric properties and certainty of evidence. The Short Physical Performance Battery, Katz Index and handgrip strength had less favourable results. There was limited data for Lawson Instrumental Activities of Daily Living and the Global Leadership Initiative on Malnutrition criteria. The risk of bias ranged from inadequate to very good. The certainty of the evidence ranged from very low to high. CONCLUSIONS: Variable evidence exists to support the clinimetric properties of the CONCISE measurement instruments. We suggest using this review alongside CONCISE to guide outcome selection for future trials of nutrition and metabolic interventions in critical illness. TRIAL REGISTRATION: PROSPERO (CRD42023438187). Registered 21/06/2023.

Core outcome measures for clinical effectiveness trials of nutritional and metabolic interventions in critical illness: an international modified Delphi consensus study evaluation (CONCISE).

BACKGROUND: Clinical research on nutritional and metabolic interventions in critically ill patients is heterogenous regarding time points, outcomes and measurement instruments used, impeding intervention development and data syntheses, and ultimately worsening clinical outcomes. We aimed to identify and develop a set of core outcome domains and associated measurement instruments to include in all research in critically ill patients. METHODS: An updated systematic review informed a two-stage modified Delphi consensus process (domains followed by instruments). Measurement instruments for domains considered 'essential' were taken through the second stage of the Delphi and a subsequent consensus meeting. RESULTS: In total, 213 participants (41 patients/caregivers, 50 clinical researchers and 122 healthcare professionals) from 24 countries contributed. Consensus was reached on time points (30 and 90 days post-randomisation). Three domains were considered 'essential' at 30 days (survival, physical function and Infection) and five at 90 days (survival, physical function, activities of daily living, nutritional status and muscle/nerve function). Core 'essential' measurement instruments reached consensus for survival and activities of daily living, and 'recommended' measurement instruments for physical function, nutritional status and muscle/nerve function. No consensus was reached for a measurement instrument for Infection. Four further domains met criteria for 'recommended,' but not 'essential,' to measure at 30 days post-randomisation (organ dysfunction, muscle/nerve function, nutritional status and wound healing) and three at 90 days (frailty, body composition and organ dysfunction). CONCLUSION: The CONCISE core outcome set is an internationally agreed minimum set of outcomes for use at 30 and 90 days post-randomisation, in nutritional and metabolic clinical research in critically ill adults.

[Advocacy for an improved training in clinical nutrition during the medical cursus]. / Plaidoyer pour l'enseignement de la nutrition clinique aux futurs médecins.

The knowledge of physicians regarding nutrition is often far below the expectations of patients, and does not comply with official recommendations. However, poor-quality nutrition and diet represent the first cause of mortality worldwide. As a result of an insufficient training and awareness, many physicians cannot meet patients' expectations. Moreover, nutrition is sometimes felt as a field of low scientific level, thereby opening the area to pseudo-scientific drifts. We advocate an improvement in the training in nutrition during the medical cursus, namely by the transversal integration of nutritional insights into medical courses, and the recognition of post-university training validated by the academic authorities. A clarification of the roles and the recognition of the competency are urgently required to promote the professionalism of nutritional counselling.

Les connaissances des médecins en matière d'alimentation et de nutrition sont souvent en-deçà des attentes des patients et en décalage par rapport aux recommandations officielles. Pourtant, la mauvaise alimentation constitue la première cause de mortalité à l'échelle planétaire. Les attentes des patients sont importantes en matière de nutrition et le médecin y est mal préparé en raison d'une formation insuffisante. De plus, la nutrition est parfois perçue comme une matière peu scientifique, et la reconnaissance des compétences en nutrition est insuffisante, ouvrant le champ à des dérives pseudo-scientifiques. Nous plaidons pour une meilleure formation en nutrition dans le cursus des études médicales, notamment en intégrant les aspects nutritionnels de manière transversale au cours de la formation des futurs médecins, et pour la reconnaissance des cursus de formation post-universitaires validés par les autorités académiques. Une clarification des rôles et une reconnaissance des compétences sont urgentes afin de professionnaliser les conseils nutritionnels.

Intensive care units follow-up: a scoping review protocol.

INTRODUCTION: Increasing numbers of patients are surviving critical illness, leading to growing concern about the potential impact of the long-term consequences of intensive care on patients, families and society as a whole. These long-term effects are together known as postintensive care syndrome and their presence can be evaluated at intensive care unit (ICU) follow-up consultations. However, the services provided by these consultations vary across hospitals and units, in part because there is no validated standard model to evaluate patients and their quality of life after ICU discharge. We describe a protocol for a scoping review focusing on models of ICU follow-up and the impact of such strategies on improving patient quality of life. METHODS AND ANALYSIS: In this scoping review, we will search the literature systematically using electronic databases (MEDLINE - from database inception to June 15th 2020) and a grey literature search. We will involve stakeholders as recommended by the Joanna Briggs Institute approach developed by Peters et al. The research will be conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews guidelines. ETHICS AND DISSEMINATION: This study does not require ethics approval, because data will be obtained through a review of published primary studies. The results of our evaluation will be published in a peer-reviewed journal and will also be disseminated through presentations at national and international conferences.

Association of transcription factor 7-like 2 gene (TCF7L2) polymorphisms with stress-related hyperglycaemia (SRH) in intensive care and resulting outcomes: The READIAB study.

OBJECTIVE: The study aimed to evaluate the impact of the single nucleotide polymorphism (SNP) rs7903146 on the transcription factor 7-like 2 (TCF7L2) gene in stress-related hyperglycaemia (SRH), defined as blood glucose≥11mmol/L in at least two blood samples during the first 3 days in the intensive care unit (ICU), and on 28-day and 1-year mortality, and incidence of type 2 diabetes (T2D) at 6 months and 1 year in patients hospitalized in the ICU. METHODS: This prospective observational (non-interventional) multicentre READIAB study, carried out during 2012-2016 in six French ICUs, involved adult patients admitted to ICUs for at least two organ failures; patients admitted for<48h were excluded. During the 3-day ICU observational period, genetic testing, blood glucose values and insulin treatment were recorded. MAIN RESULTS: The association of rs7903146 with SRH was assessed using logistic regression models. Cox proportional hazards regression models assessed the associations between rs7903146 and mortality and between SRH and mortality, both at 28 days and 1 year. A total of 991 of the 1000 enrolled patients were included in the READIAB-G4 cohort, but 242 (24.4%) had preexisting diabetes and were excluded from the analyses. SRH occurred within the first 3 days in the ICU for one-third of the non-diabetes patients. The association between the rs7903146 polymorphism and SRH did not reach significance (P=0.078): OR(peroneTcopy): 1.24, 95% CI: 0.98-1.58. A significant association was found between rs7903146 and 28-day mortality after adjusting for severity scores (P=0.026), but was no longer significant at 1 year (P=0.61). At 28 days, mortality was increased in patients with SRH (HR: 2.09, 95% CI: 1.43-3.06; P<0.001), and remained significant at 1 year after adjusting for severity scores (HR: 1.73, 95% CI: 1.32-2.28; P<0.001). On admission, non-diabetes patients with SRH had a higher incidence of T2D at 6 months vs. those without SRH (16.0% vs. 7.6%, RR: 2.11, 95% CI: 1.07-4.20; P=0.030). At 1 year, these figures were 13.4% vs. 9.2%, RR: 1.45, 95% CI: 0.71-2.96; P=0.31). Moreover, the rs7903146 polymorphism was not significantly associated with T2D development at either 6 months (P=0.72) or 1 year (P=0.64). CONCLUSION: This study failed to demonstrate any significant association between rs7903146 and SRH. Nevertheless, the issue remains an important challenge, as SRH may be associated with increased rates of both mortality and T2D development.

Early enteral nutrition in critically ill patients: ESICM clinical practice guidelines

PURPOSE: To provide evidence-based guidelines for early enteral nutrition (EEN) during critical illness. METHODS: We aimed to compare EEN vs. early parenteral nutrition (PN) and vs. delayed EN. We defined "early" EN as EN started within 48 h independent of type or amount. We listed, a priori, conditions in which EN is often delayed, and performed systematic reviews in 24 such subtopics. If sufficient evidence was available, we performed meta-analyses; if not, we qualitatively summarized the evidence and based our recommendations on expert opinion. We used the GRADE approach for guideline development. The final recommendations were compiled via Delphi rounds. RESULTS: We formulated 17 recommendations favouring initiation of EEN and seven recommendations favouring delaying EN. We performed five meta-analyses: in unselected critically ill patients, and specifically in traumatic brain injury, severe acute pancreatitis, gastrointestinal (GI) surgery and abdominal trauma. EEN reduced infectious complications in unselected critically ill patients, in patients with severe acute pancreatitis, and after GI surgery. We did not detect any evidence of superiority for early PN or delayed EN over EEN. All recommendations are weak because of the low quality of evidence, with several based only on expert opinion. CONCLUSIONS: We suggest using EEN in the majority of critically ill under certain precautions. In the absence of evidence, we suggest delaying EN in critically ill patients with uncontrolled shock, uncontrolled hypoxaemia and acidosis, uncontrolled upper GI bleeding, gastric aspirate >500 ml/6 h, bowel ischaemia, bowel obstruction, abdominal compartment syndrome, and high-output fistula without distal feeding access.

[Religious and cultural aspects of organ transplantation]. / Aspects religieux et culturels liés à la transplantation d'organes.

The number of transplantations is mainly limited by the shortage of organs, thereby leading to potentially lethal delays for patients registered on waiting lists. Among the causes of refusals of organ donation, religious reasons are often advocated. In order to make the point, we organized a debate between representatives of secularism ( " laïcité ") and of the most represented religions in Belgium, i.e. catholic, Islamic and Judaic. Even though the representation of death was variable, organ donation is authorized and even encouraged by the fundamental texts. Refusals of organ donation result more often from personal interpretations by local preachers. Therefore, the gathering of political and religious authorities in order to promote organ donation is desirable instead of sowing doubt for pseudo-religious reasons.

En médecine de transplantation, la pénurie d'organes représente le principal obstacle et cause de retard aux greffes vitales pour les receveurs inscrits sur liste d'attente. Parmi les causes de refus de don d'organes, des raisons d'ordre religieux sont souvent invoquées. Afin de faire le point sur cette problématique, nous avons organisé un débat rassemblant des représentants de la laïcité et des religions monothéistes les plus représentées en Belgique : catholicisme, islam, judaïsme. Il est apparu que, si la représentation de la mort varie selon les courants, le don d'organes est en fait autorisé, voire encouragé par les textes fondateurs des trois religions. Les refus sont plutôt le fait d'une interprétation personnelle par des prédicateurs. Dès lors, il serait judicieux de rassembler les forces politiques et spirituelles afin de promouvoir le don d'organes plutôt que de semer le doute à son sujet sous des prétextes pseudo-religieux.

Carbohydrates and insulin resistance in clinical nutrition: Recommendations from the ESPEN expert group.

Growing evidence underscores the important role of glycemic control in health and recovery from illness. Carbohydrate ingestion in the diet or administration in nutritional support is mandatory, but carbohydrate intake can adversely affect major body organs and tissues if resulting plasma glucose becomes too high, too low, or highly variable. Plasma glucose control is especially important for patients with conditions such as diabetes or metabolic stress resulting from critical illness or surgery. These patients are particularly in need of glycemic management to help lessen glycemic variability and its negative health consequences when nutritional support is administered. Here we report on recent findings and emerging trends in the field based on an ESPEN workshop held in Venice, Italy, 8-9 November 2015. Evidence was discussed on pathophysiology, clinical impact, and nutritional recommendations for carbohydrate utilization and management in nutritional support. The main conclusions were: a) excess glucose and fructose availability may exacerbate metabolic complications in skeletal muscle, adipose tissue, and liver and can result in negative clinical impact; b) low-glycemic index and high-fiber diets, including specialty products for nutritional support, may provide metabolic and clinical benefits in individuals with obesity, insulin resistance, and diabetes; c) in acute conditions such as surgery and critical illness, insulin resistance and elevated circulating glucose levels have a negative impact on patient outcomes and should be prevented through nutritional and/or pharmacological intervention. In such acute settings, efforts should be implemented towards defining optimal plasma glucose targets, avoiding excessive plasma glucose variability, and optimizing glucose control relative to nutritional support.

Metabolic response to the stress of critical illness.

The metabolic response to stress is part of the adaptive response to survive critical illness. Several mechanisms are well preserved during evolution, including the stimulation of the sympathetic nervous system, the release of pituitary hormones, a peripheral resistance to the effects of these and other anabolic factors, triggered to increase the provision of energy substrates to the vital tissues. The pathways of energy production are altered and alternative substrates are used as a result of the loss of control of energy substrate utilization by their availability. The clinical consequences of the metabolic response to stress include sequential changes in energy expenditure, stress hyperglycaemia, changes in body composition, and psychological and behavioural problems. The loss of muscle proteins and function is a major long-term consequence of stress metabolism. Specific therapeutic interventions, including hormone supplementation, enhanced protein intake, and early mobilization, are investigated. This review aims to summarize the pathophysiological mechanisms, the clinical consequences, and therapeutic implications of the metabolic response to stress.

Physiological modeling, tight glycemic control, and the ICU clinician: what are models and how can they affect practice?

Critically ill patients are highly variable in their response to care and treatment. This variability and the search for improved outcomes have led to a significant increase in the use of protocolized care to reduce variability in care. However, protocolized care does not address the variability of outcome due to inter- and intra-patient variability, both in physiological state, and the response to disease and treatment. This lack of patient-specificity defines the opportunity for patient-specific approaches to diagnosis, care, and patient management, which are complementary to, and fit within, protocolized approaches.Computational models of human physiology offer the potential, with clinical data, to create patient-specific models that capture a patient's physiological status. Such models can provide new insights into patient condition by turning a series of sometimes confusing clinical data into a clear physiological picture. More directly, they can track patient-specific conditions and thus provide new means of diagnosis and opportunities for optimising therapy.This article presents the concept of model-based therapeutics, the use of computational models in clinical medicine and critical care in specific, as well as its potential clinical advantages, in a format designed for the clinical perspective. The review is presented in terms of a series of questions and answers. These aspects directly address questions concerning what makes a model, how it is made patient-specific, what it can be used for, its limitations and, importantly, what constitutes sufficient validation.To provide a concrete foundation, the concepts are presented broadly, but the details are given in terms of a specific case example. Specifically, tight glycemic control (TGC) is an area where inter- and intra-patient variability can dominate the quality of care control and care received from any given protocol. The overall review clearly shows the concept and significant clinical potential of using computational models in critical care medicine.

Pulmonary veno-occlusive disease in myeloproliferative disorder.

The present study reports a case of biopsy-proven pulmonary veno-occlusive disease as a cause of severe pulmonary hypertension in a patient suffering from a chronic myeloproliferative disorder. The pulmonary disease evolved favourably under treatment with defibrotide, a pro-fibrinolytic medication used in hepatic veno-occlusive disease.

Churg Strauss Syndrome masquerading septic shock.

Systemic inflammatory response syndrome (SIRS) can be related to acute inflammatory conditions that can be sometimes missed and inappropriately managed as severe infections. We report a case of Churg Strauss Syndrome (CSS), presenting as septic shock with acute onset of fever and multiple organ failure including pulmonary involvement with severe hypoxemia, hypotension requiring vasoactive support and acute renal failure. Antibiotics were discontinued and intravenous steroids allowed a rapid clinical improvement in close relationship with the fall in circulating eosinophils count.

[What's new in intensive care medicine?]. / Actualités thérapeutiques en médecine intensive.

Over the last ten years, much progress has been achieved in intensive care medicine. Large randomized studies, most often their multicentric, were performed and their results were translated into rules to be followed for the most appropriate treatment of life-threatening organ failures. The place of non-invasive ventilation in the management of hypercapnic or hypoxic respiratory insufficiencies was thus defined, and the methods for less traumatic mechanical ventilation were specified. The techniques of renal replacement therapy were compared and the optimal doses of dialysis or hemofiltration were established. The metabolic support of the patients was also altered following landmark studies, such as the management of blood glucose, which deeply influenced the approach to critically ill patients.

[Management of blood glucose level in intensive care]. / Gestion de la glycémie aux soins intensifs.

The aim of this article is to describe the current status and understanding and the clinical data related to the effects of Tight Glucose Control by Intensive Insulin therapy, TGCIIT, in critically ill patients. Recent prospectively collected data, from one centre, demonstrated decreases of mortality and of various other outcomes in critically ill patients treated with TGCIIT. These results are currently awaiting confirmation, although available data from prospective multi-centre studies do not seem to support the external validity of the beneficial effects of TGCIIT titrated to restore blood glucose between 80 and 110 mg/dl. Also, recent data raised new closely related and relevant issues including the variability of blood glucose, the risks of hypoglycaemia, and the delineation of the categories of patients in whom TGCIIT could bring an actual benefit.

Nitric oxide-related products and myeloperoxidase in bronchoalveolar lavage fluids from patients with ALI activate NF-kappa B in alveolar cells and monocytes.

An increased production of NO* and peroxynitrite in lungs has been suspected during acute lung injury (ALI) in humans, and recent studies provided evidence for an alveolar production of nitrated compounds. We observed increased concentrations of nitrites/nitrates, nitrated proteins and markers of neutrophil degranulation (myeloperoxidase, elastase and lactoferrine) in the fluids recovered from bronchoalveolar lavage fluids (BALF) of patients with ALI and correlated these changes to the number of neutrophils and the severity of the ALI. We also observed that BALFs stimulated the DNA-binding activity of the nuclear transcription factor kappa B (NF-kappaB) as detected by electrophoretic mobility shift assay in human alveolar cells (A549) and monocytes (THP1). The level of activation of the NF-kappaB-binding activity was correlated to the concentration of nitrated proteins and myeloperoxidase. Furthermore, in vitro studies confirmed that NO*-derived species (peroxynitrite and nitrites) and the neutrophil enzyme myeloperoxidase by themselves increased the activation of NF-kappaB, thereby arguing for an in vivo pathogenetic role of NO*-related products and neutrophil enzymes to human ALI.

Candida sepsis with intramyocardial abscesses mimicking left ventricular noncompaction.

Left ventricular (LV) noncompaction is a rare abnormality characterized by more than three trabeculations protruding from the LV wall, distal to the papillary muscles and visible in one echocardiographic image plane. The intertrabecular spaces are perfused from the LV cavity, as visualized on color Doppler imaging. Differential diagnoses of LV noncompaction are intraventricular thrombi, false tendons, aberrant bands, intramyocardial hematoma, cardiac metastases and the apical type of hypertrophic cardiomyopathy. Intramyocardial abscesses have not been reported as a differential diagnosis of LV noncompaction. In the patient presented, cardiac microabscesses due to candida sepsis mimicked LV noncompaction and should be considered in the differential diagnosis of LV noncompaction.

Histological detection of intramyocardial abscesses in Candida sepsis mimicking left ventricular non-compaction/hypertrabeculation on echocardiography.

Left ventricular non-compaction/hypertrabeculation (LVHT) is a rare cardiac abnormality characterized by more than three trabeculations protruding from the left ventricular wall, apically to the papillary muscles, visible in one echocardiographic image plane and intertrabecular spaces, perfused from the ventricular cavity. LVHT is frequently associated with neuromuscular disorders. Differential diagnoses of LVHT are intraventricular thrombi, false tendons, aberrant bands, intramyocardial hematoma, cardiac metastases and the apical type of hypertrophic cardiomyopathy. Intramyocardial abscesses have not been reported as a differential diagnosis of left ventricular non-compaction. In the presented case, cardiac microabscesses as a result of Candida sepsis mimicked left ventricular non-compaction in a 55-year-old man with hypopharyngeal carcinoma who died 20 days after chemotherapy. These microabscesses were not visible on echocardiography but were detected only at histologic examination of the myocardium. This case shows that intramyocardial abscesses as a result of Candida sepsis are a rare differential diagnosis of LVHT.