ESPEN practical short micronutrient guideline.

BACKGROUND: Trace elements and vitamins, named together micronutrients (MNs), are essential for human metabolism. The importance of MNs in common pathologies is recognized by recent research, with deficiencies significantly impacting the outcome. OBJECTIVE: This short version of the guideline aims to provide practical recommendations for clinical practice. METHODS: An extensive search of the literature was conducted in the databases Medline, PubMed, Cochrane, Google Scholar, and CINAHL for the initial guideline. The search focused on physiological data, historical evidence (for papers published before PubMed release in 1996), and observational and/or randomized trials. For each MN, the main functions, optimal analytical methods, impact of inflammation, potential toxicity, and provision during enteral or parenteral nutrition were addressed. The SOP wording was applied for strength of recommendations. RESULTS: The limited number of interventional trials prevented meta-analysis and led to a low level of evidence for most recommendations. The recommendations underwent a consensus process, which resulted in a percentage of agreement (%): strong consensus required of >90 % of votes. Altogether the guideline proposes 3 general recommendations and specific recommendations for the 26 MNs. Monitoring and management strategies are proposed. CONCLUSION: This short version of the MN guideline should facilitate handling of the MNs in at-risk diseases, whilst offering practical advice on MN provision and monitoring during nutritional support.

The science of micronutrients in clinical practice - Report on the ESPEN symposium.

BACKGROUND & AIMS: The European Society for Clinical Nutrition and Metabolism published its first clinical guidelines for use of micronutrients (MNs) in 2022. A two-day web symposium was organized in November 2022 discussing how to apply the guidelines in clinical practice. The present paper reports the main findings of this symposium. METHODS: Current evidence was discussed, the first day being devoted to clarifying the biology underlying the guidelines, especially regarding the definition of deficiency, the impact of inflammation, and the roles in antioxidant defences and immunity. The second day focused on clinical situations with high prevalence of MN depletion and deficiency. RESULTS: The importance of the determination of MN status in patients at risk and diagnosis of deficiencies is still insufficiently perceived, considering the essential role of MNs in immune and antioxidant defences. Epidemiological data show that deficiencies of several MNs (iron, iodine, vitamin D) are a global problem that affects human health and well-being including immune responses such as to vaccination. Clinical conditions frequently associated with MN deficiencies were discussed including cancer, obesity with impact of bariatric surgery, diseases of the gastrointestinal tract, critical illness, and aging. In all these conditions, MN deficiency is associated with worsening of outcomes. The recurrent problem of shortage of MN products, but also lack of individual MN-products is a worldwide problem. CONCLUSION: Despite important progress in epidemiology and clinical nutrition, numerous gaps in practice persist. MN depletion and deficiency are frequently insufficiently searched for in clinical conditions, leading to inadequate treatment. The symposium concluded that more research and continued education are required to improve patient outcome.

Effects of an online information tool on post-traumatic stress disorder in relatives of intensive care unit patients: a multicenter double-blind, randomized, placebo-controlled trial (ICU-Families-Study).

PURPOSE: Intensive care unit (ICU) hospitalization is challenging for the family members of the patients. Most family members report some level of anxiety and depression, sometimes even resulting in post-traumatic stress disorder (PTSD). An association has been reported between lack of information and PTSD. This study had three aims: to quantify the psychological burden of family members of critically ill patients, to explore whether a website with specific information could reduce PTSD symptoms, and to ascertain whether a website with information about intensive care would be used. METHOD: A multicenter double-blind, randomized, placebo-controlled trial was carried out in Austria and Switzerland. RESULTS: In total, 89 members of families of critically ill patients (mean age 47.3 ± 12.9 years, female n = 59, 66.3%) were included in the study. 46 relatives were allocated to the intervention website and 43 to the control website. Baseline Impact of Event Scale (IES) score was 27.5 ± 12.7. Overall, 50% showed clinically relevant PTSD symptoms at baseline. Mean IES score for the primary endpoint (~ 30 days after inclusion, T1) was 24 ± 15.8 (intervention 23.9 ± 17.9 vs. control 24.1 ± 13.5, p = 0.892). Hospital Anxiety and Depression Scale (HADS - Deutsch (D)) score at T1 was 12.2 ± 6.1 (min. 3, max. 31) and did not differ between groups. Use of the website differed between the groups (intervention min. 1, max. 14 vs. min. 1, max. 3; total 1386 "clicks" on the website, intervention 1021 vs. control 365). Recruitment was prematurely stopped in February 2020 due to coronavirus disease 2019 (COVID-19). CONCLUSION: Family members of critically ill patients often have significant PTSD symptoms and online information on critical illness did not result in reduced PTSD symptoms.

A phase II dose evaluation pilot feasibility randomized controlled trial of cholecalciferol in critically ill children with vitamin D deficiency (VITdAL-PICU study).

BACKGROUND: Vitamin D deficiency (VDD) is highly prevalent in the pediatric intensive care unit (ICU) and associated with worse clinical course. Trials in adult ICU demonstrate rapid restoration of vitamin D status using an enteral loading dose is safe and may improve outcomes. There have been no published trials of rapid normalization of VDD in the pediatric ICU. METHODS: We conducted a multicenter placebo-controlled phase II pilot feasibility randomized clinical trial from 2016 to 2017. We randomized 67 critically ill children with VDD from ICUs in Canada, Chile and Austria using a 2:1 randomization ratio to receive a loading dose of enteral cholecalciferol (10,000 IU/kg, maximum of 400,000 IU) or placebo. Participants, care givers, and outcomes assessors were blinded. The primary objective was to determine whether the loading dose normalized vitamin D status (25(OH)D > 75 nmol/L). Secondary objectives were to evaluate for adverse events and assess the feasibility of a phase III trial. RESULTS: Of 67 randomized participants, one was withdrawn and seven received more than one dose of cholecalciferol before the protocol was amended to a single loading dose, leaving 59 participants in the primary analyses (40 treatment, 19 placebo). Thirty-one/38 (81.6%) participants in the treatment arm achieved a plasma 25(OH)D concentration > 75 nmol/L versus 1/18 (5.6%) the placebo arm. The mean 25(OH)D concentration in the treatment arm was 125.9 nmol/L (SD 63.4). There was no evidence of vitamin D toxicity and no major drug or safety protocol violations. The accrual rate was 3.4 patients/month, supporting feasibility of a larger trial. A day 7 blood sample was collected for 84% of patients. A survey administered to 40 participating families showed that health-related quality of life (HRQL) was the most important outcome for families for the main trial (30, 75%). CONCLUSIONS: A single 10,000 IU/kg dose can rapidly and safely normalize plasma 25(OH)D concentrations in critically ill children with VDD, but with significant variability in 25(OH)D concentrations. We established that a phase III multicentre trial is feasible. Using an outcome collected after hospital discharge (HRQL) will require strategies to minimize loss-to-follow-up. CLINICALTRIALS: gov NCT02452762 Registered 25/05/2015.

Hospitalizations, emergency room visits and causes of death in 198 patients with permanent hypoparathyroidism: a retrospective Austrian study (2005-2022).

Objective: Chronic hypoparathyroidism (HP) is associated with acute and chronic complications, especially those related to hypocalcemia. We aimed to analyze details on hospital admissions and the reported deaths in affected patients. Design and methods: In a retrospective analysis, we reviewed the medical history of 198 patients diagnosed with chronic HP over a continuous period of up to 17 years at the Medical University Graz. Results: The mean age in our mostly female cohort (70.2%) was 62.6 ± 18.7 years. The etiology was predominantly postsurgical (84.8%). About 87.4% of patients received standard medication (oral calcium/vitamin D), 15 patients (7.6%) used rhPTH1-84/Natpar® and 10 patients (4.5%) had no/unknown medication. Two hundred and nineteen emergency room (ER) visits and 627 hospitalizations were documented among 149 patients, and 49 patients (24.7%) did not record any hospital admissions. According to symptoms and decreased serum calcium levels, 12% of ER (n = 26) visits and 7% of hospitalizations (n = 44) were likely attributable to HP. A subgroup of 13 patients (6.5%) received kidney transplants prior to the HP diagnosis. In eight of these patients, parathyroidectomy for tertiary renal hyperparathyroidism was the cause of permanent HP. The mortality was 7.8% (n = 12), and the causes of death appeared to be unrelated to HP. Although the awareness for HP was low, calcium levels were documented in 71% (n = 447) of hospitalizations. Conclusions: Acute symptoms directly related to HP did not represent the primary cause of ER visits. However, comorbidities (e.g. renal/cardiovascular diseases) associated with HP played a key role in hospitalizations and deaths. Significance statement: Hypoparathyroidism (HP) is the most common complication after anterior neck surgery. Yet, it remains underdiagnosed as well as undertreated, and the burden of disease and long-term complications are usually underestimated. There are few detailed data on emergency room (ER) visits hospitalizations and death in patients with chronic HP, although acute symptoms due to hypo-/hypercalcemia are easily detectable. We show that HP is not the primary cause for presentation but that hypocalcemia is a typical laboratory finding (when ordered) and thus may contribute to subjective symptoms. Patients often present with renal/cardiovascular/oncologic illness for which HP is known to be a contributing factor. A small but very special group (n = 13, 6.5%) are patients after kidney transplantations who showed a high ER hospitalization rate. Surprisingly, HP was never the cause for their frequent hospitalizations but rather the result of chronic kidney disease. The most frequent cause for HP in these patients was parathyroidectomy due to tertiary hyperparathyroidism. The causes of death in 12 patients appeared to be unrelated to HP, but we found a high prevalence of chronic organ damages/comorbidities related to it in this group. Less than 25% documented HP correctly in the discharge letters, which indicates a high potential for improvement.

Raised FGF23 Correlates to Increased Mortality in Critical Illness, Independent of Vitamin D.

BACKGROUND: Fibroblast Growth Factor (FGF23) is an endocrine hormone classically associated with the homeostasis of vitamin D, phosphate, and calcium. Elevated serum FGF23 is a known independent risk factor for mortality in chronic kidney disease (CKD) patients. We aimed to determine if there was a similar relationship between FGF23 levels and mortality in critically ill patients. METHODS: Plasma FGF23 levels were measured by ELISA in two separate cohorts of patients receiving vitamin D supplementation: critical illness patients (VITdAL-ICU trial, n = 475) and elective oesophagectomy patients (VINDALOO trial, n = 76). Mortality data were recorded at 30 and 180 days or at two years, respectively. FGF23 levels in a healthy control cohort were also measured (n = 27). RESULTS: Elevated FGF23 (quartile 4 vs. quartiles 1-3) was associated with increased short-term (30 and 180 day) mortality in critical illness patients (p < 0.001) and long-term (two-year) mortality in oesophagectomy patients (p = 0.0149). Patients who died had significantly higher FGF23 levels than those who survived: In the critical illness cohort, those who died had 1194.6 pg/mL (range 0-14,000), while those who survived had 120.4 pg/mL (range = 15-14,000) (p = 0.0462). In the oesophagectomy cohort, those who died had 1304 pg/mL (range = 154-77,800), while those who survived had 644 pg/mL (range = 179-54,894) (p < 0.001). This was found to be independent of vitamin D or CKD status (critical illness p = 0.3507; oesophagectomy p = 0.3800). FGF23 levels in healthy controls were similar to those seen in oesophagectomy patients (p = 0.4802). CONCLUSIONS: Elevated baseline serum FGF23 is correlated with increased mortality in both the post-oesophagectomy cohort and the cohort of patients with critical illness requiring intensive care admission. This was independent of vitamin D status, supplementation, or CKD status, which suggests the presence of vitamin D-independent mechanisms of FGF23 action during the acute and convalescent stages of critical illness, warranting further investigation.

[Vitamin C and D supplementation in critically ill patients]. / Supplementierung von Vitamin C und D bei kritisch Kranken.

Micronutrient supplementation as part of the medical nutrition therapy for critically ill patients has received much attention in the past few years. Nevertheless, in clinical practice uncertainty remains about the optimal supplementation strategy, including which substance at which dosage should be administered at what time to specific groups of patients. Thus, the aim of this narrative review is to summarize the current evidence and recommendations for the micronutrients vitamin C and vitamin D. The physiological and pathophysiological roles of both vitamins are presented, recently published clinical trials are discussed, and the recommendations of the current guidelines are summarized. In addition, pragmatic tips for use in everyday clinical practice in the intensive care unit are given.

[Diagnosis and treatment of osteoporosis in patients with chronic kidney disease : Joint guidelines of the Austrian Society for Bone and Mineral Research (ÖGKM), the Austrian Society of Physical and Rehabilitation Medicine (ÖGPMR) and the Austrian Society of Nephrology (ÖGN)]. / Diagnose und Therapie der Osteoporose bei Patienten mit chronischer Niereninsuffizienz : Gemeinsame Leitlinie der Österreichischen Gesellschaft für Knochen- und Mineralstoffwechsel (ÖGKM), der Österreichischen Gesellschaft für Physikalische Medizin und Rehabilitation (ÖGPMR) und der Österreichischen Gesellschaft für Nephrologie (ÖGN).

DEFINITION AND EPIDEMIOLOGY: Chronic kidney disease (CKD): abnormalities of kidney structure or function, present for over 3 months. Staging of CKD is based on GFR and albuminuria (not graded). Osteoporosis: compromised bone strength (low bone mass, disturbance of microarchitecture) predisposing to fracture. By definition, osteoporosis is diagnosed if the bone mineral density T­score is ≤ -2.5. Furthermore, osteoporosis is diagnosed if a low-trauma (inadequate trauma) fracture occurs, irrespective of the measured T­score (not graded). The prevalence of osteoporosis, osteoporotic fractures and CKD is increasing worldwide (not graded). PATHOPHYSIOLOGY, DIAGNOSIS AND TREATMENT OF CHRONIC KIDNEY DISEASE-MINERAL AND BONE DISORDER (CKD-MBD): Definition of CKD-MBD: a systemic disorder of mineral and bone metabolism due to CKD manifested by either one or a combination of the following: abnormalities of calcium, phosphorus, PTH, or vitamin D metabolism; renal osteodystrophy; vascular calcification (not graded). Increased, normal or decreased bone turnover can be found in renal osteodystrophy (not graded). Depending on CKD stage, routine monitoring of calcium, phosphorus, alkaline phosphatase, PTH and 25-OH-vitamin D is recommended (2C). Recommendations for treatment of CKD-MBD: Avoid hypercalcemia (1C). In cases of hyperphosphatemia, lower phosphorus towards normal range (2C). Keep PTH within or slightly above normal range (2D). Vitamin D deficiency should be avoided and treated when diagnosed (1C). DIAGNOSIS AND RISK STRATIFICATION OF OSTEOPOROSIS IN CKD: Densitometry (using dual X­ray absorptiometry, DXA): low T­score correlates with increased fracture risk across all stages of CKD (not graded). A decrease of the T­score by 1 unit approximately doubles the risk for osteoporotic fracture (not graded). A T-score ≥ -2.5 does not exclude osteoporosis (not graded). Bone mineral density of the lumbar spine measured by DXA can be increased and therefore should not be used for the diagnosis or monitoring of osteoporosis in the presence of aortic calcification, osteophytes or vertebral fracture (not graded). FRAX can be used to aid fracture risk estimation in all stages of CKD (1C). Bone turnover markers can be measured in individual cases to monitor treatment (2D). Bone biopsy may be considered in individual cases, especially in patients with CKD G5 (eGFR < 15 ml/min/1.73 m2) or CKD 5D (dialysis). SPECIFIC TREATMENT OF OSTEOPOROSIS IN PATIENTS WITH CKD: Hypocalcemia should be treated and serum calcium normalized before initiating osteoporosis therapy (1C). CKD G1-G2 (eGFR ≥ 60 ml/min/1.73 m2): treat osteoporosis as recommended for the general population (1A). CKD G3-G5D (eGFR < 60 ml/min/1.73 m2 to dialysis): treat CKD-MBD first before initiating osteoporosis treatment (2C). CKD G3 (eGFR 30-59 ml/min/1.73 m2) with PTH within normal limits and osteoporotic fracture and/or high fracture risk according to FRAX: treat osteoporosis as recommended for the general population (2B). CKD G4-5 (eGFR < 30 ml/min/1.73 m2) with osteoporotic fracture (secondary prevention): Individualized treatment of osteoporosis is recommended (2C). CKD G4-5 (eGFR < 30 ml/min/1.73 m2) and high fracture risk (e.g. FRAX score > 20% for a major osteoporotic fracture or > 5% for hip fracture) but without prevalent osteoporotic fracture (primary prevention): treatment of osteoporosis may be considered and initiated individually (2D). CKD G4-5D (eGFR < 30 ml/min/1.73 m2 to dialysis): Calcium should be measured 1-2 weeks after initiation of antiresorptive therapy (1C). PHYSICAL MEDICINE AND REHABILITATION: Resistance training prioritizing major muscle groups thrice weekly (1B). Aerobic exercise training for 40 min four times per week (1B). Coordination and balance exercises thrice weekly (1B). Flexibility exercise 3-7 times per week (1B).

A Comparison of the Representation of Women in Editor Positions at Major Medical Journals in 2021 vs 2011.

PURPOSE: There continues to be a disparity in the representation of women across medicine, including in editor positions at major medical journals. The authors repeated a study they had conducted in 2011 to compare the representation of women in editor-in-chief and editorial board member positions in 2011 and 2021. METHOD: The authors included in their analysis the 60 journals from their original 2011 study and the top 5 ranked journals by Journal Impact Factor in each of 12 disciplines in 2021. This led to the inclusion of 86 journals. The authors collected the names and genders of the editors-in-chief and editorial board members at these journals, using information provided by the journals and a Google search for the photos and/or pronouns of the remaining editors. They compared results across years (2021 vs 2011), editor positions, disciplines, Journal Impact Factors, and ranks. RESULTS: Twenty-two of the 90 editors-in-chief (24.4%) were women in 2021 compared with 10 of 63 (15.9%) in 2011, an increase of 8.5%. Of the 6,285 editorial board members, 1,756 were women (27.9%) in 2021 compared with 719 of 4,112 (17.5%) in 2011, an increase of 10.4%. Journals with women editors-in-chief gained 3.5 ranks and 9.1 points in Journal Impact Factor on average over this 10-year period, compared with no gain in rank and an increase of 4.7 points in Journal Impact Factor for journals with men editors-in-chief; both are statistically significant differences (P = .045 and P = .016, respectively). CONCLUSIONS: In almost all evaluated disciplines and editor positions, there was an increase in the percentage of women at top-ranked medical journals over a 10-year period. Despite this increase, improvements are still needed to accelerate the currently slow rate of change in these positions to enhance diversity, equity, and inclusion for women in medicine.

Family support in intensive care units during COVID-19 visit ban: A multinational Delphi Study during first COVID-19 wave.

OBJECTIVES: This study assessed opinions and experiences of healthcare professionals, former patients and family members during the first wave of the COVID-19 pandemic and focuses on challenges in family-centred care for intensive care unit patients and affected families. RESEARCH METHODOLOGY/DESIGN: A two-round modified Delphi process assessed the opinions and experiences of experts such as healthcare professionals, former patients and their families (n = 151). SETTING: This study was conducted across four countries in Europe. RESULTS: In total, 121 participants (response rate 80.13%) answered the first Delphi round; the second was answered by 131 participants (response rate 86.75%). Participants perceived family support in the intensive care unit as highly important during the COVID-19 pandemic. Enabling contact amongst patients, families and clinicians is regarded as essential to build hope and confidence in the treatment and the recovery process. The extraordinary situation led to the implementation of new communication structures such as video calls and websites. CONCLUSION: A consensus was reached between healthcare professionals that virtual contact is essential for patients with COVID-19 and their families during visit restrictions. This should be done to establish confidence in the treatment.

Circulating N-formylmethionine and metabolic shift in critical illness: a multicohort metabolomics study.

BACKGROUND: Cell stress promotes degradation of mitochondria which release danger-associated molecular patterns that are catabolized to N-formylmethionine. We hypothesized that in critically ill adults, the response to N-formylmethionine is associated with increases in metabolomic shift-related metabolites and increases in 28-day mortality. METHODS: We performed metabolomics analyses on plasma from the 428-subject Correction of Vitamin D Deficiency in Critically Ill Patients trial (VITdAL-ICU) cohort and the 90-subject Brigham and Women's Hospital Registry of Critical Illness (RoCI) cohort. In the VITdAL-ICU cohort, we analyzed 983 metabolites at Intensive Care Unit (ICU) admission, day 3, and 7. In the RoCI cohort, we analyzed 411 metabolites at ICU admission. The association between N-formylmethionine and mortality was determined by adjusted logistic regression. The relationship between individual metabolites and N-formylmethionine abundance was assessed with false discovery rate correction via linear regression, linear mixed-effects, and Gaussian graphical models. RESULTS: Patients with the top quartile of N-formylmethionine abundance at ICU admission had a significantly higher adjusted odds of 28-day mortality in the VITdAL-ICU (OR, 2.4; 95%CI 1.5-4.0; P = 0.001) and RoCI cohorts (OR, 5.1; 95%CI 1.4-18.7; P = 0.015). Adjusted linear regression shows that with increases in N-formylmethionine abundance at ICU admission, 55 metabolites have significant differences common to both the VITdAL-ICU and RoCI cohorts. With increased N-formylmethionine abundance, both cohorts had elevations in individual short-chain acylcarnitine, branched chain amino acid, kynurenine pathway, and pentose phosphate pathway metabolites. CONCLUSIONS: The results indicate that circulating N-formylmethionine promotes a metabolic shift with heightened mortality that involves incomplete mitochondrial fatty acid oxidation, increased branched chain amino acid metabolism, and activation of the pentose phosphate pathway.

ESPEN micronutrient guideline.

BACKGROUND: Trace elements and vitamins, named together micronutrients (MNs), are essential for human metabolism. Recent research has shown the importance of MNs in common pathologies, with significant deficiencies impacting the outcome. OBJECTIVE: This guideline aims to provide information for daily clinical nutrition practice regarding assessment of MN status, monitoring, and prescription. It proposes a consensus terminology, since many words are used imprecisely, resulting in confusion. This is particularly true for the words "deficiency", "repletion", "complement", and "supplement". METHODS: The expert group attempted to apply the 2015 standard operating procedures (SOP) for ESPEN which focuses on disease. However, this approach could not be applied due to the multiple diseases requiring clinical nutrition resulting in one text for each MN, rather than for diseases. An extensive search of the literature was conducted in the databases Medline, PubMed, Cochrane, Google Scholar, and CINAHL. The search focused on physiological data, historical evidence (published before PubMed release in 1996), and observational and/or randomized trials. For each MN, the main functions, optimal analytical methods, impact of inflammation, potential toxicity, and provision during enteral or parenteral nutrition were addressed. The SOP wording was applied for strength of recommendations. RESULTS: There was a limited number of interventional trials, preventing meta-analysis and leading to a low level of evidence. The recommendations underwent a consensus process, which resulted in a percentage of agreement (%): strong consensus required of >90% of votes. Altogether the guideline proposes sets of recommendations for 26 MNs, resulting in 170 single recommendations. Critical MNs were identified with deficiencies being present in numerous acute and chronic diseases. Monitoring and management strategies are proposed. CONCLUSION: This guideline should enable addressing suboptimal and deficient status of a bundle of MNs in at-risk diseases. In particular, it offers practical advice on MN provision and monitoring during nutritional support.

[Ways of supporting relatives in intensive care units : Overview and update]. / Angehörigenbetreuung auf Intensivstationen : Übersicht und Update.

BACKGROUND: Relatives of patients in the intensive care unit (ICU) face a challenging situation: they often experience an existential crisis with great emotional stress and at the same time they are often actively involved in therapeutic decisions. The visiting restrictions of the coronavirus disease 2019 (COVID-19) pandemic have created new challenges in providing support to relatives. OBJECTIVES: The aim of this work is to present current and new developments in supporting relatives of critically ill patients in the form of a narrative review. RESULTS: In recent years, numerous new approaches and projects to support relatives have been developed. They can be assigned to the following six areas: 1) presence of relatives in the ICU, 2) proactive involvement in care, 3) structured communication/information and online offers, 4) multidisciplinary cooperation, 5) organizational management and 6) follow-up offers. The evidence and the current implementation status of these measures are very heterogeneous internationally and nationally. CONCLUSIONS: Measures for providing support for ICU relatives are diverse. Some can even be implemented despite visit bans. Recent digital developments enable virtual visits and a better exchange of information between the ICU team and relatives.

Sex-Specific Catabolic Metabolism Alterations in the Critically Ill following High Dose Vitamin D.

Pharmacological interventions are essential for the treatment and management of critical illness. Although women comprise a large proportion of the critically ill, sex-specific pharmacological properties are poorly described in critical care. The sex-specific effects of vitamin D3 treatment in the critically ill are not known. Therefore, we performed a metabolomics cohort study with 1215 plasma samples from 428 patients from the VITdAL-ICU trial to study sex-specific differences in the metabolic response to critical illness following high-dose oral vitamin D3 intervention. In women, despite the dose of vitamin D3 being higher, pharmacokinetics demonstrated a lower extent of vitamin D3 absorption compared to men. Metabolic response to high-dose oral vitamin D3 is sex-specific. Sex-stratified individual metabolite associations with elevations in 25(OH)D following intervention showed female-specific positive associations in long-chain acylcarnitines and male-specific positive associations in free fatty acids. In subjects who responded to vitamin D3 intervention, significant negative associations were observed in short-chain acylcarnitines and branched chain amino acid metabolites in women as compared to men. Acylcarnitines and branched chain amino acids are reflective of fatty acid B oxidation, and bioenergesis may represent notable metabolic signatures of the sex-specific response to vitamin D. Demonstrating sex-specific pharmacometabolomics differences following intervention is an important movement towards the understanding of personalized medicine.

Usefulness of the trabecular bone score in maintenance dialysis patients : A single center observational study.

BACKGROUND: The number of dialysis patients is steadily increasing. Associated comorbidities include impaired bone and mineral metabolism, termed chronic kidney disease-mineral and bone disorder (CKD-MBD), leading to a high fracture risk, increased morbidity and mortality and impaired quality of life. While the bone density is assessed with dual-energy X­ray absorptiometry (DXA), the trabecular bone score (TBS) captures the image texture as a potential index of skeletal microarchitecture. The aim of this study was to evaluate the clinical relevance of DXA and TBS in dialysis patients with and without prevalent fractures. METHODS: Bone disorders were evaluated in 82 dialysis patients (37% female) at the University Hospital of Graz, Austria, by DXA including the assessment of the TBS based on a patient interview and the local routine patient database software. The patient cohort was stratified by having sustained a fragility fracture in the past or not. Descriptive statistics, t­tests for continuous variables and χ2-tests for nominal variables including results of DXA and TBS were performed to compare these groups considering the dialysis modality and duration as well as the number of kidney transplantations. RESULTS: Of the 82 patients, 32 (39%) had a positive history of fractures. There was a significant association between dialysis duration and fracture prevalence (p < 0.05) as well as musculoskeletal pain (p < 0.01). No significant correlation between DXA/TBS parameters and musculoskeletal pain could be established. The DXA scores did not correlate with fracture prevalence with the exception of DXA radius measurements; however, fracture prevalence significantly correlated inversely with TBS (p < 0.001). CONCLUSION: The use of DXA has a limited role in fracture prediction in dialysis patients; however, the TBS seems to add information as an additional tool for fracture risk estimation in this patient population.

Nutrition during extracorporeal life support: A review of pathophysiological bases and application of guidelines.

BACKGROUND: Patients on extracorporeal life support (ECLS), either for respiratory or cardiac support, are at high risk of malnutrition; guidelines on nutrition in critical care have not incorporated solid evidence regarding these settings. The aim of this narrative review is to gather the available evidence in the existing literature and transpose general principles to the ECLS population. METHODS: A literature review of observational and interventional studies on nutrition during ECLS, and evaluation of nutrition guidelines in this perspective. RESULTS: Nutrition is paramount for improving outcomes in ECLS, as well as in critically ill patients. The caloric needs during ECLS can vary according to the severity of the clinical state, sedation, paralysis, and temperature stability. Precise evaluation of energy expenditure by indirect calorimetry is difficult because ECLS is a system dedicated to removing carbon dioxide; however, modified equations composed of carbon dioxide values taken from the membrane lung are available. Guidelines suggest starting early enteral nutrition (EN) with a hypocaloric (70%-80% of the needs) strategy, also in acute states such as septic or cardiogenic shock. Moreover, EN, despite previous concerns, is feasible in prone position, an increasingly adopted strategy during mechanical ventilation. The catabolic state is maximal in these patients, causing a protein and muscular reduction. Therefore, adequate protein delivery should be guaranteed by administering a high protein intake of up to 2 g/kg/day. CONCLUSIONS: Studies on nutrition tailored to ECLS patients are warranted. Early hypocaloric EN with high protein intake, tailored on indirect calorimetry, may be the most appropriate option.

Vitamin D deficiency in critically ill COVID-19 ARDS patients.

BACKGROUND & AIMS: Vitamin D's pleiotropic effects include immune modulation, and its supplementation has been shown to prevent respiratory tract infections. The effectivity of vitamin D as a therapeutic intervention in critical illness remains less defined. The current study analyzed clinical and immunologic effects of vitamin D levels in patients suffering from coronavirus disease 2019 (COVID-19) induced acute respiratory distress syndrome (ARDS). METHODS: This was a single-center retrospective study in patients receiving intensive care with a confirmed SARS-CoV-2 infection and COVID-19 ARDS. 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D serum levels, pro- and anti-inflammatory cytokines and immune cell subsets were measured on admission as well as after 10-15 days. Clinical parameters were extracted from the patient data management system. Standard operating procedures included the daily administration of vitamin D3 via enteral feeding. RESULTS: A total of 39 patients with COVID-19 ARDS were eligible, of which 26 were included in this study as data on vitamin D status was available. 96% suffered from severe COVID-19 ARDS. All patients without prior vitamin D supplementation (n = 22) had deficient serum levels of 25-hydroxyvitamin D. Vitamin D supplementation resulted in higher serum levels of 25-hydroxyvitamin D but not did not increase 1,25-dihydroxyvitamin D levels after 10-15 days. Clinical parameters did not differ between patients with sufficient or deficient levels of 25-hydroxyvitamin D. Only circulating plasmablasts were higher in patients with 25-hydroxyvitamin D levels ≥30 ng/ml (p = 0.029). Patients with 1,25-dihydroxyvitamin D levels below 20 pg/ml required longer mechanical ventilation (p = 0.045) and had a worse acute physiology and chronic health evaluation (APACHE) II score (p = 0.048). CONCLUSION: The vast majority of COVID-19 ARDS patients had vitamin D deficiency. 25-hydroxyvitamin D status was not related to changes in clinical course, whereas low levels of 1,25-dihydroxyvitamin D were associated with prolonged mechanical ventilation and a worse APACHE II score.