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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). 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 D 3 via enteral feeding. 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). 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. [ABSTRACT FROM AUTHOR]

Introduction: A need exists to improve the efficiency of clinical trials in burn care. The objective of this study was to validate "Persistent Organ Dysfunction" plus death as endpoint in burn patients and to demonstrate its statistical efficiency.Methods: This secondary outcome analysis of a dataset from a prospective international multicenter RCT (RE-ENERGIZE) included patients with burned total body surface area >20% and a 6-month follow-up. Persistent organ dysfunction was defined as persistence of organ dysfunction with life-supportiing technologies and ICU care.Results: In the 539 included patients, the prevalence of 0p p+ pdeath was 40% at day 14 and of 27% at day 28. At both timepoints, survivors with POD (vs. survivors without POD) had a higher mortality rate, longer ICU- and hospital-stays, and a reduced quality of life. POD + death as an endpoint could result in reduced sample size requirements for clinical trials. Detecting a 25% relative risk reduction in 28-day mortality would require a sample size of 4492 patients, whereas 1236 patients would be required were 28-day POD + death used.Conclusions: POD + death represents a promising composite outcome measure that may reduce the sample size requirements of clinical trials in severe burns patients. Further validation in larger clinical trials is warranted.Study Type: Prospective cohort study, level of evidence: II. [ABSTRACT FROM AUTHOR]

Burn patients pose a number of clinical challenges for doctors and dietitians to achieve optimal nutrition practice. The objective of this study was to describe nutrition practices in burn center intensive care units (ICUs) compared to the most recent ESPEN and SCCM/ASPEN guidelines (hereafter referenced as "the Guidelines") and highlight the variation in practice and what is "best achievable." In 2014–15, we prospectively enrolled 283 mechanically ventilated patients who were admitted to one of 14 burn ICUs for at least 72 h. Data collected included information on the estimation of energy and protein requirements, their actual delivery as well as route and time of feeding, and administration of micronutrients. We describe site practices and data per patient-day. Adherence to the Guidelines for the use of enteral nutrition (EN) over parenteral nutrition (PN) was 90.5% of patient-days (site range 79.2%–97.0%). However, adherence to the Guidelines for the measurement of energy requirements was 6.0% of patient-days (site range 0.0%–93.3%), supplementation with glutamine took place in 22.4% of patient-days (site range 0.0%–61.8%). Provision of 80% of energy requirements within 48–72 h was achieved in 35.3% of patients (site range 0.0%–80.0%), and provision of 80% of protein needs within 48–72 h was achieved in 34.3% of patients (site range 0.0%–80.0%). Average nutritional adequacy was 64.9 ± 40.0% for energy (best site: 80.2%, worst site: 42.0%) and 65.6 ± 42.1% for protein (best site: 87.3%, worst site: 43.6%). The present findings indicate that despite high adherence to providing EN over PN, there is still a large gap between many recommendations and clinical practice, and the achievement of nutrition goals for patients in burn centers is suboptimal. [ABSTRACT FROM AUTHOR]

To describe international practices on the use of calcium salts during cardiopulmonary bypass (CPB) weaning in adult cardiac surgery patients. Multiple-choice survey on current practice of CPB weaning. Online survey using the SurveyMonkey platform. Departments of cardiac anesthesiology worldwide. None. Out of 112 surveys sent, 100 centers from 32 countries replied. The majority of centers (88 of 100 = 88%) administer calcium salts intraoperatively: 71 of 100 (71%) are using these drugs for CPB weaning and 78 of 100 (78%) for correction of hypocalcemia. Among the 88 centers that use calcium salts intraoperatively, 66% (58 of 88) of respondents use calcium chloride, 22% (19 of 88) use calcium gluconate, and 12% (11 of 88) use both drugs. Calcium salts are routinely used during normal (47 of 71 centers = 66%) and difficult (59 of 71 centers = 83%) weaning from CPB. Doses of 5 to 15 mg/kg during termination of CPB were used by 55 of 71 centers (77%) either by bolus (39 of 71, 55%) or over a time period longer than 1 minute (32 of 71 = 45%). Norepinephrine is the most commonly used first line vasopressor or inotropic agent used to support hemodynamics during termination of CPB in 32 out of 100 centers (32%), and calcium is the second one, used by 23 out of 100 centers (23%). This survey demonstrates that the majority of cardiac centers use calcium in adult patients undergoing cardiac surgery, especially during weaning from CPB. There is variability on the type of drug, dose, and modality of drug administration. [ABSTRACT FROM AUTHOR]

Recent studies indicate that vitamin D deficiency is associated with increased morbidity and mortality in critically ill patients. Knowledge about the functional role and clinical relevance of vitamin D for patients undergoing cardiac surgery is sparse. Therefore, we investigated the clinical significance of vitamin D levels on outcome of cardiac surgery patients. 92 patients undergoing elective cardiac surgery with cardiopulmonary arrest were included in this prospective observational pilot study. 25-hydroxyvitamin D (25OHD) and 1,25-dihydroxyvitamin D (1,25(OH) 2 D) levels were measured prior to surgery, immediately postoperatively as well as 6, 12 and 24 h after surgery. We assessed postoperative organ dysfunctions, infections and death until hospital discharge. The serum concentration of 1,25(OH) 2 D significantly decreased intraoperatively by 29.3% (p < 0.001) and was significantly lower at any postoperative time point compared to baseline values, whereas 25OHD levels did not show significant changes during the observation period. Coronary artery bypass graft (CABG) patients had significant higher baseline 1,25(OH) 2 D values than patients with valve surgery (39.7 ± 13.9 ng/l vs. 30.1 ± 14.1 ng/l, p = 0.010) or CABG + valve surgery (39.7 ± 13.9 ng/l vs. 32.6 ± 11.8 ng/l, p = 0.044). Our data showed a significant odds ratio to develop postoperative organ dysfunction (OR 0.95; p = 0.009) and PCT levels ≥5 μg/l (OR 0.94; p = 0.046) for every ng/l increment in 1,25(OH) 2 D, when performing multivariable analysis and after adjusting for preoperative illness and demographics. In addition, multivariable-adjusted statistical analyses revealed that patients stayed significantly shorter on ICU (−0.21 h; p = 0.001) and in hospital (−2.6 days; p = 0.009) for every ng/l increment in 1,25(OH) 2 D. Our data highlight important evidence about the clinical significance of 1,25(OH) 2 D levels in cardiac surgery patients. Higher levels were associated with significantly less postoperative organ dysfunctions, elevated PCT levels, death and prolonged hospital stay. 1,25(OH) 2 D levels decreased significantly intra- and postoperatively, while serum levels of 25OHD did not. clinicaltrials.gov (NCT 02488876), registered May 1, 2015. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • A new quantitative assay detects SELENBP1 specifically in patient serum. • Circulating SELENBP1 is associated with risk for myocardial infarction and death. • SELENBP1 may qualify as biomarker for patients with acute coronary symptoms. • SELENBP1 concentrations are unrelated to established myocardial biomarkers. • Suspected Role of Selenium-Binding Protein 1 in Myocardial Infarction. Abstract Objective Selenium-binding protein 1 (SELENBP1) is an intracellular protein with variable expression in response to cellular stress. As the selenium (Se) status is affected by inflammation and hypoxia, we hypothesized that SELENBP1 contributes to disease-specific Se metabolism. To test this hypothesis, a quantitative assay was developed and used to monitor SELENBP1 in patients with acute coronary syndrome (ACS). Materials and methods SELENBP1 was expressed, antibodies were generated and a luminometric immuno assay (LIA) was established and characterized. Serum samples were collected from controls (n = 37) and patients (n = 85) admitted to the Chest Pain Unit with suspected ACS. Blood samples were available from time of first medical contact in the ambulance, at admission to hospital, and after 2, 4, 6 and 12–36 h. Results Circulating SELENBP1 was close to limit of detection in healthy controls and elevated in patients with suspected ACS. SELENBP1 was unrelated to other biomarkers of myocardial damage such as troponin T or aspartate aminotransferase. Serum SELENBP1 enabled a categorization of patients on first medical contact as either high-risk or low-risk for major adverse cardiac events (MACE) or death, when using 0.8 nmol/l as threshold. The odds-ratios (OR) for MACE and death were OR = 11 (95% CI: 2–49, p = 0.0022) and OR = 12 (2–74, p = 0.014), respectively. Conclusions Until now, SELENBP1 was mainly considered as an intracellular protein involved in Se metabolism and redox control. Our data indicate that SELENBP1 constitutes a circulating biomarker for cardiac events categorizing patients with suspected ACS at first medical contact into high-risk or low-risk for MACE and death, independent from and complimentary to current biomarkers. [ABSTRACT FROM AUTHOR]

Background: We reported earlier that the cytokine macrophage migration inhibitory factor (MIF) is a potential biomarker in burn injury. In the present study, we investigated the clinical significance of the newly discovered MIF family member d-dopachrome tautomerase (DDT or MIF-2) and their common soluble receptor CD74 (sCD74) in severely burned patients.Methods: DDT and sCD74 serum levels were measured 20 severely burned patients and 20 controls. Serum levels were correlated to the abbreviated burn severity index (ABSI) and total body surface area (TBSA) followed by receiver operating characteristic (ROC) analysis. Data were supported by gene expression dataset analysis of 31 burn patients and 28 healthy controls.Results: CD74 and DDT were increased in burn patients. Furthermore, CD74 and DDT also were elevated in septic non-survivors when compared to survivors. Serum levels of DDT showed a positive correlation with the ABSI and TBSA in the early stage after burn, and the predictive character of DDT was strongest at 24h. Serum levels of CD74 only correlated with the ABSI 5 days after injury.Conclusions: DDT may assist in the monitoring of clinical outcome and prediction of sepsis during the early post-burn period. Soluble CD74 and MIF, by contrast, have limited value as an early predictor of death due to their delayed response to burn. [ABSTRACT FROM AUTHOR]

Objectives Validated composite outcomes after complicated cardiac surgery are poorly established. Therefore, the authors evaluated a novel composite endpoint, persistent organ dysfunction (POD)+death, which is defined as any need for life-sustaining therapies or death at any time within 28 days from surgery. Design Secondary analysis extracted from a large-scale prospective randomized trial of critically ill cardiac surgery patients. Setting Multi-institutional, university hospitals. Participants Ninety-five cardiac surgery patients with complicated postoperative courses. Interventions Cardiac surgery with cardiopulmonary bypass. Measurements and Main Results At 28 days following surgery, the prevalence of POD was 15%, and 23% of patients had died (POD+death = 38%). Patients alive with POD at day 28 exhibited a significantly higher extent of organ injury and longer ICU (33 v 7 days; p<0.001) and hospital lengths of stay (49 v 21 days; p<0.001) compared to patients without POD at day 28. At 3 and 6 months, quality-of-life scores (by Short Form 36 questionnaire) showed a significantly reduced rating for most components in patients with POD at day 28 compared to those without POD. The 6-month mortality rate was 21% among patients alive with POD at day 28 compared to 5% among patients alive without POD (p = 0.05). The calculated number of patients needed per arm to detect a 25% relative risk reduction for mortality alone was 762 compared to 386 per arm for POD+ death. Conclusions POD+death at day 28 following cardiac surgery may be a valid composite endpoint and offers statistical efficiencies in terms of sample size calculations for cardiac surgical trials. [ABSTRACT FROM AUTHOR]

Objectives: We recently reported that cardiac surgical patients in our institution exhibited low selenium blood levels preoperatively, which were further aggravated during surgery and independently associated with the development of postoperative multiorgan failure. Low circulating selenium levels result in a decreased antioxidant capacity. Both can be treated effectively by sodium-selenite administration. Little is known about the kinetics of exogenously administered sodium-selenite during acute perioperative oxidative stress. The aim of this study was to assess the effects of perioperative high-dose sodium-selenite administration on selenium blood concentrations in cardiac surgical patients. Methods: One hundred four cardiac surgical patients were enrolled in this prospective observational trial. Patients received an intravenous bolus of 2000 mg selenium after an induction of anesthesia and 1000 mg selenium every day further during their intensive care unit (ICU) stay. Selenium blood levels were measured at regular intervals. Results: Preoperative sodium-selenite administration increased selenium blood concentrations to normal values on ICU admission, but failed to prevent a significant decrease of circulating selenium on the first postoperative day. During the further ICU stay, selenium blood levels were normalized by the administration strategy and did not exceed the German reference range. No acute selenium-specific side effects occurred. When matching the participating patients to a historical control group without sodium-selenite administration, the chosen strategy was associated with a decrease in SAPS II (23 ± 7 versus 29 ± 8, P = 0.005) and SOFA scores (4 3 versus 7 ± 2, P = 0.007) on the first postoperative day, but was unable to improve the postoperative outcome in patients staying >1 d in ICU. Conclusions: Despite preemptive high-dose sodium-selenite administration, cardiac surgical patients experienced a significant decrease in circulating selenium levels on the first postoperative day. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: Although animal studies document conflicting data on the influence of hypothermia on cytokine release in various settings, no data exist if hypothermia affects the inflammatory response after successful cardiopulmonary resuscitation. Materials and Methods: Arrest- and treatment-related variables of 71 patients were documented, and serum samples were analyzed for levels of interleukin 6, tumor necrosis factor-α, C-reactive protein, and procalcitonin immediately after hospital admission and after 6, 24, and 120 hours. At day 14, patients were dichotomized in those with good and bad neurological outcome. Results: Regardless of outcomes, interleukin 6 levels were significantly elevated by the use of hypothermia (n = 39). The rate of bacterial colonization was significantly higher in hypothermic patients (64.1 vs 12.5 %; P < .001). On the contrary, procalcitonin levels were, independent of the use of hypothermia, only significantly elevated in patients with bad neurological outcome. Hypothermic patients showed a strong trend to reduced mortality. However, there was no influence on neurological recovery. Conclusions: In this observational study, hypothermia influenced the inflammatory response after cardiopulmonary resuscitation and lead to a higher rate of bacterial colonization without altering ultimate neurologic recovery. [Copyright &y& Elsevier]

Facial burns frequently occur in occupational or household accidents. While dysphagia and dysphonia are known sequelae, little is known about impaired smell and taste after facial burns. In a prospective observational controlled study, we evaluated hyposmia via the Sniffin' Stick Test (SnS), hypogeusia via a taste strip test, and dysphonia and dysphagia via validated questionnaires acutely and one-year after burn, respectively. A matched control group consisting of a convenience sample of healthy volunteers underwent the same assessments. Fifty-five facial burn patients (FB) and 55 healthy controls (CTR) were enrolled. Mean burn size was 11 (IQR: 29) % total body surface area (TBSA); CTR and FB were comparable regarding age, sex and smoking status. Acutely, hyposmia was present in 29% of the FB group (CTR: 9%, p = 0.014) and burn patients scored worse on the SnS than CTR (FB: 10; CTR: 11; IQR: 2; p = 0.013). Hyposmia per SnS correlated with subjective self-assessment. Hyposmia and SnS scores improved over time (FB acute: 10.5 IQR: 2; FB one year: 11; IQR: 2; p = 0.042) and returned to normal at one-year post burn in most patients who completed the study (lost to follow-up: 21 patients). Taste strip scores were comparable between FB and CTR, as was the acute prevalence of dysphagia and dysphonia. Hyposmia acutely after facial thermal trauma appeared frequently in this study, especially when complicated by inhalation trauma or large TBSA involvement. Of all complete assessments, a fraction of burn patients retained hyposmia after one year while most improved over time to normal. Prevalence of dysphonia, dysphagia and hypogeusia was comparable to healthy controls in this study, perhaps due to overall minor burn severity. • We prospectively assessed patients with facial burns for hyposmia, hypogeusia, dysphagia and dysphonia acutely & after 1-year. • Patients with facial burns had more frequent and more severe subacute hyposmia than healthy controls. • Inhalation trauma, length of hospitalization & burn size were associated with more frequent and severe acute hyposmia. • Most cases of short-term hyposmia resolved over one year post burn. • Hypogeusia, dysphagia and dysphonia occurred less frequently, perhaps due milder burns & timing and methods of sampling. [ABSTRACT FROM AUTHOR]

The cardiac surgery-related ischemia-reperfusion-related oxidative stress triggers the release of cytotoxic reactive oxygen and nitrogen species, contributing to organ failure and ultimately influencing patients' short- and long-term outcomes. Selenium is an essential co-factor for various antioxidant enzymes, thereby contributing to the patients' endogenous antioxidant and anti-inflammatory defense mechanisms. Given these selenium's pleiotropic functions, we investigated the effect of a high-dose selenium-based anti-inflammatory perioperative strategy on functional recovery after cardiac surgery. This prospective study constituted a nested sub-study of the SUSTAIN CSX trial, a double-blinded, randomized, placebo-controlled multicenter trial to investigate the impact of high-dose selenium supplementation on high-risk cardiac surgery patients' postoperative recovery. Functional recovery was assessed by 6-min walk distance, Short Form-36 (SF-36) and Barthel Index questionnaires. 174 patients were included in this sub-study. The mean age (SD) was 67.3 (8.9) years, and 78.7 % of the patients were male. The mean (SD) predicted 30-day mortality by the European System for Cardiac Operative Risk Evaluation II score was 12.6 % (9.4 %). There was no difference at hospital discharge and after three months in the 6-min walk distance between the selenium and placebo groups (131 m [IQR: not performed – 269] vs. 160 m [IQR: not performed – 252], p = 0.80 and 400 m [IQR: 299–461] vs. 375 m [IQR: 65–441], p = 0.48). The SF-36 and Barthel Index assessments also revealed no clinically meaningful differences between the selenium and placebo groups. A perioperative anti-inflammatory strategy with high-dose selenium supplementation did not improve functional recovery in high-risk cardiac surgery patients. [ABSTRACT FROM AUTHOR]

The urea–creatinine ratio (UCR) has been proposed as potential biomarker for critical illness-associated catabolism. Its role in the context of aneurysmal subarachnoid hemorrhage (aSAH) remains to be elucidated, which was the aim of the present study. We enrolled 66 patients with aSAH with normal renal function and 36 patients undergoing elective cardiac surgery as a control group for the effects of surgery. In patients with aSAH, the predictive or diagnostic value of early (day 0–2) and critical (day 5–7) UCRs was assessed with regard to delayed cerebral ischemia (DCI), DCI-related infarction, and clinical outcome after 12 months. Preoperatively, UCR was similar both groups. Within 2 days postoperatively, UCRs increased significantly in patients in the elective cardiac surgery group (P < 0.001) but decreased back to baseline on day 5–7 (P = 0.245), whereas UCRs in patients with aSAH increased to significantly greater levels on day 5–7 (P = 0.028). Greater early or critical UCRs were associated with poor clinical outcomes (P = 0.015) or DCI (P = 0.011), DCI-related infarction (P = 0.006), and poor clinical outcomes (P < 0.001) respectively. In multivariate analysis, there was an independent association between greater early UCRs and poor clinical outcomes (P = 0.026). In this exploratory study of UCR in the context of aSAH, greater early values were predictive for a poor clinical outcome after 12 months, whereas greater critical values were associated with DCI, DCI-related infarctions, and poor clinical outcomes. The clinical implications as well as the pathophysiologic relevance of protein catabolism should be explored further in the context of aSAH. [ABSTRACT FROM AUTHOR]

Background There is evidence of abnormal cerebral dopamine transmission in nicotine-dependent smokers, but it is unclear whether dopaminergic abnormalities are due to acute nicotine abuse or whether they persist with abstinence. We addressed this question by conducting longitudinal positron emission tomography (PET) examination of smokers before and after 3 months of abstinence. Methods We obtained baseline 6-[ 18 F]fluoro-L-DOPA (FDOPA)-PET scans in 15 nonsmokers and 30 nicotine-dependent smokers, who either smoked as per their usual habit or were in acute withdrawal. All smokers then underwent cessation treatment, and successful abstainers were re-examined by FDOPA-PET after 3 months of abstinence ( n = 15). Uptake of FDOPA was analyzed using a steady-state model yielding estimates of the dopamine synthesis capacity (K); the turnover of tracer dopamine formed in living brain (k loss ); and the tracer distribution volume (V d ), which is an index of dopamine storage capacity. Results Compared with nonsmokers, K was 15% to 20% lower in the caudate nuclei of consuming smokers. Intraindividual comparisons of consumption and long-term abstinence revealed significant increases in K in the right dorsal and left ventral caudate nuclei. Relative to acute withdrawal, V d significantly decreased in the right ventral and dorsal caudate after prolonged abstinence. Severity of nicotine dependence significantly correlated with dopamine synthesis capacity and dopamine turnover in the bilateral ventral putamen of consuming smokers. Conclusions The results suggest a lower dopamine synthesis capacity in nicotine-dependent smokers that appears to normalize with abstinence. Further investigations are needed to clarify the role of dopamine in nicotine addiction to help develop smoking prevention and cessation treatments. [ABSTRACT FROM AUTHOR]

Abstract: The analytical validation of a possible biomarker is the first step in the long translational process from basic science to clinical routine. Although the chemokine-like cytokine macrophage migration inhibitory factor (MIF) has been investigated intensively in experimental approaches to various disease conditions, its transition into clinical research is just at the very beginning. Because of its presence in preformed storage pools, MIF is the first cytokine to be released under various stimulation conditions. In the first proof-of-concept studies, MIF levels correlated with the severity and outcome of various disease states. In a recent small study with acute coronary syndrome patients, elevation of MIF was described as a new factor for risk assessment. When these studies are compared, not only MIF levels in diseased patients differ, but also MIF levels in healthy control groups are inconsistent. Blood MIF concentrations in control groups vary between 0.56 and 95.6ng/ml, corresponding to a 170-fold difference. MIF concentrations in blood were analyzed by ELISA. Other than the influence of this approach due to method-based variations, the impact of preanalytical processing on MIF concentrations is unclear and has not been systematically studied yet. Before large randomized studies are performed to determine the impact of circulating MIF on prognosis and outcome and before MIF is characterized as a diagnostic marker, an accurate protocol for the determination of reproducible MIF levels needs to be validated. In this study, the measurement of MIF in the blood of healthy volunteers was investigated focusing on the potential influence of critical preanalytical factors such as anticoagulants, storage conditions, freeze/thaw stability, hemolysis, and dilution. We show how to avoid pitfalls in the measurement of MIF and that MIF concentrations are highly susceptible to preanalytical factors. MIF serum concentrations are higher than plasma concentrations and show broader ranges. MIF concentrations are higher in samples processed with latency than in those processed directly and strongly correlate with hemoglobin in plasma. Neither storage temperature nor storage length or dilution or repeated freezing and thawing influenced MIF concentrations in plasma. Preanalytical validation of MIF is essential. In summary, we suggest using plasma and not serum samples when determining circulating MIF and avoiding hemolysis by processing samples immediately after blood drawing. [Copyright &y& Elsevier]