An international RAND/UCLA expert panel to determine the optimal diagnosis and management of burn inhalation injury.

BACKGROUND: Burn inhalation injury (BII) is a major cause of burn-related mortality and morbidity. Despite published practice guidelines, no consensus exists for the best strategies regarding diagnosis and management of BII. A modified DELPHI study using the RAND/UCLA (University of California, Los Angeles) Appropriateness Method (RAM) systematically analysed the opinions of an expert panel. Expert opinion was combined with available evidence to determine what constitutes appropriate and inappropriate judgement in the diagnosis and management of BII. METHODS: A 15-person multidisciplinary panel comprised anaesthetists, intensivists and plastic surgeons involved in the clinical management of major burn patients adopted a modified Delphi approach using the RAM method. They rated the appropriateness of statements describing diagnostic and management options for BII on a Likert scale. A modified final survey comprising 140 statements was completed, subdivided into history and physical examination (20), investigations (39), airway management (5), systemic toxicity (23), invasive mechanical ventilation (29) and pharmacotherapy (24). Median appropriateness ratings and the disagreement index (DI) were calculated to classify statements as appropriate, uncertain, or inappropriate. RESULTS: Of 140 statements, 74 were rated as appropriate, 40 as uncertain and 26 as inappropriate. Initial intubation with ≥ 8.0 mm endotracheal tubes, lung protective ventilatory strategies, initial bronchoscopic lavage, serial bronchoscopic lavage for severe BII, nebulised heparin and salbutamol administration for moderate-severe BII and N-acetylcysteine for moderate BII were rated appropriate. Non-protective ventilatory strategies, high-frequency oscillatory ventilation, high-frequency percussive ventilation, prophylactic systemic antibiotics and corticosteroids were rated inappropriate. Experts disagreed (DI ≥ 1) on six statements, classified uncertain: the use of flexible fiberoptic bronchoscopy to guide fluid requirements (DI = 1.52), intubation with endotracheal tubes of internal diameter < 8.0 mm (DI = 1.19), use of airway pressure release ventilation modality (DI = 1.19) and nebulised 5000IU heparin, N-acetylcysteine and salbutamol for mild BII (DI = 1.52, 1.70, 1.36, respectively). CONCLUSIONS: Burns experts mostly agreed on appropriate and inappropriate diagnostic and management criteria of BII as in published guidance. Uncertainty exists as to the optimal diagnosis and management of differing grades of severity of BII. Future research should investigate the accuracy of bronchoscopic grading of BII, the value of bronchial lavage in differing severity groups and the effectiveness of nebulised therapies in different severities of BII.

Oropharyngolaryngeal manifestations in severe toxic epidermal necrolysis: a single-center's retrospective case series.

BACKGROUND: Toxic epidermal necrolysis is a rare and life-threatening mucocutaneous disease. Although mucosal ear, nose, and throat (ENT) involvement is common, little is known about the characteristics, treatment modalities, and outcomes of these lesions. The aim of this study was to evaluate ENT mucosal lesions in severe toxic epidermal necrolysis patients and analyze their characteristics, treatment modalities, and outcomes, as well as proposing a management algorithm to prevent long-term debilitating sequalae of these lesions. METHODS: This is a retrospective review of toxic epidermal necrolysis cases treated at the tertiary burns unit of the Lausanne University Hospital CHUV, Switzerland, between 2006 and 2019. RESULTS: Out of 19 patients with severe toxic epidermal necrolysis, 17 (89%) underwent a complete ENT examination at admission and 14 (82%) had ENT mucosal involvement. Five (26.3%) patients died during the stay in the intensive care unit. Of the 16 patients who received maximal care, 13 (81%) required orotracheal intubation for a median time of 16 (IQR: 14) days. Out of the 14 patients who survived, four (29%) had long-term ENT complications consisting of synechiaes necessitating subsequent endoscopic procedures. Those four patients all required mechanical ventilation with an orotracheal tube and suffered from hypopharyngeal synechiaes as well as oral and endonasal synechiaes in individual cases. CONCLUSION: This study suggests a high prevalence of ENT synechiaes in patients with severe toxic epidermal necrolysis and requiring orotracheal intubation. Periodic ENT examination could prevent mature synechiae formation in these patients. We propose an algorithm to prevent long-term sequalae in ENT mucosal involvement.

Effect of Pre-Hospital Intravenous Fluids on Initial Metabolic Acid-Base Status in Trauma Patients: A Retrospective Cohort Study.

Despite its known harmful effects, normal saline is still commonly used in the treatment of hypovolemia in polytrauma patients. Given the lack of pre-hospital research on this topic, the current study aims to assess the current practice of fluid administration during the pre-hospital phase of care and its effects on initial metabolic acid-base status in trauma patients. We extracted and completed data from patients recorded in the Lausanne University Hospital (CHUV) trauma registry between 2008 and 2019. Patients were selected according to their age, the availability of a blood gas analysis after arrival at the emergency room, data availability in the trauma registry, and the modality of arrival in the ED. The dominantly administered pre-hospital fluid was normal saline. No association between the type of fluid administered during the pre-hospital phase and the presence of hyperchloremic acidosis in the ED was observed.

Nutritional and metabolic characteristics of critically ill patients admitted for severe toxidermia.

INTRODUCTION: Drug-induced toxidermia is an idiosyncratic adverse skin reaction that may become life-threatening in a small portion of patients, requiring intensive care unit (ICU) admission. The treatment recommendations are extrapolated from those of major burns, while prospective data remain sparse. The objective was to observe the application of these recommendations in patients treated in a burn ICU. METHOD: Retrospective cohort study including patients requiring ICU between 2006 and 2020 in a tertiary university hospital. INCLUSION CRITERIA: Age >18 years. Patients were categorized as Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN), or other toxidermia. VARIABLES: severity scores, body surface area (BSA) involvement, nutritional and metabolic variables, trace element status, outcome variables. Descriptive statistics: median [IQR]. RESULTS: Altogether 35 patients were included (27 SJS/TEN and 8 "other"), aged 58 [48; 69] years. Skin involvement was 45% [30; 60] of body surface, 17 patients required mechanical ventilation, and length of ICU stay was 16 [6.5; 26] days. Hospital mortality was 23%. Fluid resuscitation requirements were moderate, despite intense inflammation (admission CRP (144 [89; 218] mg/L). The first 2 weeks' energy and protein intakes were below recommendations (p < 0.0001), lowest with oral feeding. Indirect calorimetry showed high energy expenditure in 11 patients (30.4 [23.9; 35.5] kcal/kg) resulting in negative energy balances (mean -245 kcal/day). Copper and zinc levels were below reference range during the first week, the low copper values being a novel finding. CONCLUSION: Trace elements should be monitored. The cohort was underfed with intakes lower than our ICU protocols, partly explained by short intubation times, and mucocutaneous involvement complicating the management and placement of feeding tubes. Oral feeding was least efficient and may become an indication for supplemental parenteral nutrition in the absence of an enteral feeding tube. CLINICALTRIALS: gov Identifier: NCT05320653.

Nutrition after severe burn injury.

PURPOSE OF REVIEW: Severe burn injury causes significant metabolic changes and demands that make nutritional support particularly important. Feeding the severe burn patient is a real challenge in regard to the specific needs and the clinical constraints. This review aims to challenge the existing recommendations in the light of the few recently published data on nutritional support in burn patients. RECENT FINDINGS: Some key macro- and micro-nutrients have been recently studied in severe burn patients. Repletion, complementation or supplementation of omega-3 fatty acids, vitamin C, vitamin D, antioxidant micronutrients may be promising from a physiologic perspective, but evidence of benefits on hard outcomes is still weak due to the studies' design. On the contrary, the anticipated positive effects of glutamine on the time to discharge, mortality and bacteremias have been disproved in the largest randomized controlled trial investigating glutamine supplementation in burns. An individualized approach in term of nutrients quantity and quality may proof highly valuable and needs to be validated in adequate trials. The combination of nutrition and physical exercises is another studied strategy that could improve muscle outcomes. SUMMARY: Due to the low number of clinical trials focused on severe burn injury, most often including limited number of patients, developing new evidence-based guidelines is challenging. More high-quality trials are needed to improve the existing recommendations in the very next future.

Females have a different metabolic response to critical illness, measured by comprehensive amino acid flux analysis.

BACKGROUND: The trajectory from healthy to critical illness is influenced by numerous factors, including metabolism, which differs substantially between males and females. Whole body protein breakdown is substantially increased in critically ill patients, but it remains unclear whether there are sex differences that could explain the different health outcomes. Hence, we performed a secondary analysis of a study, where we used a novel pulse isotope method in critically ill and matched healthy males and females. METHODS: In 51 critically ill ICU patients (26 males, 15 females) and 49 healthy controls (36 males and 27 females), we assessed their general and disease characteristics and collected arterial(ized) blood in the postabsorptive state after pulse administration of 8 ml of a solution containing 18 stable AA tracers. In contrast to the original study, we now fitted the decay curves and calculated non-compartmental whole body amino acid production (WBP) and compartmental measurements of metabolism, including intracellular amino acid production. We measured amino acid enrichments and concentrations by LC-MS/MS and derived statistics using AN(C)OVA. RESULTS: Critically ill males and females showed an increase in the WBP of many amino acids, including those related to protein breakdown, but females showed greater elevations, or in the event of a reduction, attenuated reductions. Protein breakdown-independent WBP differences remained between males and females, notably increased glutamine and glutamate WBP. Only severely ill females showed a lower increase in WBP of many amino acids in comparison to moderately ill females, suggesting a suppressed metabolism. Compartmental analysis supported the observations. CONCLUSIONS: The present study shows that females have a different response to critical illness in the production of several amino acids and changes in protein breakdown, observations made possible using our innovative stable tracer pulse approach. CLINICAL TRIAL REGISTRY: Data are from the baseline measurements of study NCT02770092 (URL: https://clinicaltrials.gov/ct2/show/NCT02770092) and NCT03628365 (URL: https://clinicaltrials.gov/ct2/show/NCT03628365).

MDCT-findings in patients with non-occlusive mesenteric ischemia (NOMI): influence of vasoconstrictor agents.

OBJECTIVES: To evaluate the influence of vasoconstrictor agents (VCAs) on signs of vasoconstriction and bowel ischemia on MDCT detected in patients with non-occlusive mesenteric ischemia (NOMI). METHODS: This 8-year single-center retrospective study consecutively included all patients with histopathologically proven NOMI who underwent MDCT ≤ 48 h prior to surgical bowel resection. Two blinded radiologists jointly reviewed each examination for signs of bowel ischemia, abdominal organ infarct, mesenteric vessel size and regularity, and ancillary vascular findings. VCA administration (length and dosage), clinical and biochemical data, risk factors, and outcomes were retrieved from patients' medical records. Subgroup comparisons were performed. RESULTS: Ninety patients were included (59 males, mean age 65 years); 40 (44.4%) had received VCAs before MDCT. Overall mortality was 32% (n = 29), with no significant difference between the two groups. In patients treated with VCAs, the calibre of the superior mesenteric artery (SMA) was smaller (p = 0.032), and vasoconstriction of its branches tended to be more important (p = 0.096) than in patients not treated with VCAs. The presence and extent of bowel ischemia did not significantly correlate with VCA administration, but abdominal organ infarcts tended to be more frequent (p = 0.005) and involved more organs (p = 0.088). The VCA group had lower mean arterial pressure (p = 0.006) and lower hemoglobin levels (p < 0.001). Several biomarkers of organ failure and inflammation, differed significantly with VCA use, proving worse clinical condition. CONCLUSIONS: MDCT demonstrates more severe SMA vasoconstriction and tends to show increased abdominal organ infarcts after VCA administration in NOMI patients compared to NOMI patients not treated with VCAs. KEY POINTS: • In critically ill patients with NOMI, MDCT demonstrates VCA support via increased vasoconstriction of the main SMA and its branches. • VCA administration in NOMI patients tends to contribute to the development of organ infarcts, as shown on MDCT. • An important degree of vasoconstriction in NOMI patients may indicate insufficient resuscitation and, thus, help clinicians in further patient management.

Impact of ß-hydroxy-ß-methylbutyrate (HMB) in critically ill patients on the endocrine axis - A post-hoc cohort study of the HMB-ICU trial.

BACKGROUND: ß-hydroxy-ß-methylbutyrate (HMB) might improve muscle function and maintain its mass in critically ill patients. We aimed to investigate whether the administration of HMB influenced the plasma levels of growth hormone (GH)/insulin-like growth factor-1 (IGF-1), C-peptide, and 25-OH vitamin-D. METHODS: Post-hoc analysis of the study HMB-ICU, a randomized, placebo-controlled double-blind trial. INCLUSION CRITERIA: Intensive care unit (ICU) patients depending on mechanical ventilation on day 3 with functional gastrointestinal tract. Patients were randomized to HMB (3 g/day) or placebo (maltodextrin) from day 4 on, for 30 days. Blood samples were collected on days 4 and 15. We determined the GH, C-peptide, 25-OH vitamin-D, and IGF-1. Statistics by ANCOVA. RESULTS: Blood samples of 26 patients were available on day 4, and 23 on day 15. While age and severity of disease did not differ, diabetes was more frequent in the HMB group (p = 0.041), and obesity was more frequent in the placebo group (p = 0.021). Glucose intake, blood glucose (BG) and amount of insulin to maintain blood glucose between 6 and 8 mM did not differ between groups. There was no difference between groups for C-peptide, GH, IGF-1, and 25-OH vitamin-D. IGF-1 increased significantly from day 4-15 (p = 0.026) in both groups. CONCLUSION: Subject to possible insufficient power of the study, we did not reach conclusive results. HMB intervention does not affect significantly the plasma concentrations of insulin, GH/IGF axis activity, C-peptide, and 25-OH vitamin-D. GOV IDENTIFIER: NCT03628365.

Post Intensive Care Syndrome (PICS) physical, cognitive, and mental health outcomes 6-months to 7 years after a major burn injury: A cross-sectional study.

OBJECTIVES: The Post Intensive Care Syndrome (PICS) has been described in intensive care (ICU) survivors, being present in 50% of patients surviving 12 months, with well-defined risk factors. Severely burned patients combine many of these risk factors, but the prevalence of PICS has not yet been documented in burns. The study aimed to answer this question and identify associations of PICS with clinical characteristics. METHODS: Cross-sectional descriptive study of major burn survivors admitted to the burn ICU between 2013 and 2019. Main inclusion criteria: major burns>20 %BSA and ICU admission. The PICS components were assessed using three questionnaires: 1) Physical with Burn Specific Health Scale-Brief (BSHS-B); 2) Cognitive health with MacNair Cognitive Difficulties Self-Rating Scale (CDS); 3) Mental health with the Hospital Anxiety and Depression Scale (HADS) questionnaire. PICS was considered present if at least one component out of three was abnormal. Data as mean±SD. RESULTS: Among the 288 patients admitted during the period, 132 met the inclusion criteria: 53 patients were finally enrolled. They were aged 44 ± 18 years at the time of injury and burned 24 ± 20 BSA % and stayed 25 ± 44 days in the ICU. PICS was identified in 35 patients (66 %): more than one component was altered in 21 patients (60 %). Principal risk factors were more than 3 general anesthetics, prolonged mechanical ventilation (>4 days), ICU stay (>8 days), and hospital stay (>25 days) CONCLUSION: PICS occurred in 66 % of major burns with two or three components affected simultaneously in 60 %, i.e. more frequently than in general ICU patients.

Computer customization errors compromised the optimization of trace element repletion dose after major burns.

BACKGROUND & AIMS: Major burns develop acute trace element (TE) deficiencies due to exudative losses of copper, selenium, and zinc from the wounds. A repletion strategy has been shown to decrease infectious and surgical complications. The TE doses have been adapted over time and the last adaptation, was not followed by the expected changes. The study aims at identifying the causes of the failure. METHODS: Retrospective cohort study including critically ill major burns patients admitted to intensive care with burns exceeding 20% of body surface area (BSA). Period A (2011-2015) included patients admitted before the dose change, and Period B patients after (2017-2020). Demographic variables, daily TE delivery, and weekly TE blood levels were extracted from the computerized information system (CIS). RESULTS: Altogether 71 patients completed the inclusion criteria (Periods A and B: 42 and 29 patients respectively). They were aged 38 (32) years and burned 35 (30) % BSA, with no severity differences. Comparing periods A and B, copper (p = 0.046) and selenium (p = 0.031) blood levels were significantly lower in B. The dose value extracted from CIS was as planned. Customization error was found: TE salts' weight had been entered instead of elemental weight in molar units. CONCLUSION: The lower TE repletion doses administered since 2017 resulted in a significant decrease in blood levels of Cu and Se. A CIS customisation error, confusing salt weight and elemental weight was the source of the error. A systematic quality control is crucial to identify systemic errors, as is the use of the standard international units.

Point-of-care lung ultrasonography for early identification of mild COVID-19: a prospective cohort of outpatients in a Swiss screening center.

OBJECTIVES: Early identification of SARS-CoV-2 infection is important to guide quarantine and reduce transmission. This study evaluates the diagnostic performance of lung ultrasound (LUS), an affordable, consumable-free point-of-care tool, for COVID-19 screening. DESIGN, SETTING AND PARTICIPANTS: This prospective observational cohort included adults presenting with cough and/or dyspnoea at a SARS-CoV-2 screening centre of Lausanne University Hospital between 31 March and 8 May 2020. INTERVENTIONS: Investigators recorded standardised LUS images and videos in 10 lung zones per patient. Two blinded independent experts reviewed LUS recording and classified abnormal findings according to prespecified criteria to investigate their predictive value to diagnose SARS-CoV-2 infection according to PCR on nasopharyngeal swabs (COVID-19 positive vs COVID-19 negative). PRIMARY AND SECONDARY OUTCOME MEASURES: We finally combined LUS and clinical findings to derive a multivariate logistic regression diagnostic score. RESULTS: Of 134 included patients, 23% (n=30/134) were COVID-19 positive and 77% (n=103/134) were COVID-19 negative; 85%, (n=114/134) cases were previously healthy healthcare workers presenting within 2-5 days of symptom onset (IQR). Abnormal LUS findings were significantly more frequent in COVID-19 positive compared with COVID-19 negative (45% vs 26%, p=0.045) and mostly consisted of focal pathologic B lines. Combining clinical findings in a multivariate logistic regression score had an area under the receiver operating curve of 80.3% to detect COVID-19, and slightly improved to 84.5% with the addition of LUS features. CONCLUSIONS: COVID-19-positive patients are significantly more likely to have lung pathology by LUS. However, LUS has an insufficient sensitivity and is not an appropriate screening tool in outpatients. LUS only adds little value to clinical features alone.

Therapeutic anticoagulation to prevent thrombosis, coagulopathy, and mortality in severe COVID-19: The Swiss COVID-HEP randomized clinical trial.

Background: Hospitalized patients with COVID-19 suffered initially from high rates of venous thromboembolism (VTE), with possible associations between therapeutic anticoagulation and better clinical outcomes in observational studies. Objective: To test whether therapeutic anticoagulation improves clinical outcomes in severe COVID-19. Patients/Methods: In this multicenter, open-label, randomized controlled trial, we recruited acutely ill medical COVID-19 patients with D-dimer >1000 ng/ml or critically ill COVID-19 patients in four Swiss hospitals, from April 2020 until June 2021, with a 30-day follow-up. Participants were randomized to in-hospital therapeutic anticoagulation versus low-dose anticoagulation in acutely ill participants/intermediate-dose anticoagulation in critically ill participants, with enoxaparin or unfractionated heparins. The primary outcome was a centrally adjudicated composite of 30-day all-cause mortality, VTE, arterial thrombosis, and disseminated intravascular coagulopathy (DIC), with screening for proximal deep vein thrombosis. Results: Among 159 participants, 55.3% were critically ill and 94.3% received corticosteroids. Before study inclusion, pulmonary embolism had been excluded in 71.7%. The primary outcome occurred in 4/79 participants randomized to therapeutic anticoagulation and 4/80 to low/intermediate anticoagulation (5.4% vs. 5.0%; risk difference +0.4%; adjusted hazard ratio 0.76, 95% confidence interval 0.18-3.21), including three deaths in each group. All primary outcomes and major bleeding (n = 3) occurred in critically ill participants. There was no asymptomatic proximal deep vein thrombosis and no difference in major bleeding. Conclusions: Among patients with severe COVID-19 treated with corticosteroids and with exclusion of pulmonary embolism at hospital admission for most, risks of mortality, thrombotic outcomes, and DIC were low at 30 days. The lack of benefit of therapeutic anticoagulation was too imprecise for definite conclusions.

Specific nutrition and metabolic characteristics of critically ill patients with persistent COVID-19.

BACKGROUND: Little is known about metabolic and nutrition characteristics of patients with coronavirus disease 2019 (COVID-19) and persistent critical illness. We aimed to compare those characteristics in patients with PCI and COVID-19 and patients without COVID-19 infection (non-CO)-primarily, their energy balance. METHODS: This is a prospective observational study including two consecutive cohorts, defined as needing intubation for >10 days. We collected demographic data, severity scores, nutrition variables, length of stay, and mortality. RESULTS: Altogether, 104 patients (52 per group) were included (59 ± 14 years old [mean ± SD], 75% men) between July 2019 and May 2020. SAPSII, Nutrition Risk Screening (NRS) score, proportion of obese patients, duration of intubation (18.2 ± 11.7 days), and mortality rates were similar. Patients with COVID-19 (vs non-CO) had lower SOFA scores (P = 0.013) and more frequently needed prone position (P < 0.0001) and neuromuscular blockade (P < 0.0001): lengths of ICU (P = 0.03) and hospital stays were shorter (P < 0.0001). Prescribed energy targets were below those of the ICU protocol. The energy balance of patients with COVID-19 was significantly more negative after day 10. Enteral nutrition (EN) started earlier (P < 0.0001). During the first 10 days, COVID-19 patients received more lipid (propofol sedation) and less protein. Higher admission C-reactive protein (P = 0.002) decreased faster (P < 0.001). Whereas intestinal function was characterized by constipation in both groups during the first 10 days, diarrhea was less common in patients with COVID-19 thereafter. CONCLUSION: Compared with non-CO patients, COVID-19 patients were not more obese, had lower SOFA scores, and were fed more rapidly with EN, because of a more normal gastrointestinal function possibly due to fewer non-respiratory organ failures: their energy balances were more negative after the first 10 days. Propofol sedation reduced protein delivery.

Exudative glutamine losses contribute to high needs after burn injury.

BACKGROUND: Burnpatients characteristically have increased energy, glucose, and protein requirements. Glutamine supplementation is strongly recommended during early-phase treatment and is associated with improved immunity, wound healing, and reduced mortality. This study evaluated if early burn exudative losses might contribute to higher supplementation needs. METHODS: Patients admitted to the burn intensive care unit (ICU) had exudate collection from tight bandages applied to arms or legs during the first week (exudate aliquot twice daily). Seven amino acids (alanine, arginine, cystEine, glutamine, leucine, lysine, and methionine) were quantified by liquid chromatography-mass spectrometry. Descriptive analysis of all results is provided as median and interquartile range or in value ranges. RESULTS: Eleven patients aged 19-77 years, presenting with burns on 18%-70% of the body surface, with a median simplified acute physiology score II of 33 (range, 16-56) were included during the study period. The highest amino acid losses were observed during the first 3 days with an important interpatient and intrapatient variability. Glutamine and alanine losses were highest, followed by leucine and lysine in all patients; amino acid exudate concentrations were in the range of normal plasma concentrations and were stable over time. Total glutamine losses were correlated to the burned surface (r2 = 0.552, P = .012), but not to enteral glutamine supplements. CONCLUSIONS: The study shows significant exudative losses during early-stage burn recovery and particularly for glutamine and alanine. Glutamine loss generally decreased with wound closure, the subsequent decline of exudation, and the evolving size of burn surfaces.

Massive Burns: Retrospective Analysis of Changes in Outcomes Indicators Across 18 Years.

The treatment and management of massive burns, defined as burns affecting at least 50% of total body surface area (TBSA), have considerably changed since the 1990s. This study aimed at analyzing if the length of intensive care unit (ICU) stay, the success of skin grafting operations, and the mortality changed in the past 18 years. Between 2000 and 2018, 77 patients were admitted for massive burns to the ICU of a university hospital. Transfers and early care withdrawal precluded inclusion for 38 patients, leaving 39 for analysis. Study variables were year of admission, demographics, burn characteristics, critical care treatment (fluid resuscitation, ventilation, and nutrition), and surgical therapy. Association between outcomes and year of admission was assessed through correlation and logistic regression analysis. Potential confounders were assessed through stepwise linear regression. Patients' characteristics were stable over time with a median age of 36 (25.0-48.0) years, burns 65% (55.0-83.0) TBSA, and deep burns 55% (50.0-68.0) TBSA. Length of ICU stay remained stable at 0.97 (0.6-1.5) days/%TBSA. Mortality was stable as well. Energy and carbohydrate delivery decreased in parallel with the number of infectious episodes per patient. The number of operations was stable, but the take rate of skin grafts increased significantly. The multivariate analysis retained year of admission, weight, the total number of infections, daily lipid intakes, and fluid resuscitation as independent predicting variables.

EBV-positive large B-cell lymphoma with an unusual intravascular presentation and associated haemophagocytic syndrome in an HIV-positive patient: report of a case expanding the spectrum of EBV-positive immunodeficiency-associated lymphoproliferative disorders.

Intravascular large B-cell lymphoma is a rare and aggressive EBV-negative large B-cell lymphoma with a dismal outcome. Here, we describe the case of a 76-year-old HIV-positive patient with an acute presentation of systemic symptoms and rapidly fatal outcome. Autopsy revealed a disseminated large B-cell lymphoma with an intravascular distribution involving the liver, lymph nodes, spleen, and bone marrow and associated to fibrin thrombi in hepatic capillary haemangiomas. The neoplastic B cells (CD79a + / - , CD20 + / - , CD30 + , MUM1 + , PD-L1 +) showed a Hodgkin and Reed-Sternberg-like morphology and were EBV-positive with a latency type II (LMP1 + , EBNA2-). Haemophagocytosis was documented in the bone marrow and lymph nodes. This case illustrates the diagnostic challenges of large B-cell lymphoma with intravascular presentation. We found only five other cases of EBV-positive large B-cell lymphoma with an intravascular presentation in the literature, three of which had an underlying immunodeficiency adding to the broad spectrum of EBV-associated lymphoma in the setting of immunosuppression.

Impact of ß-hydroxy-ß-methylbutyrate (HMB) on muscle loss and protein metabolism in critically ill patients: A RCT.

PURPOSE: Muscle wasting deteriorates life quality after critical illness and increases mortality. Wasting starts upon admission to intensive care unit (ICU). We aimed to determine whether ß-hydroxy-ß-methylbutyrate (HMB), a metabolite of leucine, can attenuate this process. METHODS: Prospective randomized, placebo-controlled double blind trial. INCLUSION CRITERIA: ICU patients depending on mechanical ventilation on day 3 having a functional gastrointestinal tract. They were randomized to HMB (3 g/day) or placebo (maltodextrin) from day 4 on for 30 days. PRIMARY OUTCOME: magnitude of loss of skeletal muscle area (SMA) of the quadriceps femoris measured by ultrasound at days 4 and 15. SECONDARY OUTCOMES: body composition, change in protein metabolism assessed by amino acids tracer pulse, and global health at 60 days. Data are mean [95% CI]. Statistics by ANCOVA with correction for confounders sex, age and/or BMI. RESULTS: Thirty patients completed the trial, aged 65 [59, 71] years, SAPS2 score 48 [43, 52] and SOFA 8.5 [7.4, 9.7]. The loss of total SMA was 11% between days 4 and 15 (p < 0.001), but not different between the groups (p = 0.86). In the HMB group, net protein breakdown (Δ Estimate HMB-Placebo: -153 [-242, -63]; p = 0.0021) and production of several amino acid was significantly reduced, while phase angle increased more (0.66 [0.09, 1.24]; p = 0.0247), and SF-12 global health improved more (Δ Estimate HMB-Placebo: 27.39 [1.594, 53.19], p = 0.04). CONCLUSION: HMB treatment did not significantly reduce muscle wasting over 10 days of observation (primary endpoint), but resulted in significantly improved amino acid metabolism, reduced net protein breakdown, a higher phase angle and better global health. CLINICALTRIALS. GOV IDENTIFIER: NCT03628365.

Comprehensive metabolic amino acid flux analysis in critically ill patients.

Amino acid (AA) metabolism is severely disturbed in critically ill ICU patients. To be able to make a more scientifically based decision on the type of protein or AA nutrition to deliver in ICU patients, comprehensive AA phenotyping with measurements of plasma concentrations and whole body production (WBP) is needed. Therefore, we studied ICU patients and matched control subjects using a novel pulse isotope method to obtain in-depth metabolic analysis. In 51 critically ill ICU patients (SOFA~6.6) and 49 healthy controls, we measured REE and body composition/phase-angle using BIA. In the postabsorptive state, we collected arterial (ized) blood for CRP and AA. Then, we administered an 8 mL solution containing 18 stable AA tracers as a pulse and calculated WBP. Enrichments: LC-MS/MS and statistics: t-test, ANCOVA. Compared to healthy, critically ill ICU patients had lower phase-angle (p < 0.00001), and higher CRP (p < 0.0001). Most AA concentrations were lower in ICU patients (p < 0.0001), except tau-methylhistidine and phenylalanine. WBP of most AA were significantly (p < 0.0001) higher with increases in glutamate (160%), glutamine (46%), and essential AA. Remarkably, net protein breakdown was lower. There were only weak relationships between AA concentrations and WBP. Critically ill ICU patients (SOFA 8-16) had lower values for phase angle (p = 0.0005) and small reductions of most plasma AA concentrations, but higher tau-methylhistidine (p = 0.0223) and hydroxyproline (p = 0.0028). Remarkably, the WBP of glutamate and glutamine were lower (p < 0.05), as was their clearance, but WBP of tau-methylhistidine (p = 0.0215) and hydroxyproline (p = 0.0028) were higher. Our study in critically ill ICU patients shows that comprehensive metabolic phenotyping was able to reveal severe disturbances in specific AA pathways, in a disease severity dependent way. This information may guide improving nutritional compositions to improve the health of the critically ill patient. CLINICAL TRIAL REGISTRY: Data are from the baseline measurements of study NCT02770092 (URL: https://clinicaltrials.gov/ct2/show/NCT02770092) and NCT03628365 (URL: https://clinicaltrials.gov/ct2/show/NCT03628365).