Risk factors and outcome associated with fungal infections in patients with severe burn injury: 10-year retrospective IFI-BURN study.

BACKGROUND: In burn patients, skin barrier disruption and immune dysfunctions increase susceptibility to invasive fungal diseases (IFDs) like invasive candidiasis (IC) and invasive mold infections (IMI). We provide an in-depth analysis of IFD-related factors and outcomes in a 10-year cohort of severe burn patients. METHOD: Retrospective cohort study including adult patients admitted to the Burn Intensive Care Unit (BICU) between April 2014 and May 2023 with Total Burn Surface Area (TBSA) ≥15%. Patients were classified as proven IFD according to EORTC/MSGERC criteria applicable for IC. Putative IMIs were defined with: ≥2 positive cultures from a skin biopsy/bronchoalveolar lavage OR ≥2 positive blood specific-qPCRs OR a combination of both. RESULTS: Among 1381 patients admitted, 276 consecutive patients with TBSA ≥15% were included. Eighty-seven (31.5%; IC n=30; IMI n=43; both n=14) patients fulfilled the criteria for probable/putative IFD. At Day 30 after the burn injury, the estimated cumulative incidence pr/pu IFD was 26.4% (95%CI 21.4-31.8%). Factors independently associated with IFDs were TBSA, severity scores and indoor burn injury (i.e., from confined space fire). Overall mortality was 15.3% and 36.8% in the no IFD, pr/pu IFD groups respectively (p<0.0001). IFD was independently associated with a risk of death (HR: 1.94 for pr/pu IFD; 95%CI, 1.12-3.36; p=0.019). DISCUSSION: This study describes 21st-century characteristics of IFDs in sever burn patients confirming known risk factors with thresholds and identifying the indoor injury as an independent factor associated to IFDs. This suggests a link to contamination caused by fire damage, which is highly susceptible to aerosolizing spores.

The role of CD146 in renal disease: from experimental nephropathy to clinics.

Vascular endothelial dysfunction is a major risk factor in the development of renal diseases. Recent studies pointed out a major interest for the inter-endothelial junction protein CD146, as its expression is modulated during renal injury. Indeed, some complex mechanisms involving this adhesion molecule and its multiple ligands are observed in a large number of renal diseases in fundamental or clinical research. The purpose of this review is to summarize the most recent literature on the role of CD146 in renal pathophysiology, from experimental nephropathy to clinical trials.

Epidemiologic features and outcomes associated with caustic ingestion among adults admitted in intensive care unit from 2013 to 2019: a French national observational study.

PURPOSE: Caustic ingestion is a potential life-threatening condition associated with high morbidity and mortality. Data on patients admitted to Intensive Care Unit (ICU) for severe caustic ingestion are lacking. We aimed to describing epidemiological features and outcomes of patients admitted to ICU for caustic ingestion in France. METHODS: In a retrospective, observational, and multicenter study, data from the national French Programme de Médicalisation des Systèmes d'Informations (PMSI) database were analysed from 2013 to 2019. In-hospital mortality rate (primary outcome) and in-ICU complications (secondary outcomes) were reported and analysed. RESULTS: 569 patients (289 males (50.8%), with median age of 49 years [interquartile (26-62)] were admitted in 65 French ICU for severe caustic ingestion. Five hundred and thirteen patients (90%) were admitted for intentional caustic ingestion. The median length of stay in ICU was 14.0 [4.0-31.0] days. In-hospital mortality occurred in 56 patients (9.8%). In multivariate analysis, age and simplified acute physiology score II were associated with in-hospital mortality age of 40-59 years [OR = 15.3 (2.0-115.3)], age of 60-79 years [OR = 23.6 (3.1-182.5)], and age > 80 years [OR = 37.0 (4.2-328.6)] and SAPS 2 score [OR = 1.0018 (1.003-1.033), p < 0.001]. During ICU stay, 423 complications (74%) were reported in 505 patients (89%). Infectious (244 (42.9%)), respiratory (207 (36.4%)), surgical 62 (10.9%), haemorrhagic (64 (11.2%)) and thrombo-embolic and (35 (6.2%)) complications were the most frequently reported during ICU stay. CONCLUSION: ICU admission for severe caustic ingestion is associated with 9.8% mortality and 74% complications. Age > 40 years and SAPS 2 score were independently associated with mortality.

Subclinical and clinical acute kidney injury share similar urinary peptide signatures and prognosis.

PURPOSE: Acute kidney injury (AKI) is a frequent and severe condition in intensive care units (ICUs). In 2020, the Acute Dialysis Quality Initiative (ADQI) group proposed a new stage of AKI, referred to as stage 1S, which represents subclinical disease (sAKI) defined as a positive biomarker but no increase in serum creatinine (sCr). This study aimed to determine and compare the urinary peptide signature of sAKI as defined by biomarkers. METHODS: This is an ancillary analysis of the prospective, observational, multinational FROG-ICU cohort study. AKI was defined according to the Kidney Disease Improving Global Outcome definition (AKIKDIGO). sAKI was defined based on the levels of the following biomarkers, which exceeded the median value: neutrophil gelatinase-associated lipocalin (pNGAL, uNGAL), cystatin C (pCysC, uCysC), proenkephalin A 119-159 (pPENKID) and liver fatty acid binding protein (uLFABP). Urinary peptidomics analysis was performed using capillary electrophoresis-mass spectrometry. Samples were collected at the time of study inclusion. RESULTS: One thousand eight hundred eighty-five patients had all biomarkers measured at inclusion, which included 1154 patients without AKI (non-AKIKDIGO subgroup). The non-AKIKDIGO subgroup consisted of individuals at a median age of 60 years [48, 71], among whom 321 (27.8%) died. The urinary peptide signatures of sAKI, regardless of the biomarkers used for its definition, were similar to the urinary peptide signatures of AKIKDIGO (inflammation, haemolysis, and endothelial dysfunction). These signatures were also associated with 1-year mortality. CONCLUSION: Biomarker-defined sAKI is a common and severe condition observed in patients within intensive care units with a urinary peptide signature that is similar to that of AKI, along with a comparable prognosis.

A universal predictive and mechanistic urinary peptide signature in acute kidney injury.

BACKGROUND: The delayed diagnosis of acute kidney injury (AKI) episodes and the lack of specificity of current single AKI biomarkers hamper its management. Urinary peptidome analysis may help to identify early molecular changes in AKI and grasp its complexity to identify potential targetable molecular pathways. METHODS: In derivation and validation cohorts totalizing 1170 major cardiac bypass surgery patients and in an external cohort of 1569 intensive care unit (ICU) patients, a peptide-based score predictive of AKI (7-day KDIGO classification) was developed, validated, and compared to the reference biomarker urinary NGAL and NephroCheck and clinical scores. RESULTS: A set of 204 urinary peptides derived from 48 proteins related to hemolysis, inflammation, immune cells trafficking, innate immunity, and cell growth and survival was identified and validated for the early discrimination (< 4 h) of patients according to their risk to develop AKI (OR 6.13 [3.96-9.59], p < 0.001) outperforming reference biomarkers (urinary NGAL and [IGFBP7].[TIMP2] product) and clinical scores. In an external cohort of 1569 ICU patients, performances of the signature were similar (OR 5.92 [4.73-7.45], p < 0.001), and it was also associated with the in-hospital mortality (OR 2.62 [2.05-3.38], p < 0.001). CONCLUSIONS: An overarching AKI physiopathology-driven urinary peptide signature shows significant promise for identifying, at an early stage, patients who will progress to AKI and thus to develop tailored treatments for this frequent and life-threatening condition. Performance of the urine peptide signature is as high as or higher than that of single biomarkers but adds mechanistic information that may help to discriminate sub-phenotypes of AKI offering new therapeutic avenues.

Two-lung ventilation in video-assisted thoracoscopic esophagectomy in prone position: a systematic review.

Esophageal cancer surgery is still carrying a high risk of morbidity and mortality. That is why some anesthesia strategies have tried to reduce those postoperative complications. In this systematic review performed in accordance with the PRISMA-S guidelines (PROSPERO (ID: CRD42022310385)), we aimed to investigate the safety and advantages of two-lung ventilation (TLV) over one-lung ventilation (OLV) in minimally invasive esophagectomy (MIE) in the prone position. Seven trials, with a total number of 1710 patients (765 patients with TLV versus 945 patients with OLV) were included. Postoperative mortality and morbidity rates were similar between TLV and OLV when realised for esophagectomy. Interestingly, we observed no difference in changes in intraoperative respiratory parameters, operative duration, thoraco-conversion rate, number of harvested lymph nodes, postoperative heart rate and respiratory rate between TLV and OLV. TLV brings better results in terms of intraoperative oxygen arterial pressure (PaO2) during the thoracic time, postoperative oxygenation, PaO2 on inspired fraction of oxygen (FiO2) ratio, duration of thoracic surgery, preoperative time, blood loss, temperature on postoperative day-1, and C-reactive protein dosage. Our study highlighted the safety of TLV for MIE in prone position when compared to OLV. Interestingly, we found better intra and postoperative ventilation parameters. The choice of ventilation modality did not influence clinical outcome after surgery and the quality of oncological resection. Large randomised controlled trials are needed to confirm these results.

Risk factors associated with COVID-19-associated pulmonary aspergillosis in ICU patients: a French multicentric retrospective cohort.

OBJECTIVES: The main objective of this study was to determine the incidence of invasive pulmonary aspergillosis (IPA) in patients with coronavirus disease 2019 (COVID-19) admitted to the intensive care unit (ICU), and to describe the patient characteristics associated with IPA occurrence and to evaluate its impact on prognosis. METHODS: We conducted a retrospective cohort study including all successive COVID-19 patients, hospitalized in four ICUs, with secondary deterioration and one or more respiratory samples sent to the mycology department. We used a strengthened IPA testing strategy including seven mycological criteria. Patients were classified as probable IPA according to the European Organization for Research and Treatment of Cancer (EORTC)/Mycoses Study Group Education and Research Consortium (MSGERC) classification if immunocompromised, and according to the recent COVID-19-associated IPA classification otherwise. RESULTS: Probable IPA was diagnosed in 21 out of the 366 COVID-19 patients (5.7%) admitted to the ICU and in the 108 patients (19.4%) who underwent respiratory sampling for deterioration. No significant differences were observed between patients with and without IPA regarding age, gender, medical history and severity on admission and during hospitalization. Treatment with azithromycin for ≥3 days was associated with the diagnosis of probable IPA (odds ratio 3.1, 95% confidence interval 1.1-8.5, p = 0.02). A trend was observed with high-dose dexamethasone and the occurrence of IPA. Overall mortality was higher in the IPA patients (15/21, 71.4% versus 32/87, 36.8%, p < 0.01). CONCLUSION: IPA is a relatively frequent complication in severe COVID-19 patients and is responsible for increased mortality. Azithromycin, known to have immunomodulatory properties, may contribute to increase COVID-19 patient's susceptibility to IPA.

The A2B trial, antibiotic prophylaxis for excision-graft surgery in burn patients: a multicenter randomized double-blind study.

BACKGROUND: The indication for antibiotic prophylaxis in burn patients remains highly controversial, with no consensus having been reached. The objective of antibiotic prophylaxis is to reduce the risk of postoperative local and systemic infections. Burn surgery is associated with a high incidence of bacteremia, postoperative infections, and sepsis. However, antibiotic prophylaxis exposes patients to the risk of selecting drug-resistant pathogens as well as to the adverse effects of antibiotics (i.e., Clostridium difficile colitis). The lack of data precludes any strong international recommendations regarding perioperative prophylaxis using systemic antibiotics in this setting. The goal of this project is therefore to determine whether perioperative systemic antibiotic prophylaxis can reduce the incidence of postoperative infections in burn patients. METHODS: The A2B trial is a multicenter (10 centers), prospective, randomized, double-blinded, placebo-controlled study. The trial will involve the recruitment of 506 adult burn patients with a total body surface area (TBSA) burn of between 5 and 40% and requiring at least one excision-graft surgery for deep burn injury. Participants will be randomized to receive antibiotic prophylaxis (antibiotic prophylaxis group) or a placebo (control group) 30 min before the incision of the first two surgeries. The primary outcome will be the occurrence of postoperative infections defined as postoperative sepsis and/or surgical site infection and/or graft lysis requiring a new graft within 7 days after surgery. Secondary outcomes will include mortality at day 90 postrandomization, skin graft lysis requiring a new graft procedure, postoperative bacteremia (within 48 h of surgery), postoperative sepsis, postoperative surgical site infection, number of hospitalizations until complete healing (> 95% TBSA), number of hospitalization days living without antibiotic therapy at day 28 and day 90, and multiresistant bacterial colonization or infection at day 28 and day 90. DISCUSSION: The trial aims to provide evidence on the efficacy and safety of antibiotic prophylaxis for excision-graft surgery in burn patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT04292054 . Registered on 2 March 2020.

Monitoring tissue perfusion: a pilot clinical feasibility and safety study of a urethral photoplethysmography-derived perfusion device in high-risk patients.

Continuous monitoring of tissue perfusion in patients with hemodynamic instability remains challenging because of the lack of tools available. Through using urethral photoplethysmography, the urethral perfusion index (uPI) could allow tissue perfusion monitoring through a modified urinary catheter. The first objective of our study was to evaluate the feasibility and safety of the IKORUS UP (Advanced Perfusion Diagnostics, Villeurbanne, France), a new device in the field. The secondary objectives were to evaluate the performance (duration and signal quality) of the IKORUS UP probe and to assess the uPI variations during hemodynamic events during major abdominal surgery. "STEP UP" was a prospective, multicenter, observational study. The inclusion criteria were age 18 years or older with signed informed consent and admitted to intensive care unit (ICU) with hemodynamic instability or high-risk surgical patient. Thirty patients were included in the study, 26 in the operating room, and four in the ICU. Of these patients, 28 were analyzed. For the primary outcome, six (21%) patients had pain scores assessed at insertion of and 22 (79%) at withdrawal of the catheter. The mean EVA score was 1.5 (IQ 1-2) and 0.7 (IQ 0-1), respectively, with the highest score being 3. One (4%) minor urethral bleeding and one (4%) catheter-associated urinary tract infection were reported. The IKORUS UP probe remained in the urethra for an average of 172 h (IQ40-328). The median signal measurement time was 33 h (IQ 5.2-46). The signal quality was recorded as good or excellent for 99% (IQ 82-100) of the insertion duration. The signal quality index was 93% (IQ 87-96) with a signal-to-noise ratio of 26 (IQ 21-36). We observed clinically relevant variations in the uPI over time during hemodynamic events or therapeutic interventions, with a strong cross-correlation with macrohemodynamic variables in some patients, while others did not display macrohemodynamic changes. The IKORUS UP probe was well tolerated and allowed urethral perfusion monitoring. Clinically relevant changes in tissue perfusion could be recorded during the observational period. Trial Registration: ( www.clinicaltrials.gov NCT03410069) registered January 25, 2018.

Association between hydroxocobalamin administration and acute kidney injury after smoke inhalation: a multicenter retrospective study.

BACKGROUND: The use of hydroxocobalamin has long been advocated for treating suspected cyanide poisoning after smoke inhalation. Intravenous hydroxocobalamin has however been shown to cause oxalate nephropathy in a single-center study. The impact of hydroxocobalamin on the risk of acute kidney injury (AKI) and survival after smoke inhalation in a multicenter setting remains unexplored. METHODS: We conducted a multicenter retrospective study in 21 intensive care units (ICUs) in France. We included patients admitted to an ICU for smoke inhalation between January 2011 and December 2017. We excluded patients discharged at home alive within 24 h of admission. We assessed the risk of AKI (primary endpoint), severe AKI, major adverse kidney (MAKE) events, and survival (secondary endpoints) after administration of hydroxocobalamin using logistic regression models. RESULTS: Among 854 patients screened, 739 patients were included. Three hundred six and 386 (55.2%) patients received hydroxocobalamin. Mortality in ICU was 32.9% (n = 243). Two hundred eighty-eight (39%) patients developed AKI, including 186 (25.2%) who developed severe AKI during the first week. Patients who received hydroxocobalamin were more severe and had higher mortality (38.1% vs 27.2%, p = 0.0022). The adjusted odds ratio (95% confidence interval) of AKI after intravenous hydroxocobalamin was 1.597 (1.055, 2.419) and 1.772 (1.137, 2.762) for severe AKI; intravenous hydroxocobalamin was not associated with survival or MAKE with an adjusted odds ratio (95% confidence interval) of 1.114 (0.691, 1.797) and 0.784 (0.456, 1.349) respectively. CONCLUSION: Hydroxocobalamin was associated with an increased risk of AKI and severe AKI but was not associated with survival after smoke inhalation. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03558646.

One-Year Prognosis of Kidney Injury at Discharge From the ICU: A Multicenter Observational Study.

OBJECTIVES: The association between outcome and kidney injury detected at discharge from the ICU using different biomarkers remains unknown. The objective was to evaluate the association between 1-year survival and kidney injury at ICU discharge. DESIGN: Ancillary investigation of a prospective observational study. SETTING: Twenty-one ICUs with 1-year follow-up. PATIENTS: Critically ill patients receiving mechanical ventilation and/or hemodynamic support for at least 24 hours were included. INTERVENTIONS: Serum creatinine, plasma Cystatin C, plasma neutrophil gelatinase-associated lipocalin, urinary neutrophil gelatinase-associated lipocalin, plasma Proenkephalin A 119-159, and estimated glomerular filtration rate (on serum creatinine and plasma Cystatin C) were measured at ICU discharge among ICU survivors. MEASUREMENTS AND MAIN RESULTS: The association between kidney biomarkers at discharge and mortality was estimated using logistic model with and without adjustment for prognostic factors previously identified in this cohort. Subgroup analyses were performed in patients with discharge serum creatinine less than 1.5-fold baseline at ICU discharge. Among 1,207 ICU survivors included, 231 died during the year following ICU discharge (19.2%). Estimated glomerular filtration rate was significantly lower and kidney injury biomarkers higher at discharge in nonsurvivors. The association between biomarker levels or estimated glomerular filtration rate and mortality remained after adjustment to potential cofounding factors influencing outcome. In patients with low serum creatinine at ICU discharge, 25-47% of patients were classified as subclinical kidney injury depending on the biomarker. The association between kidney biomarkers and mortality remained and mortality was higher than patients without subclinical kidney injury. The majority of patients who developed acute kidney injury during ICU stay had elevated biomarkers of kidney injury at discharge even with apparent recovery based on serum creatinine (i.e., subclinical acute kidney disease). CONCLUSIONS: Elevated kidney biomarkers measured at ICU discharge are associated with poor 1-year outcome, including in patients with low serum creatinine at ICU discharge.

Prediction of major adverse kidney events in critically ill burn patients.

OBJECTIVE: We aimed at assessing the predictive value of plasmatic Neutrophil Gelatinase Associated Lipocalin (pNGAL) at admission and severity scores to predict major adverse kidney events (MAKE, defined as death and/or need for renal replacement therapy (RRT) and/or non-renal recovery at day 90) in critically ill burn patients. MATERIAL AND METHODS: Single-center cohort study in a burn critical care unit in a tertiary center, including all consecutive severely burn patients (total burned body surface >20%) from January 2012 until January 2015 with a pNGAL dosage at admission. Reclassification of patients was assessed by Integrated Discrimination Improvement (IDI). MEASUREMENTS AND RESULTS: 87 patients were included. Mean age was 47.7 (IQ 25-75: 33.4-65.2) years; total burn body surface area was 40 (IQ 25-75: 30-55) % and ICU mortality 36%. 39 (44.8%) patients presented a MAKE, 32 (88.9%) patients died at day 90. pNGAL was higher in the MAKE group (423 [IQ 25-75: 327-518]pg/mL vs 184 [IQ 25-75: 147-220]pg/mL, p<0.001). In multivariate analysis, pNGAL and abbreviated burn severity index (ABSI) remained associated with MAKE (OR 1.005 [CI 95% 1.0005-1.009], p=0.03 and OR 1.682 [CI95%1.038-2.726], p=0.035 respectively). Adding pNGAL to abbreviated burn severity index, simplified organ failure assessment and the simplified acute physiology score 2 did outperform clinical scores for the prediction of MAKE and AKI and for most severe forms of AKI and allowed a statistically significant reclassification of patients compared to ABSI for MAKE, RRT, AKI at Day 7 and AKI during hospitalization with a number of patients needed to screen to detect one extra episode of MAKE was 44, 13 for severe AKI and 15 for AKI. CONCLUSIONS: pNGAL at admission is associated with the risk of MAKE in this population, and outperform severity scores when associated. Interventional studies are now needed to assess if impact of biomarkers-guided strategies would improve outcome.

Undetectable haptoglobin is associated with major adverse kidney events in critically ill burn patients.

BACKGROUND: Intravascular haemolysis has been associated with acute kidney injury (AKI) in different clinical settings (cardiac surgery, sickle cell disease). Haemolysis occurs frequently in critically ill burn patients. The aim of this study was to assess the predictive value of haptoglobin at admission to predict major adverse kidney events (MAKE) and AKI in critically ill burn patients. METHODS: We conducted a retrospective, single-centre cohort study in a burn critical care unit in a tertiary centre, including all consecutive severely burned patients (total burned body surface > 20% and/or shock and/or mechanical ventilation at admission) from January 2012 to April 2017 with a plasmatic haptoglobin dosage at admission. RESULTS: A total of 130 patients were included in the analysis. Their mean age was 49 (34-62) years, their median total body surface area burned was 29% (15-51%) and the intensive care unit (ICU) mortality was 25%. Early haemolysis was defined as an undetectable plasmatic haptoglobin at admission. We used logistic regression to identify MAKE and AKI risk factors. In multivariate analysis, undetectable haptoglobin was associated with MAKE and AKI (respectively, OR 6.33, 95% CI 2.34-16.45, p < 0.001; OR 8.32, 95% CI 2.86-26.40, p < 0.001). CONCLUSIONS: Undetectable plasmatic haptoglobin at ICU admission is an independent risk factor for MAKE and AKI in critically ill burn patients. This study provides a rationale for biomarker-guided therapy using haptoglobin in critically ill burn patients.