Mortality and prognostic factors among inpatients with systemic lupus erythematosus in China: A 20-year retrospective study.

OBJECTIVE: To summarize the causes of death and clinical characteristics of systemic lupus erythematosus (SLE) hospitalized patients in the last 20 years to improve SLE survival rates by detecting critical SLE early. METHODS: In this case-control study, 218 SLE death cases were retrospectively analyzed from January 2002 to December 2022, with 110 SLE inpatients chosen at random as controls. The clinical symptoms, causes of death, and risk factors in patients with SLE were investigated. RESULTS: There were 218 deaths among 9538 patients with SLE, including 188 women and 30 men. The death rate fell steadily from 4.14% in 2002 to 1.96% in 2013 and remained at 1.84% from 2014 to 2022. The standardized mortality ratio (SMR) was 4.98 [95% CI (4.06-5.89)] from 2002 to 2012 and 3.39 [95% CI (2.74-4.04)] from 2013 to 2022. Infection, lupus-induced multiple organ failure syndrome (MODS), and neuropsychiatric lupus (NPLE) were the leading causes of death, accounting for 31.19%, 15.14%, and 11.47% of overall deaths. Age had a significant association with the major causes of death. Logistic regression analysis showed NPLE[OR = 10.772,95% CI (3.350,34.633), p < 0.001], lupus pulmonary involvement (LP)[OR = 3.844,95%CI (1.547,9.552), p = 0.004], pneumonia[OR = 3.439,95%CI(1.552,7.621), p = 0.002], thrombocytopenia[OR = 14.941,95%CI (4.088,54.604), p < 0.001], creatinine>177 µmol/L[OR = 8.644,95%CI (2.831,26.388), p < 0.001], glutamic transaminase(AST) > 60U/L[OR = 5.762,95%CI (2.200,15.088), p < 0.001], total bilirubin > 34 µmol/L[OR = 16.701,95%CI (3.349,83.294), p = 0.001], higher SLE Disease Activity Index (SLEDAI)[OR = 1.089,95%CI (1.032,1.149), p = 0.002] and SLE Damage Index (SDI)[OR = 3.690,95%CI (2.487,5.474), p < 0.001] correlated positively with death. CONCLUSION: From 2002 to 2013, the mortality rate among patients with SLE fell steadily but remained unchanged from 2014 to 2022. Patients with SLE had significantly higher SMR than the general population. Childhood-onset SLE had a poorer prognosis than adult-onset SLE. Infection, MODS, and NPLE were the three leading causes of death. Major organ involvement and high disease activity were risk factors for mortality.

Serum Levels of Vitamin C and Thiamin in Children With Suspected Sepsis: A Prospective Observational Cohort Study.

OBJECTIVES: Vitamin C and thiamin have been trialed as adjunctive therapies in adults with septic shock but their role in critically ill children is unclear. We assessed serum levels of vitamin C and thiamin in children evaluated for sepsis. DESIGN: Single-center prospective observational study. Serum levels of vitamin C and thiamin were measured on admission and association with multiple organ dysfunction syndrome (MODS) was explored using logistic regression. SETTING: Emergency department and PICU in a tertiary children's hospital, Queensland, Australia. PATIENTS: Children greater than 1 month and less than 17 years evaluated for sepsis. INTERVENTIONS: Not applicable. MEASUREMENTS AND MAIN RESULTS: Vitamin levels were determined in 221 children with a median age of 3.5 (interquartile range [IQR] 1.6, 8.3) years. Vitamin C levels were inversely correlated with severity as measured by pediatric Sequential Organ Failure Assessment (Spearman's rho = -0.16, p = 0.018). Median (IQR) vitamin C levels on admission were 35.7 (17.9, 54.1) µmol/L, 36.1 (21.4, 53.7) µmol/L, and 17.9 (6.6, 43.0) µmol/L in children without organ dysfunction, single organ dysfunction, and MODS, respectively (p = 0.017). In multivariable analyses, low levels of vitamin C at the time of sampling were associated with greater odds of MODS (adjusted odds ratio [aOR] 3.04; 95% CI, 1.51-6.12), and vitamin C deficiency was associated with greater odds of MODS at 24 hours after sampling (aOR 3.38; 95% CI, 1.53-7.47). Median (IQR) thiamin levels were 162 (138, 192) nmol/L, 185 (143, 200) nmol/L, and 136 (110, 179) nmol/L in children without organ dysfunction, single organ dysfunction, and MODS, respectively (p = 0.061). We failed to identify an association between thiamin deficiency and either MODS at sampling (OR 2.52; 95% CI, 0.15-40.86) or MODS at 24 hours (OR 2.96; 95% CI, 0.18-48.18). CONCLUSIONS: Critically ill children evaluated for sepsis frequently manifest decreased levels of vitamin C, with lower levels associated with higher severity.

Unresponsive Low Mixed Venous Oxygen Saturation During Early Intensive Care Unit Stay is Associated With Increased Risk of Organ Dysfunction After Cardiac Surgery: A Single-Center Retrospective Study.

OBJECTIVES: The aim of the study was to determine if unresponsive mixed venous oxygen saturation (SvO2) values during early postoperative hours are associated with postoperative organ dysfunction. DESIGN: A single-center retrospective observational study. SETTING: A university hospital. PARTICIPANTS: A total of 6,282 adult patients requiring cardiac surgery who underwent surgery in a University Hospital from 2007 to 2020. INTERVENTIONS: A pulmonary artery catheter was used to gather SvO2 samples after surgery at admission to the intensive care unit (ICU) and 4 hours later. For the analysis, patients were divided into 4 groups according to their SvO2 values. The rate of organ dysfunctions categorized according to the SOFA score was then studied among these subgroups. MEASUREMENTS AND MAIN RESULTS: The crude mortality rate for the cohort at 1 year was 4.3%. Multiple organ dysfunction syndrome (MODS) was present in 33.0% of patients in the early postoperative phase. During the 4-hour initial treatment period, 43% of the 931 patients with low SvO2 on admission responded to goal-directed therapy to increase SvO2 >60%; whereas, in 57% of the 931 patients, the low SvO2 was sustained. According to the adjusted logistic regression analyses, the odds ratio for MODS (4.23 [95% CI 3.41-5.25]), renal- replacement therapy (4.97 [95% CI 3.28-7.52]), time on a ventilator (2.34 [95% CI 2.17-2.52]), and vasoactive-inotropic score >30 (3.62 [95% CI 2.96-4.43]) were the highest in the group with sustained low SvO2. CONCLUSIONS: Patients with SvO2 <60% at ICU admission and 4 hours later had the greatest risk of postoperative MODS. Responsiveness to a goal-directed therapy protocol targeting maintaining or increasing SvO2 ≥60% at and after ICU admission may be beneficial.

Trends in the Utilization of Multiorgan Support Among Adults Undergoing High-risk Cardiac Surgery in the United States.

OBJECTIVES: To examine trends in the prevalence of multiorgan dysfunction (MODS), utilization of multi-organ support (MOS), and mortality among patients undergoing cardiac surgery with MODS who received MOS in the United States. DESIGN: Retrospective cohort study. SETTING: 183 hospitals in the Premier Healthcare Database. PARTICIPANTS: Adults ≥18 years old undergoing high-risk elective or non-elective cardiac surgery. INTERVENTIONS: none. MEASUREMENTS AND MAIN RESULTS: The exposure was time (consecutive calendar quarters) January 2008 and June 2018. We analyzed hospital data using day-stamped hospital billing codes and diagnosis and procedure codes to assess MODS prevalence, MOS utilization, and mortality. Among 129,102 elective and 136,190 non-elective high-risk cardiac surgical cases across 183 hospitals, 10,001 (7.7%) and 21,556 (15.8%) of patients developed MODS, respectively. Among patients who experienced MODS, 2,181 (22%) of elective and 5,425 (25%) of non-elective cardiac surgical cases utilized MOS. From 2008-2018, MODS increased in both high-risk elective and non-elective cardiac surgical cases. Similarly, MOS increased in both high-risk elective and non-elective cardiac surgical cases. As a component of MOS, mechanical circulatory support (MCS) increased over time. Over the study period, risk-adjusted mortality, in patients who developed MODS receiving MOS, increased in high-risk non-elective cardiac surgery and decreased in high-risk elective cardiac surgery, despite increasing MODS prevalence and MOS utilization (p<0.001). CONCLUSIONS: Among patients undergoing high-risk cardiac surgery in the United States, MODS prevalence and MOS utilization (including MCS) increased over time. Risk-adjusted mortality trends differed in elective and non-elective cardiac surgery. Further research is necessary to optimize outcomes among patients undergoing high-risk cardiac surgery.

Stevens-Johnson syndrome and toxic epidermal necrolysis in Hong Kong.

INTRODUCTION: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) [hereafter, SJS/TEN] are uncommon but severe mucocutaneous reactions. Although they have been described in many populations worldwide, data from Hong Kong are limited. Here, we explored the epidemiology, disease characteristics, aetiology, morbidity, and mortality of SJS/TEN in Hong Kong. METHODS: This retrospective cohort study included all hospitalised patients who had been diagnosed with SJS/TEN in Prince of Wales Hospital from 1 January 2004 to 31 December 2020. RESULTS: There were 125 cases of SJS/TEN during the 17-year study period. The annual incidence was 5.07 cases per million. The mean age at onset was 51.4 years. The mean maximal body surface area of epidermal detachment was 23%. Overall, patients in 32% of cases required burns unit or intensive care unit admission. Half of the cases involved concomitant sepsis, and 23.2% of cases resulted in multiorgan failure or disseminated intravascular coagulation. The mean length of stay was 23.9 days. The cause of SJS/TEN was attributed to a drug in 91.9% of cases, including 84.2% that involved anticonvulsants, allopurinol, antibiotics, or analgesics. In most cases, patients received treatment comprising either best supportive care alone (35.2%) or combined with intravenous immunoglobulin (43.2%). The in-hospital mortality rate was 21.6%. Major causes of death were multiorgan failure and/or fulminant sepsis (81.5%). CONCLUSION: This study showed that SJS/TEN are uncommon in Hong Kong but can cause substantial morbidity and mortality. Early recognition, prompt withdrawal of offending agents, and multidisciplinary supportive management are essential for improving clinical outcomes.

Early, Persistent Lymphopenia Is Associated With Prolonged Multiple Organ Failure and Mortality in Septic Children.

OBJECTIVES: Sepsis-associated immune suppression correlates with poor outcomes. Adult trials are evaluating immune support therapies. Limited data exist to support consideration of immunomodulation in pediatric sepsis. We tested the hypothesis that early, persistent lymphopenia predicts worse outcomes in pediatric severe sepsis. DESIGN: Observational cohort comparing children with severe sepsis and early, persistent lymphopenia (absolute lymphocyte count < 1,000 cells/µL on 2 d between study days 0-5) to children without. The composite outcome was prolonged multiple organ dysfunction syndrome (MODS, organ dysfunction beyond day 7) or PICU mortality. SETTING: Nine PICUs in the National Institutes of Health Collaborative Pediatric Critical Care Research Network between 2015 and 2017. PATIENTS: Children with severe sepsis and indwelling arterial and/or central venous catheters. INTERVENTIONS: Blood sampling and clinical data analysis. MEASUREMENTS AND MAIN RESULTS: Among 401 pediatric patients with severe sepsis, 152 (38%) had persistent lymphopenia. These patients were older, had higher illness severity, and were more likely to have underlying comorbidities including solid organ transplant or malignancy. Persistent lymphopenia was associated with the composite outcome prolonged MODS or PICU mortality (66/152, 43% vs 45/249, 18%; p < 0.01) and its components prolonged MODS (59/152 [39%] vs 43/249 [17%]), and PICU mortality (32/152, 21% vs 12/249, 5%; p < 0.01) versus children without. After adjusting for baseline factors at enrollment, the presence of persistent lymphopenia was associated with an odds ratio of 2.98 (95% CI [1.85-4.02]; p < 0.01) for the composite outcome. Lymphocyte count trajectories showed that patients with persistent lymphopenia generally did not recover lymphocyte counts during the study, had lower nadir whole blood tumor necrosis factor-α response to lipopolysaccharide stimulation, and higher maximal inflammatory markers (C-reactive protein and ferritin) during days 0-3 ( p < 0.01). CONCLUSIONS: Children with severe sepsis and persistent lymphopenia are at risk of prolonged MODS or PICU mortality. This evidence supports testing therapies for pediatric severe sepsis patients risk-stratified by early, persistent lymphopenia.

Characterization of multiple organ failure after ruptured abdominal aortic aneurysm repair.

BACKGROUND: Multiple organ failure (MOF) is associated with poor outcomes and increased mortality in sepsis and trauma. There are limited data regarding MOF in patients after ruptured abdominal aortic aneurysm (rAAA) repair. We aimed to identify the contemporary prevalence and characteristics of patients with rAAA with MOF. METHODS: We retrospectively reviewed patients with rAAA who underwent repair (2010-2020) at our multihospital institution. Patients who died within the first 2 days after repair were excluded. MOF was quantified by modified (excluding hepatic system) Denver, Sequential Organ Failure Assessment (SOFA) score, and Multiple Organ Dysfunction Score (MODS) for postoperative days 3 to 5 to determine the prevalence of MOF. MOF was defined as a Denver score of >3, dysfunction in two or more organ systems by SOFA score, or a MODS score of >8. Kaplan-Meier curves and log-rank testing were used to evaluate differences in 30-day mortality between multiple organ failure and patients without MOF. Logistic regression was used to assess predictors of MOF. RESULTS: Of 370 patients with rAAA, 288 survived past two days (mean age, 73±10.1 years; 76.7% male; 44.1% open repair), and 143 had data for MOF calculation recorded. From postoperative days 3 to 5, 41 (14.24%) had MOF by Denver, 26 (9.03%) by SOFA, and 39 (13.54%) by MODS criteria. Among these scoring systems, pulmonary and neurological systems were impacted most commonly. Among patients with MOF, pulmonary derangement occurred in 65.9% (Denver), 57.7% (SOFA), and 56.4% (MODS). Similarly, neurological derangement occurred in 92.3% (SOFA) and 89.7% (MODS), but renal derangement occurred in 26.8% (Denver), 23.1% (SOFA), and 10.3% (MODS). MOF by all three scoring systems was associated with increased 30-day mortality (Denver: 11.3% vs 41.5% [P < .01]; DOFA: 12.6% vs 46.2% [P < .01]; MODS: 12.5% vs 35.9% [P < .01]), as was MOF by any criteria (10.8% vs 35.7 %; P < .01). Patients with MOF were more likely to have a higher body mass index (55.9±26.6 vs 49.0±15.0; P = .011) and to have had a preoperative stroke (17.9% vs 6.0%; P = .016). Patients with MOF were less likely to have undergone endovascular repair (30.4% vs 62.1%; P < .001). Endovascular repair was protective against MOF (any criteria) on multivariate analysis (odds ratio, 0.23; 95% confidence interval, 0.08-0.64; P = .019) after adjusting for age, gender, and presenting systolic blood pressure. CONCLUSIONS: MOF occurred in only 9% to 14% of patients after rAAA repair, but was associated with a three-fold increase in mortality. Endovascular repair was associated with a reduced MOF incidence.

Delay in treatment of adult hemophagocytic lymphohistiocytosis is associated with worse in-hospital outcomes.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition characterized by uncontrolled activation of the immune system leading to multiorgan failure. Timely initiation of HLH-specific treatment is believed to be essential and lifesaving. Due to the rarity of the condition in adults, there is no data available in the literature to investigate the effects of treatment delay in this age group. We used data from the National Inpatient Sample (NIS) to evaluate the inpatient practices of HLH treatment initiation over 13 years (2007-2019) and their association with clinically relevant inpatient outcomes. Patients were divided into early treatment group (<6 days) and late treatment group (≥ 6 days). We compared outcomes using multivariate logistic regression models adjusting for age, sex, race, and HLH-triggering conditions. There were 1327 and 1382 hospitalizations in the early and late treatment groups, respectively. Hospitalization in the late treatment group had higher rates of in-hospital mortality (OR 2.00 [1.65-2.43]), circulatory shock (OR 1.33 [1.09-1.63]), requiring mechanical ventilation (OR 1.41 [1.18-1.69]), venous thromboembolism (OR 1.70 [1.27-2.26]), infectious complications (OR 2.24 [1.90-2.64]), acute kidney injury (OR 2.27 [1.92-2.68]), and requiring new hemodialysis (OR 1.45 [1.17-1.81]). Additionally, we observed no significant trend in the mean time to treatment over the study period. This study shows the importance of early initiation of HLH treatment and highlights the adverse outcomes of treatment delay.

The Association of the Lactate-Albumin Ratio With Mortality and Multiple Organ Dysfunction in PICU Patients.

OBJECTIVES: To compare the relative associations of lactate, albumin, and the lactate-albumin ratio (LAR) measured early in disease course against mortality and prevalence of multiple organ dysfunction syndrome (MODS) in a general sample of critically ill pediatric patients. DESIGN: Retrospective analysis of the Health Facts (Cerner Corporation, Kansas City, MO) national database. SETTING: U.S. hospitals with PICUs. PATIENTS: Children admitted to the ICU ( n = 648) from 2009 to 2018 who had lactate and albumin measured within 6 hours of admission. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 648 admissions were included, with an overall mortality rate of 10.8% ( n = 70) and a MODS prevalence of 29.3% ( n = 190). Compared with survivors, deaths had higher initial lactates (7.3 mmol/L [2.6-11.7 mmol/L] vs 1.9 mmol/L [1.2-3.1 mmol/L]; p < 0.01), lower initial albumins (3.3 g/dL [2.7-3.8 g/dL] vs 4.2 g/dL [3.7-4.7 g/dL]; p < 0.01), and higher LARs (2.2 [1.0-4.2] vs 0.5 [0.3-0.8]; p < 0.01), with similar trends in patients with MODS versus those without MODS. LAR demonstrated a higher odds ratio (OR) for death than initial lactate alone (2.34 [1.93-2.85] vs 1.29 [1.22-1.38]) and a higher OR for MODS than initial lactate alone (2.10 [1.73-2.56] vs 1.22 [1.16-1.29]). Area under the receiver operating characteristic (AUROC) curve of LAR for mortality was greater than initial lactate (0.86 vs 0.82; p < 0.01). The LAR AUROC for MODS was greater than the lactate AUROC (0.71 vs 0.66; p < 0.01). Trends of lactate, albumin, and LAR for mortality were consistent across several diagnostic subgroups (trauma, primary respiratory failure, toxicology), but not all. CONCLUSIONS: LAR measured early in the course of critical illness is significantly associated with mortality and development of MODS when compared with initial lactate or initial albumin alone in critically ill pediatric patients.

Multiple Organ Dysfunction and Critically Ill Children With Acute Myeloid Leukemia: Single-Center Retrospective Cohort Study.

OBJECTIVES: To describe the prevalence of multiple organ dysfunction syndrome (MODS) and critical care utilization in children and young adults with acute myeloid leukemia (AML) who have not undergone hematopoietic cell transplantation (HCT). DESIGN: Retrospective cohort study of MODS (defined as dysfunction of two or more organ systems) occurring any day within the first 72 hours of PICU admission. SETTING: Large, quaternary-care children's hospital. PATIENTS: Patients 1 month through 26 years old who were treated for AML from 2011-2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Eighty patients with AML were included. These 80 patients had a total of 409 total non-HCT-related hospital and 71 PICU admissions. The majority 53 of 71 of PICU admissions (75%) were associated with MODS within the first 72 hours. MODS was present in 49 of 71 of PICU admissions (69%) on day 1, 29 of 52 (56%) on day 2, and 25 of 32 (78%) on day 3. The organ systems most often involved were hematologic, respiratory, and cardiovascular. There was an increasing proportion of renal failure (8/71 [11%] on day 1 to 8/32 [25%] on day 3; p = 0.02) and respiratory failure (33/71 [47%] to 24/32 [75%]; p = 0.001) as PICU stay progressed. The presence of MODS on day 1 was associated with a longer PICU length of stay (LOS) (ß = 5.4 [95% CI, 0.7-10.2]; p = 0.024) and over a six-fold increased risk of an LOS over 2 days (odds ratio, 6.08 [95% CI, 1.59-23.23]; p = 0.008). Respiratory failure on admission was associated with higher risk of increased LOS. CONCLUSIONS: AML patients frequently require intensive care. In this cohort, MODS occurred in over half of PICU admissions and was associated with longer PICU LOS. Respiratory failure was associated with the development of MODS and progressive MODS, as well as prolonged LOS.

Associated Risk Factors and Impact in Clinical Outcomes of Multiorgan Failure in Patients with TBI.

BACKGROUND: Individual extracerebral organ dysfunction is common after severe traumatic brain injury (TBI) and impacts outcomes. However, multiorgan failure (MOF) has received less attention in patients with isolated TBI. Our objective was to analyze the risk factors associated with the development of MOF and its impact in clinical outcomes in patients with TBI. METHODS: This was an observational, prospective, multicenter study using data from a nationwide registry that currently includes 52 intensive care units (ICUs) in Spain (RETRAUCI). Isolated significant TBI was defined as Abbreviated Injury Scale (AIS) ≥ 3 in the head area with no AIS ≥ 3 in any other anatomical area. Multiorgan failure was defined using the Sequential-related Organ Failure Assessment as the alteration of two or more organs with a score of ≥ 3. We analyzed the contribution of MOF to crude and adjusted mortality (age and AIS head) by using logistic regression analysis. A multiple logistic regression analysis was performed to analyze the risk factors associated with the development of MOF in patients with isolated TBI. RESULTS: A total of 9790 patients with trauma were admitted to the participating ICUs. Of them, 2964 (30.2%) had AIS head ≥ 3 and no AIS ≥ 3 in any other anatomical area, and these patients constituted the study cohort. Mean age was 54.7 (19.5) years, 76% of patients were men, and ground-level falls were the main mechanism of injury (49.1%). In-hospital mortality was 22.2%. Up to 185 patients with TBI (6.2%) developed MOF during their ICU stay. Crude and adjusted (age and AIS head) mortality was higher in patients who developed MOF (odds ratio 6.28 [95% confidence interval 4.58-8.60] and odds ratio 5.20 [95% confidence interval 3.53-7.45]), respectively. The logistic regression analysis showed that age, hemodynamic instability, the need of packed red blood cells concentrates in the initial 24 h, the severity of brain injury, and the need for invasive neuromonitoring were significantly associated with MOF development. CONCLUSIONS: MOF occurred in 6.2% of patients with TBI admitted to the ICU and was associated with increased mortality. MOF was associated with age, hemodynamic instability, the need of packed red blood cells concentrates in the initial 24 h, the severity of brain injury, and the need for invasive neuromonitoring.

Risk Factors Associated With Development of Multiple-Organ Dysfunction Syndrome After Pediatric Drowning.

OBJECTIVE: This study aimed to describe a single-center experience of pediatric drowning and to investigate risk factors associated with the development of pediatric multiple-organ dysfunction syndrome (MODS) after drowning events. METHODS: A single-center retrospective case-control study was performed at a tertiary children's hospital examining patients aged 1 month to 25 years who were admitted to the pediatric intensive care unit after a drowning event. The study period was June 2016 to June 2021. Patients who developed MODS at day 1 of intensive care admission were compared with those who did not. RESULTS: A total of 48 patients with a median age of 2.3 years were included. Twenty-nine (60%) had MODS at 24 hours. Those with MODS at 24 hours were more likely to require cardiopulmonary resuscitation (CPR), required longer duration of CPR, and had longer submersion times; otherwise, there were no differences in baseline characteristics. Those who developed MODS at 24 hours had longer lengths of stays, longer lengths of mechanical ventilation, and higher mortality. Multiple admission parameters were evaluated based on MODS-free survival at 24 hours. On univariable analysis, patients without MODS-free survival at 24 hours had higher rates of CPR, higher blood glucose on admission, higher illness severity scores, higher lactates, and lower Glasgow Coma Scale scores. A multivariable model was constructed using risk factors at presentation that were significant on univariable analysis; blood glucose greater than 200 mg/dL was associated with decreased odds of MODS-free survival at 24 hours after controlling for CPR administration of greater than 5 minutes and body temperature. CONCLUSIONS: Development of MODS in pediatric drowning is associated with worse patient outcomes. Hyperglycemia was identified as a potentially modifiable risk factor for the development of MODS at 24 hours and could serve as a useful prognostic parameter in this unique patient population.

Single Nucleotide Variant in FAS Associates With Organ Failure and Soluble Fas Cell Surface Death Receptor in Critical Illness.

OBJECTIVES: Multiple organ failure in critically ill patients is associated with poor prognosis, but biomarkers contributory to pathogenesis are unknown. Previous studies support a role for Fas cell surface death receptor (Fas)-mediated apoptosis in organ dysfunction. Our objectives were to test for associations between soluble Fas and multiple organ failure, identify protein quantitative trait loci, and determine associations between genetic variants and multiple organ failure. DESIGN: Retrospective observational cohort study. SETTING: Four academic ICUs at U.S. hospitals. PATIENTS: Genetic analyses were completed in a discovery (n = 1,589) and validation set (n = 863). Fas gene expression and flow cytometry studies were completed in outpatient research participants (n = 250). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In discovery and validation sets of critically ill patients, we tested for associations between enrollment plasma soluble Fas concentrations and Sequential Organ Failure Assessment score on day 3. We conducted a genome-wide association study of plasma soluble Fas (discovery n = 1,042) and carried forward a single nucleotide variant in the FAS gene, rs982764, for validation (n = 863). We further tested whether the single nucleotide variant in FAS (rs982764) was associated with Sequential Organ Failure Assessment score, FAS transcriptional isoforms, and Fas cell surface expression. Higher plasma soluble Fas was associated with higher day 3 Sequential Organ Failure Assessment scores in both the discovery (ß = 4.07; p < 0.001) and validation (ß = 6.96; p < 0.001) sets. A single nucleotide variant in FAS (rs982764G) was associated with lower plasma soluble Fas concentrations and lower day 3 Sequential Organ Failure Assessment score in meta-analysis (-0.21; p = 0.02). Single nucleotide variant rs982764G was also associated with a lower relative expression of the transcript for soluble as opposed to transmembrane Fas and higher cell surface expression of Fas on CD4+ T cells. CONCLUSIONS: We found that single nucleotide variant rs982764G was associated with lower plasma soluble Fas concentrations in a discovery and validation population, and single nucleotide variant rs982764G was also associated with lower organ dysfunction on day 3. These findings support further study of the Fas pathway as a potential mediator of organ dysfunction in critically ill patients.

Chronic critical illness in polytrauma. Results of the Spanish trauma in ICU registry.

PURPOSE: Chronic critical illness after trauma injury has not been fully evaluated, and there is little evidence in this regard. We aim to describe the prevalence and risk factors of chronic critical illness (CCI) in trauma patients admitted to the intensive care unit. MATERIAL AND METHODS: Retrospective observational multicenter study (Spanish Registry of Trauma in ICU (RETRAUCI)). Period March 2015 to December 2019. Trauma patients admitted to the ICU, who survived the first 48 h, were included. Chronic critical illness (CCI) was considered as the need for mechanical ventilation for a period greater than 14 days and/or placement of a tracheostomy. The main outcomes measures were prevalence and risk factors of CCI after trauma. RESULTS: 1290/9213 (14%) patients developed CCI. These patients were older (51.2 ± 19.4 vs 49 ± 18.9); p < .01) and predominantly male (79.9%). They presented a higher proportion of infectious complications (81.3% vs 12.7%; p < .01) and multiple organ dysfunction syndrome (MODS) (27.02% vs 5.19%; p < .01). CCI patients required longer stays in the ICU and had higher ICU and overall in-hospital mortality. Age, injury severity score, head injury, infectious complications, and development of MODS were independent predictors of CCI. CONCLUSION: CCI in trauma is a prevalent entity in our series. Early identification could facilitate specific interventions to change the trajectory of this process.

Recognition and Initial Management of Fulminant Myocarditis: A Scientific Statement From the American Heart Association.

Fulminant myocarditis (FM) is an uncommon syndrome characterized by sudden and severe diffuse cardiac inflammation often leading to death resulting from cardiogenic shock, ventricular arrhythmias, or multiorgan system failure. Historically, FM was almost exclusively diagnosed at autopsy. By definition, all patients with FM will need some form of inotropic or mechanical circulatory support to maintain end-organ perfusion until transplantation or recovery. Specific subtypes of FM may respond to immunomodulatory therapy in addition to guideline-directed medical care. Despite the increasing availability of circulatory support, orthotopic heart transplantation, and disease-specific treatments, patients with FM experience significant morbidity and mortality as a result of a delay in diagnosis and initiation of circulatory support and lack of appropriately trained specialists to manage the condition. This scientific statement outlines the resources necessary to manage the spectrum of FM, including extracorporeal life support, percutaneous and durable ventricular assist devices, transplantation capabilities, and specialists in advanced heart failure, cardiothoracic surgery, cardiac pathology, immunology, and infectious disease. Education of frontline providers who are most likely to encounter FM first is essential to increase timely access to appropriately resourced facilities, to prevent multiorgan system failure, and to tailor disease-specific therapy as early as possible in the disease process.

Association of Early Multiple Organ Dysfunction With Clinical and Functional Outcomes Over the Year Following Traumatic Brain Injury: A Transforming Research and Clinical Knowledge in Traumatic Brain Injury Study.

OBJECTIVES: Traumatic brain injury is a leading cause of death and disability in the United States. While the impact of early multiple organ dysfunction syndrome has been studied in many critical care paradigms, the clinical impact of early multiple organ dysfunction syndrome in traumatic brain injury is poorly understood. We examined the incidence and impact of early multiple organ dysfunction syndrome on clinical, functional, and disability outcomes over the year following traumatic brain injury. DESIGN: Retrospective cohort study. SETTING: Patients enrolled in the Transforming Clinical Research and Knowledge in Traumatic Brain Injury study, an 18-center prospective cohort study of traumatic brain injury patients evaluated in participating level 1 trauma centers. SUBJECTS: Adult (age > 17 yr) patients with moderate-severe traumatic brain injury (Glasgow Coma Scale < 13). We excluded patients with major extracranial injury (Abbreviated Injury Scale score ≥ 3). INTERVENTIONS: Development of early multiple organ dysfunction syndrome, defined as a maximum modified Sequential Organ Failure Assessment score greater than 7 during the initial 72 hours following admission. MEASUREMENTS AND MAIN RESULTS: The main outcomes were: hospital mortality, length of stay, 6-month functional and disability domains (Glasgow Outcome Scale-Extended and Disability Rating Scale), and 1-year mortality. Secondary outcomes included: ICU length of stay, 3-month Glasgow Outcome Scale-Extended, 3-month Disability Rating Scale, 1-year Glasgow Outcome Scale-Extended, and 1-year Disability Rating Scale. We examined 373 subjects with moderate-severe traumatic brain injury. The mean (sd) Glasgow Coma Scale in the emergency department was 5.8 (3.2), with 280 subjects (75%) classified as severe traumatic brain injury (Glasgow Coma Scale 3-8). Among subjects with moderate-severe traumatic brain injury, 252 (68%) developed early multiple organ dysfunction syndrome. Subjects that developed early multiple organ dysfunction syndrome had a 75% decreased odds of a favorable outcome (Glasgow Outcome Scale-Extended 5-8) at 6 months (adjusted odds ratio, 0.25; 95% CI, 0.12-0.51) and increased disability (higher Disability Rating Scale score) at 6 months (adjusted mean difference, 2.04; 95% CI, 0.92-3.17). Subjects that developed early multiple organ dysfunction syndrome experienced an increased hospital length of stay (adjusted mean difference, 11.4 d; 95% CI, 7.1-15.8), with a nonsignificantly decreased survival to hospital discharge (odds ratio, 0.47; 95% CI, 0.18-1.2). CONCLUSIONS: Early multiple organ dysfunction following moderate-severe traumatic brain injury is common and independently impacts multiple domains (mortality, function, and disability) over the year following injury. Further research is necessary to understand underlying mechanisms, improve early recognition, and optimize management strategies.

The effect of smoking on cumulative damage in systemic lupus erythematosus: An incident cohort study.

OBJECTIVES: To investigate the relationship between smoking history and pack-year exposure on the rate of end-organ damage in systemic lupus erythematosus (SLE). METHODS: The SLE incident cohort included patients who met American College of Rheumatology (ACR) 1997 or SLE International Collaborating Clinics (SLICC) 2012 SLE criteria and had rheumatology encounters at a US academic institution (2008-16). The primary outcome was median time to SLICC/ACR damage index (SLICC/ACR-DI) increase or death. Main explanatory variables were smoking status and pack-years. Covariates included age, sex, race, ethnicity, receipt of Medicaid, neighborhood area deprivation index, and baseline SLE damage. Damage increase-free survival was evaluated by smoking status and pack-years using Kaplan-Meier and Cox proportional hazards methods. RESULTS: Patients of Black race and Medicaid recipients were more commonly current smokers (p's < 0.05). Former smokers were older and more likely to have late-onset SLE (54% versus 33% of never and 29% of current smokers, p = 0.001). Median time to SLICC/ACR-DI increase or death was earlier in current or former compared to never smokers (4.5 and 3.4 versus 9.0 yrs; p = 0.002). In multivariable models, the rate of damage accumulation was twice as fast in current smokers (HR 2.18; 1.33, 3.57) and smokers with a >10 pack-year history (HR 2.35; 1.15, 3.64) versus never smokers. CONCLUSIONS: In this incident SLE cohort, past or current smoking predicted new SLE damage 4-5 years earlier. After adjustment, current smokers and patients with a pack-year history of >10 years accumulated damage at twice the rate of never smokers.

Ultrasound characterization of the nail bed in patients with systemic lupus erythematosus.

OBJECTIVE: To characterize the ultrasound findings of the nail plate and nail bed in systemic lupus erythematosus (SLE) and its association with nail dystrophy. METHODS: Thirty-two SLE patients, 36 patients with osteoarthritis (OA) and 20 healthy individuals were studied. High-frequency linear ultrasound was performed in nails of the second to fifth fingers in all participants. Disease activity (SLEDAI-2K index), accrued organ damage (SLICC/ACR index), autoantibody profile, and Raynaud's phenomenon were also assessed in SLE patients. RESULTS: Nail bed thickness in SLE patients was higher than in healthy individuals (1.25 ± 0.31 mm vs 1.17 ± 0.29 mm; P = 0.01) but lower than in OA (1.39 ± 0.37 mm; P < 0.001), while nail plate thickness was similar among groups. Nail dystrophy was found more frequently in SLE and OA than in healthy individuals. SLE patients with nail dystrophy were older than their counterparts with no dystrophy (39.4 ± 10.4 years vs 27.8 ± 5.6 years; P = 0.004), although nail dystrophy showed no association with SLICC/ACR, SLEDAI-2K, nail bed vascularity, or autoantibodies. CONCLUSIONS: Nail bed in SLE patients is thicker than in healthy individuals but thinner than in OA patients. Nail dystrophy in SLE is associated with advanced age, but not with accrued organ damage, disease activity, Raynaud's phenomenon, or DIP synovitis assessed by ultrasound.

Multiple organ failure might be an indication for prophylactic antifungal therapy in acute pancreatitis.

PURPOSE: Significant conflicts regarding prophylactic antifungal treatment in acute pancreatitis (AP) exist among current literatures and guidelines. The key to resolving this controversial issue is to identify risk factors for intra-abdominal fungal infection (AFI) among patients with AP. METHODS: A single-center, retrospective cohort of 826 patients with AP between January 2014 to December 2019 was analysed to study the risk factors of AFI. RESULTS: Of the 826 patients with AP, 10 patients (1.2%) developed AFI, including 2 cases in moderately severe AP (MSAP) and 8 in severe AP (SAP). The incidence of AFI was significantly higher in patients with SAP compared with MSAP and mild AP (10.3 vs. 0.8% vs. 0, P < 0.001). SAP patients with AFI were more likely to have multiple organ failure (MOF) (OR = 13.4; 95% CI 1.6-115.5), organ failure lasting more than 1 week (OR = 5.1; 95% CI 1.0-27.0), and surgical intervention within first week of admission (OR = 7.4; 95% CI 1.0-53.6). Multivariable analysis identified MOF (OR = 14.3; 95% CI 1.2-173.8) as the only independent risk factor of AFI. CONCLUSION: MOF might be the indication of prophylactic antifungal therapy in patients with AP.

Mortality, sepsis, and organ failure in hospitalized patients with cirrhosis vary by type of infection.

BACKGROUND AND AIM: Infection is associated with substantial morbidity and mortality in cirrhosis, but presumably, not all infections carry the same risk of mortality. We compared outcomes of different sites of infection in a nationally representative sample of inpatients with cirrhosis. METHODS: We queried the Nationwide Readmissions Database for patients with cirrhosis from 2011 to 2014. Cirrhosis and infection diagnoses were identified by previously used algorithms of ICD-9 codes. The following infections were compared: urinary tract infection (UTI), pneumonia, cellulitis, spontaneous bacterial peritonitis (SBP), and Clostridium difficile infection (CDI). The primary outcome was inpatient mortality. Secondary outcomes included sepsis, any organ failure, multiple organ failures, and 30-day readmission. Outcomes were analyzed using logistic regression and included a priori covariates. RESULTS: A total of 1 798 830 weighted index admissions were identified. Infection was present in 29.2% overall-including UTI (13.7%), pneumonia (8.9%), cellulitis (5.2%), CDI (2.8%), and SBP (2.0%). Mortality was significantly higher in pneumonia (19.6%), SBP (18.6%), and CDI (17.4%) compared with cellulitis (7.6%) and UTI (11.8%). Sepsis, any, and multiple organ failures were most commonly seen in pneumonia, SBP, and CDI. Multivariable analysis demonstrated that pneumonia had the highest associated mortality (odds ratio [OR] 2.73, confidence interval [CI] 2.68-2.80) and multiple organ failures (OR 3.59, CI 3.50-3.68). Significantly increased 30-day readmission was seen only with SBP (24.9%). CONCLUSIONS: Outcomes of inpatients with cirrhosis vary significantly depending on the type of infection. The severity and epidemiology of infection in cirrhosis appears to be shifting with pneumonia, not SBP, having the highest prevalence of multiple organ failures and inpatient mortality.