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.

Association between lactic acidosis and multiple organ dysfunction syndrome after cardiopulmonary bypass.

Background: The relationship between hyperlactatemia and prognosis after cardiopulmonary bypass (CPB) is controversial, and some studies ignore the presence of lactic acidosis in patients with severe hyperlactacemia. This study explored the association between lactic acidosis (LA) and the occurrence of multiple organ dysfunction syndrome (MODS) after cardiopulmonary bypass. Methods: This study was a post hoc analysis of patients who underwent cardiac surgery between February 2017 and August 2018 and participated in a prospective study at Taizhou Hospital. The data were collected at: ICU admission (H0), and 4, 8, 12, 24, and 48 h after admission. Blood lactate levels gradually increased after CPB, peaking at H8 and then gradually decreasing. The patients were grouped as LA, hyperlactatemia (HL), and normal control (NC) based on blood test results 8 h after ICU admission. Basic preoperative, perioperative, and postoperative conditions were compared between the three groups, as well as postoperative perfusion and oxygen metabolism indexes. Results: There were 22 (19%), 73 (64%), and 19 (17%) patients in the LA, HL, and NC groups, respectively. APACHE II (24h) and SOFA (24h) scores were the highest in the LA group (P < 0.05). ICU stay duration was the longest for the LA group (48.5 (42.5, 50) h), compared with the HL (27 (22, 48) h) and NC (27 (25, 46) h) groups (P = 0.012). The LA group had the highest incidence of MODS (36%), compared with the HL (14%) and NC (5%) groups (P = 0.015). In the LA group, the oxygen extraction ratio (O2ER) was lower (21.5 (17.05, 32.8)%) than in the HL (31.3 (24.8, 37.6)%) and the NC group (31.3 (29.0, 35.4) %) (P = 0.018). In the univariable analyses, patient age (OR = 1.054, 95% CI [1.003-1.109], P = 0.038), the LA group (vs. the NC group, (OR = 10.286, 95% CI [1.148-92.185], P = 0.037), and ΔPCO2 at H8 (OR = 1.197, 95% CI [1.022-1.401], P = 0.025) were risk factor of MODS after CPB. Conclusions: We speculated that there was correlation between lactic acidosis and MODS after CPB. In addition, LA should be monitored intensively after CPB.

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.

Lipid Profile as a Predictive Marker for Organ Dysfunction after Thoracoabdominal Surgery: A Cross-sectional Study.

Background: Plasma total cholesterol is considered a negative acute phase reactant. In various pathological conditions, such as trauma, sepsis, burns, and liver dysfunction, as well as post-surgery, serum cholesterol level decreases. This study aimed to investigate the role of lipid profiles in determining the probability of organ dysfunction after surgery. Methods: This cross-sectional study included patients who underwent thoracoabdominal surgery and were admitted to the intensive care unit of Imam Reza Hospital in Tabriz, Iran, between October 2016 and September 2018. During the first two days of admission, blood samples were taken, and serum levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), Low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and albumin were measured. The relation between the changes in these laboratory markers and six organ functions including cardiovascular, respiratory, renal, central nervous system, hepatic, and hematologic, length of stay in the hospital and intensive care unit, mechanical ventilation duration, and vasopressor use were investigated. The independent t test was used to compare continuous variables. The association between different variables and organ dysfunction and mortality was evaluated by using logistic regression. Results: The serum TC increased the risk of mortality (OR=1.09, 95%CI=1.06-1.11, P<0.001), renal dysfunction (OR=1.09, 95%CI=1.06-1.12; P<0.001), liver dysfunction (OR=1.07, 95%CI=1.03-1.10; P<0.001), respiratory dysfunction (OR=1.08, 95%CI=1.05-1.13; P<0.001). Moreover, LDL, HDL, and TG were found to be inversely related to mortality, organ dysfunction, length of stay in the hospital and intensive care unit, mechanical ventilation duration, and vasopressor use. Conclusion: TC could be considered a risk factor for mortality, organ dysfunction, and clinical outcomes. On the other hand, LDL, HDL, and TG played a protective role in the patients' mortality, organ dysfunction, and 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.

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.

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.

Incidence of multiple organ failure in adult polytrauma patients: A systematic review and meta-analysis.

BACKGROUND: Postinjury multiple organ failure (MOF) is the leading cause of late death in trauma patients. Although MOF was first described 50 years ago, its definition, epidemiology, and change in incidence over time are poorly understood. We aimed to describe the incidence of MOF in the context of different MOF definitions, study inclusion criteria, and its change over time. METHODS: Cochrane Library, EMBASE, MEDLINE, PubMed, and Web of Science databases were searched for articles published between 1977 and 2022 in English and German. Random-effects meta-analysis was performed when applicable. RESULTS: The search returned 11,440 results, of which 842 full-text articles were screened. Multiple organ failure incidence was reported in 284 studies that used 11 unique inclusion criteria and 40 MOF definitions. One hundred six studies published from 1992 to 2022 were included. Weighted MOF incidence by publication year fluctuated from 11% to 56% without significant decrease over time. Multiple organ failure was defined using four scoring systems (Denver, Goris, Marshall, Sequential Organ Failure Assessment [SOFA]) and 10 different cutoff values. Overall, 351,942 trauma patients were included, of whom 82,971 (24%) developed MOF. The weighted incidences of MOF from meta-analysis of 30 eligible studies were as follows: 14.7% (95% confidence interval [CI], 12.1-17.2%) in Denver score >3, 12.7% (95% CI, 9.3-16.1%) in Denver score >3 with blunt injuries only, 28.6% (95% CI, 12-45.1%) in Denver score >8, 25.6% (95% CI, 10.4-40.7%) in Goris score >4, 29.9% (95% CI, 14.9-45%) in Marshall score >5, 20.3% (95% CI, 9.4-31.2%) in Marshall score >5 with blunt injuries only, 38.6% (95% CI, 33-44.3%) in SOFA score >3, 55.1% (95% CI, 49.7-60.5%) in SOFA score >3 with blunt injuries only, and 34.8% (95% CI, 28.7-40.8%) in SOFA score >5. CONCLUSION: The incidence of postinjury MOF varies largely because of lack of a consensus definition and study population. Until an international consensus is reached, further research will be hindered. LEVEL OF EVIDENCE: Systematic Review and Meta-analysis; Level III.

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.

Acute kidney injury development in polytrauma and the safety of early repeated contrast studies: A retrospective cohort study.

BACKGROUND: The role of repeat intravenous contrast doses beyond initial contrast imaging in the development of acute kidney injury (AKI) for multiple injury patients admitted to the intensive care unit (ICU) is not fully understood. We hypothesized that additional contrast doses are potentially modifiable risk factors for worse outcomes. METHODS: An 8-year retrospective study of our institutional prospective postinjury multiple organ failure database was performed. Adult ICU admissions that survived >72 hours with Injury Severity Score (ISS) of >15 were included. Patients were grouped based on number of repeat contrast studies received after initial imaging. Initial vital signs, resuscitation data, and laboratory parameters were collected. Primary outcome was AKI (Kidney Disease: Improving Global Outcomes criteria), and secondary outcomes included contrast-induced acute kidney injury (CI-AKI; >25% or >44 µmol/L increase in creatinine within 72 hours of contrast administration), multiple organ failure, length of stay, and mortality. RESULTS: Six-hundred sixty-three multiple injury patients (age, 45.3 years [SD, 9.1 years]; males, 75%; ISS, 25 (interquartile range, 20-34); mortality, 5.4%) met the inclusion criteria. The incidence of AKI was 13.4%, and CI-AKI was 14.5%. Multivariate analysis revealed that receiving additional contrast doses within the first 72 hours was not associated with AKI (odds ratio, 1.33; confidence interval, 0.80-2.21; p = 0.273). Risk factors for AKI included higher ISS ( p < 0.0007), older age ( p = 0.0109), higher heart rate ( p = 0.0327), lower systolic blood pressure ( p = 0.0007), and deranged baseline blood results including base deficit ( p = 0.0042), creatinine ( p < 0.0001), lactate ( p < 0.0001), and hemoglobin ( p = 0.0085). Acute kidney injury was associated with worse outcomes (ICU length of stay: 8 vs. 3 days, p < 0.0001; mortality: 16% vs. 3.8%, p < 0.0001; MOF: 42% vs. 6.6%, p < 0.0001). CONCLUSION: There is a limited role of repeat contrast administration in AKI development in ICU-admitted multiple injury patients. The clinical significance of CI-AKI is likely overestimated, and it should not compromise essential secondary imaging from the ICU. Further prospective studies are needed to verify our results. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

Epidemiology and outcomes of multiple organ dysfunction syndrome following pediatric trauma.

BACKGROUND: Existing studies have found a low prevalence of multiple organ dysfunction syndrome (MODS) in pediatric trauma patients, typically applying adult criteria to single-center pediatric cohorts. We used pediatric criteria to determine the prevalence, risk factors, and outcomes of MODS among critically injured children in a national pediatric intensive care unit (PICU) database. METHODS: We conducted a retrospective cohort study of PICU patients 1 month to 17 years with traumatic injury in the Virtual Pediatric Systems, LLC database from 2009 to 2017. We used International Pediatric Sepsis Consensus Conference criteria to identify MODS on Day 1 of PICU admission and estimated the risk of mortality and poor functional outcome (Pediatric Overall/Cerebral Performance Category ≥3 with ≥1 point worsening from baseline) for MODS and for each type of organ dysfunction using generalized linear Poisson regression adjusted for age, comorbidities, injury type and mechanism, and postoperative status. RESULTS: Multiple organ dysfunction syndrome was present on PICU Day 1 in 23.1% of 37,177 trauma patients (n = 8,592), with highest risk among patients with injuries associated with drowning, asphyxiation, and abuse. Pediatric intensive care unit mortality was 20.1% among patients with MODS versus 0.5% among patients without MODS (adjusted relative risk, 32.3; 95% confidence interval, 24.1-43.4). Mortality ranged from 1.5% for one dysfunctional organ system to 69.1% for four or more organ systems and was highest among patients with hematologic dysfunction (43.3%) or renal dysfunction (29.6%). Death or poor functional outcome occurred in 46.7% of MODS patients versus 8.3% of patients without MODS (adjusted relative risk, 4.3; 95% confidence interval 3.4-5.3). CONCLUSION: Multiple organ dysfunction syndrome occurs more frequently following pediatric trauma than previously reported and is associated with high risk of morbidity and mortality. Based on existing literature using identical methodology, both the prevalence and mortality associated with MODS are higher among trauma patients than the general PICU population. Consideration of early organ dysfunction in addition to injury severity may aid prognostication following pediatric trauma. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level III.

Availability of Multiple Organ Failure Score Components in Surgical Patients.

Background: Scoring systems are often used describe the degree of multi-system organ failure (MOF), however, the data used to calculate these scores are often missing. Studies utilizing these scoring systems often underreport the frequency of missing data. No study has examined the availability of clinical data needed to calculate Sequential Organ Failure Assessment (SOFA), and other organ failure scores. The primary objective of this study is to observe how often emergency general surgery and trauma patients have missing data needed to calculate MOF scores. Patients and Methods: Patients admitted between June 2017 and September 2019 were evaluated. Data to calculate SOFA, quick SOFA (qSOFA), Marshall Multiple Organ Dysfunction Score (MODS), Denver Post-Injury Multiple Organ Failure, and systemic inflammatory response syndrome (SIRS) criteria, as well as demographic and general admission and discharge data, were collected. Results: Of the 238 patients included in this study, 66.4% were emergency general surgery and 33.6% were trauma patients. For all patients, the median intensive care unit (ICU) length of stay (LOS) was seven days (range, 4-12), the median hospital LOS was 14 days (range, 10-21), and 28 patients (11.8%) did not survive to hospital discharge. Sequential Organ Failure Assessment was calculable in 21.4%-18.1%, whereas MODS was calculable in 6.3%-5.0% on days three and five, respectively. The Denver score was calculable in 32.5%-28.8% of trauma patients on these days. Of the data points needed to calculate these scores, the partial pressure of oxygen (Pao2)/fraction of inspired oxygen (FIo2) ratio, central venous pressure (CVP), and bilirubin were the least available components. Conclusions: Data needed to fully calculate SOFA and other common MOF scores are often not readily available highlighting the degree of imputation required to calculate these scores. We recommend better reporting of the degree of missing data in the literature.

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.

Survival analysis by inflammatory biomarkers in severely injured patients undergoing damage control resuscitation.

BACKGROUND: Although early balanced blood product resuscitation has improved mortality after traumatic injury, many patients still suffer from inflammatory complications. The goal of this study was to identify inflammatory mediators associated with death and multiorgan system failure following severe injury after patients undergo blood product resuscitation. METHODS: A retrospective secondary analysis of inflammatory markers from the Pragmatic Randomized Optimal Platelet and Plasma Ratios study was performed. Twenty-seven serum biomarkers were measured at 8 time points in the first 72 hours of care and were compared between survivors and nonsurvivors. Biomarkers with significant differences were further analyzed by adjudicated cause of 30-day mortality. RESULTS: Biomarkers from 680 patients were analyzed. Seven key inflammatory markers (IL-1ra, IL-6, IL-8, IL-10, eotaxin, IP-10, and MCP-1) were further analyzed. These cytokines were also noted to have the highest hazard ratios of death. Stepwise selection was used for multivariate analysis of survival by time point. MCP-1 at 2 hours, eotaxin and IP-10 at 12 hours, eotaxin at 24 hours, and IP-10 at 72 hours were associated with all-cause mortality. CONCLUSION: Early systemic inflammatory markers are associated with increased risk of mortality after traumatic injury. Future studies should use these biomarkers to prospectively calculate risks of morbidity and causes of mortality for all trauma patients.

Anemia as a Risk Factor for Organ Dysfunctions in Patients Operated on Heart Valves.

Aim      To study the effects of pre- and postoperative anemia on the risk and the structure of internal organ dysfunction in patients undergoing surgery for acquired heart diseases (AHD).Material and methods  This was a retrospective cohort study including 610 primarily operated patients with AHD. A comparative analysis of the incidence and the structure of internal organ dysfunction was performed, and the likelihood of intraoperative hemotransfusion was determined for patients with preoperative anemia (Hb <130 g/l) and without it. The incidence and the nature of internal organ damage were compared in patients with postoperative Hb < 90 g/l and 90-130 g/l.Results The presence of postoperative anemia detected in 45 % of patients at two days after the surgery 6-fold increased the risk of acute heart failure (odds ratio [OR], 5.75; 95 % confidence interval [CI], 1.23-26.84; р=0.016), 4-fold increased the risk of multiorgan failure (MOF) (OR, 4.2; 95 % CI, 1.16-15.64; р=0.03), and 5-fold increased the likelihood of hemotransfusion (OR, 4.74; 95 % CI, 3.12-7.19; р<0.0001). Severe and moderate anemia (Hb <90 g/l) was observed in 11.2 % of patients, which presence 6-fold increased the risk of brain dysfunction (OR, 5.72; 95 % CI, 2.17-15.06; р=0.001) and MOF (OR, 5.97; 95 % CI, 1.94-18.35; р=0.004) compared to patients with Hb 90-130 g/l.Conclusion      In patients with AHD, postoperative anemia increases the risk of circulatory decompensation at two days after the surgery and of MOF and also increases the likelihood of intraoperative hemotransfusion; postoperative anemia with Hb <90 g/l increases the risk of brain damage and MOF.

Resolution of organ dysfunction as a predictor of long-term survival in necrotizing soft tissue infections: Analysis of the AB103 Clinical Composite Endpoint Study in Necrotizing Soft Tissue Infections trial and a retrospective claims database-linked chart study.

BACKGROUND: Necrotizing soft tissue infections (NSTIs) are an acute surgical condition with high morbidity and mortality. Timely identification, resuscitation, and aggressive surgical management have significantly decreased inpatient mortality. However, reduced inpatient mortality has shifted the burden of disease to long-term mortality associated with persistent organ dysfunction. METHODS: We performed a combined analysis of NSTI patients from the AB103 Clinical Composite Endpoint Study in Necrotizing Soft Tissue Infections randomized-controlled interventional trial (ATB-202) and comprehensive administrative database (ATB-204) to determine the association of persistent organ dysfunction on inpatient and long-term outcomes. Persistent organ dysfunction was defined as a modified Sequential Organ Failure Assessment (mSOFA) score of 2 or greater at Day 14 (D14) after NSTI diagnosis, and resolution of organ dysfunction defined as mSOFA score of 1 or less. RESULTS: The analysis included 506 hospitalized NSTI patients requiring surgical debridement, including 247 from ATB-202, and 259 from ATB-204. In both study cohorts, age and comorbidity burden were higher in the D14 mSOFA ≥2 group. Patients with D14 mSOFA score of 1 or less had significantly lower 90-day mortality than those with mSOFA score of 2 or higher in both ATB-202 (2.4% vs. 21.5%; p < 0.001) and ATB-204 (6% vs. 16%: p = 0.008) studies. In addition, in an adjusted covariate analysis of the combined study data sets D14 mSOFA score of 1 or lesss was an independent predictor of lower 90-day mortality (odds ratio, 0.26; 95% confidence interval, 0.13-0.53; p = 0.001). In both studies, D14 mSOFA score of 1 or less was associated with more favorable discharge status and decreased resource utilization. CONCLUSION: For patients with NSTI undergoing surgical management, persistent organ dysfunction at 14 days, strongly predicts higher resource utilization, poor discharge disposition, and higher long-term mortality. Promoting the resolution of acute organ dysfunction after NSTI should be considered as a target for investigational therapies to improve long-term outcomes after NSTI. LEVEL OF EVIDENCE: Prognostic/epidemiology study, level III.

Allogeneic Hematopoietic Stem Cell Transplantation in Extranodal Natural Killer/T-cell Lymphoma

Objective: Extranodal NK/T-cell lymphoma (ENKL) is aggressive and resistant to chemotherapy and radiotherapy. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative treatment for high-risk lymphomas owing to its associated graft-versus-lymphoma (GVL) effect. However, its application to ENKL is limited. We aim to summarize the characteristics of allo-HSCT for ENKL and, more importantly, evaluate whether allo-HSCT could offer any benefits for ENKL. Materials and Methods: A systematic review and data analysis were performed to evaluate the performance of allo-HSCT in the treatment of ENKL using studies obtained from PubMed, Medline, and Embase from January 2000 to December 2019 in the English language. Results: A total of 136 cases from 17 eligible publications were included in this study. It was found that after allo-HSCT, with an average follow-up time of 34 months (range: 1-121 months), 37.5% (52) of 136 patients had acute graft-versus-host disease (GVHD) and 31.6% (43) had chronic GVHD. Furthermore, 35.3% (48) of the patients were reported to have relapsed, but 2 of those relapsed only locally and achieved complete remission (CR) again with additional irradiation, chemotherapy, and donor lymphocyte infusions for one and rapid tapering and discontinuation of cyclosporine for the other, earning more than one year of extra survival. Finally, of the 136 patients, 51.5% (70) died because of primary disease progression (42.9%), infection (20.0%), GVHD (11.4%), organ failure (7.1%), hemorrhage (4.3%), and other causes (not specified/unknown) (14.3%). Conclusion: Allo-HSCT may be a treatment option for advanced or relapsed/refractory ENKL, but its role still requires more rigorous future studies.

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.

Is Toll-like receptor 4 involved in the severity of COVID-19 pathology in patients with cardiometabolic comorbidities?

The severe form of COVID-19 is marked by an abnormal and exacerbated immunological host response favoring to a poor outcome in a significant number of patients, especially those with obesity, diabetes, hypertension, and atherosclerosis. The chronic inflammatory process found in these cardiometabolic comorbidities is marked by the overexpression of pro-inflammatory cytokines such as interleukin-6 (IL-6) and tumoral necrosis factor-alpha (TNF-α), which are products of the Toll-Like receptors 4 (TLR4) pathway. The SARS-CoV-2 initially infects cells in the upper respiratory tract and, in some patients, spread very quickly, needing respiratory support and systemically, causing collateral damage in tissues. We hypothesize that this happens because the SARS-CoV-2 spike protein interacts strongly with TLR4, causing an intensely exacerbated immune response in the host's lungs, culminating with the cytokine storm, accumulating secretions and hindering blood oxygenation, along with the immune system attacks the body, leading to multiple organ failure.

Procalcitonin is a predictor of disseminated intravascular coagulation in patients with fatal COVID-19.

OBJECTIVE: The coagulopathies that present with COVID-19 are thrombotic microangiopathy and disseminated intravascular coagulopathy (DIC). Procalcitonin (PCT) levels have been shown to be significantly increased in COVID-19 patients in comparison with healthy subjects/asymptomatic coronavirus-positive patients. In this report, our aim was to assess the associations of the PCT level with DIC and the severity of COVID-19 infection. PATIENTS AND METHODS: In this cross-sectional, retrospective study, 71 consecutive patients with severe COVID-19 (21 with DIC and 50 without DIC) were enrolled in the study. The PCT level was obtained from hospital records. RESULTS: The PCT level was significantly higher in the patients with DIC than in those without DIC [1.9 (0.6-14.5) vs. 0.3 (0.2-0.4) (ng/mL), p<0.01]. The PCT level showed a positive and significant correlation with DIC (r=0.382, p=0.001) and was an independent predictor of DIC in patients with severe COVID-19 (OR: 6.685, CI: 1.857-24.063, p<0.01). CONCLUSIONS: In summary, the PCT level was increased in severe COVID-19 patients with DIC compared with those without DIC. An increased PCT level might suggest the presence of DIC and may help in predicting COVID-19 severity.