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Objective: To evaluate the prognostic performance of the lactate–albumin difference (LAD), maximum lactate levels, and the Sequential Organ Failure Assessment (SOFA) score taken on the first day in critically ill patients with sepsis, on in-hospital mortality and 90-day survival.Patients and Methods: Data from the Medical Information Mart for Intensive Care III (MIMIC III) version 1.4 were evaluated retrospectively. The first day data of adult patients with sepsis diagnosed according to the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) criteria were recorded. The effectiveness of all diagnostic modalities on admission was analyzed to predict in-hospital mortality and 90-day survival. Results: In-hospital mortality was 20.3% among the 2270 patients included in this study. The area below the receiver operating characteristic curve (AUC) value of the LAD was higher than lactate for predicting mortality (AUC, 0.691; 95% confidence interval [CI], 0.663–0.718; p< 0.01, and AUC, 0.675; 95% CI, 0.646–0.703; p< 0.01, respectively), and the AUC of SOFA score was the highest (AUC, 0.716; 95% CI, 0.663–0.718). The optimal cutoff of LAD was 0.7. Conclusion: In addition to its easy and simple calculability relative to the SOFA, the prognostic performance of LAD was superior to maximum lactate levels for predicting in-hospital mortality and 90-day survival in adult patients with sepsis.

Decompensated cirrhosis (DC) is associated with high mortality, mainly owing to the development of acute-on-chronic liver failure (ACLF). Identifying the patients with DC who are at high risk of mortality and ACLF development is an unmet clinical need. Liver fatty acid-binding protein (L-FABP) is expressed in several organs and correlates with liver and systemic inflammation. Herein, we aimed to assess the prognostic value of L-FABP in patients with DC.A prospective series of 444 patients hospitalized for DC was divided into 2 cohorts: study cohort (305 patients) and validation cohort (139 patients). L-FABP was measured in urine and plasma samples collected at admission. Neutrophil gelatinase-associated lipocalin (NGAL) was also measured in urine samples for comparison.Urine but not plasma L-FABP correlated with 3-month survival on univariate analysis. On multivariate analysis, urine L-FABP and model for end-stage liver disease (MELD)-Na were the only independent predictors of prognosis. Urine L-FABP levels were higher in patients with ACLF than in those without and also predicted the development of ACLF, together with MELD-Na, during follow-up. In patients with ACLF, urine L-FABP correlated with liver, coagulation, and circulatory failure. Urine L-FABP levels were also increased in patients with acute kidney injury, particularly in those with acute tubular necrosis. The ability of urinary L-FABP to predict survival and ACLF development was confirmed in the validation cohort. Urine NGAL predicted outcome on univariate but not multivariate analysis.Urinary L-FABP levels are independently associated with the 3-month clinical course in patients with DC, in terms of mortality and ACLF development. Urinary L-FABP is a promising prognostic biomarker for patients with DC.Increased levels of liver fatty acid-binding protein (L-FABP), a protein related to lipid metabolism, have been associated with liver-related diseases. The present study analyzed urinary L-FABP levels in 2 independent groups of patients with decompensated cirrhosis and showed that higher urinary L-FABP levels correlated with increased mortality and risk of acute-on-chronic liver failure development. Therefore, urinary L-FABP levels could be useful as a new tool to predict complications in patients with decompensated cirrhosis.

Background: Appropriate timing to initiate advance care planning is difficult, especially for individuals with non-malignant disease in community settings. Aim: To identify the optimal moment for, and reasons to initiate advance care planning in different illness trajectories. Design and methods: A health records survey study; health records were presented to 83 GPs with request to indicate and substantiate what they considered optimal advance care planning timing within the 2 years before death. We used quantitative and qualitative analyses. Setting and patients: We selected and anonymized 90 health records of patients who died with cancer, organ failure or multimorbidity, from a regional primary care registration database in the Netherlands. Results: The median optimal advance care planning timing according to the GPs was 228 days before death (interquartile range 392). This moment was closer to death for cancer (87.5 days before death, IQR 302) than for organ failure (266 days before death, IQR 401) and multimorbidity (290 days before death, IQR 389) ( p Conclusion: The optimal advance care planning timing and reasons to initiate advance care planning indicated by GPs differ between patients with cancer and other illnesses, and they also differ between GPs. This suggests that “the” optimal timing for ACP should be seen as a “window of opportunity” for the different disease trajectories.

Background: Timely initiation of advance care planning (ACP) in general practice is challenging, especially in patients with non-malignant conditions. Our aim was to investigate how perceived optimal timing of ACP initiation and its triggers relate to recorded actual timing in patients with cancer, organ failure, or multimorbidity. Methods: In this mixed-methods study in the Netherlands, we analysed health records selected from a database with primary care routine data and with a recorded ACP conversation in the last two years before death of patients who died with cancer, organ failure, or multimorbidity. We compared actual timing of ACP initiation as recorded in health records of 51 patients with the perceived optimal timing as determined by 83 independent GPs who studied these records. Further, to identify and compare triggers for GPs to initiate ACP, we analysed the health record documentation around the moments of the recorded actual timing of ACP initiation and the perceived optimal timing of ACP initiation. We combined quantitative descriptive statistics with qualitative content analysis. Results: The recorded actual timing of ACP initiation was significantly closer to death than the perceived optimal timing in patients with cancer (median 88 vs. 111 days before death (p = 0.049)), organ failure (227 vs. 306 days before death (p = 0.02)) and multimorbidity (113 vs. 338 days before death (p = 0.006)). Triggers for recorded actual versus perceived optimal timing were similar across the three groups, the most frequent being 'expressions of patients' reflections or wishes' (14% and 14% respectively) and 'appropriate setting' (10% and 13% respectively). Conclusion: ACP in general practice was initiated and recorded later in the illness trajectory than considered optimal, especially in patients with organ failure or multimorbidity. As triggers were similar for recorded actual and perceived optimal timing, we recommend that GPs initiate ACP shortly after a trigger is noticed the first time, rather than wait for additional or more evident triggers when the illness is in an advanced stage.

Background & Aims: Acute decompensation (AD) of cirrhosis is a heterogeneous clinical entity associated with moderate mortality. In some patients, this condition develops quickly into the more deadly acute-on-chronic liver failure (ACLF), in which other organs such as the kidneys or brain fail. The aim of this study was to characterize the blood lipidome in a large series of patients with cirrhosis and identify specific signatures associated with AD and ACLF development. Methods: Serum untargeted lipidomics was performed in 561 patients with AD (518 without and 43 with ACLF) (discovery cohort) and in 265 patients with AD (128 without and 137 with ACLF) in whom serum samples were available to perform repeated measurements during the 28-day follow-up (validation cohort). Analyses were also performed in 78 patients with AD included in a therapeutic albumin trial (43 patients with compensated cirrhosis and 29 healthy individuals). Results: The circulating lipid landscape associated with cirrhosis was characterized by a generalized suppression, which was more manifest during AD and in non-surviving patients. By computing discriminating accuracy and the variable importance projection score for each of the 223 annotated lipids, we identified a sphingomyelin fingerprint specific for AD of cirrhosis and a distinct cholesteryl ester and lysophosphatidylcholine finger-print for ACLF. Liver dysfunction and infections were the prin-cipal net contributors to these fingerprints, which were dynamic and interchangeable between patients with AD whose condition worsened to ACLF and those who improved. Notably, blood lysophosphatidylcholine levels increased in these patients after albumin therapy. Conclusions: Our findings provide insights into the lipid land-scape associated with decompensation of cirrhosis and ACLF progression and identify unique non-invasive diagnostic bio-markers of advanced cirrhosis. Lay summary: Analysis of lipids in blood from patients with advanced cirrhosis reveals a general suppression of their levels in the circulation of these patients. A specific group of lipids known as sphingomyelins are useful to distinguish between patients with compensated and decompensated cirrhosis. Another group of lipids designated cholesteryl esters further distinguishes patients with decompensated cirrhosis who are at risk of developing organ failures. (c) 2021 The Authors. Published by Elsevier B.V. on behalf of European Association for the Study of the Liver.

Introduction Acute-on-chronic liver failure (ACLF) patients are susceptible to invasive fungal infections. We evaluated the prognosis and antifungal options in ACLF patients with invasive pulmonary aspergillosis (IPA). Methods ACLF patients with IPA from 15 hospitals were retrospectively screened from 2011 to 2018, and 383 ACLF patients without lung infections were included from a prospective cohort (NCT02457637). Demographic, laboratory, clinical data, and 28-day outcomes were documented in the two cohorts. Results ACLF patients with probable IPA (n = 145) had greater 28-day mortality (33.6% vs. 15.7%, p

Chengcheng Sheng, Ying Wang, Zongxu Xu, Jun Wang Department of Obstetrics and Gynecology, Shengjing Affiliated Hospital of China Medical University, Shenyang City, Liaoning Province, People’s Republic of ChinaCorrespondence: Jun WangDepartment of Obstetrics and Gynecology, Shengjing Affiliated Hospital of China Medical University, Shenyang City, Liaoning Province, 110004, People’s Republic of ChinaTel +86 18940254480Fax +86 24-23892620Email wangj1@sj-hospital.orgPurpose: Previous studies indicated that the serum triglyceride level in patients with acute pancreatitis positively correlated with the severity of the disease among the general population. Despite the physiological hypertriglyceridemia in pregnant women, there are no reports on the relationship between serum triglyceride level and the severity of acute pancreatitis in pregnant (APIP) women. This study explores the relationship between serum triglyceride levels and the severity of APIP.Patients and Methods: Clinical information of APIP patients admitted to the Shengjing Affiliated Hospital of China Medical University was gathered from January 2012 to December 2020 to conduct retrospective research. The participating patients were divided into mild, moderately severe, and severe acute pancreatitis. The clinical outcomes of patients with different serum triglyceride levels (0– 2.3 mmol/L, 2.23– 5.65 mmol/L, 5.65– 11.2 mmol/l, ≥ 11.2 mmol/L) were analyzed by performing ordinal logistic regression analysis. Receiver operating curve analysis was used to calculate the threshold value of serum triglyceride concentration that can effectively predict the occurrence of severe acute pancreatitis (SAP).Results: Hypertriglyceridemic acute pancreatitis (HTG-AP) occurred in 47% of APIP patients within the group, with a high prevalence among the Han population. In the present study, the serum triglyceride concentration correlated positively with the severity of APIP (r=0.403, P < 0.05). The adjusted logistic model demonstrated that relative to nominal triglyceride levels, the OR value of SAP were 1.036 (95% CI: 0.401– 2.677), 3.429 (95% CI: 1.269– 9265), 8.329 (95% CI: 3.713– 18.682) with triglyceride at the level of 2.23– 5.65 mmol/L, 5.65– 11.2 mmol/l and ≥ 11.2 mmol/L. In APIP patients, a triglyceride concentration of 10.7mmol/L or more upon admission was a predictive value for the occurrence of SAP, with a sensitivity of 0.72 and a specificity of 0.65, AUC: 0.708 (95% CI: 0.620– 0.796).Conclusion: As the serum triglyceride level upon admission increased, the frequency of local and systemic complications increased significantly.Keywords: gestation, hypertriglyceridemia, acute pancreatitis, organ failure

Contains fulltext : 288481.pdf (Publisher’s version ) (Closed access) OBJECTIVES: To investigate national mortality trends over a 12-year period for patients with severe acute pancreatitis (SAP) admitted to Dutch ICUs. Additionally, an assessment of outcome in SAP was undertaken to differentiate between early (< 14 d of ICU admission) and late (> 14 d of ICU admission) mortality. DESIGN: Data from the Dutch National Intensive Care Evaluation and health insurance companies' databases were extracted. Outcomes included 14-day, ICU, hospital, and 1-year mortality. Mortality before and after 2010 was compared using mixed logistic regression and mixed Cox proportional-hazards models. Sensitivity analyses, excluding early mortality, were performed to assess trends in late mortality. SETTING: Not applicable. PATIENTS: Consecutive adult patients with SAP admitted to all 81 Dutch ICUs between 2007 and 2018. INTERVENTIONS: Not applicable. MEASUREMENTS AND MAIN RESULTS: Among 4,160 patients treated in 81 ICUs, 14-day mortality was 17%, ICU mortality 17%, hospital mortality 23%, and 1-year mortality 33%. After 2010 in-hospital mortality adjusted for age, sex, modified Marshall, and Acute Physiology and Chronic Health Evaluation III scores were lower (odds ratio [OR], 0.76; 95% CI, 0.61-0.94) than before 2010. There was no change in ICU and 1-year mortality. Sensitivity analyses excluding patients with early mortality demonstrated a decreased ICU mortality (OR, 0.45; 95% CI, 0.32-0.64), decreased in-hospital (OR, 0.48; 95% CI, 0.36-0.63), and decreased 1-year mortality (hazard ratio, 0.81; 95% CI, 0.68-0.96) after 2010 compared with 2007-2010. CONCLUSIONS: Over the 12-year period examined, mortality in patients with SAP admitted to Dutch ICUs did not change, although after 2010 late mortality decreased. Novel therapies should focus on preventing early mortality in SAP.

Due to their immunomodulatory potential and release of trophic factors that promote healing, mesenchymal stromal cells (MSCs) are considered important players in tissue homeostasis and regeneration. MSCs have been widely used in clinical trials to treat multiple conditions associated with inflammation and tissue damage. Recent evidence suggests that most of the MSC therapeutic effects are derived from their secretome, including the extracellular vesicles, representing a promising approach in regenerative medicine application to treat organ failure as a result of inflammation/fibrosis. The recent outbreak of respiratory syndrome coronavirus, caused by the newly identified agent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has forced scientists worldwide to use all available instruments to fight the infection, including the inflammatory cascade caused by this pandemic disease. The use of MSCs is a valid approach to combat organ inflammation in different compartments. In addition to the lungs, which are considered the main inflammatory target for this virus, other organs are compromised by the infection. In particular, the liver is involved in the inflammatory response to SARS-CoV-2 infection, which causes organ failure, leading to death in coronavirus disease 2019 (COVID-19) patients. We herein summarize the current implications derived from the use of MSCs and their soluble derivatives in COVID-19 treatment, and emphasize the potential of MSC-based therapy in this clinical setting.

COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still a pandemic with high mortality and morbidity rates. Clinical manifestation is widely variable, including asymptomatic or mild respiratory tract illness to severe pneumonia and death. Myocardial injury is a significant pathogenic feature of COVID-19 and it is associated with worse in-hospital outcomes, mainly due to a higher number of hospital readmissions, with over 50% mortality. These findings suggest that myocardial injury would identify COVID-19 patients with higher risk during active infection and mid-term follow-up. Potential contributors responsible for myocardial damage are myocarditis, vasculitis, acute inflammation, type 1 and type 2 myocardial infarction. However, there are few data about cardiac sequelae and its long-term consequences. Thus, the optimal screening tool for residual cardiac sequelae, clinical follow-up, and the benefits of a specific cardiovascular therapy during the convalescent phase remains unknown. This mini-review explores the different mechanisms of myocardial injury related to COVID-19 and its short and long-term implications.

Background Acute necrotizing pancreatitis (ANP) is associated with higher mortality and morbidity. We need a method which is accurate in predicting the prognosis, and when applied early in the disease process, can help in closer monitoring and early initiation of treatment for at-risk patients. Objectives The aim of this prospective study was to assess the extra pancreatic necrosis (EPN) volume in patients with ANP and compare it with outcome variables such as organ failure, death and need for intervention as well as to compare the predictive power of EPN volume with modified CT severity index (CTSI). Materials and Methods The study had 48 patients with clinical diagnosis of acute pancreatitis, who underwent Contrast enhanced CT (CECT) between 3–6 days of onset. In all these patients, EPN volume (in cubic centimetre) and modified CTSI score were calculated and compared with the patient outcome parameters such as duration of hospital/ICU stay, need for percutaneous/surgical intervention, evidence of infection and organ failure. The results were compared with assess the predictive power of EPN volume. Statistical analysis The analysis was done in SPSS version 16.0 for windows. Pearson Correlation was used to assess the significant relationship between selected objective variables. Results EPN volume (>/= to 360 cc) had a statistically significant correlation with outcome parameters as well as in predicting overall organ failure. In our study, Modified CTSI had no significant correlation with the above mentioned factors. Conclusions The volume of EPN calculated between 3rd and 6th day of onset of symptoms showed a significant correlation with the outcome in patients with ANP.

Background Multiorgan failure is a consequence of severe ischemia-reperfusion injury after traumatic hemorrhagic shock (HS), a major cause of mortality in trauma patients. Circulating uric acid (UA), released from cell lysis, is known to activate proinflammatory and proapoptotic pathways and has been associated with poor clinical outcomes among critically ill patients. Our group has recently shown a mediator role for UA in kidney and lung injury, but its role in liver and enteric damage after HS remains undefined. Therefore, the objective of this study was to evaluate the role of UA on liver and enteric injury after resuscitated HS. Methods A murine model of resuscitated HS was treated during resuscitation with a recombinant uricase, a urate oxidase enzyme (rasburicase; Sanofi-Aventis, Canada Inc, Laval, Canada), to metabolize and reduce circulating UA. Biochemical analyses (liver enzymes, liver apoptotic, and inflammatory markers) were performed at 24 hours and 72 hours after HS. Physiological testing for enteric permeability and gut bacterial product translocation measurement (plasma endotoxin) were performed 72 hours after HS. In vitro, HT-29 cells were exposed to UA, and the expression of intercellular adhesion proteins (ZO-1, E-cadherin) was measured to evaluate the influence of UA on enteric permeability. Results The addition of uricase to resuscitation significantly reduced circulating and liver UA levels after HS. It also prevented HS-induced hepatolysis and liver apoptotic/inflammatory mediators at 24 hours and 72 hours. Hemorrhagic shock-induced enteric hyperpermeability and endotoxemia were prevented with uricase. Conclusions After resuscitated HS, UA is an important mediator in liver and enteric injury. Uric acid represents a therapeutic target to minimize organ damage in polytrauma patients sustaining HS.

Aim of the study Liver transplantation remains the only definitive treatment for children with acute liver failure proven to have irreversible liver injury. Many prognostic models have been used for outcome prediction in pediatric acute liver failure to select patients in a real need of liver transplantation, but unfortunately all have shown inconsistent reproducibility and prognostic accuracy. The aim of this study was to evaluate the pediatric chronic liver failure sequential organ failure assessment (pCLIF-SOFA) score as a predictor of pediatric acute liver failure outcome. Material and methods Clinical and laboratory data of 41 children with acute liver failure admitted to the National Liver Institute – Menoufia University were collected retrospectively and used for calculation of both pCLIF-SOFA and Pediatric End-Stage Liver Disease (PELD)/Model for End-Stage Liver Disease (MELD) scores on the day of admission, then statistical analysis was performed to identify the ability of these scores to predict the outcome. Results According to the outcome, children enrolled in this study were allocated to survived (n = 16) and died (n = 25) groups, which were age and sex matched. The non-survival group had significantly higher values of both pCLIF-SOFA score (11 [7-13]) and PELD/MELD score (36 [18-42]) than those of the survival group (8 [7-11], 27.5 [15-45]; p < 0.001, p = 0.004) respectively. Both pCLIF-SOFA and PELD/MELD scores at cut-off values > 8 and > 30 respectively on admission could predict death in children with acute liver failure (ALF) with high sensitivity, but with higher specificity, positive and negative predictive values for pCLIF-SOFA. Conclusions pCLIF-SOFA is a good predictor of death in pediatric acute liver failure.

Background We investigated the diagnostic and prognostic value of presepsin among patients with organ failure, including sepsis, in accordance with the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). Methods This prospective observational study included 420 patients divided into three groups: non-infectious organ failure (n = 142), sepsis (n = 141), and septic shock (n = 137). Optimal cut-off values of presepsin to discriminate between the three groups were evaluated using receiver operating characteristic curve analysis. We determined the optimal cut-off value of presepsin levels to predict mortality associated with sepsis and performed Kaplan–Meier survival curve analysis according to the cut-off value. Cox proportional hazards model was performed to determine the risk factors for 30-day mortality. Results Presepsin levels were significantly higher in sepsis than in non-infectious organ failure cases (p p = 0.002). The optimal cut-off value of the presepsin level to discriminate between sepsis and non-infectious organ failure was 582 pg/mL (p p p = 0.005) for patients with sepsis. Patients with higher presepsin levels (≥ 821 pg/mL) had significantly higher mortality rates than those with lower presepsin levels (p = 0.004). In the multivariate Cox proportional hazards model, presepsin could predict the 30-day mortality in sepsis cases (hazard ratio, 1.003; 95% confidence interval 1.001–1.005; p = 0.042). Conclusions Presepsin levels could effectively differentiate sepsis from non-infectious organ failure and could help clinicians identify patients with sepsis with poor prognosis. Presepsin was an independent risk factor for 30-day mortality among patients with sepsis and septic shock.

Introduction Ground-glass opacity is commonly seen on radiographic imaging tests of patients admitted for COVID-19. The main objective of this study is to determine if the presence of ground-glass opacity on chest X-rays carried out at the Emergency Department correlates with significantly higher mortality. A secondary objective is to clarify which characteristics are associated with those patients who presented ground-glass opacity. Methods Data were obtained from our 2020 hospital admission records. Consequently, this is a retrospective cohort study. Our cohort consists of 300 admissions from a group of elderly with a mean age of 81.6. There were 49.3% women (148/300) and 50.7% men (152/300). Results The presence of ground-glass opacity on chest X-rays is a risk factor for in-hospital mortality (RR = 1.6), heart failure (RR = 4.3), respiratory failure (RR = 1.5), acute kidney injury (RR = 1.3) and ICU admission (RR = 2.7). Conclusion Based on these results, the variable 'finding ground-glass opacity on chest X-rays carried out at the Emergency Department' should be assessed for inclusion in the different calculators that estimate the prognosis/mortality rate of patients admitted for COVID-19.

Background Timely initiation of advance care planning (ACP) in general practice is challenging, especially in patients with non-malignant conditions. Our aim was to investigate how perceived optimal timing of ACP initiation and its triggers relate to recorded actual timing in patients with cancer, organ failure, or multimorbidity. Methods In this mixed-methods study in the Netherlands, we analysed health records selected from a database with primary care routine data and with a recorded ACP conversation in the last two years before death of patients who died with cancer, organ failure, or multimorbidity. We compared actual timing of ACP initiation as recorded in health records of 51 patients with the perceived optimal timing as determined by 83 independent GPs who studied these records. Further, to identify and compare triggers for GPs to initiate ACP, we analysed the health record documentation around the moments of the recorded actual timing of ACP initiation and the perceived optimal timing of ACP initiation. We combined quantitative descriptive statistics with qualitative content analysis. Results The recorded actual timing of ACP initiation was significantly closer to death than the perceived optimal timing in patients with cancer (median 88 vs. 111 days before death (p = 0.049)), organ failure (227 vs. 306 days before death (p = 0.02)) and multimorbidity (113 vs. 338 days before death (p = 0.006)). Triggers for recorded actual versus perceived optimal timing were similar across the three groups, the most frequent being ‘expressions of patients’ reflections or wishes’ (14% and 14% respectively) and ‘appropriate setting’ (10% and 13% respectively). Conclusion ACP in general practice was initiated and recorded later in the illness trajectory than considered optimal, especially in patients with organ failure or multimorbidity. As triggers were similar for recorded actual and perceived optimal timing, we recommend that GPs initiate ACP shortly after a trigger is noticed the first time, rather than wait for additional or more evident triggers when the illness is in an advanced stage.

(1) Background: As the introduction of “positive” diagnostic criteria for metabolic dysfunction-associated fatty liver disease (MAFLD) does not exclude alcohol consumption, some patients originally diagnosed with alcoholic fatty liver disease (AFLD) may be diagnosed with dual- etiology fatty liver disease (AFLD&MAFLD), which requires us to urgently explore the impact of the changes in this classification of AFLD on clinical manifestations. (2) Methods: Utilizing data from the Nationwide Inpatient Sample database 2016–2018, a total of 9269 participants with AFLD were selected. With the definition of MAFLD, these patients were further categorized into two groups: single AFLD and AFLD&MAFLD. The primary outcome was the risk of comorbidities and organ failures. The secondary outcomes were the length of stay, total charges, and in-hospital all-cause mortality. (3) Results: The patients with AFLD&MAFLD were older, were predominantly male, and had more comorbidities and organ failures compared to the patients with AFLD. These comorbidities included coronary atherosclerosis, myocardial infarction, cerebrovascular disease, arrhythmia, asthma, chronic obstructive pulmonary disease, and chronic kidney disease (all p values < 0.05). The patients with AFLD&MAFLD were more likely to develop acute and chronic heart and/or kidney failures than those with single AFLD (all p < 0.05). The length of stay and total charges of the patients in the AFLD&MAFLD group were greater than the single AFLD group (p = 0.029 and p < 0.001, respectively). No significant difference in all-cause mortality was observed. (4) Conclusions: The patients with AFLD&MAFLD have more comorbidities and organ failures, longer hospital stays, and higher hospitalization costs than the patients with single AFLD. Hence, patients with dual-etiology fatty liver disease deserve more attention from clinical staff during treatment.

This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). Sepsis is a dysregulated host response to infection that causes potentially life-threatening organ dysfunction. We investigated the serum metabolomic profile at hospital admission for patients with bacterial sepsis. The study included 60 patients; 35 patients fulfilled the most recent 2016 Sepsis-3 criteria whereas the remaining 25 patients only fulfilled the previous Sepsis-2 criteria and could therefore be classified as having systemic inflammatory response syndrome (SIRS). A total of 1011 identified metabolites were detected in our serum samples. Ninety-seven metabolites differed significantly when comparing Sepsis-3 and Sepsis-2/SIRS patients; 40 of these metabolites constituted a heterogeneous group of amino acid metabolites/peptides. When comparing patients with and without bacteremia, we identified 51 metabolites that differed significantly, including 16 lipid metabolites and 11 amino acid metabolites. Furthermore, 42 metabolites showed a highly significant association with the maximal total Sequential Organ Failure Assessment (SOFA )score during the course of the disease (i.e., Pearson’s correlation test, p-value < 0.005, and correlation factor > 0.6); these top-ranked metabolites included 23 amino acid metabolites and a subset of pregnenolone/progestin metabolites. Unsupervised hierarchical clustering analyses based on all 42 top-ranked SOFA correlated metabolites or the subset of 23 top-ranked amino acid metabolites showed that most Sepsis-3 patients differed from Sepsis-2/SIRS patients in their systemic metabolic profile at the time of hospital admission. However, a minority of Sepsis-3 patients showed similarities with the Sepsis-2/SIRS metabolic profile even though several of them showed a high total SOFA score. To conclude, Sepsis-3 patients are heterogeneous with regard to their metabolic profile at the time of hospitalization.

Biomedicines : open access journal 11(2), 313 (2023). doi:10.3390/biomedicines11020313 special issue: "Special Issue "10th Anniversary of Biomedicines—Recent Advances on Adipokines" / Special Issue Editor: Dr. Christa Buechler, Guest Editor", Published by MDPI, Basel

Sepsis-induced metabolic dysfunction is associated with mortality, but the signatures that differentiate variable clinical outcomes among survivors are unknown. Our aim was to determine the relationship between host metabolism and chronic critical illness (CCI) in patients with septic shock. We analyzed metabolomics data from mechanically ventilated patients with vasopressor-dependent septic shock from the placebo arm of a recently completed clinical trial. Baseline serum metabolites were measured by liquid chromatography-mass spectrometry and 1H-nuclear magnetic resonance. We conducted a time-to-event analysis censored at 28 days. Specifically, we determined the relationship between metabolites and time to extubation and freedom from vasopressors using a competing risk survival model, with death as a competing risk. We also compared metabolite concentrations between CCI patients, defined as intensive care unit level of care ≥ 14 days, and those with rapid recovery. Elevations in two acylcarnitines and four amino acids were related to the freedom from organ support (subdistributional hazard ratio < 1 and false discovery rate < 0.05). Proline, glycine, glutamine, and methionine were also elevated in patients who developed CCI. Our work highlights the need for further testing of metabolomics to identify patients at risk of CCI and to elucidate potential mechanisms that contribute to its etiology.

Mechanisms involved in thyroid dysfunction in critically ill coronavirus disease 2019 (COVID-19) patients are not clear. Our objective was to correlate the thyroid response with the pro- and anti-inflammatory cytokines profile in critically ill COVID-19 patients. This was a prospective single-center study. We studied the relationship between continuous variables by using Pearson correlation and simple linear regression. Multiple logistic regression analysis was performed to analyze the factors independently associated with mortality. Seventy-eight patients were included in the study at intensive care unit (ICU) admission and 72 had a measurement of the thyroid and inflammatory profile at day 5. No significant correlations were found between thyroid stimulating hormone (TSH), free triiodothyronine (fT3) and free thyroxine (fT4) and inflammatory cytokines at ICU admission. At day 5, fT4, was inversely correlated with IL-10 (p = 0.035). IL-10 was associated with maximum lactate (p < 0.001) and SOFA score values (p = 0.012). The multiple logistic regression analysis showed that there was a significant relationship between IL-10 (day 5) and in-hospital mortality after adjusting by age and severity of illness. In conclusion, we found that the thyroid hormone profile and inflammatory cytokines had a weak correlation at ICU admission. Associations of interest between fT4 and IL-10 were found at day 5. IL-10 at day 5 was found to be correlated with low fT4 and markers of organ failure and death.

Diagnostics : open access journal 12(12), 3010 (2022). doi:10.3390/diagnostics12123010 special issue: "Special Issue "Biomarkers of Sepsis" / Special Issue Editor: Prof. Dr. Marcello Ciaccio, Guest Editor", Published by MDPI, Basel

COVID-19 mortality risk stratification tools could improve care, inform accurate and rapid triage decisions, and guide family discussions regarding goals of care. A minority of COVID-19 prognostic tools have been tested in external cohorts. Our objective was to compare machine learning algorithms and develop a tool for predicting subsequent clinical outcomes in COVID-19. We conducted a retrospective cohort study that included hospitalized patients with COVID-19 from March 2020 to March 2021. Seven Hundred Twelve consecutive patients from University of Washington and 345 patients from Tongji Hospital in China were included. We applied three different machine learning algorithms to clinical and laboratory data collected within the initial 24 h of hospital admission to determine the risk of in-hospital mortality, transfer to the intensive care unit, shock requiring vasopressors, and receipt of renal replacement therapy. Mortality risk models were derived, internally validated in UW and externally validated in Tongji Hospital. The risk models for ICU transfer, shock and RRT were derived and internally validated in the UW dataset but were unable to be externally validated due to a lack of data on these outcomes. Among the UW dataset, 122 patients died (17%) during hospitalization and the mean days to hospital mortality was 15.7 +/− 21.5 (mean +/− SD). Elastic net logistic regression resulted in a C-statistic for in-hospital mortality of 0.72 (95% CI, 0.64 to 0.81) in the internal validation and 0.85 (95% CI, 0.81 to 0.89) in the external validation set. Age, platelet count, and white blood cell count were the most important predictors of mortality. In the sub-group of patients > 50 years of age, the mortality prediction model continued to perform with a C-statistic of 0.82 (95% CI:0.76,0.87). Prediction models also performed well for shock and RRT in the UW dataset but functioned with lower accuracy for ICU transfer. We trained, internally and externally validated a prediction model using data collected within 24 h of hospital admission to predict in-hospital mortality on average two weeks prior to death. We also developed models to predict RRT and shock with high accuracy. These models could be used to improve triage decisions, resource allocation, and support clinical trial enrichment.

Background SARS-CoV-2 can cause acute pancreatitis (AP) and SARS-CoV-2 superinfection can occur in patients with AP during prolonged hospitalisation. Our objective was to characterize SARS-CoV-2 related AP and study the impact of SARS-CoV-2 superinfection on outcomes in AP. Methods In this multicentre prospective study, all patients with AP and SARS-CoV-2 infection between August 2020 and February 2021 were divided into two groups: SARS-CoV-2-related AP and superadded SARS-CoV-2 infection in patients with AP. The two groups were compared with each other and the whole cohort was compared with a non-COVID AP cohort. Results A total of 85 patients with SARS-CoV-2 and AP (SARS-CoV-2-related AP; n = 18 and AP with SARS-CoV-2 superadded infection; n = 67) were included during the study period. They had a higher mortality [28 (32.9%) vs. 44 (19.1%), aOR 2.8 (95% CI, 1.5–5.3)] than 230 propensity matched non-COVID AP patients. Mortality in SARS-CoV-2 and AP patients was due to critical COVID. SARS-CoV-2-related- AP (n = 18) had a higher but statistically insignificant mortality than SARS-CoV-2 superinfection in AP [8/18 (44.4%) vs 20/67 (29.8%), p = 0.24]. On multivariable analysis, infection with SARS-CoV-2 (aHR 2.3; 95% CI, 1.43.7) was a predictor of in-hospital mortality in addition to organ failure (OF) in patients with AP. Conclusion Patients with AP and SARS-CoV-2 infection had a higher mortality than matched non-COVID AP patients which was largely attributable to the severity of COVID-19. SARS-CoV-2 related AP had higher OF and in-hospital mortality., Graphical abstract Image 1

BackgroundReduced cholesterol levels are associated with increased organ failure and mortality in sepsis. Cholesterol levels may vary by infection type (gram negative vs positive), possibly reflecting differences in cholesterol-mediated bacterial clearance.MethodsThis was a secondary analysis of a combined data set of 2 prospective cohort studies of adult patients meeting Sepsis-3 criteria. Infection types were classified as gram negative, gram positive, or culture negative. We investigated quantitative (levels) and qualitative (dysfunctional high-density lipoprotein [HDL]) cholesterol differences. We used multivariable logistic regression to control for disease severity.ResultsAmong 171 patients with sepsis, infections were gram negative in 67, gram positive in 46, and culture negative in 47. Both gram-negative and gram-positive infections occurred in 11 patients. Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and HDL cholesterol (HDL-C) levels were lower for culture-positive sepsis at enrollment (TC, P < .001; LDL-C, P < .001; HDL-C, P = .011) and persisted after controlling for disease severity. Similarly, cholesterol levels were lower among culture-positive patients at 48 hours (TC, P = .012; LDL-C, P = .029; HDL-C, P = .002). Triglyceride (TG) levels were lower at enrollment (P =.033) but not at 48 hours (P = .212). There were no differences in dysfunctional HDL. Among bacteremic patients, cholesterol levels were lower at enrollment (TC, P = .010; LDL-C, P = .010; HDL-C, P ≤ .001; TG, P = .005) and at 48 hours (LDL-C, P = .027; HDL-C, P < .001; TG, P = .020), except for 48 hour TC (P = .051). In the bacteremia subgroup, enrollment TC and LDL-C were lower for gram-negative versus gram-positive infections (TC, P = .039; LDL-C, P = .023).ConclusionCholesterol levels are significantly lower among patients with culture-positive sepsis and bacteremia.

Immunoglobulin light chain (AL) amyloidosis is an incurable plasma cell disorder characterized by deposition of fibrils of misfolded immunoglobulin free light chains (FLC) in target organs, leading to failure. Cardiac involvement is common in AL amyloidosis and represents the single most adverse prognostic feature. A high index of clinical suspicion with rapid tissue diagnosis and commencement of combinatorial, highly effective cytoreductive therapy is crucial to arrest the process of amyloid deposition and preserve organ function. The clinical use of molecularly targeted drugs, such as proteasome inhibitors and immunomodulatory agents, monoclonal antibodies such as daratumumab, and risk-adjusted autologous stem cell transplant in eligible patients, has radically changed the natural history of AL amyloidosis. Here, we review the state-of-the-art treatment landscape in AL amyloidosis with an eye toward future therapeutic venues to impact the outcome of this devastating illness., Central Illustration, Highlights • Cardiac involvement in AL amyloidosis is common and represents the single most adverse prognostic factor. • Chemo-immunotherapies and autologous stem cell transplant lead to prolonged remission and survival in low-stage patients. • Early diagnosis is critical in AL amyloidosis to avoid irreversible organ damage. • Rapid and deep FLC reduction is necessary to ensure long-term survival and functional recovery of affected organs.

Introduction and objectives Graft failure and postoperative mortality are the most serious complications after liver transplantation. The aim of this study is to establish a prognostic scoring system to predict graft and patient survival based on serum transaminases levels that are routinely used during the postoperative period in human cadaveric liver transplants. Patients and methods Postoperative graft failure and patient mortality after liver transplant were analyzed from a consecutive series of 1299 patients undergoing cadaveric liver transplantation. This was correlated with serum liver function tests and the rate of reduction in transaminase levels over the first postoperative week. A cut-off transaminase level correlating with graft and patient survival was calculated and incorporated into a scoring system. Results Aspartate-aminotransferase (AST) on postoperative day one showed significant correlation with early graft failure for levels above 723 U/dl and early postoperative mortality for levels above 750 U/dl. AST reduction rate (day 1 to 3) greater than 1.8 correlated with reduced graft failure and greater than 2 with mortality. Alanine-aminotransferase (ALT) reduction in the first 48 h post transplantation also correlated with outcomes. Conclusion A scoring system with these three variables allowed us to classify our patients into three groups of risk for early graft failure and mortality.

Summary: In the era of the “sickest first” policy, patients with very high model for end-stage liver disease (MELD) scores have been increasingly admitted to the intensive care unit with the expectation that they will receive a liver transplant (LT) in the absence of improvement on supportive therapies. Such patients are often admitted in a context of acute-on-chronic liver failure with extrahepatic failures. Sequential assessment of scores or classification based on organ failures within the first days after admission help to stratify the risk of mortality in this population. Although the prognosis of severely ill cirrhotic patients has recently improved, transplant-free mortality remains high. LT is still the only curative treatment in this population. Yet, the increased relative scarcity of graft resource must be considered alongside the increased risk of losing a graft in the initial postoperative period when performing LT in “too sick to transplant” patients. Variables associated with poor immediate post-LT outcomes have been identified in large studies. Despite this, the performance of scores based on these variables is still insufficient. Consideration of a patient’s comorbidities and frailty is an appealing predictive approach in this population that has proven of great value in many other diseases. So far, local expertise remains the last safeguard to LT. Using this expertise, data are accumulating on favourable post-LT outcomes in very high MELD populations, particularly when LT is performed in a situation of stabilization/improvement of organ failures in selected candidates. The absence of “definitive” contraindications and the control of “dynamic” contraindications allow a “transplantation window” to be defined. This window must be identified swiftly after admission given the poor short-term survival of patients with very high MELD scores. In the absence of any prospect of LT, withdrawal of care could be discussed to ensure respect of patient life, dignity and wishes. Keywords: liver transplantation, cirrhosis, acute-on-chronic liver failure, organ failure, acute decompensation, transplantation window

Goals: We aimed to investigate significant factors influencing the long-term prognosis of patients who survived acute-on-chronic liver failure (ACLF). Background: The mortality of ACLF is predominantly affected by the organ failure severity. However, long-term outcomes of patients who survive ACLF are not known. Study: A cohort of 1084 cirrhotic patients who survived for more than 3 months following acute deterioration of liver function was prospectively followed. ACLF was defined by the European Association for the Study of the Liver Chronic Liver Failure Consortium definition. Results: The mean follow-up duration was 19.4±9.9 months. In the subgroup of patients without previous acute decompensation (AD), ACLF occurrence did not affect long-term outcomes. However, in patients with previous AD, ACLF negatively affected long-term transplant-free survival even after overcoming ACLF (hazard ratio, 2.00, P=0.012). Previous AD was the significant predictive factor of long-term mortality and was independent of the Model for End-stage Liver Disease score in these ACLF-surviving patients. Organ failure severity did not affect transplant-free survival in patients who survived an ACLF episode. Conclusions: A prior history of AD is the most important factor affecting long-term outcomes following an ACLF episode regardless of Model for End-stage Liver Disease score. Prevention of a first AD episode may improve the long-term transplant-free survival of liver cirrhosis patients.

Background/Aims The relationship between nonpulmonary organ failure and the development of acute respiratory distress syndrome (ARDS) in patients with sepsis has not been well studied. Methods We retrospectively reviewed the medical records of patients with septic bacteremia admitted to the medical intensive care unit (ICU) of a tertiary academic hospital between January 2013 and December 2016. Results The study enrolled 125 patients of median age 73.0 years. Urinary (n = 47), hepatobiliary (n = 30), and pulmonary infections (n = 28) were the most common causes of sepsis; the incidence of ARDS was 17.6%. The total number of nonpulmonary organ failures at the time of ICU admission was higher in patients with ARDS than in those without (p = 0.011), and the cardiovascular, central nervous system (CNS), and coagulation scores were significantly higher in ARDS patients. On multivariate analysis, apart from pneumonia sepsis, the CNS (odds ratio [OR], 1.917; 95% confidence interval [CI], 1.097 to 3.348) and coagulation scores (OR, 2.669; 95% CI, 1.438 to 4.954) were significantly associated with ARDS development. The 28-day and in-hospital mortality rates were higher in those with ARDS than in those without (63.6 vs. 8.7%, p < 0.001; 72.7% vs. 11.7%, p < 0.001), and ARDS development was found to be an independent risk factor for 28-day mortality. Conclusions Apart from pneumonia, CNS dysfunction and coagulopathy were significantly associated with ARDS development, which was an independent risk factor for 28-day mortality.

Background and Aim Acute kidney injury (AKI) in severe acute pancreatitis (SAP) has a high mortality rate. Traditionally used serum creatinine is an insensitive biomarker for the early detection of AKI. We aimed to study the role of plasma and urinary neutrophil gelatinase‐associated lipocalin (NGAL) in predicting AKI and a severe course in patients with acute pancreatitis (AP). Methods Consecutive patients of AP who presented within 72 h of symptom onset and age‐ and gender‐matched healthy controls were included. Urinary and serum NGAL levels [enzyme‐linked immunosorbent assay (ELISA)] were evaluated within 24 h of and 72 h after admission and once in controls. Urine and serum NGAL levels were correlated with development of AKI, severity, and outcomes of AP. Results Fifty patients with AP and 30 controls were enrolled. The mean serum and urine NGAL levels in patients on day 1 were significantly higher than the serum and urine NGAL levels in controls (P

Liver transplantation for critically ill cirrhotic patients with acute deterioration of liver function associated with extrahepatic organ failures is controversial. While transplantation has been shown to be beneficial on an individual basis, the potentially poorer post-transplant outcome of these patients taken as a group can be held as an argument against allocating livers to them. Although this issue concerns only a minority of liver transplants, it calls into question the very heart of the allocation paradigms in place. Indeed, most allocation algorithms have been centered on prioritizing the sickest patients by using the model for end-stage liver disease score. This has led to allocating increasing numbers of livers to increasingly critically ill patients without setting objective or consensual limits on how sick patients can be when they receive an organ. Today, finding robust criteria to deem certain cirrhotic patients too sick to be transplanted seems urgent in order to ensure the fairness of our organ allocation protocols. This review starts by fleshing out the argument that finding such criteria is essential. It examines five types of difficulties that have hindered the progress of recent literature on this issue and identifies various strategies that could be followed to move forward on this topic, taking into account the recent discussion on acute on chronic liver failure. We move on to review the literature along four axes that could guide clinicians in their decision-making process regarding transplantation of critically ill cirrhotic patients.

Objectives Clinical practice lacks biomarkers to predict the severity of acute pancreatitis (AP). We studied if intracellular signaling of circulating leukocytes could predict persistent organ dysfunction (OD) and secondary infections in AP. Methods A venous blood sample was taken from 174 patients with AP 72 hours or less from onset of symptoms and 31 healthy controls. Phosphorylation levels (p) of appropriately stimulated signal transducer and activator of transcription 1 (STAT1), STAT6, nuclear factor-kappa B (NF-kappa B), Akt, and nonstimulated STAT3 in monocytes, neutrophils, and lymphocytes was measured using phosphospecific flow cytometry. Results The patients showed higher pSTAT3 and lower pSTAT1, pSTAT6, pNF-kappa B, and pAkt than healthy controls. pSTAT3 in all leukocyte subtypes studied increased, and pSTAT1 in monocytes and T cells decreased in an AP severity-wise manner. In patients without OD at sampling, high pSTAT3 in monocytes and T lymphocytes were associated with development of persistent OD. In patients with OD, low interleukin-4-stimulated pSTAT6 in monocytes and neutrophils and Escherichia coli-stimulated pNF-kappa B in neutrophils predicted OD persistence. High pSTAT3 in monocytes, CD8(+) T cells, and neutrophils; low pSTAT1 in monocytes and T cells; and low pNF-kappa B in lymphocytes predicted secondary infections. Conclusions Leukocyte STAT3, STAT1, STAT6, and NF-kappa Beta phosphorylations are potential predictors of AP severity.

Background Selection of patients for open abdomen (OA) treatment in severe acute pancreatitis (SAP) is challenging. Treatment related morbidity and risk of adverse events are high; however, refractory abdominal compartment syndrome (ACS) is potentially lethal. Factors influencing the decision to initiate OA treatment are clinically important. We aimed to study these factors to help understand what influences the selection of patients for OA treatment in SAP. Methods A single center study of patients with SAP that underwent OA treatment compared with conservatively treated matched controls. Results Within study period, 47 patients treated with OA were matched in a 1:1 fashion with conservatively treated control patients. Urinary output under 20 ml/h (OR 5.0 95% CI 1.8-13.7) and ACS (OR 4.6 95% CI 1.4-15.2) independently associated with OA treatment. Patients with OA treatment had significantly more often visceral ischemia (34%) than controls (6%), P = 0.002. Mortality among patients with visceral ischemia was 63%. Clinically meaningful parameters predicting developing ischemia were not found. OA treatment associated with higher overall 90-day mortality rate (43% vs 17%, P = 0.012) and increased need for necrosectomy (55% vs 21%, P = 0.001). Delayed primary fascial closure was achieved in 33 (97%) patients that survived past OA treatment. Conclusion Decreased urine output and ACS were independently associated with the choice of OA treatment in patients with SAP. Underlying visceral ischemia was strikingly common in patients undergoing OA treatment, but predicting ischemia in these patients seems difficult. Supplementary Information The online version contains supplementary material available at 10.1186/s13017-021-00376-x.

Sepsis leads to systemic hypotension, disturbed perfusion, inflammation and tissue toxicity in vital organs. Neuropeptide W (NPW) has modulatory effects in the control of blood pressure and inflammatory processes, implicating a potential beneficial effect against sepsis-induced oxidative damage. Under anesthesia, male Sprague Dawley rats underwent cecal ligation and puncture. Immediately after surgery, either saline or TNF-alpha inhibitor (etanercept; 1 mg/kg) antibiotic (ceftriaxon; 100 mg/kg) combination or NPW (0.1, 1 or 3 µg/kg) was given subcutaneously, and injections were repeated at 12th and 24th h. The sham-operated control group was treated with saline at the same time points. All rats were euthanized at the 25th h of surgery. Sepsis resulted in oxidative damage of the brain, heart, lung, liver and kidney. Elevations in blood urea nitrogen and alkaline phosphatase, showing renal and hepatic dysfunction, were not evident when septic rats were treated with NPW. NPW reduced serum levels of C-reactive protein, corticosterone and interleukin-6, while histopathologically verified tissue damage in all the studied tissues was ameliorated. NPW treatment suppressed lipid peroxidation in the heart, lung and brain, and the depleted antioxidant GSH levels of the brain and heart were replenished by NPW. Moreover, sepsis-related neutrophil recruitment to liver and lung was also suppressed by NPW. Although survival rate of the rats was not significantly prolonged by NPW, most of these improvements in systemic and local inflammatory events were comparable with those reached by the etanercept and antibiotic combination, suggesting the therapeutic impact of NPW during the acute period of sepsis.

Purpose: This study was aimed to compare the quick Sequential Organ Failure Assessment (qSOFA), Systemic Inflammatory Response Syndrome (SIRS), and National Early Warning Score (NEWS) scoring systems for diagnosing sepsis and predicting mortality and morbidity. Patients and methods: A prospective study was designed. qSOFA, SIRS, and NEWS scores were calculated at the admission. The diagnosis of sepsis was made with SOFA scoring initially. The morbidity and mortality of the patients were identified during follow-up. Also, the sensitivity, specificity, negative predictive value, and positive predictive value of three scoring systems were calculated. The scoring systems were compared with ROC analysis. Results: A total of 463 patients were evaluated. There were 287 (62.0%) patients diagnosed with sepsis, and septic shock occurred in 64 (13.8%) of patients. Seven-day mortality rate was 8.4% (n = 39), 30-day mortality rate was 18.1% (n = 84). The sensitivity for qSOFA, SIRS, and NEWS for diagnosis of sepsis was 23%, 77%, 58%, and specificity was 99%, 35%, 81% respectively. The sensitivity of the qSOFA, SIRS and NEWS scoring systems for mortality was 39%, 82%, 77% and specificity 91%, 29%, and 64%, respectively. AUROC values for mortality detected as NEWS = 0.772, qSOFA = 0.758, SIRS = 0.542. According to the ROC analysis, the SIRS system was significantly less useful than the qSOFA and NEWS system in the diagnosis of sepsis and mortality (p < 0.0001). Conclusion: NEWS and qSOFA scoring systems have similar prognosis in both diagnosing sepsis and predicting mortality and both are superior to SIRS. (c) 2021 Elsevier Inc. All rights reserved.

Objective Our aim was to assess the accuracy of angiopoietin-2 (Ang-2) as a prognostic marker for acute pancreatitis (AP) with organ failure (OF). Methods We undertook a systematic search of the PubMed, Cochrane Library, Embase, Chinese Journals Full-text, Wanfang, China Biology Medicine disc, and Weipu databases to identify eligible cohort studies on the predictive value of Ang-2 for AP with OF. The main outcome measures were sensitivity and specificity. The effects were pooled using a bivariate mixed-effects model. Results Six articles with seven case-control studies (n = 650) were included. Pooled sensitivity, specificity, and positive and negative likelihood ratios with 95% confidence intervals (CI) for AP with OF were 0.93 (95%CI: 0.75–0.99), 0.85 (95%CI: 0.75–0.92), 6.40 (95%CI: 3.36–12.19), and 0.08 (95%CI: 0.02–0.36), respectively. The area under the summary receiver operating characteristic curve was 0.95 (95%CI: 0.92–0.96), and the diagnostic odds ratio was 83.18 (95%CI: 11.50–623.17). Subgroup analysis showed that admission time of AP onset (< or ≥24 hours) was a source of overall heterogeneity. Sensitivity analysis supported this finding. Conclusion Ang-2 had high diagnostic accuracy for AP with OF; the best prediction of Ang-2 may be 24 to 72 hours after onset of AP.

Background In traumatic bleeding, transfusion practice has shifted toward higher doses of platelets and plasma transfusion. The aim of this systematic review was to investigate whether a higher platelet‐to‐red blood cell (RBC) transfusion ratio improves mortality without worsening organ failure when compared with a lower ratio of platelet‐to‐RBC. Methods Pubmed, Medline, and Embase were screened for randomized controlled trials (RCTs) in bleeding trauma patients (age ≥16 years) receiving platelet transfusion between 1946 until October 2020. High platelet:RBC ratio was defined as being the highest ratio within an included study. Primary outcome was 24 hour mortality. Secondary outcomes were 30‐day mortality, thromboembolic events, organ failure, and correction of coagulopathy. Results In total five RCTs (n = 1757 patients) were included. A high platelet:RBC compared with a low platelet:RBC ratio significantly improved 24 hour mortality (odds ratio [OR] 0.69 [0.53–0.89]) and 30‐ day mortality (OR 0.78 [0.63–0.98]). There was no difference between platelet:RBC ratio groups in thromboembolic events and organ failure. Correction of coagulopathy was reported in five studies, in which platelet dose had no impact on trauma‐induced coagulopathy. Conclusions In traumatic bleeding, a high platelet:RBC improves mortality as compared to low platelet:RBC ratio. The high platelet:RBC ratio does not influence thromboembolic or organ failure event rates.

Objective Coronavirus disease 2019 [COVID-19] infection in patients with chronic liver disease [CLD] may precipitate acute-on-chronic liver failure [ACLF]. In a large multi-center cohort of COVID-19-infected patients, we aim to analyze (1) the outcomes of patients with underlying CLD [with and without cirrhosis] and (2) the development and impact of ACLF on in-hospital mortality. Design We identified 192 adults with CLD from among 10,859 patients with confirmed COVID-19 infection (admitted to any of 12 hospitals in a New York health care system between March 1, 2020 and April 27, 2020). ACLF was defined using the EASL-CLIF Consortium definition. Patient follow-up was through April 30, 2020, or until the date of discharge, transfer, or death. Results Of the 84 patients with cirrhosis, 32 [38%] developed ACLF, with respiratory failure [39%] and renal failure [26%] being the most common. Hispanic/Latino ethnicity was particularly at higher risk of in-hospital mortality [adjusted HR 4.92, 95% 1.27–19.09, p

Introduction: Acute pancreatitis is associated with various complications leading to morbidity and mortality. In inflammation it is common that number and proportion of inflammatory cells vary. In acute pancreatitis it has been observed in various studies that Neutrophil to Lymphocyte Ratio (NLR) can predict prognosis of the disease. Hence, a prospective study was conducted with an aim to determine the clinical significance of NLR in predicting adverse outcomes in acute pancreatitis. Aim: To compare the NLR at 0 hour, 24 hours and 48 hours between mild and Severe Acute Pancreatitis (SAP) and set an optimal NLR in predicting severity of acute pancreatitis and development of organ failure in acute pancreatitis. Materials and Methods: A prospective observational study was conducted between September 2017 to August 2019 in a tertiary care teaching institute at Kasturba Medical College and Hospital, Manipal, Karnataka, India. After obtaining Institutional Ethical Committee (IEC) clearance and fulfilling the inclusion and exclusion criteria, 180 patients with age 18 years and above with acute pancreatitis were evaluated. Patient’s clinical characteristics, imaging features, biochemical, pathological, microbiological and laboratory parameters were noted. Statistical analysis was done with Statistical Package for the Social Sciences (SPSS) software version 20.0. Unpaired student’s t-test was used to compare the mean differences of the two groups. A p-value 10.80 should be considered as having severe pancreatitis and managed aggressively to treat any potential complications.

Aim To develop a procedure‐based organ failure assessment model for intensive care unit (ICU) patients and to examine the ability of this model to predict in‐hospital mortality, with reference to the Sequential Organ Failure Assessment (SOFA) score. Methods Using the Japanese nationwide Diagnosis Procedure Combination database, we identified patients aged ≥15 years who were admitted to the ICUs April 2018–March 2019. Since April 2018, Japanese health care providers have been required to input ICU patients' SOFA scores into this database. We extracted data on the following procedures on ICU admission: oxygen supplementation, invasive mechanical ventilation, blood transfusions, catecholamines, chest compression, extracorporeal membrane oxygenation, and renal replacement therapy. A procedure‐based organ failure assessment model (Model 1) for in‐hospital mortality was developed using therapeutic procedures for organ failure on the day of ICU admission in the derivation cohort. We also constructed a model using the SOFA score (Model 2). Discriminatory ability was assessed using area under the receiver operating characteristic curve (AUROC) in the validation cohort, and the discriminatory abilities of the models were compared. Results In total, 69,019 patients were included. Overall in‐hospital mortality was 7.2%. The AUROCs for Model 1 (0.810) and Model 2 (0.817) in the validation cohort did not show a statistically significant difference (P = 0.20). Conclusion The models established using procedure‐based organ failure assessment showed no statistically significant differences from those using the SOFA score, suggesting that procedure records in administrative databases can be used for risk adjustment in clinical studies on ICU mortality., Area under the receiver operating characteristic curve for discriminatory capacity for in‐hospital mortality in Models 1 and 2 in the derivation cohort. Model 1: procedure‐based organ failure; Model 2: Sequential Organ Failure Assessment (SOFA) score on the day of intensive care unit admission.

Objectives Cholesterol may be protective in sepsis. Patients with early sepsis may have critically low cholesterol levels that are associated with poor outcomes. The study objective was to test the safety of a fish oil–containing lipid injectable emulsion for stabilizing early cholesterol levels in sepsis. Methods Phase I Bayesian optimal interval design trial of adult patients with septic shock (Sequential Organ Failure Assessment score ≥4 or vasopressor dependence). Using sequential dose escalation, participants received 2 doses of 1.0 to 1.6 g/kg of lipid emulsion (Smoflipid 20% lipid emulsion) within 48 hours of enrollment. Cholesterol levels, function, and organ failure were assessed serially during the first 7 days of hospital admission. Measurements and Main Results A total of 10 patients with septic shock were enrolled. One patient withdrew for social reasons. Another patient had an unrelated medical complication and received 1 drug dose. Of 9 patients, mean age was 58 years (SD 16), median Sequential Organ Failure Assessment was 8, and 28‐day mortality was 30%. No serious adverse events related to lipid infusion occurred. The six occurrences of non‐serious adverse events possibly related to lipid infusion included hyperglycemia (1), elevated triglycerides (3), anemia (1), and vascular access redness/pain (1) for all doses. The mean change in total cholesterol levels from enrollment was −7 (SD 16.6) at 48 hours and 14 (SD 25.2) at 7 days. Conclusions Fish oil–containing lipid emulsion administration during early septic shock was safe. Further studies are needed to assess effects on cholesterol levels, function, and organ failure. Clinical Trial Registration NCT03405870.

Current sepsis biomarkers may be helpful in determining organ failure and evaluating patient clinical course; however, direct molecular biomarkers to predict subsequent organ failure have not yet been discovered. Exosomes, a small population of extracellular vesicles, play an important role in the inflammatory response, coagulation process and cardiac dysfunction in sepsis. Nonetheless, the association of plasma exosome with severity and mortality of sepsis is not well known. Therefore, the overall levels of plasma exosome in sepsis patients were assessed and whether exosome levels were associated with organ failure and mortality was evaluated in the present study. Plasma level of exosomes was measured by ELISA. Among 220 patients with sepsis, 145 (66%) patients were diagnosed with septic shock. A trend of increased exosome levels in control, sepsis and septic shock groups was observed (204 µg/mL vs 525 µg/mL vs 802 µg/mL, P

Background Recent studies have shown that bile acids (BAs) are closely related to metabolic and inflammatory diseases. Our study aimed to investigate whether circulating total bile acid (TBA) levels were associated with the severity of acute pancreatitis (AP). Methods We retrospectively collected data on patients diagnosed with AP in a tertiary center from 01 January 2014 to 31 December 2016. The highest TBA value during the first 1,2,3,5,7 days after admission was determined as D1, D2, D3, D5, D7 TBAmax. Patients were divided into the high TBA (HTBA) group and the normal TBA (NTBA) group according to whether the TBAmax was ≥10 μmol/L. The prognosis and complications, including death, organ failure (OF) and pancreatic necrosis, were compared between the two groups. Logistic regression analysis and receiving operating characteristic (ROC) curve were used to evaluate the relationship between circulating TBA and organ failure in AP patients. Results Through stratified analysis of each time period, we found that the incidence of OF in the HTBA group was significantly higher than that in the NTBA group, and the AP severity classification in the HTBA group was more serious than that in the NTBA group. In addition, according to the D7 TBAmax values, the pancreatic necrosis rate, percutaneous catheter drainage (PCD) rate and mortality in the HTBA group were higher than those in the NTBA group. Multivariate regression analysis showed that HTBA (odds ratio (OR), 4.894; P = 0.002) was an independent risk factor for AP complicated with OF, which was verified in the grouping based on D7 TBAmax. ROC analysis revealed that a circulating D7 TBAmax cutoff point of 6.450 umol/L had optimal predictive value for the development of OF in AP patients with an area under the curve of the ROC curve (AUCROC) of 0.777. Conclusions The increase of circulating TBA in early stage of AP is independently related to organ failure, which indicates the adverse prognosis of AP patients.

Background Multiple organ failure and early surgery are associated with high morbimortality after open necrosectomy. Data are mostly derived from historical cohorts with early necrosectomy bereft of step-up treatment algorithm implementation. Thus, mostly circumstantial evidence suggests a better clinical course following mini-invasive surgical and endoscopic necrosectomy. We studied the results of open necrosectomy in a contemporary cohort of patients with complicated pancreatic necrosis treated at a tertiary center. Methods A retrospective cohort study from a university teaching hospital. Results of 109 consecutive patients treated with open necrosectomy during a 12-year period are reported. Results The overall 90-day mortality rate was 22.9%. The 90-day mortality rate was 10.6% if necrosectomy could be delayed until 4 weeks from symptom onset and the necrosis had become walled off on preoperative imaging. The risk factors for 90-day mortality were age over 60 years (OR 19.4), pre-existing co-morbidities (OR 16.9), necrosectomy within 4 weeks (OR 6.5), multiple organ failure (OR 12.2), white blood cell count over 23 × 109 (OR 21.4), and deterioration or prolonged organ failure as an indication for necrosectomy (OR 10.4). None or one of these risk factors was present in 52 patients (47.7% of all patients), and these patients had no mortality. Conclusion Late open necrosectomy for walled-off necrosis has a low mortality risk. Open necrosectomy can be done without mortality in the absence of multiple risk factors for surgery.

Objectives Acute pancreatitis (AP) is a sudden onset, rapidly evolving inflammatory response with systemic inflammation and multiorgan failure (MOF) in a subset of patients. New highly accurate clinical decision support tools are needed to allow local doctors to provide expert care. Methods Ariel Dynamic Acute Pancreatitis Tracker (ADAPT) is a digital tool to guide physicians in ordering standard tests, evaluate test results and model progression using available data, propose emergent therapies. The accuracy of the severity score calculators was tested using 2 prospectively ascertained Acute Pancreatitis Patient Registry to Examine Novel Therapies in Clinical Experience cohorts (pilot University of Pittsburgh Medical Center, n = 163; international, n = 1544). Results The ADAPT and post hoc expert-calculated AP severity scores were 100% concordant in both pilot and international cohorts. High-risk criteria of all 4 severity scores at admission were associated with moderately-severe or severe AP and MOF (both P < 0.0001) and prediction of no MOF was 97.8% to 98.9%. The positive predictive value for MOF was 7.5% to 14.9%. Conclusions The ADAPT tool showed 100% accuracy with AP predictive metrics. Prospective evaluation of ADAPT features is needed to determine if additional data can accurately predict and mitigate severe AP and MOF.

Introduction Clinical guidelines state that disseminated intravascular coagulation (DIC) treatment should be based on three clinical phenotypes: the marked bleeding type (e.g. leukemia, trauma, obstetric diseases, or aortic diseases); organ failure type (sepsis or pancreatitis); and asymptomatic type of DIC (solid cancer). However, among the various underlying disorders of DIC, the clinical presentations of bleeding or organ failure have not to date been well documented. The present study aimed to evaluate whether underlying disorders of DIC would affect clinical outcome including death, organ failure, and bleeding. Methods Using the Japanese Diagnosis Procedure Combination inpatient database, we identified all adult patients diagnosed with DIC during hospitalization from July 1, 2010, to March 31, 2018. We collected data on patient characteristics and underlying disorders of DIC including sepsis, solid cancer, leukemia, trauma, obstetric diseases, aortic diseases, pancreatitis, and miscellaneous diseases. We counted major bleeding events and calculated an organ failure score for patients during hospitalization. Results We identified 337,132 patients with DIC. The major disorders underlying DIC were sepsis (42%) and solid cancer (31%). The average organ failure scores of patients with aortic diseases, sepsis, and trauma were 2.8, 2.2, and 2.2, respectively. The percentages with major bleeding events among patients with aortic diseases, trauma, obstetric diseases, and solid cancer were 24%, 15%, 10%, and 10%, respectively. Conclusions This study suggests that the clinical presentations of bleeding and organ failure are not associated with the three existing clinical phenotypes of DIC or with the underlying disorders of DIC. Therefore, clinical presentation alone may not be sufficient for identifying the clinical phenotypes of DIC. Further research is necessary to develop new strategies for identifying the phenotypes of DIC and improving treatment strategies for individual patients.

Background Noncardiac organ failure has been associated with worse outcomes among a cardiac intensive care unit (CICU) population. Hypothesis We hypothesized that early organ failure based on the sequential organ failure assessment (SOFA) score would be associated with mortality in CICU patients. Methods Adult CICU patients from 2007 to 2015 were reviewed. Organ failure was defined as any SOFA organ subscore ≥3 on the first CICU day. Organ failure was evaluated as a predictor of hospital mortality and postdischarge survival after adjustment for illness severity and comorbidities. Results We included 10 004 patients with a mean age of 67 ± 15 years (37% female). Admission diagnoses included acute coronary syndrome in 43%, heart failure in 46%, cardiac arrest in 12%, and cardiogenic shock in 11%. Organ failure was present in 31%, including multiorgan failure in 12%. Hospital mortality was higher in patients with organ failure (22% vs 3%, adjusted OR 3.0, 95% CI 2.5‐3.7, P

AIM: With increased survival after out-of-hospital cardiac arrest (OHCA), impact of the post-resuscitation course has become important. Among 30-day OHCA survivors, we investigated associations between organ support therapy in the Intensive Care Unit (ICU) and return to work.METHODS: This Danish nationwide cohort-study included 30-day-OHCA-survivors who were employed prior to arrest. We linked OHCA data to information on in-hospital care and return to work. For patients admitted to an ICU and based on renal replacement therapy (RRT), cardiovascular support and mechanical ventilation, we assessed the prognostic value of organ support therapies in multivariable Cox regression models.RESULTS: Of 1,087 30-day survivors, 212 (19.5%) were treated in an ICU with 0-1 types of organ support, 494 (45.4%) with support of two organs, 26 (2.4%) with support of three organs and 355 (32.7%) were not admitted to an ICU. Return to work increased with decreasing number of organs supported, from 53.8% (95% CI: 49.5-70.1%) in patients treated with both RRT, cardiovascular support and mechanical ventilation to 88.5% (95% CI: 85.1-91.8%) in non-ICU-patients. In 732 ICU-patients, ICU-patients with support of 3 organs had significantly lower adjusted hazard ratios (HR) of returning to work (0.50 [95% CI: 0.30-0.85] compared to ICU-patients with support of 0-1 organ. The corresponding HR was 0.48 [95% CI: 0.30-0.78] for RRT alone.CONCLUSIONS: In 30-day survivors of OHCA, number of organ support therapies and in particular need of RRT were associated with reduced rate of return to work, although more than half of these latter patients still returned to work.