Association Between Nonthyroidal Illness Syndrome and Disseminated Intravascular Coagulation in Sepsis.

Purpose: Both nonthyroidal illness syndrome (NTIS) and disseminated intravascular coagulation (DIC) are commonly occurred in sepsis. The objective of this study is to evaluate the association between NTIS and DIC, as well as their impacts on the mortality in adults with sepsis. Patients and methods: A total of 1219 septic patients in two Chinese academic centers from October 2012 and October 2022 were enrolled in analysis. We conduct logistic regression models to analyze the independent risk factors for DIC. Modified Poisson regression models are used to estimate the relative risk (RR) of NTIS on the 28 days mortality in septic patients with DIC. Correlation analysis between thyroid function parameters and coagulation parameters is performed with Pearson coefficient be reported. Results: DIC is diagnosed on 388 (31.8%) of all the 1219 enrolled septic patients within 72 hours after admission. In multivariate logistic regression models, NTIS (OR 3.19; CI 2.31-4.46; p<0.001) is a statistically significant independent risk factor for DIC after adjustment for potential confounders. Twenty-eight days mortality is significantly higher in DIC patients complicated with NTIS compared with the other DIC patients (23.2% vs 14.0%, p=0.024). This result is also robust in different modified Poisson regression models (Model 1: RR 1.46; CI 1.25-1.70; p<0.001; Model 2: RR 1.35; CI 1.14-1.60; p<0.001; Model 3: RR 1.18; CI 1.02-1.37; p=0.026). Correlation analysis reveals that the thyroid function parameters of FT3, FT4 and TSH only have weak correlations with coagulation parameters of platelet count, fibrinogen, FDP, D-dimers, PT, APTT and INR in sepsis. Conclusion: NTIS is an independent risk factor for DIC in adults with sepsis. DIC patients complicated with NTIS have significantly higher severity and higher rate of mortality.

Early encapsulation of peripancreatic fluid/necrosis collections on imaging (CECT) in acute pancreatitis: influential factors and clinical significance for prognosis.

BACKGROUND: To identify the factors influencing the early encapsulation of peripancreatic fluid/necrosis collections via contrast-enhanced computed tomography (CECT) and to determine the clinical significance of early encapsulation for determining the prognosis of acute pancreatitis (AP) patients. METHODS: AP patients who underwent CECT between 4 and 10 days after disease onset were enrolled in this study. Early encapsulation was defined as a continuous enhancing wall around peripancreatic fluid/necrosis collections on CECT. Univariate and multivariate logistic regression analyses were performed to assess the associations between the variables and early encapsulation. Clinical outcomes were compared between the non-encapsulation and early encapsulation groups with 1:1 propensity score matching. RESULTS: A total of 289 AP patients were enrolled. The intra-observer and inter-observer agreement were considered good (kappa statistics of 0.729 and 0.614, respectively) for identifying early encapsulation on CECT. The ratio of encapsulation increased with time, with a ratio of 12.5% on day 5 to 48.7% on day 9. Multivariate logistic regression analysis revealed that the longer time from onset to CECT examination (OR 1.55, 95% CI 1.23-1.97), high alanine aminotransferase level (OR 0.98, 95% CI 0.97-0.99), and high APACHE II score (OR 0.89, 95% CI 0.81-0.98) were found to be independent factors associated with delayed encapsulation. The incidence of persistent organ failure was significantly lower in the early encapsulation group after matching (22.4% vs 6.1%, p = 0.043). However, there was no difference in the incidence of infected pancreatic necrosis, surgical intervention, or in-hospital mortality. CONCLUSIONS: AP patients without early encapsulation of peripancreatic fluid/necrosis collections have a greater risk of persistent organ failure. In addition to longer time, the high APACHE II score and elevated alanine aminotransferase level are factors associated with delayed encapsulation.

Effect of high-dose intravenous vitamin C therapy on the prognosis in patients with moderately severe and severe acute pancreatitis: protocol of a prospective, randomized, double-blinded, placebo-controlled study.

Introduction: Acute pancreatitis is a common gastrointestinal disease. The mortality of patients affected by severe acute pancreatitis (SAP) remains high. It is unclear whether high-dose intravenous vitamin C (HDIVC) therapy could improve the prognosis of these patients. The current prospective, randomized, double-blinded, placebo-controlled study will explore the effect of high-dose intravenous vitamin C therapy on the prognosis in patients with moderately severe and severe acute pancreatitis. Methods and design: A total of 418 participants with moderately severe and severe acute pancreatitis who meet the eligible criteria will be randomly assigned in a 1:1 ratio to receive treatment with HDIVC (200 mg/kg/24 h) or placebo (saline) for a period of 7 days. The primary outcome is 28-day mortality in these patients. The secondary outcomes include organ functions and interventions, laboratory tests, healthcare, and 90-day mortality. Ethics and dissemination: This protocol was approved by the institutional ethics board of the Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China (Registration Number: 2019-90). The report of the study will be published in peer-reviewed journals and presented at conferences, both nationally and internationally. Clinical trial registration: Chinese Clinical Trial Registry (ChiCTR1900022022). Version 1.5.

Different subtypes of nonthyroidal illness syndrome on the prognosis of septic patients: a two-centered retrospective cohort study.

Background: Nonthyroidal illness syndrome (NTIS) is a common endocrine dysfunction predicting unfavorable outcomes in critical illness. The objective of the study is to evaluate the association between different NTIS subtypes with outcomes in septic patients. Methods: Septic patients in two Chinese academic centers from October 2012 and October 2022 are enrolled in analysis. Multivariable regressions are used to assess associations between NTIS and outcomes. Outcomes include in-hospital mortality, length of stay in hospital (LOS), non-invasive ventilation failure and weaning failure. Patients with NTIS are categorized into 4 types according to the different levels of FT4 and TSH. The association between different NTIS subtypes and mortality are further analyzed. Survival curve is plotted using the Kaplan-Meier method. Results: After screening, a total of 1226 septic patients with complete thyroid hormones result are eventually enrolled. Among them, 520 (42.4%) patients are diagnosed as NTIS. In multivariable regression analysis, NTIS is independently associated with increased 30-days mortality (OR=1.759, CI 1.009-3.104, p=0.047), but has no association with 60-days mortality (OR=1.524, CI 0.893-2.618, p=0.123), 90-days mortality (OR=1.411, CI 0.831-2.408, p=0.203), LOS, non-invasive ventilation failure or weaning failure. In NTIS subtypes, NTIS patients with low FT3 and TSH levels, regardless of the FT4 values, have significantly higher mortality than euthyroid patients (30-days mortality, OR= 6.488, CI 1.546-27.808, p=0.01; 60-days mortality, OR=3.973, CI 1.006-15.579, p=0.046; 90-days mortality, OR=3.849, CI 0.977-15.088, p=0.051). This result is consistent in patients with low FT3 and FT4 levels, regardless of the TSH values (30-days mortality, OR=3.349, CI 1.402-7.957, p=0.006; 60-days mortality, OR= 2.594, CI 1.122-5.930, p=0.024; 90-days mortality, OR=2.55, CI 1.110-5.804, p=0.025). There is no survival difference between NTIS patients with low FT3 only and euthyroid patients. Survival plot shows the worst prognosis is in NTIS patients with low FT3, FT4 and TSH level. Conclusions: NTIS is frequent in sepsis. A reduction of FT3 together with FT4 or TSH, but not FT3 only, is associated with an increased risk of mortality.

High-Dose Vitamin C Alleviates Pancreatic Necrosis by Inhibiting Platelet Activation Through the CXCL12/CXCR4 Pathway in Severe Acute Pancreatitis.

Background: Platelet activation in the early stage of pancreatitis is the key step developing into pancreatic necrosis. Studies suggested that vitamin C (Vit C) can inhibit platelet activity by targeting CXCL12/CXCR4 pathway. High-dose Vit C were showed to reduce pancreatic necrosis in severe acute pancreatitis (SAP) but the mechanism remains unclear. Here we speculate high-dose Vit C reduce pancreatic necrosis by inhibiting platelet activation through downregulating CXCL12/CXCR4 pathway. Methods: The pancreatic microcirculation of rats was observed by intravital microscopy. The platelet activity of SAP rats treated with or without high-dose Vit C was analyzed by platelet function test. Besides, the activity of platelets preincubated with high-dose Vit C or vehicle from SAP patients was also evaluated. Then, the TFA (CXCR4 agonist) and rCXCL12 were used to neutralize the effect of high-dose Vit C in SAP rats treated with high-dose Vit C. Meanwhile, the levels of enzymes and inflammatory cytokines in rat plasma, and rats' pancreatic histopathology and mortality were assessed. Results: Platelets from animals and patients with SAP are more sensitive to agonists and are more easily activated. Administration of high-dose Vit C significantly ameliorated excessive activation of platelets in SAP rats, ultimately increasing the microvessel density and inducing microthrombus and blood stasis; these results were consistent with clinical sample analysis. Moreover, high-dose Vit C significantly inhibited the release of amylase, lipase, TNF-α, and IL-6 in SAP rat plasma, reducing pancreatic damage and the mortality of SAP rats. However, using TFA and rCXCL12 significantly reversed the effect of high-dose Vit C on excessive activation of platelets, aggravating microcirculation impairment and pancreatic damage. Conclusion: The present study suggests that high-dose Vit C can ameliorate pancreatic necrosis by improving microcirculation disorders of SAP. For the first time, the underlying mechanism is related with inhibiting platelet activation through the CXCL12/CXCR4 pathway.

Prognostic performance of the NRS2002, NUTRIC, and modified NUTRIC to identify high nutritional risk in severe acute pancreatitis patients.

Background: Acute pancreatitis (AP) is the most common gastrointestinal disease requiring hospital admission. AP patients are categorized as mild, moderately severe, and severe AP (SAP). For SAP patients, malnutrition increases susceptibility to infection and mortality. The Nutritional Risk Screening 2002 (NRS 2002), the Nutrition Risk in Critically Ill (NUTRIC) score and modified Nutrition Risk in Critically Ill (mNUTRIC) are nutritional risk screening tools of critically ill patients and have not been validated in patients with SAP. It is essential to evaluate the prognostic performance of these nutritional risk screening tools. Materials and methods: A retrospective study was designed to validate the NRS 2002, NUTRIC, and mNUTRIC when applied to SAP patients. Receiver operating characteristic curves were plotted to investigate the predictive ability of clinical outcomes by comparing areas under the curve (AUC). Appropriate cut-offs were calculated by using Youden's index. Patients were identified as being at high nutritional risk according to the calculated cut-off values. The effects of different scoring systems on mortalities were calculated using the Cox proportional hazards model. Logistic regression was used to assess the association between the energy provision and 28-day mortality. Results: From January 2013 to December 2019, 234 SAP patients were included and analyzed. Patients categorized as high nutritional risk by the NRS 2002 (12.6% versus 1.9% for 28-day and 20.5% versus 3.7% for 90-day), NUTRIC (16.2% versus 0.0% for 28-day and 27.0% versus 0.0% for 90-day), and mNUTRIC (16.4% versus 0.0% for 28-day and 26.4% versus 0.8% for 90-day) had significant higher mortality than those categorized as low nutritional risk. The NUTRIC (AUC: 0.861 for 28-day mortality and 0.871 for 90-day mortality, both cut-off value ≥3) and mNUTRIC (AUC: 0.838 for 28-day and 0.828 for 90-day mortality, both cut-off value ≥3) showed better predictive ability of the 28- and 90-day mortality than the NRS 2002 (AUC: 0.706 for 28-day mortality and 0.695 for 90-day mortality, both cut-off value ≥5). Conclusion: The NRS 2002, NUTRIC, and mNUTRIC scores were predictors for the 28- and 90-day mortalities. The NUTRIC and mNUTRIC showed better predictive ability compared with the NRS 2002 when applied to SAP patients.

Association between albumin or prealbumin levels at different stages and prognosis in severe acute pancreatitis: a 5-year retrospective study.

Severe acute pancreatitis (SAP) is a common abdominal disorder contributing to high mortality and open laparotomy rates. The role of exogenous infused albumin in fluid resuscitation or continuous therapy has always been an unanswered question. In early stage after onset, SAP patients with higher serum albumin or prealbumin show a better prognosis. In this study, we tried to disclose the linkage between albumin/prealbumin and SAP prognosis and establish a new goal-directed therapy involving albumin and prealbumin. Pearson's chi-squared test and the Mann-Whitney U test were used to compare the descriptive data between surviving and non-surviving patients. Three days, 4-7 days, 8-14 days and 15-28 days after SAP onset were defined as stages 1-4. The average concentrations of albumin and prealbumin were calculated, and receiver operating characteristic (ROC) curves were drawn to screen out the best cutoff values associated with poor prognostic outcomes, including laparotomy and failure to survive. Kaplan-Meier survival curves and log-rank tests were used to validate the effect of the cut-off values. A total of 199 admitted patients were enrolled in this study. According to the analysis of the ROC curve, the serum albumin value should be raised to 35, 37, 40 and 42 g/L in the 1-4 stage after onset. Serum prealbumin values should be raised to 108, 180, and 181 g/L in stages 2-4 after onset. The validity of the above data was confirmed by Kaplan-Meier survival curves. Serum albumin and prealbumin levels in the early stage of SAP are significantly relevant to prognosis. Albumin should be infused from the fluid resuscitation stage to continuous therapy in order to reach the targets mentioned above. The increase in prealbumin depends on the early initiation of enteral nutrition and this also helps to ameliorate the prognosis.

High-dose vitamin C on sepsis: Protocol of a prospective, multi-centered, double-blinded, randomized, and placebo-controlled superiority study.

Background: Sepsis is an inflammatory syndrome with life-threatening organ dysfunction and high mortality. In the recent 10 years, high-dose intravenous injection of vitamin C, the first-line antioxidant of humans, has received highlighted attention in the field of critical care. The study aims to examine the efficacy and safety of high-dose intravenous injection of vitamin C in the treatment of sepsis. Methods and design: Here, we are conducting a prospective, multi-centered, double-blinded, randomized, and placebo-controlled superiority study named High-Dose Vitamin C on Sepsis (HDVCOS). A total of 620 participants diagnosed with sepsis in four participating sites across China that satisfy the eligibility criteria will be randomized at a ratio of 1:1 to receive treatment with a high-dose intravenous injection of vitamin C (200 mg/kg/24 h) or placebo (saline) for 4 days. The primary outcome is 28 days of mortality. The secondary outcomes include the incidence of organ failure, Sequential Organ Failure Assessment (SOFA) score change, organ support, the relationship between plasma vitamin C concentration and outcomes, and adverse events. Conclusion: The findings of this study will provide potential evidence for high-dose intravenous injection of vitamin C in the treatment of sepsis. Clinical trial registration: [http://www.chictr.org.cn/showprojen.aspx?proj=29851], identifier [ChiCTR1800017633].

NORAD modulates miR-30c-5p-LDHA to protect lung endothelial cells damage.

Acute lung injury (ALI) is a devastating human malignancy characterized by excessively uncontrolled inflammation and lung endothelial dysfunction. Non-coding RNAs play essential roles in endothelial protections during the pathological processes of ALI. The precise functions and molecular mechanisms of the lncRNA-NORAD-mediated endothelial protection remain obscure. This study reports NORAD was significantly induced in human pulmonary microvascular endothelial cells (HPMECs) under lipopolysaccharide (LPS) treatment. Silencing NORAD effectively protected HPMECs against the LPS-induced cell dysfunction. In addition, RNA pull-down and luciferase assay validated that NORAD sponged miR-30c-5p, which showed reverse functions of NORAD in the LPS-induced cell injury of HPMECs. Furthermore, the glucose metabolism of HPMECs was significantly elevated under LPS stimulation which promoted the glucose consumption and extracellular acidification rate (ECAR) of HPMECs. Inhibiting NORAD or overexpressing miR-30c-5p suppressed glucose metabolism in HPMECs, leading to protective effects on HPMECs under LPS stimulation. The glycolysis key enzyme, lactate dehydrogenase-A (LDHA), was subsequently identified as a direct target of miR-30c-5p. Finally, recovery of miR-30c-5p in NORAD-overexpressing HPMECs effectively overrode the NORAD-promoted glycolysis and impaired endothelial dysfunction under LPS stimulation by targeting LDHA. Summarily, we demonstrated a NORAD-miR-30c-5p-LDHA-glycolysis axis in the LPS-induced HPMECs dysfunction in vitro and in vivo, contributing to the development of anti-ALI therapeutic approaches.

Moderate level platelet count might be a good prognostic indicator for intra-abdominal infection in acute pancreatitis: A retrospective cohort study of 1,363 patients.

Background: Early recognition of the risk factors is important for acute pancreatitis management. The aim of this study is to investigate the relationship between platelet count and clinical outcomes in patients with acute pancreatitis. Methods: The data are collected from a university-affiliated hospital between January 2013 and December 2020. A generalized additive model and a two-piecewise linear regression model are used to estimate the association between platelet count and the risks of intra-abdominal infection, surgical intervention, in-hospital mortality, and length of hospital stay. Results: Among the 1,363 patients, 99 (7.3%) patients suffered intra-abdominal infection, 190 (13.9%) patients underwent surgical intervention, and 38 (2.8%) patients died in the hospital. The median length of hospital stay is 21 days. Generalized additive model and two-piecewise linear regression analysis show that the risk of intra-abdominal infection decreases as the platelet count increases to 160 × 109/L (OR: 0.991, 95% CI: 0.984-0.998, p = 0.015) and then increases as the platelet count levels up (OR: 1.007, 95% CI: 1.004-1.010, p < 0.001). The trend is similar to the risk of surgical intervention and length of hospital stay. Even though there seems a declining trend in mortality, no significant association is found after adjustment for potential confounders. Further analysis shows that changes in platelet count within the first 3 days after admission have no obvious association with clinical outcomes. Conclusion: A platelet count of approximately 160 × 109/L on admission is associated with the lowest risk of intra-abdominal infection, surgical intervention, and shortest hospital stay in patients with acute pancreatitis.

The effects of early restrictive fluid resuscitation on the clinical outcomes in sepsis patients.

OBJECTIVE: To investigate the effects of early restrictive fluid resuscitation (RFR) on the clinical outcomes in sepsis patients. METHODS: A total of 122 sepsis patients admitted to our hospital were recruited for this study and divided into a study group (the SG, n=56) and a control group (the CG, n=66) according to the treatment method each patient was administered. The SG was administered early RFR, and the CG was administered adequate fluid resuscitation. The clinical data were analyzed retrospectively in both groups. The total infusion volumes, the hemorrhage amounts, the urine outputs, and the Acute Physiology and Chronic Health Evaluation (APACHE II) scores were compared between the two groups. In addition, the heart rates, the mean arterial pressure levels, the central venous pressure levels, and the cardiac function indices were compared between the two groups at 1-7 days after the procedures. The survival and the complication incidence rates were followed up. RESULTS: The SG showed significantly lower heart rates and mean arterial pressure levels and higher central venous pressure levels than the CG at 1-7 days after the procedures (P<0.05). The cardiac troponin, N-terminal brain pro-natriuretic peptide, and C-reactive protein levels at 3-7 days after the procedures in the SG were significantly lower than the levels in the CG (P<0.05). The cardiac output, stroke volume, and left ventricular ejection fraction scores in the SG were significantly higher than they were in the CG (P<0.05). The survival rate in the SG was significantly higher than it was in the CG at 16, 32, and 64 days after the procedures (P<0.05). The incidence of complications in the SG was lower than it was in the CG (P<0.05). CONCLUSION: Early RFR can remarkably improve the clinical outcomes, the myocardial injury and survival rates, and the multiple complications incidence rate in sepsis patients.

Different Resting Methods in Improving Laypersons Hands-Only Cardiopulmonary Resuscitation Quality and Reducing Fatigue: A Randomized Crossover Study.

OBJECTIVE: To determine the effects of different resting methods with various rest-start points or rest-compression ratios on improving cardiopulmonary resuscitation (CPR) quality and reducing fatigue during continuous chest compressions (CCC) in 10-min hands-only CPR scenario. METHODS: This prospective crossover study was conducted in 30 laypersons aged 18-65. Trained participants were randomized to follow different orders to perform following hands-only CPR methods: (1) CCC, 10-min CCC; (2) 4+6, 4-min CCC + 6-min of 10-s pause after 60-s compressions; (3) 2+8 (10/60), 2-min CCC + 8-min of 10-s pause after 60-s compressions; (4) 5/30, 2-min CCC + 8-min of 5-s pause after 30-s compressions; (5) 3/15, 2-min CCC + 8-min of 3-s pause after 15-s compressions. CPR quality (depth, rate, hands-off duration, chest compression fraction (CCF)) and participants' fatigue indicators (heart rate, blood pressure, rating of perceived exertion (RPE)) were compared among methods of different rest-start points and different rest-compression ratios with CCC. RESULTS: Twenty-eight participants completed all methods. All resting methods reduced the trend of declining compression depth and the trend of increasing RPE while maintaining CCF of more than 86%. In methods with different rest-start points, the 2+8 method showed no difference in overall CPR quality or fatigue, but better CPR quality of every minute than 4+6 method. In methods with different rest-compression ratios, the 3/15 method showed the best CPR quality and the highest heart rate increment. CONCLUSION: During prolonged hands-only CPR, appropriate transient rests were associated with higher CPR quality and lower subjectively perceived fatigue in laypersons.

Leukocyte cell population data from the blood cell analyzer as a predictive marker for severity of acute pancreatitis.

BACKGROUND: The prediction for severe acute pancreatitis (SAP) is the key to give timely targeted treatment. Leukocyte cell population data (CPD) have been widely applied in early prediction and diagnosis of many diseases, but their predictive ability for SAP remains unexplored. We aim to testify whether CPD could be an indicator of AP severity in the early stage of the disease. METHODS: The prospective observational study was conducted in the emergency department ward of a territory hospital in Shanghai. The enrolled AP patients should meet 2012 Atlanta guideline. RESULTS: Totally, 103 AP patients and 62 healthy controls were enrolled and patients were classified into mild AP (n = 30), moderate SAP (n = 42), and SAP (n = 31). Forty-two CPD parameters were examined in first 3 days of admission. Four CPD parameters were highest in SAP on admission and were constantly different among 3 groups during first 3 days of hospital stay. Eighteen CPD parameters were found correlated with the occurrence of SAP. Stepwise multivariate logistic regression analysis identified a scoring system of 4 parameters (SD_LALS_NE, MN_LALS_LY, SD_LMALS_MO, and SD_AL2_MO) with a sensitivity of 96.8%, specificity of 65.3%, and AUC of 0.87 for diagnostic accuracy on early identification of SAP. AUC of this scoring system was comparable with MCTSI, SOFA, APACHE II, MMS, BISAP, or biomarkers as CRP, PCT, and WBC in prediction of SAP and ICU transfer or death. CONCLUSIONS: Several leukocyte CPD parameters have been identified different among MAP, MSAP, and SAP. They might be ultimately incorporated into a predictive system marker for severity of AP.

Cardiac indicator CK-MB might be a predictive marker for severity and organ failure development of acute pancreatitis.

BACKGROUND: The prediction of severe acute pancreatitis (SAP) is the key to providing timely and targeted intensive care for acute pancreatitis (AP). The heart is one of multiple organs involved in the early stage of SAP, but the predictive ability of cardiac dysfunction for SAP remains elusive. We sought to determine if the serum levels of three cardiac indicators (CI) including N-terminal pro-brain natriuretic peptide (NT-proBNP), cardiac troponin I (cTNI), and creatine kinase myocardial band (CK-MB) at admission could predict the occurrence of SAP and the development of related organ failure (OF). METHODS: A retrospective, single-center cohort study was conducted on the files of patients presenting to the emergency intensive care unit and medical ward of a regional hospital in Shanghai. Patients diagnosed as having AP and who met the 2012 Atlanta guideline were admitted within 48 hours after disease onset. RESULTS: Of the 670 AP patients screened, 238 were enrolled into the study and divided into mild acute pancreatitis (MAP) (n=59), moderate severe acute pancreatitis (MSAP) (n=123), and SAP (n=56) groups. No significant difference was found in baseline age, gender, duration from disease onset to admission, comorbidity, or substance abuse. As the levels of three CIs were significantly higher in the SAP group than in the MAP and MSAP groups, the enrolled patients were regrouped into non-SAP and SAP groups for predictive evaluation. Multivariate analysis and nomogram modelling showed that CK-MB, but not cTNI or NT-proBNP predicted the occurrence of SAP [area under curve (AUC) =0.805, confidence interval (CI): 0.794-0.905]. Specifically, 89 patients with OF (Modified Marshall score ≥2) upon admission were selected and CK-MB was shown to predict (AUC =0.805, CI: 0.794-0.905) persistent OF (n=48, duration of OF >48 hours) compared to transient organ failure (TOF) (n=41, duration of OF <48 hours). CONCLUSIONS: CIs including NT-proBNP, cTNI, and CK-MB were elevated in the early stage of AP. CK-MB might be used as an efficient predictive biomarker for SAP occurrence and OF development at admission.

Low fluid intake volume during the first 24 h and persistent negative fluid balance from the second day are associated with favorable prognosis for patients with sepsis.

For patients with sepsis and septic shock, it remains controversial when to restrict fluid intake and achieve a negative fluid balance. The present study aimed to evaluate the effects of the fluid intake volume during the first 24 h as well as fluid balance for 7 days on the prognosis of sepsis or septic shock. A total of 337 patients diagnosed with sepsis or septic shock at Ruijin Hospital (Shanghai, China) were enrolled in the present retrospective study. Patients with a low fluid intake volume during the first 24 h (fluid intake, 28.1±10.6 ml/kg) had lower in-hospital mortality rates (18.0 vs. 27.3%, P=0.043) and a shorter duration of mechanical ventilation [0 (0-6) vs. 3 (0-11), P=0.025] than the high-fluid volume intake group (62.6±17.6 ml/kg). Furthermore, survivors exhibited a daily negative net fluid balance from the second day (48 h), whereas non-survivors had a daily positive net fluid balance for 7 days, where fluid balance volumes were significantly lower in survivors compared with those in non-survivors. Finally, binary logistic regression analysis was used to determine whether the mean daily fluid balance (P<0.001) and the Acute Physiologic and Chronic Health Evaluation II score (P=0.048) were independent prognostic factors for patients with sepsis or septic shock. It was indicated that a low fluid intake volume during the first 24 h and a persistent negative fluid balance from the second day were associated with favorable outcomes. The mean daily fluid balance was an independent prognostic factor or patients with sepsis or septic shock.

Effect of high-dose intravenous vitamin C on point-of-care blood glucose level in septic patients: a retrospective, single-center, observational case series.

INTRODUCTION: High-dose vitamin C is an essential adjunctive drug for sepsis treatment. This study aimed to determine if high-dose vitamin C could lead to erroneous point-of-care glucose testing results. METHODS AND MATERIALS: This retrospective, single-center, observational case series involved septic patients treated with high-dose vitamin C. We monitored their paired point-of-care glucose and laboratory glucose levels for statistical analysis. The glucose oxidase-peroxidase colorimetric method and hexokinase spectrophotometric method were applied for point-of-care glucose and laboratory glucose monitoring, respectively. Parkes Consensus Error Grid Analysis was used to assess the clinical influence of paired blood glucose values. Subgroup analyses were conducted to explore the effect of different vitamin C dosages and various renal function levels on point-of-care glucose readings. RESULTS: During a 3-year period, 82 eligible septic patients who accepted at least three days of high-dose vitamin C treatment were included in this study. Compliance with ISO15197:2013 criteria was met in 30 (36.59%) paired values, a proportion considerably lower than the minimum criteria for accuracy. Subgroup analysis showed that worse renal function or higher vitamin C dosage could lead to greater bias in point-of-care glucose readings; however, these inaccuracies rarely represented a clinical risk. CONCLUSIONS: High-dose intravenous ascorbate acid infusion may interfere with point-of-care glucose testing results. Thus, laboratory glucose measurements are recommended for more accurate results. Nonetheless, the inaccuracies magnitude of point-of-care glucose readings does not represent a significant clinical risk when physicians alter clinical action based on these results.

[Epidemiology and risk factors for hospital acquired Clostridium difficile infection and colonization in emergency intensive care unit of a general hospital in Shanghai].

OBJECTIVE: To investigate the clinical features, risk factors and prognosis of Clostridium difficile infection/colonization (CDI/CDC) in emergency intensive care unit (EICU) of Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, then provides theoretical basis for clinical treatment. METHODS: A retrospective case-control study was conducted. The data of EICU patients admitted to Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine from June 2016 to June 2020 were collected. Taking the CDI/CDC patients as research objects [Clostridium difficile (CD) positive group] and the CD negative patients with the same gender and age difference less than 5 years who were admitted to the hospital during the same period as the control (CD negative group). Demographic information, risk factors, prognosis and stool samples were collected. Single factor analysis and binary Logistic regression were used to analyze the CD positive infection rate, risk factors, and hospital death of patients with different clinical characteristics. RESULTS: About 487 patients in EICU were included, 76 cases were taken into CD positive group, CD positive rate was 15.6%, including CDI 11 cases, CDC 65 cases. Among the CD positive group, all of the cases used proton pump inhibitor (PPI), and 75 cases used at least one antibiotic. Seventy-six CD negative patients with or without diarrhea (CD negative group) were included in this study. Among them, 75 patients used PPI and 74 patients used at least one antibiotic. Univariate analysis showed that acute physiology and chronic health evaluation II (APACHE II), duration of hospitalization, and carbapenem use were the risk factors for CDI/CDC. There were significant differences in the above indicators between CD positive group and CD negative group [APACHE II: 18.0 (12.2, 25.8) vs. 10.0 (7.0, 14.0), duration of hospitalization (days): 46.0 (30.5, 72.5) vs. 18.5 (9.2, 37.0), proportion of carbapenems: 81.6% (62/76) vs. 64.5% (49/76), all P < 0.05]. Binary Logistic analysis regression analysis showed that APACHE II score [odds ratio (OR) = 0.802, 95% confidence interval (95%CI) was 0.730-0.882, P < 0.01] and duration of hospitalization (OR = 0.960, 95%CI was 0.942-0.978, P < 0.01) were independent risk factors for CDI/CDC. There was no difference in overall mortality between the CD positive group and CD negative group [27.6% (21/76) vs. 38.2% (29/76), P = 0.167]. CONCLUSIONS: Critically ill patients in EICU routinely use PPI and antibiotics, and the use of antibiotics does not affect the CD positive rate. The independent risk factors of CDI/CDC are the APACHE II score and the duration of hospitalization, but fecal CD positive has no obvious influence on death.

Effects of fluid balance on prognosis of acute respiratory distress syndrome patients secondary to sepsis.

BACKGROUND: Fluid management is crucial to acute respiratory distress syndrome (ARDS) secondary to sepsis. However, choices of fluid resuscitation strategies and fluid input volumes remain a thorny problem. Our study aimed to elucidate the relationship between fluid balance and prognosis of ARDS patients secondary to sepsis. METHODS: Our study included 322 sepsis patients from Ruijin Hospital between 2014 and 2018, and 84 patients were diagnosed as ARDS within 72 hours after onset of sepsis according to Berlin ARDS Definition. RESULTS: Among the 322 sepsis patients, 84 (26.1%) were complicated with ARDS within 72 hours. ARDS patients had a lower oxygenation index (PaO2/FiO2 166.4±71.0 vs. 255.0±91.2, P<0.05), longer duration of mechanical ventilation (11 [6-24] days vs. 0 [0-0] days, P<0.05) than those without ARDS. Sepsis patients with ARDS showed daily positive net fluid balance during seven days compared with those without ARDS who showed daily negative net fluid balance since the second day with significant statistical differences. Among the 84 sepsis patients with ARDS, 58 (69.0%) died. Mean daily fluid input volumes were much lower in survivors than in non-survivors (43.2±16.7 mL/kg vs. 51.0±25.2 mL/kg, P<0.05) while output volumes were much higher in survivors (45.2±19.8 mL/kg vs. 40.2±22.7 mL/kg, P<0.05). Using binary logistic regression analysis, we found that the mean daily fluid balance was independently associated with mortality of sepsis patients complicating with ARDS (P<0.05). CONCLUSIONS: Early negative fluid balance is independently associated with a better prognosis of sepsis patients complicated with ARDS.

High-dose vitamin C alleviates pancreatic injury via the NRF2/NQO1/HO-1 pathway in a rat model of severe acute pancreatitis.

BACKGROUND: Oxidative stress plays a pivotal role in the progress of severe acute pancreatitis (SAP). Vitamin C (VC) is the most important antioxidant in plasma. However, the effects of an intravenous administration of high-dose VC and the mechanisms by which it exerts its antioxidant function in an experimental model of SAP have not been determined. METHODS: Sodium taurocholate was used to induce rat pancreatic injury and AR42J cells injury. After the establishment of SAP model, SAP rat and injured AR42J cells were treated with VC. For the injured AR42J cells, small interfering RNA-mediated knockdown of NRF2 was conducted after VC treatment. The histopathological characteristics, the apoptosis of pancreatic acinar cells, oxidative stress markers and levels of enzymes, biochemical indicators, and inflammatory cytokines were examined in vivo and in vitro. Furthermore, the mortality of rats was assessed. RESULTS: In vivo and in vitro results demonstrated that VC treatment ameliorated apoptosis of pancreatic acinar cells, as evidenced by the increase in Bcl-2, Bcl-XL, and MCL-1 expressions and decrease in Bax and cleaved caspase-3 expression along with decreased TUNEL-positive cells. Also, we found that the elevation of MDA and decrease of SOD, GPx, GSH/GSSG, and T-AOC induced by SAP were reversed by VC treatment in vivo and in vitro, and VC treatment increased expressions of Nrf2, NQO1, and HO-1 in SAP model at protein and gene level, indicating that VC attenuated oxidative stress via the NRF2/NQO1/HO-1 pathway. Meanwhile, it was found that sodium taurocholate significantly induced the release of amylase, lipase, IL-1ß, and IL-6 in rat plasma and AR42J cells, which were declined by VC treatment. In vitro results also revealed that these alterations in sodium taurocholate-injured AR42J cells due to VC treatment was attenuated by NRF2 knockdown. In addition, VC at a dose of 500 mg/kg decreased the levels of lactic acid, Cre, NGAL, AST, and ALT in the plasma of SAP rats, suggesting the improvement of renal and pancreatic injury and liver function of SAP rats. Furthermore, the mortality of SAP rats was 50%, which declined to 30% after VC treatment. CONCLUSIONS: The present study suggests that high-dose of VC ameliorate pancreatic injury of SAP via the NRF2/NQO1/HO-1 pathway to inhibit oxidative stress.

TUDCA Ameliorates Liver Injury Via Activation of SIRT1-FXR Signaling in a Rat Hemorrhagic Shock Model.

OBJECTIVE: The aim of this study was to investigate the changes of bile acids in the liver during hemorrhagic shock (HS) and their potential to attenuate liver injury via activation of SIRT1 (sirtuin 1)-FXR (farnesoid X receptor) signaling. METHODS: A Sprague-Dawley (SD) rat HS model was established, whereas HepG2 cells were hypoxically cultured to simulate HS in vitro. Liver bile acids (BA) were profiled with ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). FXR expression was detected by western blot and immunohistochemistry. The mRNA levels of SIRT1 and FXR were detected by polymerase chain reaction. Protein expression of SIRT1, FoxM1, NF-κB, acetyl-NF-κB, p53, and acetyl-p53 was analyzed by western blot. Hepatocyte apoptosis and proliferation were measured by TUNEL assay and Ki-67 staining, respectively. Serum and supernatant cytokines were analyzed using ELISA assays. Liver injury was also assessed. To investigate the possible mechanisms, SIRT1 agonist (SRT1720), SIRT1 inhibitor (EX527), and FXR inhibitor (Z-guggulsterone) were used. RESULTS: Tauroursodeoxycholic acid (TUDCA) in the liver decreased significantly after HS. SIRT1 and FXR expression was time-dependently downregulated by HS or hypoxia condition. TUDCA upregulated SIRT1-FXR activity, which inhibited expression and acetylation of NF-κB and p53 and increased FoxM1 expression, leading to decreased inflammatory response and apoptosis and increased proliferative capacity in hepatocytes, and attenuation of liver injury. EX527 pretreatment reversed the protective effect of TUDCA. Moreover, Z-guggulsterone supplementation decreased the protective effect of TUDCA in vitro. CONCLUSION: TUDCA in the liver decreased during HS. TUDCA supplementation might attenuate HS-induced liver injury by upregulating SIRT1-FXR signaling.