Serum soluble suppression of tumorigenicity 2 as a novel inflammatory marker predicts the severity of acute pancreatitis

BACKGROUNDAcute pancreatitis (AP) is an inflammatory disease in which the regulatory pathway is complex and not well understood. Soluble suppression of tumorigenicity 2 (sST2) protein receptor functions as a decoy receptor for interleukin (IL)-33 to prevent IL-33/suppression of tumorigenicity 2L (ST2L)-pathway-mediated T helper (Th)2 immune responses.AIMTo investigate the role of sST2 in AP.METHODSWe assessed the association between sST2 and severity of AP in 123 patients enrolled in this study. The serum levels of sST2, C-reactive protein (CRP) and Th1- and Th2-related cytokines, including interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL-2, IL-4, IL-5 and IL-13, were measured by highly sensitive ELISA, and the severity of AP in patients was evaluated by the 2012 Atlanta Classification Criteria. RESULTSSerum sST2 levels were significantly increased in AP patients, and further, these levels were significantly elevated in severe AP (SAP) patients compared to moderately severe AP (MSAP) and mild AP (MAP) patients. Logistic regression showed sST2 was a predictor of SAP [odds ratio (OR): 1.003 (1.001–1.006), P = 0.000]. sST2 cutoff point was 1190 pg/mL, and sST2 above this cutoff was associated with SAP. sST2 was also a predictor of any organ failure and mortality during AP [OR: 1.006 (1.003–1.009), P = 0.000, OR: 1.002 (1.001–1.004), P = 0.012, respectively]. Additionally, the Th1-related cytokines IFN-γ and TNF-α in the SAP group were higher and the Th2-related cytokine IL-4 in the SAP group was significantly lower than those in MSAP and MAP groups. CONCLUSIONsST2 may be used as a novel inflammatory marker in predicting AP severity and may regulate the function and differentiation of IL-33/ST2-mediated Th1 and Th2 Lymphocytes in AP homeostasis.     

Noninvasive positive pressure ventilation for the treatment of acute respiratory distress syndrome following esophagectomy for esophageal cancer: a clinical comparative study

Objective

To evaluate the therapeutic efficacy of noninvasive positive pressure ventilation (NPPV) in the treatment of acute respiratory distress syndrome (ARDS) following esophagectomy for esophageal cancer.

Methods

In this retrospective evaluation, we included 64 patients with ARDS following esophagectomy for esophageal cancer between January 2009 and December 2011. The primary evaluations were 28-day fatality and actual fatality. The secondary evaluations were sex, age, onset time, pH value, PaO₂/FiO₂, sequential organ failure assessment (SOFA) score, acute physiology and chronic health evaluation (APACHE-II) score, and presence or absence after surgery of major surgery-related complications such as cardiac arrest, anastomotic fistula, and acute renal dysfunction.

Results

NPPV applied as the first-line intervention for ARDS following esophagectomy for esophageal cancer avoided intubation in 30 patients (30/64, 48.4%). There were no significant differences in gender, age, PaO₂/FiO₂, SOFA score, or APACHE-II score between the NPPV group and the patients who required invasive positive pressure ventilation (IPPV group) (P>0.05) at the time of onset, while differences in the PaO₂/FiO₂ (P<0.05) after 24 h of NPPV and presence of major surgery-related complications were highly significant (P<0.01).

Conclusions

NPPV may be an effective option for the treatment of ARDS/acute lung injury (ALI) following esophagectomy for esophageal cancer. However, conversion to invasive mechanical ventilation should be considered in patients with severe postoperative complications such as acute renal dysfunction and cardiac arrest and in those with PaO₂/FiO₂ <180 after 2 h of NPPV.KEYWORDS : Noninvasive positive pressure ventilation (NPPV), esophagectomy, acute respiratory distress syndrome (ARDS)     

Combined APACH II score and arterial blood lactate clearance rate to predict the prognosis of ARDS patients

ObjectiveTo explore the easily applicable indicators of practical value to evaluate the prognosis of acute respiratory distress syndrome (ARDS).MethodsBlood and biochemical tests and blood-gas analyses were performed upon entry into the ICUs, 12 h, 24 h, 48 h and 72 h after that in 72 ARDS patients (who were admitted to the ICUs of our hospital from January 2000 to December 2009). Then APACHE Π scores were achieved by combining relevant physiological parameters and laboratory results.ResultsThere was a statistical difference between the death group and survival group at different time points upon entering the ICUs in terms of APACHE Π score, alveolar-arterial oxygen difference and arterial blood lactate clearance rate. PaO₂/FiO₂ values were recorded to be statistically different between the death group and survival group 24 h, 48 h and 72 h, respectively after entry into the ICUs. In addition, registered linear regression existed between APACHE Π score, alveolar-arterial oxygen difference or PaO₂/FiO₂ value and time. APACHE Π score 24 h and 72 h after entering ICUs predicted mortality with an area under the ROC curve (AUC) standing respectively at 0.919 and 0.955. Arterial blood lactate clearance rate 12 h, 24 h, 48 h and 72 h after entering ICUs predicted mortality with an area under the ROC curve (AUC) at 0.918, 0.918, 0.909 and 0.991, respectively.ConclusionsAPACHE Π score applied in combination with arterial blood lactate clearance rate is of clinical significance in assessing the prognosis of ARDS patients.     

Lower incidence of acute respiratory distress syndrome in community‐acquired pneumonia patients aged 85 years or older

Background and objective: The incidence of and risk factors for ARDS among elderly patients with community‐acquired pneumonia (CAP) have not been well characterized. Methods: The clinical details of 221 consecutive patients aged ≥65 years, who were admitted with CAP during the period April 2006 to June 2008, were investigated by review of patient charts. Clinical variables and laboratory data at admission for CAP were compared between patients with and without ARDS. Results: Eighteen patients (8.1%) developed ARDS 1–5 days after admission. The mortality rate was 44% in patients with ARDS and 10.3% in those without ARDS (P < 0.001). The incidence of ARDS was 8.5–20% among patients aged <85 years and 1.1% in patients aged ≥85 years (P < 0.001), while overall mortality rates were not significantly different among the age groups. Predictors for the development of ARDS included higher serum levels of CRP and glucose, lower PaO₂/fraction of inspired O₂ (FiO₂), PaCO₂ and HCO₃^‐, and the presence of systemic inflammatory response syndrome at admission. ARDS developed less frequently among patients with pneumonia associated with oropharyngeal aspiration (AP). Multivariate analysis indicated that lower age, serum glucose, pre‐existence of systemic inflammatory response syndrome and non‐oropharyngeal AP were significant risk factors for ARDS. The Pneumonia Severity Index and confusion, urea, respiratory rate, blood pressure, age ≥65 score were not correlated with the incidence of ARDS. Conclusions: Predictors for ARDS appeared to differ from the determinants of severity of CAP in the elderly. ARDS developed less frequently in patients aged ≥85 years and in those with oropharyngeal AP. It is important to identify subjects at high risk for ARDS upon admission and to observe them closely.     

Clinical utility of the Revised Atlanta Classification of acute pancreatitis in a prospective cohort: Have all loose ends been tied?

Background and aimRevision of the Atlanta classification for acute pancreatitis (AP) was long awaited. The Revised Atlanta Classification has been recently proposed. In this study, we aim to prospectively evaluate and validate the clinical utility of the new definitions.Patient and methods163 consecutive patients with AP were followed till death/6 mths after discharge. AP was categorized as mild (MAP) (no local complication[LC] and organ failure[OF]), moderate (MSAP)(transient OF and/or local/systemic complication but no persistent OF) and severe (SAP) AP (persistent OF). LC included acute peripancreatic fluid collections, pseudocyst, acute necrotic collection, walled-off necrosis, gastric outlet dysfunction, splenic/portal vein thrombosis, and colonic necrosis. Baseline characteristics (age/gender/hematocrit/BUN/SIRS/BISAP) and outcomes (total hospital stay/need for ICU care/ICU days/primary infected (peri)pancreatic necrosis[IN]/in-hospital death) were compared.Results43 (26.4%) patients had ANP, 87 (53.4%) patients had MAP, 58 (35.6%) MSAP and 18 (11.04%) SAP. Among the baseline characteristics, BISAP score was significantly higher in MSAP compared to MAP [1.6 (1.5–2.01) vs 1.2 (1.9–2.4); p = 0.002]; and BUN was significantly higher in SAP compared to MSAP[64.9 (50.7–79.1) vs 24.9 (20.7–29.1); p < 0.0001]. All outcomes except mortality were significantly higher in MSAP compared to MAP. Need for ICU care (83.3%vs43.1%; p = 0.01), total ICU days[7.9 (4.8–10.9) vs 3.5 (2.7–5.1); p = 0.04] and mortality (38.9%vs1.7%; p = 0.0002) was significantly more in SAP compared to MSAP. 8/18 (44.4%) patients had POF within seven days of disease onset (early OF). This was associated with 37.5% of total in-hospital mortality. Patients with MSAP who had primary IN (n = 10) had similar outcomes as SAP.ConclusionsThis study prospectively validates the clinical utility of the Revised Atlanta definitions of AP. However, MSAP patients with primary infected necrosis may behave as SAP. Furthermore, patients with early severe acute pancreatitis (early OF) could represent a subgroup that needs to be dealt with separately in classification systems.     

The risk factors for acute respiratory distress syndrome in patients with severe acute pancreatitis: A retrospective analysis

Acute respiratory distress syndrome (ARDS) is very common in patients with severe acute pancreatitis (SAP), the early interventions are essential to the prognosis of SAP patients. We aimed to evaluate the risk factors for ARDS in SAP patients, to provide insights into the management of SAP.SAP patients treated in our hospital from June 1, 2018 to May 31, 2020 were included. The characteristics and lab test results were collected and compared, and we conducted the logistic regression analyses were conducted to identify the potential risk factors for ARDS in patients with SAP.A total of 281 SAP patients were included finally, the incidence of ARDS in patients with SAP was 30.60%. There were significant differences on the respiratory rate, heart rate, APACHE II and Ranson score between 2 groups (all P < .05). And there were significant differences on the polymorphonuclear, procalcitonin, C-reactive protein, serum creatinine, albumin and PO₂/FiO₂ between 2 groups (all P < .05), and no significant differences on the K⁺, Na⁺, Ca⁺, white blood cell, neutrophils, urine and blood amylase, trypsin, lipase, alanine aminotransferase, aspartate aminotransferase, total bilirubin, triglyceride, total cholesterol, total bilirubin, fasting blood glucose, and pH were found (all P > .05). Respiratory rate >30/min (odds ratio [OR]: 2.405, 95% confidence interval[CI]: 1.163–4.642), APACHE II score >11 (OR: 1.639, 95% CI: 1.078–2.454), Ranson score >5 (OR: 1.473, 95% CI: 1.145–2.359), polymorphonuclear >14 × 10⁹/L (OR: 1.316, 95% CI: 1.073–2.328), C-reactive protein >150 mg/L (OR: 1.127, 95% CI: 1.002–1.534), albumin ≤30 g/L (OR: 1.113, 95% CI: 1.005–1.489) were the independent risk factors for ARDS in patients with SAP (all P < .05).The incidence of ARDS in SAP patients is relatively high, and it is necessary to carry out targeted early prevention and treatment for the above risk factors.     

Fluid resuscitation in acute pancreatitis: Normal saline or lactated Ringer's solution?

AIM: To investigate whether administration of Ringer’s solution (RL) could have an impact on the outcome of acute pancreatitis (AP).METHODS: We conducted a retrospective study on 103 patients [68 men and 35 women, mean age 51.2 years (range, 19-92 years)] hospitalized between 2011 and 2012. All patients admitted to the Department of Gastroenterology of the Central Clinical Hospital of the Ministry of Interior (Poland) with a diagnosis of AP who had disease onset within 48 h of presentation were included in this study. Based on the presence of persistent organ failure (longer than 48 h) as a criterion for the diagnosis of severe AP (SAP) and the presence of local complications [diagnosis of moderately severe AP (MSAP)], patients were classified into 3 groups: mild AP (MAP), MSAP and SAP. Data were compared between the groups in terms of severity (using the revised Atlanta criteria) and outcome. Patients were stratified into 2 groups based on the type of fluid resuscitation: the 1-RL group who underwent standard fluid resuscitation with a RL 1000 mL solution or the 2-NS group who underwent standard fluid resuscitation with 1000 mL normal saline (NS). All patients from both groups received an additional 5% glucose solution (1000-1500 mL) and a multi-electrolyte solution (500-1000 mL).RESULTS: We observed 64 (62.1%) patients with MAP, 26 (25.24%) patients with MSAP and 13 (12.62%) patients with SAP. No significant difference in the distribution of AP severity between the two groups was found. In the 1-RL group, we identified 22 (55.5%) MAP, 10 (25.5%) MSAP and 8 (20.0%) SAP patients, compared with 42 (66.7%) MAP, 16 (24.4%) MSAP and 5 (7.9%) SAP cases in the 2-NS group (P = 0.187). The volumes of fluid administered during the initial 72-h period of hospitalization were similar among the patients from both the 1-RL and 2-NS groups (mean 3400 mL vs 3000 mL, respectively). No significant differences between the 1-RL and 2-NS groups were found in confirmed pancreatic necrosis [10 patients (25%) vs 12 patients (19%), respectively, P = 0.637]. There were no statistically significant differences between the 1-RL and 2-NS groups in the percentage of patients who required enteral nutrition (23 patients vs 17 patients, respectively, P = 0.534). Logistic regression analysis confirmed these findings (OR = 1.344, 95%CI: 0.595-3.035, P = 0.477). There were no significant differences between the 1-RL and 2-NS groups in mortality and the duration of hospital stay (median of 9 d for both groups, P = 0.776).CONCLUSION: Our study failed to find any evidence that the administration of RL in the first days of AP leads to improved clinical outcomes.     

Clinical significance of melatonin concentrations in predicting the severity of acute pancreatitis

AIM: To assess the value of plasma melatonin in pre-dicting acute pancreatitis when combined with the acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) and bedside index for severity in acute pancreatitis (BISAP) scoring systems. METHODS: APACHEⅡ and BISAP scores were calculated for 55 patients with acute physiology (AP) in the first 24 h of admission to the hospital. Additionally, morning (6:00 AM) serum melatonin concentrations were measured on the first day after admission. According to the diagnosis and treatment guidelines for acute pancreatitis in China, 42 patients suffered mild AP (MAP). The other 13 patients developed severe AP (SAP). A total of 45 healthy volunteers were used in this study as controls. The ability of melatonin and the APACHEⅡ and BISAP scoring systems to predict SAP was evaluated using a receiver operating characteristic (ROC) curve. The optimal melatonin cutoff concentration for SAP patients, based on the ROC curve, was used to classify the patients into either a high concen-tration group (34 cases) or a low concentration group (21 cases). Differences in the incidence of high scores, according to the APACHEⅡ and BISAP scoring sys- tems, were compared between the two groups. RESULTS: The MAP patients had increased melatonin levels compared to the SAP (38.34 ng/L vs 26.77 ng/L) (P = 0.021) and control patients (38.34 ng/L vs 30.73 ng/L) (P = 0.003). There was no significant difference inmelatoninconcentrations between the SAP group and the control group. The accuracy of determining SAP based on the melatonin level, the APACHEⅡ score and the BISAP score was 0.758, 0.872, and 0.906, respectively, according to the ROC curve. A melatonin concentration ≤ 28.74 ng/L was associated with an increased risk of developing SAP. The incidence of high scores (≥ 3) using the BISAP system was significantly higher in patients with low melatonin concentration (≤ 28.74 ng/L) compared to patients with high melatonin concentration (> 28.74 ng/L) (42.9% vs 14.7%, P = 0.02). The     

The course of acute pancreatitis in patients with different BMI groups

ObjectivesTo evaluate the risk factors, Atlanta severity score, Balthazar-CTSI score, and disease course in patients of varying weight with acute pancreatitis (AP).MethodsA retrospective evaluation was made of normal weight (NW), overweight (OW), and obese (OB) patients (n:1134) with respect to demographic findings, diabetes (DM)/hypertension, smoking/alcohol use, etiologies, laboratory findings, Balthazar/Atlanta severity scores, and disease outcomes. After consistency and associations among the BMI, Balthazar, and Atlanta groups were evaluated, combined effects of risk factors on mortality, hospital and ICU stays were re-examined statistically.ResultsIn the OB group, mean age (p < 0.001), female gender (p < 0.001), increased BUN(p < 0.027) and Hct (p = 0.039), DM(p < 0.024), and mortality (p < 0.011) were statistically significant. In the non-NW groups, the rates of complications (40.6%/38.6%), mortality (3.7%/4.9%), interventional procedures (36%/39%), and length of hospital stay (11.6%/9.8%) were increased. Obesity constituted 23.7% of severe AP(SAP) and 50% of mortality. There was no significant relationship between Atlanta and Balthazar groups and BMI, nor between Balthazar and moderate AP (MSAP) to SAP. Old age (p = 0.000), male sex (p = 0.05), obesity (p = 0.046), alcohol (p = 0.014), low Hct (p = 0.044), high CRP (p = 0.024), MSAP/SAP (p = 0.02/(p < 0.001), and any complications (p < 0.001) increased the mortality risk. Female gender (p = 0.024), smoking (p = 0.021), hypertriglyceridemia (p = 0.047), idiopathic etiology (p = 0.023), and MSAP/SAP (p < 0.001) associations increased ICU admission. Co-occurrences of higher Balthazar score (p < 0.001), MSAP/SAP (p < 0.001), all kinds of complications (p < 0.001), and recurrence (p = 0.040) increased the hospital stay (≥11 days).ConclusionsAlthough complications, mortality, longer hospitalization, and interventional procedures were observed more in the overweight and obese, successful prediction of Atlanta severity and Balthazar-CTSI scores based on BMI does not appear to be accurate. OB carries an increased risk for morbidity and mortality. The combined effects of risk factors increased mortality, longer hospital stays, and ICU admission.     

Activated matrix metalloproteinase 8 in serum predicts severity of acute pancreatitis

ObjectivesSevere acute pancreatitis (SAP) has high morbidity and mortality but there are no widely accepted predictive biomarkers in clinical use. Matrix metalloproteinases (MMPs) are active in tissue destruction and inflammatory responses. We studied whether serum levels of activated MMP-8 (aMMP-8), MMP-9 and their regulators tissue inhibitor of matrix metalloproteinases (TIMP)-1, myeloperoxidase (MPO) and human neutrophil elastase (HNE) could predict the development of SAP.MethodsThe study comprised 214 AP patients (revised Atlanta classification: 142 mild, MAP; 54 moderately severe, MSAP; 18 SAP) referred to Helsinki University Hospital. A venous blood sample was taken within 72 h from the onset of symptoms. Serum levels of aMMP-8 were determined using immunofluorometric assay, and those of MMP-9, TIMP-1, MPO and HNE using enzyme-linked immunosorbent assay. AP groups were compared using Jonckheere-Terpstra test and predictive value for SAP was analyzed using receiver operating characteristics (ROC) analysis.ResultsSerum aMMP-8 levels were higher in SAP (median 657 ng/ml, interquartile range 542–738 ng/ml) compared to MSAP (358 ng/ml, 175–564 ng/ml; p < 0.001) and MAP (231 ng/ml, 128–507 ng/ml; p < 0.001). Similar trend was seen with TIMP-1 and MPO. In ROC analysis aMMP-8, MPO and TIMP-1 emerged as potential markers for the development of SAP (areas under ROC curves 0.83, 0.71 and 0.69, respectively).ConclusionsSerum aMMP-8 measured early in the course of AP (within 72 h of symptom onset) predicted the development of SAP.     

Initial synchronized intermittent mandatory ventilation versus assist/control ventilation in treatment of moderate acute respiratory distress syndrome: a prospective randomized controlled trial

Background

Assist/control (A/C) ventilation may induce delirium in patients with acute respiratory distress syndrome (ARDS). We conducted a trial to determine whether initial synchronized intermittent mandatory ventilation with pressure support (SIMV + PS) could improve clinical outcomes in these patients.

Methods

Intubated patients with moderate ARDS were enrolled and we compared SIMV + PS with A/C. Identical sedation, analgesia and ventilation strategies were performed. The co-primary outcomes were early (≤72 h) partial pressure of arterial oxygen to fraction of inspired oxygen (PaO₂/FiO₂) and incidence of delirium. The secondary outcomes were all-cause in-hospital mortality, dosages of analgesics and sedatives, incidence of patient-ventilator asynchrony, and duration of mechanical ventilation and hospital stay.

Results

We screened 2,684 patients and 40 patients were enrolled in our study. In SIMV + PS, early (≤72 h) PaO₂/FiO₂ was greater improved than that at baseline and that in A/C (P<0.05) with lower positive end-expiratory pressure (PEEP) (8.7±3.0 vs. 10.3±3.2, P<0.001) and FiO₂ (58%±18% vs. 67%±19%, P<0.001). We found more SIMV + PS success (defined as SIMV + PS successfully applied without switching to A/C) (100.0% vs. 16.7%, P<0.001), less male (46.3% vs. 85.7%, P=0.015) and pulmonary etiology of ARDS (53.8% vs. 92.9%, P=0.015), and lower PEEP (9.1±3.1 vs. 10.3±3.3, P=0.004) and FiO₂ (58%±19% vs. 71%±19%, P<0.001) in survival patients. However, there were no significant differences in incidence of delirium and mortality, dosages of analgesics and sedatives, incidence of patient-ventilator asynchrony, duration of mechanical ventilation and hospital stay (P>0.05).

Conclusions

In patients with moderate ARDS, SIMV + PS can safely and effectively improve oxygenation, but does not decrease mortality, incidence of delirium and patient-ventilator asynchrony, dosages of analgesics and sedatives, and duration of mechanical ventilation and hospital stay.     

2012年亚特兰大急性胰腺炎严重程度分类的临床特征研究

目的 比较1992年和2012年亚特兰大急性胰腺炎（AP）严重程度分类的临床特征有无差异.方法 回顾性分析广西医科大学第一附属医院近3年的AP患者临床资料,分别按1992年和2012年AP分类标准将患者分为轻症组（MAP组）、重症组（SAP组）及轻度组（MAP1组）、中度组（MSAP组）、重度组（SAP1组）.比较两种分类方法的临床资料有无差异.结果 纳入的162例AP患者中,男115例,女47例,平均发病年龄（48.62 ±15.37）岁,女性发病年龄高于男性（P =0.006）,病因以胆源性、特发性及饱餐后为主,胆源性AP以女性为主（P＜0.001）.不同的性别、年龄段及病因的住院日、住院费用差异均无统计学意义（P均＞0.05）.MAP组及SAP组的性别、年龄、病因分布差异均无统计学意义（P均＞0.05）.MSAP组的女性比例、发病年龄及胆源性比例均低于MAP1组及SAP1组.各组的住院日及住院费用随AP严重程度升高而升高,且SAP1组＞SAP组（P均＜0.001）.结论 2012年AP严重程度分类标准下,不同AP严重程度的临床特征有一定的差异,较1992年分类标准更有临床指导意义.     

Effects of disease severity and necrosis on pancreatic dysfunction after acute pancreatitis

AIM:To evaluate the effects of disease severity and necrosis on organ dysfunctions in acute pancreatitis(AP).METHODS:One hundred and nine patients treated as AP between March 2003 and September 2007 with at least 6 mo follow-up were included.Patients were classified according to severity of the disease,necrosis ratio and localization.Subjective clinical evaluation and fecal pancreatic elastase-Ⅰ(FPE-Ⅰ)were used for exocrine dysfunction evaluation,and oral glucose tolerance test was completed for endocrine dysfunction.The correlation of disease severity,necrosis ratio and localization with exocrine and endocrine dysfunction were investigated.RESULTS:There were 58 male and 51 female patients,and mean age was 56.5±15.7.Of the patients,35.8%had severe AP(SAP)and 27.5%had pancreatic necrosis.Exocrine dysfunction was identified in 13.7%of the patients[17.9%were in SAP,11.4%were in mild AP(MAP)]and 34.7%of all of the patients had endocrine dysfunction(56.4%in SAP and 23.2%in MAP).In patients with SAP and necrotizing AP(NAP),FPE-Ⅰlevels were lower than the others(P<0.05 and0.001 respectively)and in patients having pancreatic head necrosis or near total necrosis,FPE-1 levels were lower than 200μg/g stool.Forty percent of the patients who had undergone necrosectomy developed exocrine dysfunction.Endocrine dysfunction was more significant in patients with SAP and NAP(P<0.001).All of the patients in the necrosectomy group had endocrine dysfunction.CONCLUSION:Patients with SAP,NAP,pancreatic head necrosis and necrosectomy should be followed for pancreatic functions.     

C/EBP homologous protein deficiency aggravates acute pancreatitis and associated lung injury

AIM:To investigate the pathophysiological role of C/EBP homologous protein(CHOP)in severe acute pancreatitis and associated lung injury.METHODS:A severe acute pancreatitis model was induced with 6 injections of cerulein(Cn,50μg/kg)at 1-h intervals,then intraperitoneal injection of lipopolysaccharide(LPS,7.5 mg/kg)in CHOP-deficient(Chop-/-)mice and wild-type(WT)mice.Animals were sacrificed under anesthesia,3 h or 18 h after LPS injection.Serum amylase,lipase,and cytokines[interleukin(IL)-6 and tumor necrosis factor(TNF)-α],pathological changes,acute lung injury,and apoptosis in the pancreas were evaluated.Serum amylase and lipase activities were detected using a medical automatic chemical analyzer.Enzyme-linked immunosorbent assay kits were used to evaluate TNF-αand IL-6 levels in mouse serum and lung tissue homogenates.Apoptotic cells in sections of pancreatic tissues were determined by terminal deoxynucleotidyl transferase-mediated dUTPbiotin nick-end labeling(TUNEL)analysis.The mouse carotid arteries were cannulated and arterial blood samples were collected for PaO2analysis.The oxygenation index was expressed as PaO2/FiO2.RESULTS:Administration of Cn and LPS for 9 and 24 h induced severe acute pancreatitis in Chop-/-and WT mice.When comparing Chop-/-mice and WT mice,we observed that CHOP-deficient mice had greater increases in serum TNF-α(214.40±19.52 pg/mL vs 150.40±16.70 pg/mL;P=0.037),amylase(4236.40±646.32U/L vs 2535.30±81.83 U/L;P=0.041),lipase(1678.20±170.57 U/L vs 1046.21±35.37 U/L;P=0.008),and IL-6(2054.44±293.81 pg/mL vs 1316.10±108.74pg/mL;P=0.046)than WT mice.The histopathological changes in the pancreases and lungs,decreased PaO2/FiO2ratio,and increased TNF-αand IL-6 levels in the lungs were greater in Chop-/-mice than in WT mice(pancreas:Chop-/-vs WT mice,hemorrhage,P=0.005;edema,P=0.005;inflammatory cells infiltration,P=0.005;total scores,P=0.006;lung:hemorrhage,P=0.017;edema,P=0.017;congestion,P=0.017;neutrophil infiltration,P=0.005,total scores,P=0.001;PaO2/FiO2ratio:393±17.65 vs     

Triglyceride and glucose (TyG) index is an effective biomarker to identify severe acute pancreatitis

BackgroundEarly diagnosis of severe acute pancreatitis (AP) is important to reduce morbidity and mortality. We investigated the association between the triglyceride and glucose index (TyG index) and the prognosis of severe AP (SAP).MethodsThe TyG index was calculated as: ln [fasting triglycerides (mg/dL) x fasting plasma glucose (mg/dL)]/2. Multivariable logistic regression analyses were used to investigate the independent association between the TyG index and the severity of AP.ResultsIn this study, 373 patients with AP were recruited from three hospitals. The TyG index was higher in the SAP group than in the non-SAP group. Further, the TyG index was higher than in patients admitted to an intensive care unit and those who died of AP. The TyG index was an independent predictive factor for SAP (odds ratio 7.14, 95% confidence interval 2.80–18.19). The area under the curve increased significantly, from 0.738 to 0.830, after adding the TyG index to a predictive SAP model.ConclusionsOur findings suggest that the TyG index is an independent prognostic factor in patients with AP and could be used as a simple prognostic indicator for SAP.     

Effects of acute kidney injury on acute pancreatitis patients’ survival rate in intensive care unit: A retrospective study

BACKGROUNDAcute kidney injury (AKI) is one of the most common acute pancreatitis (AP)-associated complications that has a significant effect on AP, but the factors affecting the AP patients’ survival rate remains unclear.AIMTo assess the influences of AKI on the survival rate in AP patients. METHODSA total of 139 AP patients were included in this retrospective study. Patients were divided into AKI group (n = 72) and non-AKI group (n = 67) according to the occurrence of AKI. Data were collected from medical records of hospitalized patients. Then, these data were compared between the two groups and further analysis was performed.RESULTSAKI is more likely to occur in male AP patients (P = 0.009). AP patients in AKI group exhibited a significantly higher acute physiologic assessment and chronic health evaluation II score, higher Sequential Organ Failure Assessment score, lower Glasgow Coma Scale score, and higher demand for mechanical ventilation, infusion of vasopressors, and renal replacement therapy than AP patients in non-AKI group (P < 0.01, P < 0.01, P = 0.01, P = 0.001, P < 0.01, P < 0.01, respectively). Significant differences were noted in dose of norepinephrine and adrenaline, duration of mechanical ventilation, maximum and mean values of intra-peritoneal pressure (IPP), maximum and mean values of procalcitonin, maximum and mean serum levels of creatinine, minimum platelet count, and length of hospitalization. Among AP patients with AKI, the survival rate of surgical intensive care unit and in-hospital were only 23% and 21% of the corresponding rates in AP patients without AKI, respectively. The factors that influenced the AP patients’ survival rate included body mass index (BMI), mean values of IPP, minimum platelet count, and hospital day, of which mean values of IPP showed the greatest impact.CONCLUSIONAP patients with AKI had a lower survival rate and worse relevant clinical outcomes than AP patients without AKI, which necessitates further attention to AP patients with AKI in surgical intensive care unit.     

Predictors of high flow oxygen therapy failure in COVID-19-related severe hypoxemic respiratory failure

BackgroundDuring COVID-19 pandemic, people who developed pneumonia and needed supplemental oxygen, where treated with low-flow oxygen therapy systems and non-invasive methods, including oxygen therapy using high flow nasal cannula (HFNC) and the application of bi-level or continuous positive airway pressure (BiPAP or CPAP). We aimed to investigate the outcomes of critical COVID-19 patients treated with HFNC and unveil predictors of HFNC failure.MethodsWe retrospectively enrolled patients admitted to COVID-19 wards and treated with HFNC for COVID-19-related severe hypoxemic respiratory failure. The primary outcome of this study was treatment failure, such as the composite of intubation or death during hospital stay. The association between treatment failure and clinical features was evaluated using logistic regression models.ResultsOne hundred thirty-two patients with a median (IQR) PaO₂/FiO₂ ratio 96 (63–173) mmHg at HFNC initiation were studied. Overall, 45.4% of the patients were intubated. Hospital mortality was 31.8%. Treatment failure (intubation or death) occurred in 50.75% and after adjustment for age, gender, Charlson Comorbidity index (CCI) score and National Early Warning Score 2 (NEWS2) score on admission and PaO₂/FiO₂ ratio and acute respiratory distress syndrome (ARDS) severity at the time of HFNO initiation, it was significantly associated with the presence of dyspnea [adjusted OR 2.48 (95% CI: 1.01–6.12)], and higher Urea serum levels [adjusted OR 1.25 (95% CI: 1.03–1.51) mg/dL].ConclusionsHFNC treatment was successful in almost half of the patients with severe COVID-19-related acute hypoxemic respiratory failure (AHRF). The presence of dyspnea and high serum Urea levels on admission are closely related to HFNC failure.     

Hospital Mortality and Effect of Adjusting PaO2/FiO2 According to Altitude Above the Sea Level in Acclimatized Patients Undergoing Invasive Mechanical Ventilation. A Multicenter Study

Objective(i) Analyze the effect of altitude above the sea level on the mortality rate in patients undergoing invasive mechanical ventilation. (ii) Validate the traditional equation for adjusting PaO₂/FiO₂ according to the altitude.DesignA prospective, observational, multicenter and international study conducted during August 2016.PatientsInclusion criteria: (i) age between 18 and 90 years old, (ii) admitted to intensive care unit (ICU) situated at the same altitude above the sea level (AASL) in which the patients has stayed, at least, during the previous 40 days and (iii) received invasive MV for at least 12 h.Material and methodsAll variables were registered the day of intubation (day 0). Patients were followed until death, ICU discharge or day 28. PaO₂/FiO₂ ratio was adjusted by the AASL according to: PaO₂/FiO₂ * (barometric pressure/760). Categorical variables were compared with χ² and Cochran–Mantel–Haenszel test. Continuous variables with Mann–Whitney. Correlation between continuous variables was analyzed graphically and analytically. Logistic regression model was constructed to identify factors associated to mortality. Kapplan–Meier method was used to estimate the probability of survival according to the altitude. A 2-side p value <0.05 was consider significant.Results249 patients (<1500 m n = 55; 1500 to <2500 m n = 20; 2500 to <3500 m n = 155 and ≥3500 m n = 19) were included. Adjusted and non-adjusted PaO₂/FiO₂ were correlated with several respiratory and non respiratory variables. None discordances between non adjusted and adjusted PaO₂/FiO₂ were identified. However, several correlations were appreciated only in patients situated <1500 m or in >1500 m. Seventy-nine patients died during the ICU stayed (32%). The mortality curve was not affected by the altitude above the sea level. Variables independently associated to mortality are: PEEP, age, systolic arterial blood pressure, and platelet count. AUROC: 0.72.ConclusionIn acclimatized patients undergoing invasive mechanical ventilation, the traditional equation for adjusting PaO₂/FiO₂ according the elevation above the sea level seems to be inaccurate and the altitude above the sea level does not affect the mortality risk.     

Abdominal paracentesis drainage attenuates intestinal inflammation in rats with severe acute pancreatitis by inhibiting the HMGB1-mediated TLR4 signaling pathway

BACKGROUND Our previous studies confirmed that abdominal paracentesis drainage(APD)attenuates intestinal mucosal injury in rats with severe acute pancreatitis(SAP),and improves administration of enteral nutrition in patients with acute pancreatitis(AP).However,the underlying mechanisms of the beneficial effects of APD remain poorly understood.AIM To evaluate the effect of APD on intestinal inflammation and accompanying apoptosis induced by SAP in rats,and its potential mechanisms.METHODS SAP was induced in male adult Sprague-Dawley rats by 5%sodium taurocholate.Mild AP was induced by intraperitoneal injections of cerulein(20μg/kg body weight,six consecutive injections).Following SAP induction,a drainage tube connected to a vacuum ball was placed into the lower right abdomen of the rats to build APD.Morphological changes,serum inflammatory mediators,serum and ascites high mobility group box protein 1(HMGB1),intestinal barrier function indices,apoptosis and associated proteins,and toll-like receptor 4(TLR4)signaling molecules in intestinal tissue were assessed.RESULTS APD significantly alleviated intestinal mucosal injury induced by SAP,as demonstrated by decreased pathological scores,serum levels of D-lactate,diamine oxidase and endotoxin.APD reduced intestinal inflammation and accompanying apoptosis of mucosal cells,and normalized the expression of apoptosis-associated proteins in intestinal tissues.APD significantly suppressed activation of the intestinal TLR4 signaling pathway mediated by HMGB1,thus exerting protective effects against SAP-associated intestinal injury.CONCLUSION APD improved intestinal barrier function,intestinal inflammatory response and accompanying mucosal cell apoptosis in SAP rats.The beneficial effects are potentially due to inhibition of HMGB1-mediated TLR4 signaling.