Prediction of Severe Acute Pancreatitis Using a Decision Tree Model Based on the Revised Atlanta Classification of Acute Pancreatitis

Objective

To develop a model for the early prediction of severe acute pancreatitis based on the revised Atlanta classification of acute pancreatitis.

Methods

Clinical data of 1308 patients with acute pancreatitis (AP) were included in the retrospective study. A total of 603 patients who were admitted to the hospital within 36 hours of the onset of the disease were included at last according to the inclusion criteria. The clinical data were collected within 12 hours after admission. All the patients were classified as having mild acute pancreatitis (MAP), moderately severe acute pancreatitis (MSAP) and severe acute pancreatitis (SAP) based on the revised Atlanta classification of acute pancreatitis. All the 603 patients were randomly divided into training group (402 cases) and test group (201 cases). Univariate and multiple regression analyses were used to identify the independent risk factors for the development of SAP in the training group. Then the prediction model was constructed using the decision tree method, and this model was applied to the test group to evaluate its validity.

Results

The decision tree model was developed using creatinine, lactate dehydrogenase, and oxygenation index to predict SAP. The diagnostic sensitivity and specificity of SAP in the training group were 80.9% and 90.0%, respectively, and the sensitivity and specificity in the test group were 88.6% and 90.4%, respectively.

Conclusions

The decision tree model based on creatinine, lactate dehydrogenase, and oxygenation index is more likely to predict the occurrence of SAP.     

Anti-inflammatory effect and the effect on acute pharyngitis rats model of compound Lobelia oral liquid

Objective

Observe anti-inflammatory effect and the effect on acute pharyngitis rats model induced by ammonia water of compound Lobelia oral liquid, providing experimental basis for its clinical use.

The Decrease of Peripheral Blood CD4+ T Cells Indicates Abdominal Compartment Syndrome in Severe Acute Pancreatitis

Objective

Few data are available on the role of T lymphocytes and inflammatory cytokines in abdominal compartment syndrome (ACS) in severe acute pancreatitis (SAP). We conducted a retrospective study to assess the risk factors associated with ACS in SAP.

Methods

A total of 76 SAP patients who were admitted within 24 hours after symptom onset in our study. There were 36 patients suffering from ACS and 40 from intra-abdominal hypertension (IAH). On the 1^st, 3^rd and 7^th days after hospital admission, the following variables were assessed: serum value of C-reactive protein (CRP), and the proportions of peripheral CD4⁺ and CD8⁺ T lymphocytes. Acute Physiology and Chronic Health Evaluation II (APACHE II) score, and computed tomography severity index (CTSI) score were assessed on days 1 and 7 after hospitalization.

Results

Compared with the patients with IAH, ACS patients showed statistically higher CRP value on 7^th day after hospital admission, proportions of CD4⁺ T cells on days 1, 3, 7 and CD4⁺ / CD8⁺ ratio on day 1 were significantly lower (P < 0.05, respectively). A CD4⁺ T cell proportion of 30.3% on the 1^st day indicated ACS with an area under the curve (AUC) of 0.774, a sensitivity with 82.5% and specificity with 72.0%, respectively. Sensitivity / specificity for predicting ACS in SAP patients on day 1 was 70.0% / 68.0% for CD4⁺ / CD8⁺ ratio, 72.2% / 65.0% for APACHE II score.

Conclusions

The reduction of peripheral blood CD4⁺ T lymphocytes is associated with ACS in SAP, and may act as a potential predictor of ACS in SAP.     

Ross operation in children and young adults: the Alder Hey case series

Background

Plasma levels of tumor necrosis factor (TNF)-α and of C-reactive protein (CRP) are elevated in smokers. Previous studies failed to show an association between the G-308A polymorphism in the promoter region of the TNF-α gene and coronary artery disease (CAD). We investigated whether smoking would interact with the TNF-α G-308A polymorphism in determining plasma levels of TNF-α and CRP.

Methods

Study participants with a complete data set in terms of smoking and the TNF-α G-308A polymorphism were 300 middle-aged male and female industrial employees. After excluding 24 irregular smokers, analyses were performed on 198 "non-smokers" (life-long non-smokers or subjects who quit smoking >6 months ago) as compared to 78 "regular smokers" (subjects currently smoking >3 cigarettes/day). All subjects had a fasting morning blood draw to measure plasma levels of TNF-α and CRP by high-sensitive enzyme-linked immunosorbent assays.

Results

The cardiovascular risk factor adjusted analysis regressing log-transformed CRP levels against smoking status, genotype, and smoking-status-genotype interaction revealed a significant main effect for smoking status (F_1,250 = 5.67, p = .018) but not for genotype (F_1,250 = 0.33, p = .57). The interaction-term between genotype and smoking status was not significant (F_1,250 = 0.09, p = .76). The fully adjusted model with plasma TNF-α failed to show significant main effects for smoking and genotype, as well as for the smoking-status-genotype interaction.

Conclusions

The findings suggest that the TNF-α G-308A polymorphism does not mediate the effect of smoking on plasma CRP levels. It remains to be seen whether other genetic polymorphisms along the inflammatory pathway may modulate vascular risk in smokers.     

Perfusion-CT - Can We Predict Acute Pancreatitis Outcome within the First 24 Hours from the Onset of Symptoms?

Purpose

Severe acute pancreatitis (AP) is still a significant clinical problem which is associated with a highly mortality. The aim of this study was the evaluation of prognostic value of CT regional perfusion measurement performed on the first day of onset of symptoms of AP, in assessing the risk of developing severe form of acute pancreatitis.

Material and Methods

79 patients with clinical symptoms and biochemical criteria indicative of acute pancreatitis (acute upper abdominal pain, elevated levels of serum amylase and lipase) underwent perfusion CT within 24 hours after onset of symptoms. The follow-up examinations were performed after 4–6 days to detect progression of the disease. Perfusion parameters were compared in 41 people who developed severe form of AP (pancreatic and/or peripancreatic tissue necrosis) with parameters in 38 consecutive patients in whom course of AP was mild. Blood flow, blood volume, mean transit time and permeability surface area product were calculated in the three anatomic pancreatic subdivisions (head, body and tail). At the same time the patient''s clinical status was assessed by APACHE II score and laboratory parameters such as CRP, serum lipase and amylase, AST, ALT, GGT, ALP and bilirubin were compared.

Results

Statistical differences in the perfusion parameters between the group of patients with mild and severe AP were shown. Blood flow, blood volume and mean transit time were significantly lower and permeability surface area product was significantly higher in patients who develop severe acute pancreatitis and presence of pancreatic and/or peripancreatic necrosis due to pancreatic ischemia. There were no statistically significant differences between the two groups in terms of evaluated on admission severity of pancreatitis assessed using APACHE II score and laboratory tests.

Conclusions

CT perfusion is a very useful indicator for prediction and selection patients in early stages of acute pancreatitis who are at risk of developing pancreatic and/or peripancreatic necrosis already on the first day of the onset of symptoms and can be used for treatment planning and monitoring of therapy of acute pancreatitis. Early suspicion of possible pancreatic necrosis both on the basis of scores based on clinical status and laboratory tests have low predictive value.     

Overexpression of Sirtuin2 prevents high glucose-induced vascular endothelial cell injury by regulating the p53 and NF-κB signaling pathways

Objectives

To investigate the potential role and underlying mechanism of Sirtuin2 (SIRT2) in regulating high glucose (HG)-induced vascular endothelial cell injury by using human umbilical vein endothelial cells (HUVECs).

Results

SIRT2 mRNA and protein expression levels were decreased in HG-treated HUVECs. SIRT2 overexpression increased viability, decreased apoptosis and reduced levels of reactive oxygen species in HG-treated HUVECs. SIRT2 overexpression decreased TNF-α expression (146.5 ± 22.8 pg TNF-α ml^?1) relative to that in the empty vector group (263.5 ± 18.5 pg TNF-α ml^?1) and decreased MCP-1 expression (63.8 ± 9.85 pg MCP-1 ml^?1) relative to that in the empty vector group (105.8 ± 8.5 pg MCP-1 ml^?1). SIRT2 overexpression decreased the acetylation of p53 by 33% and decreased the acetylation of NF-κB p65 by 58% in HG-treated HUVECs.

Conclusion

SIRT2 prevents HG-induced vascular endothelial cell injury through suppressing the p53 and NF-κB signaling pathways.

     

The KL-VS polymorphism of KLOTHO gene is protective against retinopathy incidence in patients with type 1 diabetes

Background and aims

KLOTHO is an anti-ageing circulating hormone involved in insulin signaling, inflammation and vascular homeostasis through its protective effects on the endothelium and antioxidant actions. The common functional “KL-VS” variant of the KLOTHO gene is reproducibly associated with longevity in humans. Large number of studies have evaluated close relationship between KLOTHO protein and diabetes but the association between KL-VS variant and retinopathy in type 1 diabetes mellitus (T1D) is unknown. Therefore, in the present study we examined the association between the KL-VS polymorphism and the risk of diabetic retinopathy (DR) in patients with T1D.

Development of peptide inhibitor as a therapeutic agent against head and neck squamous cell carcinoma (HNSCC) targeting p38α MAP kinase

Background

The p38α MAP kinase pathway is involved in inflammation, cell differentiation, growth, apoptosis and production of pro-inflammatory cytokines TNF-α and IL-1β. The overproduction of these cytokines plays an important role in cancer. The aim of this work was to design a peptide inhibitor on the basis of structural information of the active site of p38α.

Methods

A tetrapeptide, VWCS as p38α inhibitor was designed on the basis of structural information of the ATP binding site by molecular modeling. The inhibition study of peptide with p38α was performed by ELISA, binding study by Surface Plasmon Resonance and anti-proliferative assays by MTT and flow cytometry.

Results

The percentage inhibition of designed VWCS against pure p38α protein and serum of HNSCC patients was 70.30 and 71.5%, respectively. The biochemical assay demonstrated the K_D and IC₅₀ of the selective peptide as 7.22 × 10^− 9 M and 20.08 nM, respectively. The VWCS as inhibitor significantly reduced viability of oral cancer KB cell line with an IC₅₀ value of 10 μM and induced apoptosis by activating Caspase 3 and 7.

Conclusions

VWCS efficiently interacted at the ATP binding pocket of p38α with high potency and can be used as a potent inhibitor in case of HNSCC.

General significance

VWCS can act as an anticancer agent as it potentially inhibits the cell growth and induces apoptosis in oral cancer cell-line in a dose as well as time dependent manner. Hence, p38α MAP kinase inhibitor can be a potential therapeutic agent for human oral cancer.     

快速序贯器官衰竭评分联合血清同型半胱氨酸、三酰甘油对急性胰腺炎短期预后的预测价值研究

摘要 目的：探讨快速序贯器官衰竭评分（qSOFA）联合血清同型半胱氨酸（Hcy）、三酰甘油（TG）对急性胰腺炎（AP）短期预后的预测价值。方法：选取2019年9月至2021年9月苏州大学附属第一医院消化科收治的210例AP患者为研究对象,根据亚特兰大AP分类指南分为轻症AP（MAP组）125例,中重症AP（MSAP组）45例和重症AP（SAP组）40例。对比三组的qSOFA评分和Hcy、TG水平。根据入院后28d预后结局,将所有患者分为存活组192例、死亡组18例。单因素及多因素Logistic回归分析AP患者预后的影响因素。采用受试者工作特征（ROC）曲线分析qSOFA评分、Hcy和TG对AP患者短期预后的预测价值。结果：SAP组和MSAP组患者的qSOFA评分、Hcy、TG水平均高于MAP组患者,且SAP组高于MSAP组（P＜0.05）;单因素、多因素Logistic回归最终分析结果显示,qSOFA评分较高、TG、Hcy水平升高是AP患者死亡的危险因素（P＜0.05）;qSOFA评分联合Hcy、TG预测AP患者短期预后的曲线下面积（AUC）为0.982,明显高于三指标单独检测的0.715、0.780、0.782。结论：qSOFA评分、TG、Hcy水平均是AP患者短期预后的影响因素,并且联合检测qSOFA评分和Hcy、TG水平对AP患者的短期预后具有较高的预测价值。     

Implications of advanced oxidation protein products (AOPPs), advanced glycation end products (AGEs) and other biomarkers in the development of cardiovascular diseases

Objective

To study the putative effects of Advanced Oxidation Protein Products (AOPPs) and Advanced Glycation End Products (AGEs) in the development and progression of cardiovascular disease (CVD).

Biomarkers of systemic inflammation and depression and fatigue in moderate clinically stable COPD

Introduction

COPD is an inflammatory disease with major co-morbidities. It has recently been suggested that depression may be the result of systemic inflammation. We aimed to explore the association between systemic inflammation and symptoms of depression and fatigue in patients with mainly moderate and clinically stable COPD using a range of inflammatory biomarkers, 2 depression and 2 fatigue scales.

Method

We assessed 120 patients with moderate COPD (FEV₁% 52, men 62%, age 66). Depression was assessed using the BASDEC and CES-D scales. Fatigue was assessed using the Manchester COPD-fatigue scale (MCFS) and the Borg scale before and after 6MWT. We measured systemic TNF-α, CRP, TNF-α-R1, TNF-α-R2 and IL-6.

Results

A multivariate linear model of all biomarkers showed that TNF-α only had a positive correlation with BASDEC depression score (p = 0.007). TNF-α remained positively correlated with depression (p = 0.024) after further adjusting for TNF-α-R1, TNF-α-R2, 6MWD, FEV₁%, and pack-years. Even after adding the MCFS score, body mass and body composition to the model TNF-α was still associated with the BASDEC score (p = 0.044). Furthermore, patients with higher TNF-α level (> 3 pg/ml, n = 7) had higher mean CES-D depression score than the rest of the sample (p = 0.03). Borg fatigue score at baseline were weakly correlated with TNF-α and CRP, and with TNF-α only after 6MWT. Patients with higher TNF-α had more fatigue after 6MWD (p = 0.054).

Conclusion

This study indicates a possible association between TNF-α and two frequent and major co-morbidities in COPD; i.e., depression and fatigue.     

Turning off NADPH oxidase-2 by impeding p67phox activation in infected mouse macrophages reduced viral entry and inflammation

Background

Targeting cells of the host immune system is a promising approach to fight against Influenza A virus (IAV) infection. Macrophage cells use the NADPH oxidase-2 (NOX2) enzymatic complex as a first line of defense against pathogens by generating superoxide ions O₂^– and releasing H₂O₂. Herein, we investigated whether targeting membrane -embedded NOX2 decreased IAV entry via raft domains and reduced inflammation in infected macrophages.

The utility of inflammation and platelet biomarkers in patients with acute coronary syndromes

Introduction

Thrombotic and inflammatory mechanisms are involved in the pathophysiology of acute coronary syndrome (ACS). The aim of the study was the evaluation of inflammation (white blood cells count/WBC, C-reactive protein/CRP, interleukin-6/IL-6) and platelet (platelet count/PLT, mean platelet volume/MPV, large platelet/LPLT, beta-thromboglobulin/β-TG) biomarkers in the groups of ACS patients depending on the severity of signs and symptoms and compared to controls without coronary artery disease.

A single-nucleotide polymorphism in tumor necrosis factor-α (− 308 G/A) as a biomarker in chronic pancreatitis

Objective

Chronic pancreatitis is a gradual, long-term inflammation of the pancreas that results in alteration of its normal structure and function. The study aims to investigate the role of − 308 (G/A) polymorphism of TNF-α gene in chronic pancreatitis.

Material and methods

A total of 200 subjects were included in this case–control study. A total of 100 in patients admitted in the Gastroenterology Unit of Gandhi Hospital and Osmania General Hospital, Hyderabad were included in the present study. An equal number of healthy control subjects were randomly selected for the study. The genotyping of TNF-α gene was carried out by tetra-primer ARMS PCR followed by gel electrophoresis. The TNF-α levels were assayed by enzyme-linked immunosorbent assay.

Results

A significant variation with respect to the genotypic and allelic distribution in the disease group when compared to control subjects [OR = 2.001 (1.33–3.005), p < 0.0001**] was observed. Subjects homozygous for the A allele had higher TNF-α levels compared to G allele.

Conclusion

The present study revealed a significant association of the TNF-α gene promoter polymorphism with chronic pancreatitis. Thus, TNF-α genotype can be considered as one of the biological markers in the etiology of chronic pancreatitis.     

Tumor necrosis factor-α and transforming growth factor-β1 facilitate differentiation and proliferation of tendon-derived stem cells in vitro

Objectives

To investigate the effects of tumor necrosis factor-α (TNF-α) and transforming growth factor-β1 (TGF-β1) on the proliferation and differentiation of tendon-derived stem cells (TDSC).

Results

TNF-α inhibits the proliferation and tenogenic/osteogenic differentiation of TDSC but, after simultaneous or sequential treatment with TGF-β1 and TNF-α, the expression of tenogenic/osteogenic-related marker and proliferation of TDSC was significantly increased. During these processes, Smad2/3 and Smad1/5/8 were highly phosphorylated, meaning that the TGF-β and BMP signaling pathways were highly activated. Further study revealed that the expression of Inhibitor-Smad appeared to be negatively correlated to the proliferation and differentiation of TDSC.

Conclusions

Combining the use of TNF-α and TGF-β1 could improve the proliferation and differentiation of TDSC in vitro, and the expression of I-Smad is negatively correlated with TDSC proliferation and differentiation.

     

The level of hypotension during hemorrhagic shock is a major determinant of the post-resuscitation systemic inflammatory response: an experimental study

Background

To evaluate whether the level of hypotension during hemorrhagic shock may influence the oxidative and inflammatory responses developed during post-ischemic resuscitation.

Methods

Fifteen rabbits were equally allocated into three groups: sham-operated (group sham); bled within 30 minutes to mean arterial pressure (MAP) of 40 mmHg (group shock-40); bled within 30 minutes to MAP of 30 mmHg (group shock-30). Shock was maintained for 60 min. Resuscitation was performed by reinfusing shed blood with two volumes of Ringer's lactate and blood was sampled for estimation of serum levels aminotransferases, creatinine, TNF-α, IL-1β, IL-6, malondialdehyde (MDA) and total antioxidant status (TAS) and for the determination of oxidative burst of polymorhonuclears (PMNs) and mononuclear cells (MCs).

Results

Serum AST of group shock-30 was higher than that of group shock-40 at 60 and 120 minutes after start of resuscitation; serum creatinine of group shock-30 was higher than group shock-40 at 120 minutes. Measured cytokines, MDA and cellular oxidative burst of groups, shock-40 and shock-30 were higher than group sham within the first 60 minutes after start of resuscitation. Serum concentrations of IL-1β, IL-6 and TNF-α of group shock-30 were higher than group shock-40 at 120 minutes (p < 0.05). No differences were found between two groups regarding serum MDA and TAS and oxidative burst on PMNs and MCs but both groups were different to group sham.

Conclusion

The level of hypotension is a major determinant of the severity of hepatic and renal dysfunction and of the inflammatory response arising during post-ischemic hemorrhagic shock resuscitation. These findings deserve further evaluation in the clinical setting.     

Procalcitonin Levels Predict Acute Kidney Injury and Prognosis in Acute Pancreatitis: A Prospective Study

Background

Acute kidney injury (AKI) has been proposed as a leading cause of mortality for acute pancreatitis (AP) patients admitted to the intensive care unit (ICU). This study investigated the predictive value of procalcitonin (PCT) for AKI development and relevant prognosis in patients with AP, and compared PCT’s predictive power with that of other inflammation-related variables.

Methods

Between January 2011 and March 2013, we enrolled 305 cases with acute pancreatitis admitted to ICU. Serum levels of PCT, serum amyloid A (SAA), interleukin-6 (IL-6), and C reactive protein (CRP) were determined on admission. Serum PCT was tested in patients who developed AKI on the day of AKI occurrence and on either day 28 after occurrence (for survivors) or on the day of death (for those who died within 28 days).

Results

Serum PCT levels were 100-fold higher in the AKI group than in the non-AKI group on the day of ICU admission (p<0.05). The area under the receiver-operating characteristic (ROC) curve of PCT for predicting AKI was 0.986, which was superior to SAA, CRP, and IL-6 (p<0.05). ROC analysis revealed all variables tested had lower predictive performance for AKI prognosis. The average serum PCT level on day 28 (2.67 (0.89, 7.99) ng/ml) was significantly (p<0.0001) lower than on the day of AKI occurrence (43.71 (19.24,65.69) ng/ml) in survivors, but the serum PCT level on death (63.73 (34.22,94.30) ng/ml) was higher than on the day of AKI occurrence (37.55 (18.70,74.12) ng/ml) in non-survivors, although there was no significant difference between the two days in the latter group (p = 0.1365).

Conclusion

Serum PCT is superior to CRP, IL-6, and SAA for predicting the development of AKI in patients with AP, and also can be used for dynamic evaluation of AKI prognosis.     

Metabolic reprogramming in colon cancer reversed by DHTS through regulating PTEN/AKT/HIF1α mediated signal pathway

Background

Metabolic reprogramming and hypoxia contribute to the resistance of conventional chemotherapeutic drugs in kinds of cancers. In this study, we investigated the effect of dihydrotanshinone I (DHTS) on reversing dysregulated metabolism of glucose and fatty acid in colon cancer and elucidated its mechanism of action.