Acute Pancreatitis Group Research Articles

Clinical significance of peripheral blood DDR1 and CtBP gene methylation detection in patients with acute pancreatitis

ABSTRACT To investigate the clinical value of methylation levels of peripheral blood DDR1 and CtBP genes in evaluating the severity of acute pancreatitis (AP). Collect 90 blood samples from AP patients and healthy volunteers, and test methylation levels of SPINK1, STAT3, KIT, CFTR, DDR1, CtBP1, CtBP2 genes by bisulfite amplicon sequencing (BSAS). The gene methylation and clinical predictors of SAP early prediction were determined by univariate and multifactorial analysis, respectively. (1) The methylation level of CtBP1 gene and MCTSI score were independent predictors of SAP, with AUC values of 0.723 and 0.8895, respectively. (2) The methylation levels of DDR1, CtBP2, CFTR and SPINK1 genes were statistically significant in HC group vs AP group, HC group vs MAP group, and HC group vs SAP group. (3) The combined detection of CtBP1 gene methylation level and MCTSI score predicted the sensitivity, specificity, AUC, and 95%CI of SAP were 0.750, 0.957, 0.902, and 0.816–0.989, respectively. (1) The methylation level of CtBP1 gene in peripheral blood is an independent risk factor for predicting SAP and is a potentially good predictor of SAP, and the combined testing with the MCTSI score does not further significantly improve the early predictive value for SAP. (2) The methylation levels of DDR1, SPINK1, CtBP2, and CFTR genes were potential indicators for recognizing AP.

Normal saline versus lactated Ringer’s solution for acute pancreatitis resuscitation, an open-label multicenter randomized controlled trial: the WATERLAND trial study protocol

BackgroundSome evidence suggests that fluid resuscitation with lactated Ringer’s solution (LR) may have an anti-inflammatory effect on acute pancreatitis (AP) when compared to normal saline (NS) and may be associated with a decrease in severity, but existing single-center randomized controlled trials showed conflicting results. The WATERLAND trial aims to investigate the efficacy and safety of fluid resuscitation using LR compared to NS in patients with AP.MethodsThe WATERLAND trial is an international multicenter, open-label, parallel-group, randomized, controlled, superiority trial. Patients will be randomly assigned in a 1:1 ratio to receive LR versus NS-based fluid resuscitation for at least 48 h. The primary outcome will be moderately severe or severe AP, according to the revision of the Atlanta classification. The secondary objectives of the WATERLAND trial are to determine the effect of LR versus NS fluid resuscitation on several efficacy and safety outcomes in patients with AP.A total sample of 720 patients, 360 in the LR group and 360 in the NS group, will achieve 90% power to detect a difference between the group proportions of 10%, assuming that the frequency of moderately severe or severe AP in the LR group will be 17%. A loss to follow-up of 10% of patients is expected, so the total sample size will be 396 patients in each treatment arm (792 patients overall). The test statistic used is the two-sided Z test with pooled variance set at a 0.05 significance level.DiscussionThe WATERLAND study aims to improve the early management of AP. Fluid resuscitation is an inexpensive treatment available in any hospital center worldwide. If a better evolution of pancreatitis is demonstrated in one of the treatment arms, it would have important repercussions in the management of this frequent disease.Trial registrationClinicalTrials.gov, NCT05781243. Registration date on January 4, 2023. EudraCT number 2023–000010-18, first posted March 23, 2023.

The role of ischaemia-modified albumin in the prognosis of acute pancreatitis and its correlation with the NF-κB-mediated inflammatory response.

To investigate the correlation between the serum levels of ischaemia-modified albumin (IMA) and disease severity in rats with acute pancreatitis (AP). A rat AP model was established and blood samples from each group were analysed at different time points. After the experiment, the pancreatic tissues of the rats were collected for pathological examination and the measurement of protein levels of NF-κB and NF-κB p65. Serum levels of amylase (α-AMY), tumour necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-8 were also compared between groups of rats. The serum IMA concentration in the severe acute pancreatitis (SAP) group was greater than that in the mild acute pancreatitis (MAP) group. The levels of the NF-κB and NF-κB p65 proteins were increased in the MAP and SAP groups in a time-dependent manner. α-AMY, TNF-α and IL-6 were increased at all time points in the MAP and SAP groups. The increases were greatest at 24 h in the SAP group. In terms of pathological changes in the pancreas, renal and lung tissues, the damage in the SAP group was more obvious than that in the MAP group. Serum IMA level was associated with inflammatory markers and NF-κB p65 in rats with AP.

Diagnostic Value of Serum Amylase and Coagulation Function Indices in Distinguishing Acute Pancreatitis from Aortic Dissection.

Due to similar symptoms of abdominal pain, acute pancreatitis (AP) is often difficult to differentiate from acute aortic dissection (AAD) in clinical practice. It is unknown whether serum amylase and coagulation function indices can be used to distinguish AP from AAD. In this retrospective study, 114 AP patients (AP group) and 48 cases with AAD (AAD group) admitted for acute abdominal pain were enrolled for a final analysis. The levels of serum amylase and coagulation function indices, including prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (APTT), fibrinogen (FIB), and D-dimer (DD), were tested before or on admission and compared between the two groups. Student's t-test was adopted for comparing the mean. Model discrimination was evaluated by using the area under the receiver operating characteristic curve (AUC). Comparison of AUC was performed by using the Z-test. Compared with the AAD group, amylase and FIB were both significantly increased, while DD was significantly lower in the AP group (all p < 0.01). There were no statistically significant differences of PT, INR, and APTT between AP and AAD (all p > 0.05). The AUCs in distinguishing AP from AAD were 0.913, 0.854, and 0.837 for amylase, FIB, and DD, respectively, but there were no significant differences observed among amylase, FIB, and DD (all p > 0.05). Finally, the cutoff values (specificity, sensitivity, and Youden index) in distinguishing between AP and AAD were 114 µ/L (80.70%, 95.83%, 0.765) for amylase, 2.62 g/L (76.32%, 85.42%, 0.617) for FIB, and 2.74 mg/L (95.61%, 62.50%, 0.581) for DD, respectively. Amylase, FIB, and DD can demonstrate accurate and reliable diagnostic values, suggesting that they are useful and potential biomarkers in distinguishing AP from AAD.

Serum Claudin-5 levels facilitate the early prediction of severe acute pancreatitis: a prospective observational study

To investigate the value of early tight junction protein Claudin-5 levels in predicting the severity of acute pancreatitis (AP). A prospective observational study was conducted, including patients diagnosed with AP and admitted to the Northern Jiangsu People's Hospital from December 1, 2021 to November 30, 2022. Eligible healthy volunteers were randomly selected to serve as healthy controls during the same period. Patients were classified into mild acute pancreatitis (MAP) group, moderate-severe acute pancreatitis (MSAP) group, and severe acute pancreatitis (SAP) group based on the 2012 Atlanta classification criteria. Patients with SAP were then divided into three subgroups of 1, 3, and 7 days based on the duration of hospitalization. Baseline data, such as gender, age, underlying disease, and probable etiology, was collected from all enrolled individuals. The enzyme-linked immunosorbent assay (ELISA) was employed to detect serum Claudin-5 levels in each cohort of enrollees. Data on additional serologic indicators, including hematocrit (HCT), albumin (Alb), serum Ca2+, C-reactive protein (CRP), and procalcitonin (PCT) levels, were obtained via the in-hospital test query system in each group of patients with AP. The modified Marshall score (mMarshall), modified CT severity index (mCTSI) score, bedside severity index of severity in acute pancreatitis (BISAP) score, and acute physiology and chronic health evaluation II (APACHE II) were recorded for each group of patients with AP. Differences in the above indicators between groups were analyzed and compared. Spearman's correlation method was employed to examine the relationship between Claudin-5 levels and each influential factor. The receiver operator characteristic curve (ROC curve) was plotted to analyze the predictive value of each influencing factor on SAP. Ridge regression was used to screen for independent risk factors for SAP. A total of 109 patients with AP were enrolled, comprising 66 in the MAP group, 15 in the MSAP group, and 28 in the SAP group. Additionally, 27 healthy volunteers were enrolled as the healthy control group. No statistically significant differences were observed in gender and age among the enrolled groups, and no statistically significant differences were identified among the three groups of patients with AP in terms of underlying disease and etiologic composition. As the disease progressed, serum Claudin-5 levels exhibited a notable increase across all AP patient groups, and they were all significantly higher than those in the healthy control group [ng/L: 888.58 (574.52, 1 141.59), 3 749.02 (2 784.93, 5 789.92), 4 667.81 (3 935.21, 7 315.66) vs. 291.13 (250.19, 314.75), all P < 0.05]. Subgroup analyses showed that as the disease duration prolonged, patients in the SAP group exhibited a notable decline in Claudin-5 levels at 3 days post-admission, compared with those at 1 day post-admission [ng/L: 2 052.59 (1 089.43, 4 006.47) vs. 4 667.81 (3 935.21, 7 315.66), P < 0.05]. Spearman correlation analysis showed that serum Claudin-5 levels in patients with AP were significantly positively correlated with CRP, PCT, HCT, and mMarshall, mCTSI, and BISAP scores (r values were 0.570, 0.525, 0.323, 0.774, 0.670, 0.652, all P < 0.001), and significantly negatively correlated with Alb (r = -0.394, P < 0.001). A significant trend was observed in patients with AP, with an increase of HCT levels and a decrease of Alb levels as the disease progressed (both P < 0.05). An improvement of aforementioned phenomena was observed in patients with SAP following treatment, indirectly indicating that serum Claudin-5 level was a positive indicator of vascular leakage. ROC curve analysis showed that serum Claudin-5 levels in patients with AP exhibited the highest accuracy for early prediction of SAP, with the area under the ROC curve (AUC) of 0.948. When serum Claudin-5 levels ≥2 997 ng/L, the sensitivity for early screening for SAP was 100% and the specificity was 88.89%. Multifactorial ridge regression analysis showed that serum Claudin-5 level, PCT and APACHE II score could be used as independent risk factors for early prediction of SAP (all P < 0.05). Serum Claudin-5 levels facilitate early prediction of SAP and are strongly associated with inflammatory response and vascular leakage.

Biochemical indices of patients with enteric fever and pancreatitis: A comparative cross-sectional study

ObjectiveEnteric fever (EF), a potentially fatal febrile illness, is prevalent in developing countries. Elevated levels of lipase and amylase in serum, typically associated with acute pancreatitis (AP), have been observed in patients with EF. The elevated enzymes in both conditions may lead to diagnostic confusion and care delays. This study aimed to determine biochemical indices that are peculiar to EF and AP. MethodsA cross-sectional comparative study was conducted at the Korle-Bu Teaching Hospital, Ghana. Volunteers were categorized into three groups: EF (n = 32), AP (n = 30) and healthy controls (n = 31). A standard questionnaire was used to collect socio-demographic and clinical information from the participants. Blood and stool samples were obtained, followed by biochemical analysis: total amylase, lipase, pancreatic amylase, serum elastase 1, hepatic enzymes, calcium, magnesium, phosphate, stool colour, stool pH, and stool fat presence. ResultsThe AP group displayed higher total amylase, lipase, elastase-1, alkaline phosphatase, aspartate aminotransferase, and gamma-glutamyl transferase levels compared to the EF and control groups (p < 0.05 respectively). Elastase 1 levels were found to be high in all AP participants, whereas no elevations were observed in the EF group. Positive associations were observed in the AP and EF groups for lipase vs total amylase (ρ = .543, p = 0.001; ρ = .543, p = 0.001 for both). ConclusionsElevated levels of total/pancreatic amylase and lipase were found to be indicative of a patient with AP and EF. Further, elastase-1 was found to be a good biomarker to distinguish between AP and EF.

Assessment of early factors for identification or prediction severe acute pancreatitis in pregnancy

BACKGROUND Acute pancreatitis in pregnancy (APIP) is a rare and serious condition, and severe APIP (SAPIP) can lead to pancreatic necrosis, abscess, multiple organ dysfunction, and other adverse maternal and infant outcomes. Therefore, early identification or prediction of SAPIP is important. AIM To assess factors for early identification or prediction of SAPIP. METHODS The clinical data of patients with APIP were retrospectively analyzed. Patients were classified with mild acute pancreatitis or severe acute pancreatitis, and the clinical characteristics and laboratory biochemical indexes were compared between the two groups. Logical regression and receiver operating characteristic curve analyses were performed to assess the efficacy of the factors for identification or prediction of SAPIP. RESULTS A total of 45 APIP patients were enrolled. Compared with the mild acute pancreatitis group, the severe acute pancreatitis group had significantly increased (P &lt; 0.01) heart rate (HR), hemoglobin, neutrophil ratio (NEUT%), and neutrophil–lymphocyte ratio (NLR), while lymphocytes were significantly decreased (P &lt; 0.01). Logical regression analysis showed that HR, NEUT%, NLR, and lymphocyte count differed significantly (P &lt; 0.01) between the groups. These may be factors for early identification or prediction of SAPIP. The area under the curve of HR, NEUT%, NLR, and lymphocyte count in the receiver operating characteristic curve analysis was 0.748, 0.732, 0.821, and 0.774, respectively. The combined analysis showed that the area under the curve, sensitivity, and specificity were 0.869, 90.5%, and 70.8%, respectively. CONCLUSION HR, NEUT%, NLR, and lymphocyte count can be used for early identification or prediction of SAPIP, and the combination of the four factors is expected to improve identification or prediction of SAPIP.

Serum uric acid concentration in acute pancreatitis is significantly higher than healthy population

Acute pancreatitis (AP) is a common disease caused by a variety of causes. Is uric acid associated with the onset of AP? The objective of this study was to assess whether uric acid concentration in AP patients was higher than that in healthy population, and whether there were associations between uric acid concentration and serological indicators related to AP. A total of 205 AP patients were included in this study. Two hundred and five people who underwent physical examination in our hospital were randomly selected as controls. We analyzed whether there was difference in uric acid concentrations between the two groups. If the difference was statistically significant, the correlations between uric acid concentration and serological indicators in AP patients was further analyzed. There was significant difference in uric acid concentration (P < 0.001) between AP patients and healthy population. Serum uric acid concentration in AP group was significantly higher than that in control group. Two hundred and five AP patients were divided into mild AP group and non-mild AP group. There was no statistically significant difference in uric acid concentration between the two groups (P = 0.176). There was a low linear correlation between serum uric acid concentration and triglyceride level (r = 0.316, P < 0.001). But there was no linear correlation between serum uric acid concentration and hypersensitive C-reactive protein (r = 0.126, P = 0.072), white blood cell (r = 0.192, P = 0.006), albumin (r = 0.183, P = 0.009), total cholesterol concentration (r = 0.133, P = 0.058), fasting blood-glucose (r = 0.133, P = 0.058) and blood calcium (r = 0.155, P = 0.026). Uric acid concentration in patients with AP was significantly higher than healthy population. There was correlation between uric acid concentration and triglyceride in AP patients.

Acute Pancreatitis in Pediatric Acute Lymphoblastic Leukemia (AcuPA Study): A Nationwide Survey in Poland.

This study aimed to identify the risk factors for acute pancreatitis (AP) and its impact on outcomes in Polish children treated for ALL. The study group included 2303 children receiving intensive chemotherapy for ALL. The group was divided into patients with at least one episode of AP and those who did not develop AP after treatment for ALL. The cumulative incidence of AP in the study group was 4.08%. Older age was an independent risk factor for the development of AP (OR = 1.05; 95%CI = 1.006-1.098; p = 0.03). The overall mortality associated with AP was 2.13%. The probabilities of disease-free survival (p-DFS) and event-free survival (p-EFS) in both subgroups were 0.84 vs. 0.86, log-rank p = 0.65 and 0.75 vs. 0.80, log-rank p = 0.12, respectively. A total of 22 out of 94 patients (23.4%) with AP were re-exposed to asparaginase (ASP) during the subsequent treatment phases. Only one patient re-exposed to ASP (4.5%) developed a second episode of AP. There were no significant differences in p-DFS and p-EFS between patients re-exposed and not re-exposed to asparaginase (0.78 vs. 0.86, log-rank p = 0.27 and 0.63 vs. 0.79, log-rank p = 0.09, respectively). The incidence of AP in children with ALL is low and related to patients' age. The development of AP does not seem to influence p-DFS and p-EFS in children with ALL. Recurrence of AP after re-exposure to asparaginase in patients with ALL and a history of AP is low (4.5%). Re-exposure to asparaginase after the first episode of AP does not improve either p-DFS or p-EFS in children with ALL.

Predictive value of immature granulocyte percentage and neutrophil lymphocyte ratio in terms of prognosis in the course of acute pancreatitis.

We aimed to investigate the role and importance of immature granulocyte percentage and neutrophil/lymphocyte ratio in the etiology, diagnosis and follow-up of acute pancreatitis (AP) in patients tentatively diagnosed with AP in the emergency department. We evaluated these factors alongside other established markers proven effective in the diagnosis and follow-up of AP. Atotal of 139 patients with atentative diagnosis of acute pancreatitis who were hospitalized and followed up in the gastroenterology clinic in 2021‒2022 were included in the study. In addition, acontrol group, consisting of 139 individuals admitted to the clinic for various other reasons, was established. The cases were also compared with the control group in terms of NLR, ICG and IG%. There was asignificant difference in the NLR, IGC and IG% measurements between the patients in the AP group and the control group. In all three markers, the average values of the patient group were higher than those of the control group. Furthermore, asignificant difference in IGC and IG% blood measurements was noted between sub-groups of patients categorized based on the severity of acute pancreatitis, particularly the patients with severe pancreatitis exhibited higher mean IGC and IG% blood measurements compared to those with mild or moderate pancreatitis. IGC and IG% values emerged as superior indicators to other acute-phase reactants for detecting inflammation, determining its severity, and establishing prognosis in acute pancreatitis. While the N/L ratio remains an important parameter in acute pancreatitis, our findings indicate that it was not significantly superior to other investigated markers in terms of prognosis (Tab. 5, Ref. 35).

Elevated IRF9 raised cell apoptosis and tissue damages through suppressing SIRT1 in hyperlipidemia acute pancreatitis with liver injury

BackgroundHyperlipidemia is a vital etiology of acute pancreatitis (AP), 12 to 20% of which have a history of hyperlipidemia. Multiple organ failure is the major cause of the high mortality rate of AP. Liver injury has been discovered in 80% of AP patients. The relationship and role of IRF9 and SIRT1 have not been presented in AP and hyperlipidemia AP (HLAP) with liver injury. This investigation was designed to explore the function and relationship of IRF9 and SIRT1.MethodsHLAP model in vivo was performed by feeding high-fat forage and induced by peritoneal injection with 20% L-arginine. The severity of pancreas and liver tissues was assessed. Cell apoptosis in the liver was determined by the TUNEL experiment. IRF9, SIRT1, p53, and acetylated p53 (Ac-p53) expression levels in liver tissues were detected by qRT-PCR and Western blot. The association of IRF9 expression with SIRT1 levels was evaluated. The relevance of triglyceride level to tissue damage was analyzed.ResultsOur observation exhibited more distinct liver damage, a large number of hepatic cell apoptosis, marked raised IRF9, Ac-p53, and sharply dropped SIRT1 in the AP and HLAP groups. Compared with other groups, HLAP showed the most significant changes in liver injury, hepatic cell apoptosis, protein, and mRNA levels. The declined expression of SIRT1 was correlated with the elevated expression of IRF9. The damage of the pancreas and liver exacerbated with the increase in triglyceride levels.ConclusionElevated IRF9 in pancreatitis with liver injury raised cell apoptosis and tissue damage by decreasing SIRT1 expression.

Clinical characteristics and prognosis of 227 children with acute pancreatitis

To analyze the clinical characteristics and prognosis of acute pancreatitis (AP) in children, and provide reference for clinical prevention and treatment of AP in children. Based on the electronic medical record system of the Affiliated Hospital of Zunyi Medical University, the clinical data of children with AP in the hospital from January 2011 to December 2020 were retrospectively analyzed. According to the severity of the disease, the children were divided into mild acute pancreatitis (MAP) group and severe acute pancreatitis (SAP) group. The general data, laboratory tests and outcomes indicators of the two groups were collected and compared. The epidemiological characteristics of children with AP were analyzed. Multivariate Logistic regression was used to analyze the risk factors of SAP in children. A total of 227 children with AP were enrolled, including 161 in MAP group and 66 in SAP group. The median age of children with AP was 12.00 (8.00, 16.00) years old, and 126 cases (55.51%) were male. The main initial clinical symptoms were abdominal pain, nausea, vomiting and abdominal distension (97.36%, 61.67% and 14.10%, respectively), 21 cases (9.25%) were admitted to intensive care unit (ICU), and 4 cases (1.76%) died in hospital due to sepsis, multiple organ dysfunction or traumatic shock. The epidemiological characteristics showed that the first onset age of AP was mainly 7-17 years old (85.02%); the main etiologies were biliary tract disease (29.96%), viral infection (29.07%) and idiopathic factors (19.82%). From 2011 to 2020, the number of children with AP showed a fluctuating trend, and from 2018 to 2020, the number of children with AP increased for three consecutive years. Compared with MAP group, the age of SAP group was significantly older, the proportion of female, the proportion of rural source, acute physiology and chronic health evaluation II (APACHE II), body mass index (BMI), and the levels of white blood cell count (WBC), C-reactive protein (CRP), hospitalization expenses, the proportion of AP caused by traumatic factors and drug factors in SAP group were significantly higher (all P < 0.05). The level of blood calcium and the proportion of AP caused by virus infection were significantly lower, and the length of hospital stay in SAP group was significantly longer (all P < 0.05). The multivariate Logistic regression analysis showed that APACHE II score [odds ratio (OR) = 1.495, 95% confidence interval (95%CI) was 1.293-1.728] and age (OR = 1.352, 95%CI was 1.182-1.546) were closely related to SAP in children (all P < 0.001). Children with AP mostly occurs in preschool and adolescence, and the overall mortality is relatively low; biliary tract disease, viral infection and idiopathic factors are common causes; APACHE II score and age may be risk factors for SAP in children.

Identification of Biomarkers Associated with Oxidative Stress and Immune Cells in Acute Pancreatitis.

Oxidative stress promotes disease progression by stimulating the humoral and cellular immune responses. However, the molecular mechanisms underlying oxidative stress and immune responses in acute pancreatitis (AP) have not been extensively studied. We analyzed the GSE194331 dataset and oxidative stress-related genes (OSRGs). We identified differentially expressed immune cell-associated OSRGs (DE-ICA-OSRGs) by overlapping key module genes from weighted gene co-expression network analysis, OSRGs, and DEGs between AP and normal samples. Functional enrichment analysis was performed to investigate the functions of DE-ICA-OSRGs. We then filtered diagnostic genes using receiver operating characteristic curves and investigated their molecular mechanisms using single-gene set enrichment analysis (GSEA). We also explored the correlation between diagnostic genes and differential immune cells. Finally, we constructed a transcription factor-microRNA-messenger RNA (TF-miRNA-mRNA) network of biomarkers. In this study, three DE-ICA-OSRGs (ARG1, NME8 and VNN1) were filtered by overlapping key module genes, OSRGs and DEGs. Functional enrichment results revealed that DE-ICA-OSRGs were involved in the cellular response to reactive oxygen species and arginine biosynthesis. Latterly, a total of two diagnostic genes (ARG1 and VNN1) were derived and their expression was higher in the AP group than in the normal group. The single-gene GSEA enrichment results revealed that diagnostic genes were mainly enriched in macroautophagy and Toll-like receptor signaling pathways. Correlation analysis revealed that CD8 T cells, resting memory T CD4 cells, and resting NK cells were negatively correlated with ARG1, and neutrophils were positively correlated with ARG1, which was consistent with that of VNN1. The TF-miRNA-mRNA regulatory network included 11 miRNAs, 2 mRNAs, 10 transcription factors (TFs), and 26 pairs of regulatory relationships, like NFKB1-has-miR-2909-VNN1. In this study, two immune cell oxidative stress-related AP diagnostic genes (ARG1 and VNN1) were screened to offer a new reference for the diagnosis of patients with AP.

Predictive value of thrombin-antithrombin III complex and tissue plasminogen activator-inhibitor complex biomarkers in assessing the severity of early-stage acute pancreatitis.

The development of acute pancreatitis (AP) is strongly linked to blood clotting and fibrinolysis issues. Modern clinical practices now utilize advanced blood markers like thrombin-antithrombin III complex (TAT), plasmin-α2-plasmin inhibitor complex, thrombomodulin (TM), and tissue plasminogen activator-inhibitor complex (t-PAIC) to assess thrombosis risk. Our study used a highly sensitive chemiluminescence technique to measure these markers in AP patients, aiming to determine their early predictive value for AP severity. There were 173 patients with AP, all of whom developed symptoms within 72h; 102 individuals had onset symptoms within 48h. The biomarkers were measured upon admission before determining the severity of AP. The levels of TAT, plasmin-α2-plasmin inhibitor complex, TM, and t-PAIC were significantly higher in the severe acute pancreatitis (SAP) group compared with the mild acute pancreatitis and moderate severe acute pancreatitis groups. For the patients within 72h of onset, TAT, TM, and t-PAIC predicted the occurrence of SAP. For the patients within 48h of onset, TAT and t-PAIC predicted the occurrence of SAP. The area under the curve (AUC) of prediction models is similar to Bedside Index for Severity in Acute Pancreatitis (BISAP) but significantly higher than C-reactive protein (P<0.05). Notably, t-PAIC had a larger AUC than TAT, BISAP, and C-reactive protein. In the initial 48h, plasma TAT and t-PAIC levels may predict the development of SAP. Within 72h, plasma levels of TAT, TM, and t-PAIC may predict the development of SAP, and the TAT+TM+t-PAIC prediction model achieved a maximum AUC of 0.915, comparable to BISAP.

Sitagliptin ameliorates L-arginine-induced acute pancreatitis via modulating inflammatory cytokines expression and combating oxidative stress.

Acute pancreatitis (AP) is an inflammatory condition that resolves spontaneously, but occasionally, develops into systemic inflammation, organ failure and mortality. Oxidative stress and activation of inflammatory pathways represent major players in AP pathogenesis. Current management of AP relies on attenuating injuries to the pancreas and putting the inflammatory process under control. In this study, we investigated the role of sitagliptin in modulating L-arginine-induced AP in rats. Swiss rats were subdivided into a healthy control group, AP group (a single dose of L-arginine 250mg/100g, intraperitoneal), and sitagliptin + L-arginine-treated group (10mg sitagliptin/kg body weight/day, orally). Sitagliptin treatment started 1hour after L-arginine injection and continued for 3days. Biochemical and histopathological investigations were performed on serum and tissue samples collected from test animals. L-arginine increased pancreatic meyloperoxidase and serum amylase- and lipase activities and serum levels of TNF-α, LT-α, IFN-γ, IL-1α/β, IL-6, IL-10, IL-12, and IL-15. AP animals showed elevated MDA and NO and decreased GSH and serum calcium levels. Histopathological changes were observed by H&E staining. Sitagliptin treatment significantly ameliorated these biochemical and histological changes diminishing the signs of AP. Sitagliptin treatment was effective in ameliorating L-arginine-induced AP which can be regarded to its anti-inflammatory and antioxidant effect.

Pancreatic Iodine Density and Fat Fraction on Dual-Energy Computed Tomography in Acute Pancreatitis.

The aim of our study was to investigate iodine density (ID) and fat fraction (FF) on dual-energy computed tomography (DECT) in patients with acute pancreatitis (AP). This retrospective study included 72 patients with clinically confirmed AP and 62 control subjects with DECT of the abdomen. Two radiologists assessed necrosis and measured attenuation values, ID, and FF in three pancreatic segments. We used receiver operating characteristic (ROC) analysis to determine the optimal threshold for ID for the differentiation between AP groups. The ID was significantly higher in interstitial edematous AP compared to necrotizing AP and the control group (both p < 0.05). The ROC curve analysis revealed the thresholds of ID for detecting pancreatic necrosis ≤ 2.2, ≤2.3, and ≤2.4 mg/mL (AUC between 0.880 and 0.893, p > 0.05) for the head, body, and tail, respectively. The FF was significantly higher for pancreatitis groups when compared with the control group in the head and body segments (both p < 0.001). In the tail, the difference was significant in necrotizing AP (p = 0.028). The ID values were independent of attenuation values correlated with the FF values in pancreatic tissue. Iodine density values allow for differentiation between morphologic types of AP.

Certolizumab Has Favorable Efficacy on Preventing Pancreas and Target Organs Damage in Acute Pancreatitis.

It was targeted to assess the efficacy of certolizumab on pancreas and target organs via biochemical parameters and histopathologic scores in experimental acute pancreatitis (AP). Forty male Sprague Dawley rats were divided into the following 5 equal groups: group 1 (sham group), group 2 (AP group), group 3 (AP + low-dose certolizumab group), group 4 (AP + high-dose certolizumab group), and group 5 (placebo group). Rats in all groups were sacrificed 24 hours after the last injection and amylase, tumor necrosis factor α, transforming growth factor β, interleukin 1β, malondialdehyde, superoxide dismutase, and glutathione peroxidase levels were studied in blood samples. Histopathological investigation of both the pancreas and target organs (lungs, liver, heart, kidneys) was performed by a pathologist blind to the groups. In silico analysis were also accomplished. The biochemical results in the certolizumab treatment groups were identified to be significantly favorable compared to the AP group (P < 0.001). The difference between the high-dose group (group 4) and low-dose treatment group (group 3) was found to be significant in terms of biochemical parameters and histopathological scores (P < 0.001). In terms of the effect of certolizumab treatment on the target organs (especially on lung tissue), the differences between the low-dose treatment group (group 3) and high-dose treatment group (group 4) with the AP group (group 2) were significant. Certolizumab has favorable protective effects on pancreas and target organs in AP. It may be a beneficial agent for AP treatment and may prevent target organ damage.

The Predictive Value of Serum DAO, HDC, and MMP8 for the Gastrointestinal Injury in the Early Stage of Acute Pancreatitis in an Animal Model and a Clinical Study.

This study was aimed at exploring the use of the acute gastrointestinal injury (AGI) grade and sensitive biomarkers to investigate gastrointestinal (GI) injury in early stage of acute pancreatitis (AP). The AGI grade was used to evaluate intestinal function. Any GI injury above grade I (grades II-IV) was considered as severe. An AP rat model was created by retrograde injection of 4% sodium taurocholate. The pancreatic and intestinal histopathology scores were calculated by hematoxylin-eosin staining. Human and rat sera were assessed using ELISA. Tight junction (TJ) proteins were detected by Western blotting. In clinical study, the GI injury rate in mild acute pancreatitis (MAP), moderate severe acute pancreatitis (MSAP), and severe acute pancreatitis (SAP) groups was 26.8%, 78.4%, and 94.8%, respectively (P < 0.05). Diamine oxidase (DAO), histidine decarboxylase (HDC), and matrix metalloproteinase 8 (MMP8) serum levels were higher in AP patients than in healthy people (P < 0.05). Patients with GI injury had higher serum levels of DAO, HDC, and MMP8 than those without GI injury (P < 0.05). In animal experiments, the serum levels of DAO, HDC, and MMP8 were higher in the AP group than in normal and sham-operated (SO) groups (P < 0.05). The expressions of tricellulin, claudin-1, ZO-1, and occludin were significantly lower in the AP group than in normal and SO groups (P < 0.05). The serum levels of DAO, HDC, and MMP8 are novel biomarkers of GI injury in the early stage of AP; their elevation indicates the development of GI injury in AP. The intestinal TJ disruption may be a primary mechanism of GI injury and requires more in-depth research.

Development and Validation of a Nomogram for Predicting the Severity of the First Episode of Hyperlipidemic Acute Pancreatitis.

Early detection of hyperlipidemic acute pancreatitis (HLAP) with exacerbation tendency is crucial for clinical decision-making and improving prognosis. The aim of this study was to establish a reliable model for the early prediction of HLAP severity. A total of 225 patients with first-episode HLAP who were admitted to Fujian Medical University Union Hospital from June 2012 to June 2023 were included. Patients were divided into mild acute pancreatitis (MAP) or moderate-severe acute pancreatitis and severe acute pancreatitis (MSAP+SAP) groups. Independent predictors for progression to MSAP or SAP were identified through univariate analysis and least absolute shrinkage and selection operator regression. A nomogram was established through multivariate logistic regression analysis to predict this progression. The calibration, receiver operating characteristic(ROC), and clinical decision curves were employed to evaluate the model's consistency, differentiation, and clinical applicability. Clinical data of 93 patients with first-episode HLAP who were admitted to the First Affiliated Hospital of Fujian Medical University from October 2015 to October 2022 were collected for external validation. White blood cell count, lactate dehydrogenase, albumin, serum creatinine, serum calcium, D-Dimer were identified as independent predictors for progression to MSAP or SAP in patients with HLAP and used to establish a predictive nomogram. The internally verified Harrell consistency index (C-index) was 0.908 (95% CI 0.867-0.948) and the externally verified C-index was 0.950 (95% CI 0.910-0.990). The calibration, ROC, and clinical decision curves showed this nomogram's good predictive ability. We have established a nomogram that can help identify HLAP patients who are likely to develop MSAP or SAP at an early stage, with high discrimination and accuracy.

Diagnostic utility of HFLC% and IG% for acute Pancreatitis—A retrospective Case-Control study

ObjectiveTo evaluate the occurrence, development and outcome value of hyperfluorescent lymphocyte percentage (HFLC%) and immature granulocyte percentage (IG%) for acute pancreatitis (AP). MethodsThe laboratory data collected from 1533 patients diagnosed with AP between August 2018 and August 2022 were retrospectively analyzed. The patients were classified into mild acute pancreatitis (MAP) and non-mild acute pancreatitis (Non-MAP) groups; non-MAP groups were additionally subgrouped based on HFLC% at day 7. White blood cells (WBC), HFLC%, and IG% were examined from day 1 (baseline) to day 14 post-admission using Sysmex XN Series Hematology Analyzers. C-reactive protein (CRP), serum amylase (AMY), and lipase (LPS) were detected by Beckman AU5800. ResultsA total of 623 patients were finally included in the study [MAP group (n = 358) and Non-MAP group (n = 265)]. WBC, IG%, and CRP were higher in the Non-MAP group from day 1 to day 12 (all P<0.05). The HFLC% was not statistically significant from day 1 to day 6; yet, it increased on day 6 and 7 in the Non-MAP group. We divided patients in the Non-MAP group with complete data(101 patients) into HFLC% ≥ 2.9 %(31 patients) and HFLC% < 2.9 %(70 patients) according to the threshold of 7th day HFLC%. WBC, HFLC%, IG%, and CRP effectively predicted the progression of MAP to Non-MAP (all P < 0.001). HFLC% was the most obvious value, followed by CRP and IG%. Combined with HFLC%, IG%,CRP and WBC in day7, the ROC analysis showed that the area under ROC curve of the combined indicators was the largest (AUC = 0.912, P < 0.001) and had higher sensitivity and specificity than single-item assessment of AP outcomes(P < 0.05). HFLC% < 2.9 %, IG% > 1.7 %, CRP >28.66 mg/L, and WBC >9.24 × 109/L indicated the possibility of AP disease aggravation. Also, HFLC% <2.9 % was directly associated with infection, SIRS, APPACHII grade, and ICU admission (all P < 0.05). In non-MAP there was a significant negative correlation between HFLC% and APACHE-II score (rs = −0.312, P = 0.023). ConclusionHFLC% <2.9 % on 7th day was directly indicated more infection, systemic inflammatory response syndrome(SIRS), higher APPACH II grade and ICU admission. HFLC% may be an independent laboratory marker for prognosis in AP. Combining HFLC% with IG%, CRP, and WBC helps evaluate AP patients' disease development and outcome.