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1.
PeerJ ; 12: e17283, 2024.
Article in English | MEDLINE | ID: mdl-38708354

ABSTRACT

Objective: To investigate the impact of the third lumbar skeletal muscle index (L3-SMI) assessed by CT on the in-hospital severity and short-term prognosis of acute pancreatitis. Methods: A total of 224 patients with severe acute pancreatitis admitted to Yantaishan Hospital from January 2021 to June 2022 were selected as the subjects. Based on the in-hospital treatment outcomes, they were divided into a mortality group of 59 cases as well as a survival group of 165 cases. Upon admission, general information such as the Acute Physiology and Chronic Health Evaluation II (APACHE II) score, along with the abdominal CT images of each patient, were analyzed. The L3-SMI was calculated, and the Modified CT Severity Index (MCTSI) and Balthazar CT grade were used to assess the severity of in-hospital complications of acute pancreatitis. The evaluation value of L3-SMI for the prognosis of severe acute pancreatitis was analyzed, as well as the factors influencing the prognosis of severe acute pancreatitis. Results: No statistically significant differences in gender, age, BMI, etiology, duration of anti-inflammatory drug use, and proportion of surgical patients between the survival and mortality groups were observed. But the mortality group showed higher proportions of patients with an elevated APACHE II score upon admission, mechanical ventilation, and renal replacement therapy, compared to the survival group, with statistically significant differences (P < 0.001). Furthermore, the mortality group had higher MCTSI scores (6.42 ± 0.69) and Balthazar CT grades (3.78 ± 0.45) than the survival group, with statistically significant differences (P < 0.001). The mortality group also had a lower L3-SMI (39.68 ± 3.25) compared to the survival group (42.71 ± 4.28), with statistically significant differences (P < 0.001). L3-SMI exhibited a negative correlation with MCTSI scores and Balthazar CT grades (r = -0.889, -0.790, P < 0.001). Logistic regression analysis, with mortality of acute pancreatitis patients as the dependent variable and MCTSI scores, Balthazar CT grades, L3-SMI, APACHE II score upon admission, mechanical ventilation, and renal replacement therapy as independent variables, revealed that MCTSI scores and L3-SMI were risk factors for mortality in acute pancreatitis patients (P < 0.001). Logistic regression analysis using the same variables confirmed that all these factors were risk factors for mortality in acute pancreatitis patients. Conclusion: This study confirmed that diagnosing muscle depletion using L3-SMI is a valuable radiological parameter for predicting in-hospital severity and short-term prognosis in patients with acute pancreatitis.


Subject(s)
APACHE , Lumbar Vertebrae , Muscle, Skeletal , Pancreatitis , Severity of Illness Index , Tomography, X-Ray Computed , Humans , Male , Female , Middle Aged , Prognosis , Retrospective Studies , Pancreatitis/mortality , Pancreatitis/therapy , Pancreatitis/physiopathology , Pancreatitis/diagnostic imaging , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/physiopathology , Muscle, Skeletal/diagnostic imaging , Muscle, Skeletal/physiopathology , Muscle, Skeletal/pathology , Adult , Aged , Hospital Mortality
2.
Sci Rep ; 14(1): 9740, 2024 04 28.
Article in English | MEDLINE | ID: mdl-38679620

ABSTRACT

Prolonged elevated heart rate (peHR) is recognized as a risk factor for poor prognosis among critically ill patients. However, there is currently a lack of studies investigating the association between peHR and patients with acute pancreatitis. Multiparameter Intelligent Monitoring in Intensive Care IV (MIMIC-IV) database was used to identify patients with acute pancreatitis. PeHR was defined as a heart rate exceeding 100 beats per minute for at least 11 out of 12 consecutive hours. Cox regression analysis was used to assess the association between peHR and the 90-Day mortality. A total of 364 patients (48.9%) experienced a peHR episode. The 90-day mortality was 25%. PeHR is an independent risk factor for 90-day mortality (HR, 1.98; 95% CI 1.53-2.56; P < 0.001). KM survival curves exhibited a significant decrease in the survival rate at 90 days among patients who experienced a peHR episode (P < 0.001, 84.5% vs. 65.1%). We revealed a significant association of peHR with decreased survival in a large cohort of ICU patients with acute pancreatitis.


Subject(s)
Heart Rate , Pancreatitis , Humans , Male , Pancreatitis/mortality , Pancreatitis/physiopathology , Female , Middle Aged , Aged , Risk Factors , Prognosis , Intensive Care Units , Acute Disease , Adult , Survival Rate , Proportional Hazards Models
3.
Intern Emerg Med ; 19(3): 681-688, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38372886

ABSTRACT

Stress hyperglycemia has been confirmed as a strong predictor of poor short-term prognosis in acute pancreatitis. However, whether stress hyperglycemia affects the long-term prognosis of patients with acute pancreatitis is unclear. We aimed to investigate the effect of stress hyperglycemia on the long-term prognosis of non-diabetic patients with acute pancreatitis. This retrospective observational study was conducted on 4055 patients with acute pancreatitis from 1 January 2016 to 31 October 2020. The association between stress hyperglycemia and the prognosis was evaluated using regression modeling. There were 935(71.5%) normoglycemic and 373(28.5%) stress hyperglycemia patients. 46(12.3%) patients with stress hyperglycemia had evidence of diabetes compared with 33(3.5%) patients without stress hyperglycemia (P < 0.001). After multivariate adjustment, patients with stress hyperglycemia were more likely to have evidence of diabetes (OR 2.905, 95% CI 1.688-4.999) compared with normoglycemic. However, stress hyperglycemia is not associated with the recurrence of pancreatitis and progression to chronic pancreatitis. Stress hyperglycemia was independently associated with diabetes secondary to acute pancreatitis. Accordingly, a follow-up diabetes-screening program for AP with stress hyperglycemia is an important part of identifying the disease as soon as possible, delaying islet damage, and improving the prognosis of post-acute pancreatitis diabetes mellitus.


Subject(s)
Hyperglycemia , Pancreatitis , Humans , Male , Female , Retrospective Studies , Hyperglycemia/complications , Middle Aged , Prognosis , Pancreatitis/complications , Pancreatitis/physiopathology , Adult , Aged , Diabetes Mellitus/epidemiology
4.
Int J Mol Sci ; 24(14)2023 Jul 17.
Article in English | MEDLINE | ID: mdl-37511311

ABSTRACT

Ninjurin 1 (NINJ1) is a double-transmembrane cell-surface protein that might mediate plasma membrane rupture (PMR) and the diffusion of inflammatory factors. PMR is a characteristic of acinar cell injury in severe acute pancreatitis (SAP). However, the involvement of NINJ1 in mediating the PMR of acinar cells in SAP is currently unclear. Our study has shown that NINJ1 is expressed in acinar cells, and the expression is significantly upregulated in sodium-taurocholate-induced SAP. The knockout of NINJ1 delays PMR in acinar cells and alleviates SAP. Moreover, we observed that NINJ1 expression is mediated by Ca2+ concentration in acinar cells. Importantly, we found that Ca2+ overload drives mitochondrial stress to upregulate the P53/NINJ1 pathway, inducing PMR in acinar cells, and amlodipine, a Ca2+ channel inhibitor, can reduce the occurrence of PMR by decreasing the concentration of Ca2+. Our results demonstrate the mechanism by which NINJ1 induces PMR in SAP acinar cells and provide a potential new target for treatment of SAP.


Subject(s)
Acinar Cells , Calcium , Cell Membrane , Pancreatitis , Tumor Suppressor Protein p53 , Humans , Acinar Cells/metabolism , Acinar Cells/pathology , Acute Disease , Calcium/metabolism , Calcium, Dietary/metabolism , Cell Adhesion Molecules, Neuronal/metabolism , Cell Membrane/metabolism , Cell Membrane/pathology , Nerve Growth Factors/metabolism , Pancreatitis/metabolism , Pancreatitis/pathology , Pancreatitis/physiopathology , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolism
5.
Acta Cir Bras ; 37(7): e370706, 2022.
Article in English | MEDLINE | ID: mdl-36327405

ABSTRACT

PURPOSE: Abnormal activation of NOD-like receptor protein 3 (NLRP3) inflammasome can lead to the occurrence and progression of acute pancreatitis. This study investigated the protective effect of MCC950 on pancreatitis mice. METHODS: Eighteen mice were randomly divided into control group, severe acute pancreatitis (SAP) group and SAP+MCC950 group. Serum interleukin (IL)-1ß, IL-6 and tumor necrosis factor-α (TNF-α) were measured by ELISA. Hematoxylin and eosin (HE) staining was used to evaluate the pathological damage. Western blotting was used to detect the expression of NLRP3 inflammasome and tight junction proteins in the small intestine and pancreas. RESULTS: MCC950 could reduce the levels of IL-6 and IL-1ß in SAP mice. After treatment with MCC950, the expression levels of NLRP3 inflammasome in the pancreas of SAP mice were significantly reduced and the pathological damage to the pancreas and intestine was alleviated. Compared with the control group, the expression of tight junction protein (ZO-1,occludin and claudin-4) in the intestinal mucosa of SAP mice was decreased, and the expression of claudin-4 and occludin were upregulated after MCC950 treatment. CONCLUSIONS: MCC950 can inhibit NLRP3 inflammasome activation and significantly reduce the inflammatory response and delay the process of pancreatitis. It has therapeutic potential in the treatment of acute pancreatitis.


Subject(s)
Inflammasomes , NLR Family, Pyrin Domain-Containing 3 Protein , Pancreatitis , Animals , Mice , Acute Disease , Claudin-4/metabolism , Inflammasomes/metabolism , Interleukin-6 , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Occludin/metabolism , Pancreatitis/drug therapy , Pancreatitis/physiopathology
6.
Dis Markers ; 2022: 6373757, 2022.
Article in English | MEDLINE | ID: mdl-35256892

ABSTRACT

Objective: This study focused on investigating the effects of microRNA551b-5p (miR-551b-5p) on severe acute pancreatitis. Methods: Initially, quantitative real-time polymerase chain reaction (qPCR) is employed to determine the expression of miR-551b-5p in differentiated human umbilical vein endothelial cells (HUVECs). Further, the effects of aberrantly expressed miR-551b-5p in HUVECs Transwell assay. The expressions of proteins associated with severe acute pancreatitis capillary leakage syndrome are determined by Western blot, FITC-phalloidin, and immunofluorescence stainings. Finally, the correlative factor and the target genes of miR-551b-5p, as well as their contributions, are assessed. Results: We observed that overexpression of miR-551b-5p distinctly promoted the expression of EGFR, AKT3, and AQP5, while it suppressed the expression of JAM3, AQP1, and occludin. Functionally, the cytoskeleton of the miR-551b-5p overexpression was relatively loose with apparent vacuoles, and overexpression of miR-551b-5p increased the permeability of HUVECs. Conclusion: miR-551b-5p overexpression promoted changes in vascular endothelial permeability via upregulation of the EGFR/AKT3 pathway and downregulation of occludin and JAM3.


Subject(s)
Capillary Leak Syndrome/etiology , MicroRNAs/metabolism , Pancreatitis/genetics , Pancreatitis/physiopathology , Acute Disease , Biomarkers/metabolism , Blotting, Western , Capillary Leak Syndrome/metabolism , Down-Regulation , Human Umbilical Vein Endothelial Cells/metabolism , Humans , Pancreatitis/metabolism , Real-Time Polymerase Chain Reaction , Up-Regulation
8.
Int J Mol Sci ; 23(3)2022 Jan 23.
Article in English | MEDLINE | ID: mdl-35163177

ABSTRACT

Triptolide (TP), the main active ingredient of Tripterygium wilfordii Hook.f., displays potent anti-inflammatory, antioxidant, and antiproliferative activities. In the present study, the effect of TP on acute pancreatitis and the underlying mechanisms of the disease were investigated using a caerulein-induced animal model of acute pancreatitis (AP) and an in vitro cell model. In vivo, pretreatment with TP notably ameliorated pancreatic damage, shown as the improvement in serum amylase and lipase levels and pancreatic morphology. Meanwhile, TP modulated the infiltration of neutrophils and macrophages (Ly6G staining and CD68 staining) and decreased the levels of proinflammatory factors (TNF-α and IL-6) through inhibiting the transactivation of nuclear factor-κB (NF-κB) in caerulein-treated mice. Furthermore, TP reverted changes in oxidative stress markers, including pancreatic glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA), in acute pancreatitis mice. Additionally, TP pretreatment inhibited intracellular reactive oxygen species (ROS) levels via upregulated nuclear factor erythroid 2-related factor 2 (Nrf2) expression and Nrf2-regulated redox genes expression (HO-1, SOD1, GPx1 and NQO1) in vitro. Taken together, our data suggest that TP exert protection against pancreatic inflammation and tissue damage by inhibiting NF-κB transactivation, modulating immune cell responses and activating the Nrf2-mediated antioxidative system, thereby alleviating acute pancreatitis.


Subject(s)
Diterpenes/pharmacology , Pancreatitis/drug therapy , Phenanthrenes/pharmacology , Acute Disease , Animals , Antioxidants/pharmacology , Ceruletide/adverse effects , Ceruletide/pharmacology , China , Disease Models, Animal , Diterpenes/metabolism , Epoxy Compounds/metabolism , Epoxy Compounds/pharmacology , Gene Expression Regulation/drug effects , Hep G2 Cells , Humans , Inflammation/drug therapy , Inflammation/metabolism , Male , Mice , Mice, Inbred ICR , NF-E2-Related Factor 2/genetics , NF-E2-Related Factor 2/metabolism , NF-kappa B/metabolism , Oxidative Stress/drug effects , Pancreas/metabolism , Pancreatitis/immunology , Pancreatitis/physiopathology , Phenanthrenes/metabolism , Reactive Oxygen Species
9.
Inflammation ; 45(1): 45-58, 2022 Feb.
Article in English | MEDLINE | ID: mdl-35061151

ABSTRACT

We have previously shown that diallyl disulfide (DADS) protects mice against cerulein-induced acute pancreatitis (AP) and associated lung injury. However, the molecular mechanisms underlying its effect and the components involved have not been studied. We hypothesized that DADS may reduce TNF-α, CSE expression, H2S production, STAT3, and NF-κB activation and induce SOCS3 expression through peroxisome proliferator-activated receptor γ (PPAR-γ) pathway in cerulein-induced mice. Male Swiss mice were treated with hourly intraperitoneal injections of cerulein (50 µg/kg) for 6 h. Diallyl disulfide (200 µg/kg) was administered in the presence or absence of PPAR-γ antagonist GW9662 (0.3 mg/kg) (i.p) 1 h after the induction of AP. Our findings revealed that DADS blocked TNF-α, CSE expression, H2S production, and STAT3, and NF-κB activation was reversed by GW9662. Furthermore, GW9662 abrogated DADS-induced SOCS3 expression. The results show for the first that DADS-induced anti-inflammatory effect in acute pancreatitis is regulated through PPAR-γ.


Subject(s)
Allyl Compounds/pharmacology , Anti-Inflammatory Agents/pharmacology , Disulfides/pharmacology , Lung Injury/prevention & control , NF-kappa B/metabolism , PPAR gamma/metabolism , Pancreatitis/prevention & control , STAT3 Transcription Factor/metabolism , Allyl Compounds/therapeutic use , Animals , Anti-Inflammatory Agents/therapeutic use , Ceruletide , Disulfides/therapeutic use , Lung/drug effects , Lung/metabolism , Lung/physiopathology , Lung Injury/chemically induced , Lung Injury/metabolism , Lung Injury/physiopathology , Male , Mice , Pancreas/drug effects , Pancreas/metabolism , Pancreas/physiopathology , Pancreatitis/chemically induced , Pancreatitis/metabolism , Pancreatitis/physiopathology , Random Allocation , Signal Transduction/drug effects
10.
Med Sci Monit ; 28: e933230, 2022 Jan 24.
Article in English | MEDLINE | ID: mdl-35067670

ABSTRACT

BACKGROUND Acute pancreatitis (AP) is a common acute abdominal disease. Rapid evaluation of the severity is important for AP prognosis and treatment. Free triiodothyronine (fT3) level is associated with the prognosis of AP patients. This study aimed to investigate the fT3 level in patients with acute pancreatitis; early warning signs of inflammation, including interleukin-6 (IL-6) and interleukin-10 (IL-10); and the correlation of fT3 level with illness severity. MATERIAL AND METHODS Enrolled AP patients (N=312) were divided into an SAP group (N=92) and a non-SAP group (N=220) according to the Revision of Atlanta classification. Blood or tissue samples and baseline clinical characteristics were recorded. The t test and chi-square test were used to evaluate differences between the 2 groups. Multivariate logistic regression analysis and receiver operating characteristic (ROC) curves were used to investigate protective factors. One-way repeated measures analysis of variance was used to evaluate the prognosis of SAP patients. RESULTS In our study, compared with APACHII score (AUC 0.829 [95% CIs 0.769-0.889]) and Ranson score (AUC 0.629 [95% CIs 0.542-0.715]), our predictive model (AUC 0.918 [95% CIs 0.875-0.961]) showed better prognostic performance in predicting poor patient outcomes. In the SAP group, changes in fT3 level were significantly associated with prognosis (P<0.05). CONCLUSIONS The predictive model can improve the diagnostic accuracy and prediction of the severity of disease. FT3 level could be used as an independent risk factor to predict the mortality of SAP patients.


Subject(s)
Interleukin-10/blood , Interleukin-6/blood , Pancreatitis/blood , Pancreatitis/physiopathology , Triiodothyronine/blood , Female , Humans , Male , Middle Aged , Severity of Illness Index
11.
Pediatr Res ; 91(1): 56-63, 2022 01.
Article in English | MEDLINE | ID: mdl-33742133

ABSTRACT

For children, there are very few published reviews focusing on severe acute pancreatitis (AP). PubMed, EMBASE, Web of Science, Scopus, Chinese National Knowledge Infrastructure (CNKI), Wanfang data, EBSCO, and Cochrane Library were searched from inception until March 2020. Meta-regression analyses were used to estimate the etiology, case fatality, recurrence, and severity of pediatric AP in different regions (North America, Asia, South America, Europe, and Oceania). Pooled data from 47 papers (48 studies) found that main causes of pediatric AP were gallstones in Asia; trauma in Oceania; and idiopathic in Europe, North America, and South America. The case-fatality rate (CFR) of pediatric AP is 4.7% (North America), 6.2% (Europe), 2.4% (Asia), 3.1% (South America), and 7.4% (Oceania). The incidence rates of recurrent acute pancreatitis (RAP) in children who have had an episode of acute pancreatitis in North American, Asia, and Europe were 15.3, 13.1, and 13.8%, respectively. The incidence of severe acute pancreatitis (SAP) in different regions was 30.3% (Oceania), 29.2% (South America), 20.8% (Europe), 15.8% (Asia), and 13.7% (North America). It suggests that physicians should notice the etiology of pediatric AP for the initial assessment, diagnosis, prediction of relapse, and appropriate treatment at a later stage. IMPACT: It indicates the etiology of pediatric acute pancreatitis for the initial assessment, diagnosis, and prediction of relapse. Main causes of pediatric AP were gallstones in Asia; trauma in Oceania; and idiopathic in Europe, North America, and South America. The case-fatality rate of pediatric AP is diverse worldwide. It suggests that physicians noticed the etiology of pediatric AP for the initial assessment, diagnosis, prediction of relapse, and appropriate treatment at a later stage.


Subject(s)
Pancreatitis/etiology , Pancreatitis/mortality , Child , Humans , Pancreatitis/physiopathology , Recurrence , Severity of Illness Index
12.
Transfus Apher Sci ; 61(1): 103292, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34711519

ABSTRACT

The psychosocial consequences of the COVID-19 pandemic caused multifaceted challenges in clinical and therapeutic practices. This was the case at the Therapeutic Apheresis Unit of the Padua University Hospital too. Several published reports describe the increase in alcohol and food addiction diseases. In this context, during the last months, the Padua Therapeutic Apheresis Unit treated many more patients with acute pancreatitis due to severe hypertriglyceridemia with therapeutic plasma exchange than in the previous ten years. Furthermore, retrospective cohort studies have been recently published describing the onset of acute pancreatitis during the COVID-19 infection even if, to date, there is still insufficient evidence to estabilish a direct causality. Anyway, the COVID-19 pandemic translated into changes of the overall disease prevalence scenario and therefore the Padua Therapeutic Apheresis Unit will need to reorganise its Therapeutic Apheresis activity.


Subject(s)
Hypertriglyceridemia/complications , Pancreatitis/etiology , Pancreatitis/physiopathology , Pancreatitis/therapy , Plasma Exchange/methods , Adult , COVID-19 , Female , Humans , Hypertriglyceridemia/physiopathology , Male , Middle Aged , SARS-CoV-2
13.
J Perinat Med ; 50(1): 68-73, 2022 Jan 27.
Article in English | MEDLINE | ID: mdl-34523294

ABSTRACT

OBJECTIVES: Acute pancreatitis is a rare condition that can be associated with significant complications. The objective of this study is to evaluate the maternal and newborn outcomes associated with acute pancreatitis in pregnancy. METHODS: A retrospective cohort study using the Healthcare Cost and Utilization Project-Nationwide Inpatient Sample from the United States was performed. All pregnant patients with acute pancreatitis were identified using International Classification of Disease-9 coding from 1999 to 2015. The effect of acute pancreatitis on maternal and neonatal outcomes in pregnancy was evaluated using multivariate logistic regression, while adjusting for baseline maternal characteristics. RESULTS: From 1999 to 2015, there were a total of 13,815,919 women who gave birth. There were a total of 14,258 admissions of women diagnosed with acute pancreatitis, including 1,756 who delivered during their admission and 12,502 women who were admitted in the antepartum period and did not deliver during the same admission. Acute pancreatitis was associated with increased risk of prematurity, OR 3.78 (95% CI 3.38-4.22), preeclampsia, 3.81(3.33-4.36), postpartum hemorrhage, 1.90(1.55-2.33), maternal death, 9.15(6.05-13.85), and fetal demise, 2.60(1.86-3.62) among women diagnosed with acute pancreatitis. Among women with acute pancreatitis, delivery was associated with increased risk of requiring transfusions, 6.06(4.87-7.54), developing venous thromboembolisms, 2.77(1.83-4.18), acute respiratory failure, 3.66(2.73-4.91), and disseminated intravascular coagulation, 8.12(4.12-16.03). CONCLUSIONS: Acute pancreatitis in pregnancy is associated with severe complications, such as maternal and fetal death. Understanding the risk factors that may lead to these complications can help prevent or minimize them through close fetal and maternal monitoring.


Subject(s)
Pancreatitis , Pregnancy Complications , Acute Disease , Adult , Female , Fetal Death/etiology , Humans , Infant, Newborn , Logistic Models , Male , Pancreatitis/mortality , Pancreatitis/physiopathology , Pregnancy , Pregnancy Complications/mortality , Pregnancy Complications/physiopathology , Pregnancy Outcome , Retrospective Studies , Risk Factors
14.
Eur Rev Med Pharmacol Sci ; 25(23): 7460-7467, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34919248

ABSTRACT

OBJECTIVE: In this study, we aimed to investigate the effect of type of fluid (Normal Saline solution: NSS or Lactated Ringer's solution: LRS) to be selected in fluid replacement in acute pancreatitis (AP) treatment on disease severity. SUBJECTS AND METHODS: This study is a prospective, single-center study. Patients diagnosed with acute pancreatitis in emergency service were included in the study and randomized to receive LRS or NSS. The severity of AP was determined regarding Revised Atlanta Classification. C-reactive protein (CRP) levels and serum pH and bicarbonate (HCO3) levels were measured to evaluate the systemic inflammatory response and to detect changes in acid-base balance, respectively. RESULTS: Sixty-five and seventy-seven patients receiving NSS and LRS, respectively, were analyzed. Eighty-nine (67.4%) and 43 (32.6%) patients were with mild and moderate AP, respectively; however, there was no patient with severe AP. The frequency of moderate AP was significantly lower in the LRS group than the NSS group in terms of the severity of AP (p=0.011). Subjects that were randomized to receive LRS had lower CRP levels when compared to the participants in the NSS treatment arm 48 hours after resuscitation (p=0.010). In addition to these results, serum pH and HCO3 level in patients resuscitated with NSS reduced in comparison to LRS (p<0.001). CONCLUSIONS: Resuscitation with LRS is associated with decreased severity of AP in patients with AP. It may derive from how it causes lower CRP levels.


Subject(s)
Fluid Therapy/methods , Pancreatitis/therapy , Resuscitation/methods , Adult , Aged , Bicarbonates/blood , C-Reactive Protein/metabolism , Female , Humans , Hydrogen-Ion Concentration , Male , Middle Aged , Pancreatitis/physiopathology , Prospective Studies , Ringer's Lactate/administration & dosage , Saline Solution/administration & dosage , Severity of Illness Index
15.
Biomed Res Int ; 2021: 1516855, 2021.
Article in English | MEDLINE | ID: mdl-34712726

ABSTRACT

Acute pancreatitis (AP) is an inflammatory disease of the pancreas. The severity is classified as mild (MAP), moderately severe (MSAP), or severe (SAP). In patients with SAP, organ dysfunction can occur in the early stage of the disease course, accompanied by secondary infection, with a mortality rate of 36%-50%. In the late stage SAP, infection-related complications caused by pancreatic necrotic tissue and peripancreatic effusion are the main causes of death in patients. Dysbacteriosis of intestinal microflora, barrier dysfunction of intestinal mucosa, and translocation of enteric bacteria are considered to be the main causes of infection of pancreatic necrotic tissue and peripancreatic effusion. During the past few years, increasing attention has been paid to the metabolic activities of intestinal microflora in SAP, which plays an important role in the metabolic activities of the human body. This review is aimed at bringing together the most recent findings and advances regarding the gut microbial community and associated gut microbial community metabolites and illustrating the role of these metabolites in disease progression in severe acute pancreatitis. We hope that this review will provide new ideas and schemes for the treatment of SAP in the clinical settings.


Subject(s)
Gastrointestinal Microbiome , Metabolome , Pancreatitis/metabolism , Pancreatitis/microbiology , Severity of Illness Index , Animals , Bacterial Translocation , Biodiversity , Humans , Pancreatitis/etiology , Pancreatitis/physiopathology
16.
Science ; 373(6561): eabj0486, 2021 Sep 17.
Article in English | MEDLINE | ID: mdl-34529467

ABSTRACT

Inflammation is a major risk factor for pancreatic ductal adenocarcinoma (PDAC). When occurring in the context of pancreatitis, KRAS mutations accelerate tumor development in mouse models. We report that long after its complete resolution, a transient inflammatory event primes pancreatic epithelial cells to subsequent transformation by oncogenic KRAS. Upon recovery from acute inflammation, pancreatic epithelial cells display an enduring adaptive response associated with sustained transcriptional and epigenetic reprogramming. Such adaptation enables the reactivation of acinar-to-ductal metaplasia (ADM) upon subsequent inflammatory events, thereby limiting tissue damage through a rapid decrease of zymogen production. We propose that because activating mutations of KRAS maintain an irreversible ADM, they may be beneficial and under strong positive selection in the context of recurrent pancreatitis.


Subject(s)
Acinar Cells/pathology , Carcinogenesis , Carcinoma, Pancreatic Ductal/pathology , Genes, ras , Pancreas/pathology , Pancreatitis/physiopathology , Animals , Carcinoma, Pancreatic Ductal/genetics , Carcinoma, Pancreatic Ductal/immunology , Carcinoma, Pancreatic Ductal/physiopathology , Cell Transformation, Neoplastic , Cells, Cultured , Cellular Reprogramming , Chromatin/metabolism , Early Growth Response Protein 1/genetics , Early Growth Response Protein 1/metabolism , Enzyme Precursors/metabolism , Epigenesis, Genetic , Epithelial Cells/pathology , Epithelial Cells/physiology , Female , MAP Kinase Signaling System , Male , Metaplasia , Mice , Mutation , Pancreas/metabolism , Pancreatitis/genetics , Pancreatitis/immunology , Spheroids, Cellular , Transcriptome
17.
Sci Rep ; 11(1): 15930, 2021 08 05.
Article in English | MEDLINE | ID: mdl-34354184

ABSTRACT

Post Endoscopic Retrograde Cholangiopancreatography (ERCP) pancreatitis is one of the most serious complications of ERCP. Our study aims to investigate the risk, predisposing factors and prognosis of pancreatitis after ERCP in elderly patients. Patients referred to the ERCP unit between April 2008 and 2012 and admitted to the hospital at least 1 day after the ERCP procedure were included to the study. Information including patient's demographics, diagnosis, imaging findings, biochemical analysis, details of the ERCP procedure and complications were recorded. The severity of post ERCP pancreatitis (PEP) was determined by revised Atlanta Criteria as well as APACHE II and Ranson scores. A total of 2902 ERCP patients were evaluated and 988 were included to the study. Patients were divided into two groups as ≥ 65 years old (494 patients, 259 F, 235 M) and < 65 years old (494 patients, 274 F, 220 M). PEP was diagnosed in 4.3% of patients aged 65 years and older. The female gender was risk factors in elderly for PEP. The Sphincter Oddi Dysfunction (SOD) and Juxta papillary diverticula (JPD) were higher in elderly patients with PEP. Age did not increase the risk of PEP development. The most important post ERCP pancreatitis risk factor in the elderly is the female gender, while the risk is enhanced slightly by SOD and JPD.


Subject(s)
Cholangiopancreatography, Endoscopic Retrograde/adverse effects , Pancreatitis/etiology , Adult , Aged , Female , Humans , Male , Middle Aged , Pancreatitis/physiopathology , Postoperative Complications/etiology , Prognosis , Retrospective Studies , Risk Factors , Stents/adverse effects
18.
Basic Clin Pharmacol Toxicol ; 129(5): 357-368, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34384137

ABSTRACT

The management of acute pancreatitis (AP) remains a challenge to clinicians worldwide for limited effective interventions. Retinoid orphan receptor gamma t (RORγt) is a therapeutic target for several diseases; however, it is unclear whether inhibiting RORγt can ameliorate AP. The relative expression of RORγt, IL-17 and IL-23 in the peripheral blood mononuclear cells of AP patients was measured by RT-PCR. An AP mouse model was induced by ceruletide, and SR1001 was injected before ceruletide administration. RORγt+ cells, T helper 17 cells (Th17), regulatory T cells (Tregs) and γδ T cells were assessed in the pancreas and spleen by flow cytometry. Higher RORγt expression in patients indicated the potential role of RORγt in AP progression. Analyses of the IL-17/IL-23 axis confirmed its role. SR1001 significantly alleviated AP histologically in the mouse model. Serum levels of amylase, IL-6, TNFalpha, IL-17 and IL-23 decreased upon SR1001 treatment. SR1001 selectively decreased the number of RORγt+, Th17, Tregs and γδ T cells in the pancreas but not the spleen. Collectively, these results showed that SR1001 exerted therapeutic effects on AP by suppressing IL-17-secreting Th17 and γδ T cells in the pancreas. Thus, SR1001 may be a promising drug for the treatment of AP in the clinic.


Subject(s)
Nuclear Receptor Subfamily 1, Group F, Member 3/antagonists & inhibitors , Pancreatitis/drug therapy , Sulfonamides/pharmacology , Thiazoles/pharmacology , Acute Disease , Adult , Aged , Animals , Case-Control Studies , Ceruletide , Disease Models, Animal , Disease Progression , Female , Humans , Interleukin-17/blood , Intraepithelial Lymphocytes/metabolism , Leukocytes, Mononuclear/metabolism , Male , Mice , Mice, Inbred C57BL , Middle Aged , Pancreatitis/physiopathology , Th17 Cells/metabolism
19.
Pancreatology ; 21(7): 1285-1290, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34344610

ABSTRACT

BACKGROUND: In this study, we determined the pancreatic stiffness (PS) changes in the course of acute pancreatitis (AP) by ultrasound elastography and evaluated its relation with prognosis. MATERIAL/METHODS: Pancreatic shear wave velocity measurements (SWM) were evaluated at the time of admission to the hospital, following clinical improvement, and one-month after for AP patients and compared to healthy volunteers. Its relationship with clinical severity indexes was evaluated. RESULTS: The pancreatic SWM value in the healthy group was 7.72 ± 2.50 kPa, and in AP group was 10.97 ± 2.26 kPa (p = 0.000). There was no difference between mild and severe pancreatitis. The mean SWM was 8.96 ± 1.53 kPa after disease remission, and 8.83 ± 1.24 kPa after 1-month. CONCLUSIONS: PS increases significantly during AP and decreases with clinical improvement, but this was still higher than controls, and it kept its elevation after 1-month. We think that larger, long-term studies are needed to determine the clinicopathological significance of this.


Subject(s)
Elasticity Imaging Techniques , Pancreas , Pancreatitis , Adult , Cross-Sectional Studies , Elasticity , Female , Humans , Male , Middle Aged , Pancreas/diagnostic imaging , Pancreas/physiopathology , Pancreatitis/diagnostic imaging , Pancreatitis/physiopathology , Prognosis , Prospective Studies , Reproducibility of Results , Severity of Illness Index
20.
Ulus Travma Acil Cerrahi Derg ; 27(4): 410-420, 2021 Jul.
Article in English | MEDLINE | ID: mdl-34212994

ABSTRACT

BACKGROUND: Organ failures that develop due to acute pancreatitis (AP), some laboratory values and the anthropometric characteristics of the patients have been shown to play a role in the prognosis AP and have been increasingly used to investigate the prognosis of the disease although classification systems, such as Ranson's criteria, are still used habitually. In this stud, we aimed to investigate the relationship of the organ failures observed during the course of AP, the biochemical parameters and the anthropometric characteristics of the patients and compare using Ranson's and Atlanta Classifica-tion (AC) systems. METHODS: Laboratory values, anthropometric data, including the waist circumference and body mass index, Systemic inflammatory response syndrome (SIRS) and organ failures developed during the course of the disease, were investigated prospectively in 153 AP patients and the Ranson and Modified Atlanta Classifications (MAC) were made. RESULTS: A relationship was observed between the organ failures that were established in the course of the disease (lung, liver, kidney, heart and MOF (multiple organ failure)) and higher Ranson's and MAC scores (p<0.05). Among the patients included in this study, 13 (8.4%) had multiple organ failure and 17 (11.1%) had SIRS. Exitus occurred in 10 patients (6.5%). A statistically significant relationship was found with organ failure, multiple organ failure and SIRS; and ensuing exitus (p<0.05). While no relationship was observed between the waist circumference, body mass index, Ranson's score, there was a significant relationship between the MAC and the waist circumference (p<0.01). Among the laboratory values, high urea and ALT values showed a relationship with the Ranson and MAC (p<0.001), while between the CRP values tested at the 0 time point and the 48th hour, only the CRP value at the 48th hour had a relationship with Ranson's score (p<0.05). Organ failure, MOF, and SIRS showed a correlation with both the severity scores and the mortality rate. In addition, a significant corre-lation was observed between the cholesterol, triglycerides and the CRP level at the time of hospitalisa-tion and mortality. On the contrary, no significant relationship was observed with the other laboratory results, including calcium, lipase and hematocrit. CONCLUSION: In conclusion, to determine the severity and prognosis of acute pancreatitis, and ex-pect the organ failures that may occur in severe pancreatitis, the body mass index, waist circumference and laboratory values, including cholesterol, triglycerides, ALT, and CRP may supply important prog-nostic data besides the conventional disease severity scoring methods.


Subject(s)
Multiple Organ Failure , Pancreatitis , Humans , Lung/physiopathology , Multiple Organ Failure/diagnosis , Multiple Organ Failure/physiopathology , Pancreas/physiopathology , Pancreatitis/diagnosis , Pancreatitis/physiopathology , Prognosis
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