Diagnostic accuracy of endoscopic ultrasonographic shear wave elastography for assessing early chronic pancreatitis using the Japanese diagnostic criteria 2019.

Background and Aim: Endoscopic ultrasound shear wave elastography (EUS-SWE) can facilitate an objective evaluation of pancreatic fibrosis. Although it is primarily applied in evaluating chronic pancreatitis, its efficacy in assessing early chronic pancreatitis (ECP) remains underinvestigated. This study evaluated the diagnostic accuracy of EUS-SWE for assessing ECP diagnosed using the Japanese diagnostic criteria 2019. Methods: In total, 657 patients underwent EUS-SWE. Propensity score matching was used, and the participants were classified into the ECP and normal groups. ECP was diagnosed using the Japanese diagnostic criteria 2019. Pancreatic stiffness was assessed based on velocity (Vs) on EUS-SWE, and the optimal Vs cutoff value for ECP diagnosis was determined. A practical shear wave Vs value of ≥50% was considered significant. Results: Each group included 22 patients. The ECP group had higher pancreatic stiffness than the normal group (2.31 ± 0.67 m/s vs. 1.59 ± 0.40 m/s, p < 0.001). The Vs cutoff value for the diagnostic accuracy of ECP, as determined using the receiver operating characteristic curve, was 2.24m/s, with an area under the curve of 0.82 (95% confidence interval: 0.69-0.94). A high Vs was strongly correlated with the number of EUS findings (rs = 0.626, p < 0.001). Multiple regression analysis revealed that a history of acute pancreatitis and ≥2 EUS findings were independent predictors of a high Vs. Conclusions: There is a strong correlation between EUS-SWE findings and the Japanese diagnostic criteria 2019 for ECP. Hence, EUS-SWE can be an objective and invaluable diagnostic tool for ECP diagnosis.

Immunoglobulin G4 -related gastrointestinal disease associated with type 1 autoimmune pancreatitis: A case report.

Immunoglobulin G4 (IgG4)-related diseaseis a systemic inflammatory condition of unknown etiology characterized by increases in serum IgG4 and in the number of IgG4-positive cells in affected tissues. One of the commonly involved locations is the pancreas; this condition is known as type 1 autoimmune pancreatitis (AIP). Type 1 AIP, which shows a biliary stricture in the intrapancreatic bile duct, can be misdiagnosed as a malignancy due to similar cholangiography findings and clinical presentation. In rare cases complicated by post-bulbar duodenal ulcers, differentiating between type 1 AIP and malignancies is even more difficult. An 81-year-old male was referred to our hospital for the treatment of a pancreatic head mass and obstructive jaundice. Serological and radiological findings were consistent with both type 1 AIP and a malignancy. Gastroduodenoscopy revealed a post-bulbar duodenal ulcer with endoscopic features that evoked malignant duodenal invasion. Although biopsies were negative for malignant cells, subsequent bleeding from the lesion suggested the progression of malignancy, which led to surgical resection. Pancreatoduodenectomy and pathological examination indicated that type 1 AIP was present. Simultaneously, the involvement of IgG4-related disease in the ulcerative lesion was suggested. To our knowledge, this is the first reported case of type 1 AIP complicated by post-bulbar duodenal ulcers, which was misdiagnosed as malignancy and considered an IgG4-related gastrointestinal disease associated with type 1 AIP.

Early detection of necrosis in low-enhanced pancreatic parenchyma using contrast-enhanced computed tomography was a better predictor of clinical outcomes than pancreatic inflammation: A multicentric cohort study of severe acute pancreatitis.

OBJECTIVES: We aim to assess the early use of contrast-enhanced computed tomography (CECT) of patients with severe acute pancreatitis (SAP) using the computed tomography severity index (CTSI) in prognosis prediction. The CTSI combines quantification of pancreatic and extrapancreatic inflammation with the extent of pancreatic necrosis. METHODS: Post-hoc retrospective analysis of a large, multicentric database (44 institutions) of SAP patients in Japan. The area under the curve (AUC) of the CTSI for predicting mortality and the odds ratio (OR) of the extent of pancreatic inflammation and necrosis were calculated using multivariable analysis. RESULTS: In total, 1097 patients were included. The AUC of the CTSI for mortality was 0.65 (95 % confidence interval [CI:] [0.59-0.70]; p < 0.001). In multivariable analysis, necrosis 30-50 % and >50 % in low-enhanced pancreatic parenchyma (LEPP) was independently associated with a significant increase in mortality, with OR 2.04 and 95 % CI 1.01-4.12 (P < 0.05) and OR 3.88 and 95 % CI 2.04-7.40 (P < 0.001), respectively. However, the extent of pancreatic inflammation was not associated with mortality, regardless of severity. CONCLUSIONS: The degree of necrosis in LEPP assessed using early CECT of SAP was a better predictor of mortality than the extent of pancreatic inflammation.

TREATMENT OF SEVERE HYPERTRIGLYCERIDEMIA THROUGH THERAPEUTIC PLASMA EXCHANGE IN PATIENTS WITH ACUTE PANCREATITIS OR AT RISK OF DEVELOPING IT. / TRATAMIENTO DE LA HIPERTRIGLICERIDEMIA GRAVE MEDIANTE RECAMBIO PLASMÁTICO TERAPÉUTICO EN PACIENTES CON PANCREATITIS AGUDA O EN RIESGO DE PADECERLA.

INTRODUCTION AND OBJECTIVES: TPE drastically reduces serum triglyceride (sTG), but its role in the treatment of hypertriglyceridemia-induced acute pancreatitis (HTG-AP) or at risk of developing it, is not well established. The objectives were to assess the effectiveness and safety of TPE in the treatment of severe HTG (sHTG), as well as to evaluate the severity of HTG-AP treated with TPE. MATERIALS AND METHODS: Observational-retrospective-single-center study, in which a descriptive analysis of sHTG treated with TPE was conducted, with the aim of treating HTG-AP or preventing its recurrence. TPE was performed if sTG≥ 1000 mg/dL after 24 hours of admission. RESULTS: 42 TPE were performed to treat 35 sHTG in 23 patients: 29 HTG-AP, and 6 sHTG with previous HTG-AP. Among the patients, 37% (13/55) were women, with 37±14 years-old, 74.3% had normal BMI (25/35), 34% (12/35) were drinking >40 g/alcohol/day and 54% (19/35) were diabetics. TPE significantly reduced the baseline sTG (4425±2782 mg/dL vs. 709±353 mg/dL, p<0.001) in a single session, achieving a mean percentage reduction of 79±13%; 20% (7/35) of sHTG cases required two TPE sessions to reduce sTG to <1000 mg/dL. Adverse effects were reported in 4/42 TPE sessions (9,5%). sHTG-AP was observed in 3% of cases (1/29), and there were no deaths. sTG at 24 hours of admission showed no relation with the severity of APs. CONCLUSION: The treatment of sHTG with TPE, with the aim of treating HTG-AP or preventing its recurrence, reduces sTG quickly and safety.

Hypertriglyceridemia, Hypercholesterolemia, Body Mass Index, and the Risk of Acute Pancreatitis.

OBJECTIVE: The purpose of this work was to check the connection between parameters of lipid profile and body mass index (BMI) in relation to the occurrence of acute pancreatitis within a sample of adults from northern China. METHODOLOGY: A total of 123,214 participants from the Kailuan Group were incorporated into this prospective study. The subjects were categorized into quartiles on the basis of their initial levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). On the basis of BMI classification, the individuals in the study were divided into three distinct groups: normal weight, overweight, and obese. The data were analyzed to explore the correlation between lipid profile and BMI with acute pancreatitis. RESULTS: Over a period of 12.59 ± 0.98 years, during the median follow-up duration, a total of 410 new patients with acute pancreatitis were recorded. The occurrence rate and total occurrence of acute pancreatitis demonstrated an upward trend in correlation with elevated levels of TG, TC, and BMI. Following adjustment for multiple variables, it was observed that individuals in the fourth quartile of TG and TC levels demonstrated the highest likelihood of developing acute pancreatitis. Furthermore, our analysis revealed that a proportion of 19.29% of the correlation between BMI and the likelihood of experiencing acute pancreatitis can be attributed to the influence of elevated TG levels, whereas 12.69% of the association was mediated by higher TC. CONCLUSIONS: We found that hypertriglyceridemia, hypercholesterolemia, and obesity were risk factors for acute pancreatitis, especially in young and middle-aged men.TG and TC were the mediating factors between BMI and the risk of acute pancreatitis.

A Rare Case of Pancreaticopleural Fistula That Presented as a Recurrent Pleural Effusion at a Regional Hospital in Guyana.

Pancreaticopleural fistula is a rare complication of pancreatitis. We present a rare case of pancreaticopleural fistula in a 43-year-old alcoholic male. He presented with recurrent episodes of left pleural effusion that were managed with aspiration and chest tube placement. An MRI of the chest and upper abdomen revealed a pancreaticopleural fistula. The patient underwent distal pancreatectomy with splenectomy and Roux-en-Y pancreaticojejunostomy. The surgical approach was our first-line management due to the unavailability of octreotide and endoscopic retrograde cholangiopancreatography. His recovery was complicated by an empyema that was managed by tube thoracostomy and IV antibiotics. There was no issue detected at his 3-month follow-up clinic visit.

Chronic pancreatitis of jejunal ectopic pancreas: a rare cause of chronic abdominal pain.

Ectopic pancreas (EP) is an uncommon, congenital focus of pancreatic tissue that is discontinuous with the principal pancreas. A 62-year-old female underwent multiple investigations for chronic epigastric pain. EP was identified intra-operatively. On retrospection, earlier imaging showed a thickened segment of jejunum with inflammation of the surrounding small bowel mesentery, suggestive of jejunal EP pancreatitis. Histology confirmed ectopic pancreatic tissue, with sections of the EP showing evidence of previous acute and chronic pancreatitis. When no cause for chronic abdominal pain is found, diagnostic laparoscopy should be considered, and the small bowel inspected, to further investigate for rare causes of abdominal pain, such as EP.

Psychological experience and coping strategies of pregnant women with acute pancreatitis: a qualitative descriptive study.

BACKGROUND: To clarify the psychological experience and coping strategies in patients with acute pancreatitis in pregnancy (APIP) and propose interventional measures to improve pregnancy outcomes in these women. With an increasing trend of pregnant women in advanced ages and multiparous women, the incidence of APIP has significantly increased. Pregnancy accompanied by concurrent pancreatitis may subject these women to notable psychological stress, which is a factor that has been infrequently reported in previous studies. METHODS: APIP patients were interviewed from December 2020 to June 2021. Data were collected through semi-structured interviews based on an outline, including six questions. The interviews were recorded and analyzed using qualitative content analysis until data saturation was reached. RESULTS: Ten APIP patients were interviewed and four themes were identified, including excessive psychological burden, uncomfortable experience, urgent requirement for adequate medical resources, and importance of social support. CONCLUSION: Patients with APIP suffer from significant psychological stress due to their medical conditions and management. They desired adequate medical resources and social support. The local health department, hospital administrators, and medical staff should understand the psychological requirements and provide adequate healthcare and education that are easily accessible to these APIP patients. In addition, family support should also be encouraged to promote APIP patients' recovery.

Yinchenhao Decoction Protects Against Acute Liver Injury in Mice With Biliary Acute Pancreatitis by Regulating the Gut Microflora-Bile Acids-Liver Axis.

Background and Aims: Acute liver injury (ALI) often follows biliary acute pancreatitis (BAP), but the exact cause and effective treatment are unknown. The aim of this study was to investigate the role of the gut microflora-bile acids-liver axis in BAP-ALI in mice and to assess the potential therapeutic effects of Yinchenhao decoction (YCHD), a traditional Chinese herbal medicine formula, on BAP-ALI. Methods: Male C57BL/6 mice were allocated into three groups: negative control (NC), BAP model, and YCHD treatment groups. The severity of BAP-ALI, intrahepatic bile acid levels, and the gut microbiota were assessed 24 h after BAP-ALI induction in mice. Results: Our findings demonstrated that treatment with YCHD significantly ameliorated the severity of BAP-ALI, as evidenced by the mitigation of hepatic histopathological changes and a reduction in liver serum enzyme levels. Moreover, YCHD alleviated intrahepatic cholestasis and modified the composition of bile acids, as indicated by a notable increase in conjugated bile acids. Additionally, 16S rDNA sequencing analysis of the gut microbiome revealed distinct alterations in the richness and composition of the microbiome in BAP-ALI mice compared to those in control mice. YCHD treatment effectively improved the intestinal flora disorders induced by BAP-ALI. Spearman's correlation analysis revealed a significant association between the distinct compositional characteristics of the intestinal microbiota and the intrahepatic bile acid concentration. Conclusions: These findings imply a potential link between gut microbiota dysbiosis and intrahepatic cholestasis in BAP-ALI mice and suggest that YCHD treatment may confer protection against BAP-ALI via the gut microflora-bile acids-liver axis.

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

Purpose: 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. Patients and Methods: 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. Results: 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. Conclusion: 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.

Association between acute peripancreatic fluid collections and early readmission in acute pancreatitis: A propensity-matched analysis.

BACKGROUND: Patients with acute pancreatitis (AP) frequently experience hospital readmissions, posing a significant burden to healthcare systems. Acute peripancreatic fluid collection (APFC) may negatively impact the clinical course of AP. It could worsen symptoms and potentially lead to additional complications. However, clinical evidence regarding the specific association between APFC and early readmission in AP remains scarce. Understanding the link between APFC and readmission may help improve clinical care for AP patients and reduce healthcare costs. AIM: To evaluate the association between APFC and 30-day readmission in patients with AP. METHODS: This retrospective cohort study is based on the Nationwide Readmission Database for 2016-2019. Patients with a primary diagnosis of AP were identified. Participants were categorized into those with and without APFC. A 1:1 propensity score matching for age, gender, and Elixhauser comorbidities was performed. The primary outcome was early readmission rates. Secondary outcomes included the incidence of inpatient complications and healthcare utilization. Unadjusted analyses used Mann-Whitney U and χ 2 tests, while Cox regression models assessed 30-day readmission risks and reported them as adjusted hazard ratios (aHR). Kaplan-Meier curves and log-rank tests verified readmission risks. RESULTS: A total of 673059 patients with the principal diagnosis of AP were included. Of these, 5.1% had APFC on initial admission. After propensity score matching, each cohort consisted of 33914 patients. Those with APFC showed a higher incidence of inpatient complications, including septic shock (3.1% vs 1.3%, P < 0.001), portal venous thrombosis (4.4% vs 0.8%, P < 0.001), and mechanical ventilation (1.8% vs 0.9%, P < 0.001). The length of stay (LOS) was longer for APFC patients [4 (3-7) vs 3 (2-5) days, P < 0.001], as were hospital charges ($29451 vs $24418, P < 0.001). For 30-day readmissions, APFC patients had a higher rate (15.7% vs 6.5%, P < 0.001) and a longer median readmission LOS (4 vs 3 days, P < 0.001). The APFC group also had higher readmission charges ($28282 vs $22865, P < 0.001). The presence of APFC increased the risk of readmission twofold (aHR 2.52, 95% confidence interval: 2.40-2.65, P < 0.001). The independent risk factors for 30-day readmission included female gender, Elixhauser Comorbidity Index ≥ 3, chronic pulmonary diseases, chronic renal disease, protein-calorie malnutrition, substance use disorder, depression, portal and splenic venous thrombosis, and certain endoscopic procedures. CONCLUSION: Developing APFC during index hospitalization for AP is linked to higher readmission rates, more inpatient complications, longer LOS, and increased healthcare costs. Knowing predictors of readmission can help target high-risk patients, reducing healthcare burdens.

Symptomatic uncomplicated gallstone disease is associated with a high short-term risk of gallstone-related complications: a contemporary cohort study.

BACKGROUND: The natural history of symptomatic uncomplicated gallstone disease is largely unknown. We examined the risk of progressing from symptomatic uncomplicated to complicated gallstone disease in a large regional cohort of patients, where disruptions in elective surgical capacities have led to the indefinite postponement of surgery for benign conditions, including cholecystectomies. METHODS: Patients with radiologically diagnosed incident symptomatic and uncomplicated gallstone disease were identified from outpatient clinics and emergency departments on the Island of Funen, Denmark. The absolute risk of complications (cholecystitis, cholangitis, pancreatitis, acute cholecystectomy for unremitting pain) was calculated using death and elective cholecystectomies as competing risks using the Aalen-Johansen method. Cox proportional hazards regression analysis was used to estimate hazard ratios (HRs) of gallstone complications associated with patient and gallstone characteristics. RESULTS: Two hundred eighty-six patients diagnosed with incident symptomatic, uncomplicated gallstone disease from 1 January 2020 to 1 July 2023 were identified. During 79,170 person-years of observation, 176 (61.5%) patients developed a gallstone-related complication. The 6-, 12- and 24-month risk of developing gallstone-related complications were 36%, 55% and 81%. The risk of developing complications related to common bile duct stones was lowest with larger stones (aHR per millimeter increase = 0.89 (0.82-0.97), p < 0.01), while no covariates were statistically significantly associated with the risk of cholecystitis. Eighty-five (30%) patients underwent elective laparoscopic cholecystectomy, with one patient (1.2%) developing a gallstone-related complication afterward. CONCLUSIONS: The risk of developing complications to symptomatic gallstones in a general Scandinavian population is high, and prophylactic cholecystectomy should be considered.

Pancreatic Schwann cell reprogramming supports cancer-associated neuronal remodeling.

The peripheral nervous system is a key regulator of cancer progression. In pancreatic ductal adenocarcinoma (PDAC), the sympathetic branch of the autonomic nervous system inhibits cancer development. This inhibition is associated with extensive sympathetic nerve sprouting in early pancreatic cancer precursor lesions. However, the underlying mechanisms behind this process remain unclear. This study aimed to investigate the roles of pancreatic Schwann cells in the structural plasticity of sympathetic neurons. We examined the changes in the number and distribution of Schwann cells in a transgenic mouse model of PDAC and in a model of metaplastic pancreatic lesions induced by chronic inflammation. Schwann cells proliferated and expanded simultaneously with new sympathetic nerve sprouts in metaplastic/neoplastic pancreatic lesions. Sparse genetic labeling showed that individual Schwann cells in these lesions had a more elongated and branched structure than those under physiological conditions. Schwann cells overexpressed neurotrophic factors, including glial cell-derived neurotrophic factor (GDNF). Sympathetic neurons upregulated the GDNF receptors and exhibited enhanced neurite growth in response to GDNF in vitro. Selective genetic deletion of Gdnf in Schwann cells completely blocked sympathetic nerve sprouting in metaplastic pancreatic lesions in vivo. This study demonstrated that pancreatic Schwann cells underwent adaptive reprogramming during early cancer development, supporting a protective antitumor neuronal response. These finding could help to develop new strategies to modulate cancer associated neural plasticity.

X-Box binding protein 1 downregulates SIRT6 to promote injury in pancreatic ductal epithelial cells.

OBJECTIVE: Acute pancreatitis (AP) stands as a frequent cause for clinical emergency hospital admissions. The X-box binding protein 1 (XBP1) was found to be implicated in pancreatic acinar cell apoptosis. The objective is to unveil the potential mechanisms governed by XBP1 and SIRT6 in the context of AP. METHODS: Caerulein-treated human pancreatic duct epithelial (HPDE) cells to establish an in vitro research model. The levels and regulatory role of SIRT6 in the treated cells were evaluated, including its effects on inflammatory responses, oxidative stress, apoptosis, and endoplasmic reticulum stress. The relationship between XBP1 and SIRT6 was explored by luciferase and ChIP experiments. Furthermore, the effect of XBP1 overexpression on the regulatory function of SIRT6 on cells was evaluated. RESULTS: Caerulein promoted the decrease of SIRT6 and the increase of XBP1 in HPDE cells. Overexpression of SIRT6 slowed down the secretion of inflammatory factors, oxidative stress, apoptosis level, and endoplasmic reticulum stress in HPDE cells. However, XBP1 negatively regulated SIRT6, and XBP1 overexpression partially reversed the regulation of SIRT6 on the above aspects. CONCLUSION: Our study illuminates the role of XBP1 in downregulating SIRT6 in HPDE cells, thereby promoting cellular injury. Inhibiting XBP1 or augmenting SIRT6 levels holds promise in preserving cell function and represents a potential therapeutic avenue in the management of AP.

Ehmt2 inactivation in pancreatic epithelial cells shapes the transcriptional landscape and inflammation response of the whole pancreas.

Introduction: The Euchromatic Histone Methyl Transferase Protein 2 (EHMT2), also known as G9a, deposits transcriptionally repressive chromatin marks that play pivotal roles in the maturation and homeostasis of multiple organs. Recently, we have shown that Ehmt2 inactivation in the mouse pancreas alters growth and immune gene expression networks, antagonizing Kras-mediated pancreatic cancer initiation and promotion. Here, we elucidate the essential role of Ehmt2 in maintaining a transcriptional landscape that protects organs from inflammation. Methods: Comparative RNA-seq studies between normal postnatal and young adult pancreatic tissue from Ehmt2 conditional knockout animals (Ehmt2 fl/fl ) targeted to the exocrine pancreatic epithelial cells (Pdx1-Cre and P48 Cre/+ ), reveal alterations in gene expression networks in the whole organ related to injury-inflammation-repair, suggesting an increased predisposition to damage. Thus, we induced an inflammation repair response in the Ehmt2 fl/fl pancreas and used a data science-based approach to integrate RNA-seq-derived pathways and networks, deconvolution digital cytology, and spatial transcriptomics. We also analyzed the tissue response to damage at the morphological, biochemical, and molecular pathology levels. Results and discussion: The Ehmt2 fl/fl pancreas displays an enhanced injury-inflammation-repair response, offering insights into fundamental molecular and cellular mechanisms involved in this process. More importantly, these data show that conditional Ehmt2 inactivation in exocrine cells reprograms the local environment to recruit mesenchymal and immunological cells needed to mount an increased inflammatory response. Mechanistically, this response is an enhanced injury-inflammation-repair reaction with a small contribution of specific Ehmt2-regulated transcripts. Thus, this new knowledge extends the mechanisms underlying the role of the Ehmt2-mediated pathway in suppressing pancreatic cancer initiation and modulating inflammatory pancreatic diseases.

Case Report: Chronic pancreatitis in children as the cumulative effect of bilio-pancreatic abnormalities and genetic mutations.

Pancreatitis, in general, is a high-morbidity condition. Genetic conditions and anatomic variants are sometimes seen, especially in children, where biliary etiologies and alcohol are less common than in adults. The decision to intervene, the combined operative-endoscopic strategy, and the timing pose unique challenges. We report the case of a 10-year-old boy with PRSS1 mutation and pancreatic duct duplication, discussing the management and reviewing the recent reports in the Literature.

COVID-19-Induced Hypertriglyceridemia Leading to Pancreatitis in a 51-Year-Old Female.

There are increasing reports of the effects of COVID-19 on the pancreas. Pancreatitis, as a result of hypertriglyceridemia, has also been reported. Hypothesized mechanisms include hemophagocytic lymphohistiocytosis (HLH) syndrome and acquired lipoprotein lipase (LPL) inhibitors. We present a 51-year-old female patient who presented with nausea, vomiting, and epigastric abdominal pain radiating to the back. On examination, she had generalized abdominal tenderness without guarding or rebound tenderness. Our workup revealed elevated lipase of 1150 units/L, triglycerides (TG) of 11340 mg/dL, and mild pancreatitis on an abdominal computed tomography (CT) scan. On day 2, she developed a new oxygen requirement and tested positive for COVID-19. She was treated with fluids and opiates for pancreatitis, plasmapheresis, and an insulin infusion to treat her hypertriglyceridemia. She was treated with remdesivir for an acute COVID-19 infection. Triglycerides decreased to <500 mg/dL with treatment, and she was discharged home on oral lipid-lowering agents. By discussing this case, we aim to shed light on the association between COVID-19 and hypertriglyceridemia, which can further lead to life-threatening complications such as acute pancreatitis. Further studies are needed to identify the exact mechanisms, preventive measures, and long-term effects of COVID-19 on triglycerides and the pancreas.

Secretagogue-induced pancreatitis in mice devoid of chymotrypsin.

The serine protease chymotrypsin protects the pancreas against pancreatitis by degrading trypsinogen, the precursor to the digestive protease trypsin. Taking advantage of previously generated mouse models with either the Ctrb1 gene (encoding chymotrypsin B1) or the Ctrl gene (encoding chymotrypsin-like protease) disrupted, here we generated the novel Ctrb1-del ×Ctrl-KO strain in the C57BL/6N genetic background, which harbors a naturally inactivated Ctrc gene (encoding chymotrypsin C). The newly created mice are devoid of chymotrypsin yet the animals develop normally, breed well, and show no spontaneous phenotype, indicating that chymotrypsin is dispensable under laboratory conditions. When given cerulein, the Ctrb1-del ×Ctrl-KO strain exhibited markedly increased intrapancreatic trypsin activation and more severe acute pancreatitis, relative to wild-type C57BL/6N mice. After the acute episode, Ctrb1-del ×Ctrl-KO mice spontaneously progressed to chronic pancreatitis while C57BL/6N mice recovered rapidly. The cerulein-induced pancreas pathology in Ctrb1-del ×Ctrl-KO mice was highly similar to that previously observed in Ctrb1-del mice, however, trypsin activation was more robust and pancreatitis severity was increased. Taken together, the results confirm and extend prior observations demonstrating that chymotrypsin safeguards the pancreas against pancreatitis by limiting pathologic trypsin activity. In mice, the CTRB1 isoform, which constitutes about 90% of the total chymotrypsin content, is responsible primarily for the anti-trypsin defenses and protection against pancreatitis, however, the minor isoform CTRL also contributes to an appreciable extent.

Overexpression of Plakophilin2 Mitigates Capillary Leak Syndrome in Severe Acute Pancreatitis by Activating the p38/MAPK Signaling Pathway.

Purpose: Capillary leak syndrome (CLS) is an intermediary phase between severe acute pancreatitis (SAP) and multiple organ failure. As a result, CLS is of clinical importance for enhancing the prognosis of SAP. Plakophilin2 (PKP2), an essential constituent of desmosomes, plays a critical role in promoting connections between epithelial cells. However, the function and mechanism of PKP2 in CLS in SAP are not clear at present. Methods: We detected the expression of PKP2 in mice pancreatic tissue by transcriptome sequencing and bioinformatics analysis. PKP2 was overexpressed and knocked down to assess its influence on cell permeability, the cytoskeleton, tight junction molecules, cell adhesion junction molecules, and associated pathways. Results: PKP2 expression was increased in the pancreatic tissues of SAP mice and human umbilical vein endothelial cells (HUVECs) after lipopolysaccharide (LPS) stimulation. PKP2 overexpression not only reduced endothelial cell permeability but also improved cytoskeleton relaxation in response to acute inflammatory stimulation. PKP2 overexpression increased levels of ZO-1, occludin, claudin1, ß-catenin, and connexin43. The overexpression of PKP2 in LPS-induced HUVECs counteracted the inhibitory effect of SB203580 (a p38/MAPK signaling pathway inhibitor) on the p38/MAPK signaling pathway, thereby restoring the levels of ZO-1, ß-catenin, and claudin1. Additionally, PKP2 suppression eliminated the enhanced levels of ZO-1, ß-catenin, occludin, and claudin1 induced by dehydrocorydaline. We predicted that the upstream transcription factor PPARγregulates PKP2 expression, and our findings demonstrate that the PPARγactivator rosiglitazone significantly upregulates PKP2, whereas its antagonist GW9662 down-regulates PKP2. Administration of rosiglitazone significantly reduced the increase in HUVECs permeability stimulated by LPS. Conversely, PKP2 overexpression counteracted the GW9662-induced reduction in ZO-1, phosphorylated p38/p38, and claudin1. Conclusion: The activation of the p38/MAPK signaling pathway by PKP2 mitigates CLS in SAP. PPARγactivator rosiglitazone can up-regulate PKP2. Overall, directing efforts toward PKP2 could prove to be a feasible treatment approach for effectively managing CLS in SAP.