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.

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.

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.

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.

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.

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.

Corrigendum: Material basis and molecular mechanisms of Chaihuang Qingyi Huoxue Granule in the treatment of acute pancreatitis based on network pharmacology and molecular docking-based strategy.

[This corrects the article DOI: 10.3389/fimmu.2024.1353695.].

Clinical study of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in hypertriglyceridemia-induced acute pancreatitis and acute biliary pancreatitis with persistent organ failure.

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are novel inflammatory indicators that can be used to predict the severity and prognosis of various diseases. We categorize acute pancreatitis by etiology into acute biliary pancreatitis (ABP) and hypertriglyceridemia-induced acute pancreatitis (HTGP). AIM: To investigate the clinical significance of NLR and PLR in assessing persistent organ failure (POF) in HTGP and ABP. METHODS: A total of 1450 patients diagnosed with acute pancreatitis (AP) for the first time at Shanxi Bethune Hospital between January 2012 and January 2023 were enrolled. The patients were categorized into two groups according to the etiology of AP: ABP in 530 patients and HTGP in 241 patients. We collected and compared the clinical data of the patients, including NLR, PLR, and AP prognostic scoring systems, within 48 h of hospital admission. RESULTS: The NLR (9.1 vs 6.9, P < 0.001) and PLR (203.1 vs 160.5, P < 0.001) were significantly higher in the ABP group than in the HTGP group. In the HTGP group, both NLR and PLR were significantly increased in patients with severe AP and those with a SOFA score ≥ 3. Likewise, in the ABP group, NLR and PLR were significantly elevated in patients with severe AP, modified computed tomography severity index score ≥ 4, Japanese Severity Score ≥ 3, and modified Marshall score ≥ 2. Moreover, NLR and PLR showed predictive value for the development of POF in both the ABP and HTGP groups. CONCLUSION: NLR and PLR vary between ABP and HTGP, are strongly associated with AP prognostic scoring systems, and have predictive potential for the occurrence of POF in both ABP and HTGP.

Physiotherapy to Alleviate Chest Complications in Acute Pancreatitis With Comorbidities: A Rare Case of Young Female.

An abnormal buildup of pleural fluid, known as a pleural effusion, results from an imbalance between excessive formation and absorption. Despite the wide range of pleural effusion causes, including pneumonia, congestive heart failure, and cancer, the majority of cases are attributed to pleural fluid buildup. Acute pancreatitis also leads to complications such as systemic inflammatory response syndrome. A complex pathophysiologic reaction to a range of wounds, including trauma and infections, burns, and pancreatitis, is known as systemic inflammatory response syndrome. It was recognized that a variety of injuries exhibited a similar inflammatory response, making them prime candidates for new anti-inflammatory molecules designed to stop the spread of inflammation or provide targeted therapy. Localized inflammation, a protective response that the body regulates at the site of the injury, can, if lost or overly activated, result in a heightened systemic response known as systemic inflammatory response syndrome. The patient is a 19-year-old female who arrived at Acharya Vinoba Bhave Rural Hospital with complaints of abdominal pain for eight days, abdominal distension for three to four days, breathing difficulty for three to four days, and fever. According to the patient's condition, she was unable to perform normal activities of daily living for eight days. She had breathlessness for eight days, which worsened four days ago. She was diagnosed with pleural effusion, acute pancreatitis, and systemic inflammatory response syndrome. This case is unique as the patient is very young and she has multiple health issues such as severe pancreatitis, ischemic heart disease, systemic inflammatory response syndrome, pulmonary consolidation, and pleural effusion at the same time which makes this condition critical. This study aimed to identify the improvement in this patient after getting physiotherapy treatment. Physiotherapy treatment included lifestyle modifications to reduce weight, performing exercise on a daily basis, breathing exercises airway clearance technique, volumetric incentive spirometer segmental expansion, inspiratory muscle training, chest mobilization, chest proprioceptive neuromuscular facilitation (PNF), and graded mobilization to improve patient condition. When added to standard care, a physiotherapy program improves radiological results, spirometric parameters, and hospital stays in pleural effusion patients.

Application of psychological intervention in intensive care unit nursing for patients with severe acute pancreatitis.

BACKGROUND: Severe acute pancreatitis (SAP) is a familiar critical disease in the intensive care unit (ICU) patients. Nursing staff are important spiritual pillars during the treatment of patients, and in addition to routine nursing, more attention needs be paid to the patient's psychological changes. AIM: To investigate the effects of psychological intervention in ICU patients with SAP. METHODS: One hundred ICU patients with SAP were hospitalized in the authors' hospital between 2020 and 2023 were selected, and divided into observation and control groups per the hospitalization order. The control and observation groups received routine nursing and psychological interventions, respectively. Two groups are being compared, using the Self-rating Anxiety Scale (SAS), Self-Determination Scale (SDS), Acute Physiology and Chronic Health Evaluation (APACHE) II, and 36-item Short Form Health Survey (SF-36) scores; nursing satisfaction of patients; ICU care duration; length of stay; hospitalization expenses; and the incidence of complications. RESULTS: After nursing, the SDS, SAS, and APACHE II scores in the experimental group were significantly lower than in the control group (P < 0.05). The SF-36 scores in the observation group were significantly higher than those in the control group (P < 0.05). The nursing satisfaction of patients in the experimental group was 94.5%, considerably higher than that of 75.6% in the control group (P < 0.05). The ICU care duration, length of stay, and hospitalization expenses in the observation group were significantly lower than those in the control group, and the incidence of complications was lower (P < 0.05). CONCLUSION: For patients with SAP, the implementation of standardized psychological intervention measures can effectively alleviate adverse psychological conditions.

Does the site, size, and number of necrotic collections affect the outcome of necrotizing pancreatitis? - a prospective analysis.

PURPOSE: In patients with acute necrotizing pancreatitis (ANP), the site, size, and the number of acute necrotic collections (ANC) may determine the outcome of patients. The current study aimed to correlate the nature of ANC with the adverse outcomes in ANP patients. METHODS: This was a single-center, prospective study (August 2019-August 2022) recruiting patients with ANP, correlating the site, size, and number of ANC with the length of hospital stay, intensive care unit (ICU) stays, development of organ failure and infection, need for intervention, and mortality. RESULTS: A total of 114 patients (mean age: 37.3 ± 13.4 years, 85.1% males) with ANP were included in the study. The number and maximum diameter of collections significantly correlated with the length of the hospital and ICU stay and the need for intervention. Taking a cut-off size of 8 cm, the sensitivity and specificity for predicting the need for intervention were 82.7% and 74.2%, respectively. ANCs located in the perinephric, paracolic, subhepatic, and epigastric regions had a significant correlation with two or more adverse outcomes. Additional points were added to the modified CT severity index (mCTSI) based on the present study's findings. The new score had significantly higher AUROC than mCTSI for predicting infection, need for intervention, ICU stay > 1 week, and mortality. CONCLUSION: The site, size, and number of EPNs have a significant correlation with adverse clinical outcomes in patients with ANP. The inclusion of these parameters, along with present scoring systems, will help further improve the prognostication of patients.

Combination of the CRAC Channel Inhibitor CM4620 and Galactose as a Potential Therapy for Acute Pancreatitis.

Acute pancreatitis (AP) is a life-threatening inflammatory disease with no specific therapy. Excessive cytoplasmic Ca2+ elevation and intracellular ATP depletion are responsible for the initiation of AP. Inhibition of Ca2+ release-activated Ca2+ (CRAC) channels has been proposed as a potential treatment, and currently, a novel selective CRAC channel inhibitor CM4620 (Auxora, CalciMedica) is in Phase 2b human trials. While CM4620 is on track to become the first effective treatment for AP, it does not produce complete protection in animal models. Recently, an alternative approach has suggested reducing ATP depletion with a natural carbohydrate galactose. Here, we have investigated the possibility of using the smallest effective concentration of CM4620 in combination with galactose. Protective effects of CM4620, in the range of 1-100 n m, have been studied against necrosis induced by bile acids, palmitoleic acid, or l-asparaginase. CM4620 markedly protected against necrosis induced by bile acids or asparaginase starting from 50 n m and palmitoleic acid starting from 1 n m. Combining CM4620 and galactose (1 m m) significantly reduced the extent of necrosis to near-control levels. In the palmitoleic acid-alcohol-induced experimental mouse model of AP, CM4620 at a concentration of 0.1 mg/kg alone significantly reduced edema, necrosis, inflammation, and the total histopathological score. A combination of 0.1 mg/kg CM4620 with galactose (100 m m) significantly reduced further necrosis, inflammation, and histopathological score. Our data show that CM4620 can be used at much lower concentrations than reported previously, reducing potential side effects. The novel combination of CM4620 with galactose synergistically targets complementary pathological mechanisms of AP.

Construction and validation of a nomogram for predicting survival in elderly patients with severe acute pancreatitis: a retrospective study from a tertiary center.

PURPOSE: There is a lack of adequate models specifically designed for elderly patients with severe acute pancreatitis (SAP) to predict the risk of death. This study aimed to develop a nomogram for predicting the overall survival of SAP in elderly patients. METHODS: Elderly patients diagnosed with SAP between January 1, 2017 and December 31, 2022 were included in the study. Risk factors were identified through least absolute shrinkage and selection operator regression analysis. Subsequently, a novel nomogram model was developed using multivariable logistic regression analysis. The predictive performance of the nomogram was evaluated using metrics such as the receiver operating characteristic curve, calibration curve, and decision curve analysis (DCA). RESULTS: A total of 326 patients were included in the analysis, with 260 in the survival group and 66 in the deceased group. Multivariate logistic regression indicated that age, respiratory rate, arterial pH, total bilirubin, and calcium were independent prognostic factors for the survival of SAP patients. The nomogram demonstrated a performance comparable to sequential organ failure assessment (P = 0.065). Additionally, the calibration curve showed satisfactory predictive accuracy, and the DCA highlighted the clinical application value of the nomogram. CONCLUSION: We have identified key demographic and laboratory parameters that are associated with the survival of elderly patients with SAP. These parameters have been utilized to create a precise and user-friendly nomogram, which could be an effective and valuable clinical tool for clinicians.

Study on the Prediction of Liver Injury in Acute Pancreatitis Patients by Radiomic Model Based on Contrast-Enhanced Computed Tomography.

OBJECTIVES: to predict liver injury in acute pancreatitis (AP) patients by establishing a radiomics model based on contrast-enhanced computed tomography (CECT). METHODS: a total of 1223 radiomic features were extracted from late arterial-phase pancreatic CECT images of 209 AP patients (146 in the training cohort and 63 in the test cohort), and the optimal radiomic features retained after dimensionality reduction by least absolute shrinkage and selection operator (LASSO) were used to construct a radiomic model through logistic regression analysis. In addition, clinical features were collected to develop a clinical model, and a joint model was established by combining the best radiomic features and clinical features to evaluate the practicality and application value of the radiomic models, clinical model and combined model. RESULTS: four potential features were selected from the pancreatic parenchyma to construct the radiomic model, and the area under the receiver operating characteristic curve (AUC) of the radiomic model was significantly greater than that of the clinical model for both the training cohort (0.993 vs. 0.653, p = 0.000) and test cohort (0.910 vs. 0.574, p = 0.000). The joint model had a greater AUC than the radiomics model for both the training cohort (0.997 vs. 0.993, p = 0.357) and test cohort (0.925 vs. 0.910, p = 0.302). CONCLUSIONS: the radiomic model based on CECT has good performance in predicting liver injury in AP patients and can guide clinical decision-making and improve the prognosis of patients with AP.

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

AIM: 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. MATERIAL AND METHODS: A total of 139 patients with a tentative diagnosis of acute pancreatitis who were hospitalized and followed up in the gastroenterology clinic in 2021‒2022 were included in the study. In addition, a control 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%. RESULTS: There was a significant 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, a significant 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. CONCLUSION: 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).

Biomimetic Trypsin-Responsive Structure-Bridged Mesoporous Organosilica Nanomedicine for Precise Treatment of Acute Pancreatitis.

Developing strategies to target injured pancreatic acinar cells (PACs) in conjunction with primary pathophysiology-specific pharmacological therapy presents a challenge in the management of acute pancreatitis (AP). We designed and synthesized a trypsin-cleavable organosilica precursor bridged by arginine-based amide bonds, leveraging trypsin's ability to selectively identify guanidino groups on arginine via Asp189 at the active S1 pocket and cleave the carboxy-terminal (C-terminal) amide bond via catalytic triads. The precursors were incorporated into the framework of mesoporous silica nanoparticles (MSNs) for encapsulating the membrane-permeable Ca2+ chelator BAPTA-AM with a high loading content (∼43.9%). Mesenchymal stem cell membrane coating and surface modification with PAC-targeting ligands endow MSNs with inflammation recruitment and precise PAC-targeting abilities, resulting in the highest distribution at 3 h in the pancreas with 4.7-fold more accumulation than that of naked MSNs. The outcomes transpired as follows: After bioinspired MSNs' skeleton biodegradation by prematurely and massively activated trypsin, BAPTA-AM was on-demand released in injured PACs, thereby effectively eliminating intracellular calcium overload (reduced Ca2+ level by 81.3%), restoring cellular redox status, blocking inflammatory cascades, and inhibiting cell necrosis by impeding the IκBα/NF-κB/TNF-α/IL-6 and CaMK-II/p-RIP3/p-MLKL/caspase-8,9 signaling pathways. In AP mice, a single dose of the formulation significantly restored pancreatic function (lipase and amylase reduced more by 60%) and improved the survival rate from 50 to 91.6%. The formulation offers a potentially effective strategy for clinical translation in AP treatment.