Treatment Of Acute Pancreatitis Research Articles

Current Diagnosis and Treatment of Acute Pancreatitis in Korea: A Nationwide Survey.

: Acute pancreatitis (AP) is a leading cause of emergency hospitalization. We present the current diagnostic and therapeutic status of AP as revealed by analysis of a large multicenter dataset. : The medical records of patients diagnosed with AP between 2018 and 2019 in 12 tertiary medical centers in Korea were retrospectively reviewed. : In total, 676 patients were included; of these, were 388 (57.4%) males, and the mean age of all patients was 58.6 years. There were 355 (52.5%), 301 (44.5%), and 20 (3.0%) patients with mild, moderate, and severe AP, respectively, as assessed by the revised Atlanta classification. The most common etiologies of AP were biliary issues (41.6%) and alcohol consumption (24.6%), followed by hypertriglyceridemia (6.8%). The etiology was not identified in 111 (16.4%) patients at the time of initial admission. The overall mortality rate was 3.3%, increasing up to 45.0% among patients with severe AP. Notably, 70.0% (14/20) of patients with severe AP and 81.5% (154/189) of patients with systemic inflammatory response syndrome had received <4 L per day during the initial 24 hours of admission. Only 23.8% (67/281) of acute biliary pancreatitis patients underwent cholecystectomy during their initial admission. In total, 17.8% of patients experienced recurrent attacks during follow-up. However, none of the patients with acute biliary pancreatitis experienced recurrent attacks if they had undergone cholecystectomy during their initial admission. : This study provides insights into the current status of AP in Korea, including its etiology, severity, and management. reveal disparities between clinical guidelines and their practical implementation for AP treatment.

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

ObjectivesThis study aimed to analyze active compounds and signaling pathways of CH applying network pharmacology methods, and to additionally verify the molecular mechanism of CH in treating AP.Materials and methodsNetwork pharmacology and molecular docking were firstly used to identify the active components of CH and its potential targets in the treatment of AP. The pancreaticobiliary duct was retrogradely injected with sodium taurocholate (3.5%) to create an acute pancreatitis (AP) model in rats. Histological examination, enzyme-linked immunosorbent assay, Western blot and TUNEL staining were used to determine the pathway and mechanism of action of CH in AP.ResultsNetwork pharmacological analysis identified 168 active compounds and 276 target proteins. In addition, there were 2060 targets associated with AP, and CH had 177 targets in common with AP. These shared targets, including STAT3, IL6, MYC, CDKN1A, AKT1, MAPK1, MAPK3, MAPK14, HSP90AA1, HIF1A, ESR1, TP53, FOS, and RELA, were recognized as core targets. Furthermore, we filtered out 5252 entries from the Gene Ontology(GO) and 186 signaling pathways from the Kyoto Encyclopedia of Genes and Genomes(KEGG). Enrichment and network analyses of protein-protein interactions predicted that CH significantly affected the PI3K/AKT signaling pathway, which played a critical role in programmed cell death. The core components and key targets showed strong binding activity based on molecular docking results. Subsequently, experimental validation demonstrated that CH inhibited the phosphorylation of PI3K and AKT in pancreatic tissues, promoted the apoptosis of pancreatic acinar cells, and further alleviated inflammation and histopathological damage to the pancreas in AP rats.ConclusionApoptosis of pancreatic acinar cells can be enhanced and the inflammatory response can be reduced through the modulation of the PI3K/AKT signaling pathway, resulting in the amelioration of pancreatic disease.

Certolizumab has favorable efficacy on preventing pancreas and target organs damage in acute pancreatitis

Abstract Objective It was targeted to assess the efficacy of certolizumab on pancreas and target organs via biochemical parameters and histopathologic scores in experimental acute pancreatitis (AP) model in rats. Methods 40 male Sprague Dawley rats were divided into 5 equal groups: Group 1 (sham group), Group 2 (AP group), Group 3 (AP + low-dose certolizumab group), Group 4 (AP + high-dose certolizumab group), and Group 5 (placebo group). Rats in all groups were sacrificed 24 hours after the last injection and amylase, TNF-alpha, TGF-β, IL-1 β, MDA, SOD, and GPx levels were studied in blood samples. Histopathological investigation of both the pancreas and target organs (lungs, liver, heart, kidneys) were performed by a pathologist blind to the groups. In silico analysis were also accomplished. Results The biochemical results in the certolizumab treatment groups were identified to be significantly favorable compared to the AP group (p &lt; 0.001). The difference between the high-dose group (Group 4) and low-dose treatment group (Group 3) was found to be significant in terms of biochemical parameters and histopathological scores (p &lt; 0.001). In terms of the effect of certolizumab treatment on the target organs (especially on lung tissue), the differences between the low-dose treatment group (Group 3) and high-dose treatment group (Group 4) with the AP group (Group 2) were found to be significant. Conclusion Certolizumab has favorable protective effects on pancreas and target organs in AP. It may be a beneficial agent for AP treatment and may prevent target organ damage.

Screening of amino acids as a safe energy source for isolated rat pancreatic acini.

Amino acids play an essential role in protein synthesis, metabolism and survival of pancreatic acini. Adequate nutritional support is important for acute pancreatitis treatment. However, high concentrations of arginine and lysine may induce acute pancreatitis. The study aimed to identify the most suitable L-amino acids as safe energy sources for pancreatic acinar cells. Pancreatic acini were isolated from male Wistar rats. Effects of amino acids (0.1-20 mM) on uncoupled respiration of isolated acini were studied with a Clark electrode. Cell death was evaluated with fluorescent microscopy and DNA gel electrophoresis. Among the tested amino acids, glutamate, glutamine, alanine, lysine and aspartate were able to stimulate the uncoupled respiration rate of isolated pancreatic acini, while arginine, histidine and asparagine were not. Lysine, arginine and glutamine (20 mM) caused complete loss of plasma membrane integrity of acinar cells after 24 h of incubation. Glutamine also caused early (2-4 h) cell swelling and blebbing. Aspartate, asparagine and glutamate only moderately decreased the number of viable cells, while alanine and histidine were not toxic. DNA fragmentation assay and microscopic analysis of nuclei showed no evidence of apoptosis in cells treated with amino acids. Alanine and glutamate are safe and effective energy sources for mitochondria of pancreatic acinar cells.

Inflammation and Acinar Cell Dual-Targeting Nanomedicines for Synergistic Treatment of Acute Pancreatitis via Ca2+ Homeostasis Regulation and Pancreas Autodigestion Inhibition.

Severe acute pancreatitis (AP) is a life-threatening pancreatic inflammatory disease with a high mortality rate (∼40%). Existing pharmaceutical therapies in development or in clinical trials showed insufficient treatment efficacy due to their single molecular therapeutic target, poor water solubility, short half-life, limited pancreas-targeting specificity, etc. Herein, acid-responsive hollow mesoporous Prussian blue nanoparticles wrapped with neutrophil membranes and surface modified with the N,N-dimethyl-1,3-propanediamine moiety were developed for codelivering membrane-permeable calcium chelator BAPTA-AM (BA) and trypsin activity inhibitor gabexate mesylate (Ga). In the AP mouse model, the formulation exhibited efficient recruitment at the inflammatory endothelium, trans-endothelial migration, and precise acinar cell targeting, resulting in rapid pancreatic localization and higher accumulation. A single low dose of the formulation (BA: 200 μg kg-1, Ga: 0.75 mg kg-1) significantly reduced pancreas function indicators to close to normal levels at 24 h, effectively restored the cell redox status, reduced apoptotic cell proportion, and blocked the systemic inflammatory amplified cascade, resulting in a dramatic increase in the survival rate from 58.3 to even 100%. Mechanistically, the formulation inhibited endoplasmic reticulum stress (IRE1/XBP1 and ATF4/CHOP axis) and restored impaired autophagy (Beclin-1/p62/LC3 axis), thereby preserving dying acinar cells and restoring the cellular "health status". This formulation provides an upstream therapeutic strategy with clinical translation prospects for AP management through synergistic ion homeostasis regulation and pancreatic autodigestion inhibition.

Clinical predictive value of control attenuation parameters in combination with miR-192-5p in patients with acute pancreatitis in nonalcoholic fatty liver disease.

Control attenuation parameters (CAP) can detect nonalcoholic fatty liver disease (NAFLD). Our previous study found that miR-192-5p could screen for acute pancreatitis (AP) in NAFLD patients. This study focused on the role of CAP and miR-192-5p in NAFLD of acute AP. AP patients and controls were enrolled. Classification of AP patients into NAFLD/AP patients and non-NAFLD/AP was made based on the CAP value. CAP was measured by liver transient elastography. Serum miR-192-5p was measured by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Logistic regression analysis was conducted to examine the risk factors for the development of NAFLD. Receiver operating characteristic (ROC) was assessed for the predictive value of AP severity. NAFLD was more common in the AP group than in the controls (35.00% vs. 8.75%). The CAP value was higher in AP patients with NAFLD than in non-NAFLD, whereas miR-192-5p was significantly lower in AP patients with NAFLD. Additionally, AP patients with NALFD are more likely to experience respiratory failure, systemic inflammatory response syndrome (SIRS), and pancreatic necrosis with longer hospitalisation and exacerbate the incidence of moderate to severe AP. Both miR-192-5p and TG are potential risk factors for the development of NAFLD in patients with AP. Furthermore, the CAP value gradually increased with increasing AP severity, while miR-192-5p gradually decreased. Finally, the sensitivity and specificity of CAP combined with miR-192-5p for the prediction of moderate to severe AP were scored as 82.61% and 82.43%, respectively. NAFLD exacerbated the progression of AP, and CAP combined with miR-192-5p could predict the severity of AP. Our study may provide more reference for AP disease progression and treatment.

Revealing Prdx4 as a potential diagnostic and therapeutic target for acute pancreatitis based on machine learning analysis

Acute pancreatitis (AP) is a common systemic inflammatory disease resulting from the activation of trypsinogen by various incentives in ICU. The annual incidence rate is approximately 30 out of 100,000. Some patients may progress to severe acute pancreatitis, with a mortality rate of up to 40%. Therefore, the goal of this article is to explore the key genes for effective diagnosis and treatment of AP. The analysis data for this study were merged from two GEO datasets. 1357 DEGs were used for functional enrichment and cMAP analysis, aiming to reveal the pathogenic genes and potential mechanisms of AP, as well as potential drugs for treating AP. Importantly, the study used LASSO and SVM-RFE machine learning to screen the most likely AP occurrence biomarker for Prdx4 among numerous candidate genes. A receiver operating characteristic of Prdx4 was used to estimate the incidence of AP. The ssGSEA algorithm was employed to investigate immune cell infiltration in AP. The biomarker Prdx4 gene exhibited significant associations with a majority of immune cells and was identified as being expressed in NKT cells, macrophages, granulocytes, and B cells based on single-cell transcriptome data. Finally, we found an increase in Prdx4 expression in the pancreatic tissue of AP mice through immunohistochemistry. After treatment with recombinant Prdx4, the pathological damage to the pancreatic tissue of AP mice was relieved. In conclusion, our study identified Prdx4 as a potential AP hub gene, providing a new target for treatment.

[Current issues related to treatment of acute pancreatitis from the surgeon's point of view].

[Current issues related to treatment of acute pancreatitis from the surgeon's point of view].

Inhibition of xanthine oxidase alleviated pancreatic necrosis via HIF-1α-regulated LDHA and NLRP3 signaling pathway in acute pancreatitis

Acute pancreatitis (AP) is a potentially fatal condition with no targeted treatment options. Although inhibiting xanthine oxidase (XO) in the treatment of AP has been studied in several experimental models and clinical trials, whether XO is a target of AP and what its the main mechanism of action is remains unclear. Here, we aimed to re-evaluate whether XO is a target aggravating AP other than merely generating reactive oxygen species that trigger AP. We first revealed that XO expression and enzyme activity were significantly elevated in the serum and pancreas of necrotizing AP models. We also found that allopurinol and febuxostat, as purine-like and non-purine XO inhibitors, respectively, exhibited protective effects against pancreatic acinar cell death in vitro and pancreatic damage in vivo at different doses and treatment time points. Moreover, we observed that conditional Xdh overexpression aggravated pancreatic necrosis and severity. Further mechanism analysis showed that XO inhibition restored the hypoxia-inducible factor 1-alpha (HIF-1α)-regulated lactate dehydrogenase A (LDHA) and NOD-like receptor family pyrin domain containing 3 (NLRP3) signaling pathways and reduced the enrichment of 13C6-glucose to 13C3-lactate. Lastly, we observed that clinical circulatory XO activity was significantly elevated in severe cases and correlated with C-reactive protein levels, while pancreatic XO and urate were also increased in severe AP patients. These results together indicated that proper inhibition of XO might be a promising therapeutic strategy for alleviating pancreatic necrosis and preventing progression of severe AP by downregulating HIF-1α-mediated LDHA and NLRP3 signaling pathways.

Management of analgesia in acute pancreatitis: Results of a national survey

IntroductionAcute pancreatitis is one of the main reasons for digestive admissions. Adequate pain treatment is crucial in its management. However, there are hardly any descriptions of the analgesic guidelines used in our setting. MethodsOn-line survey on analgesic management in acute pancreatitis, aimed at attending physicians and residents practising in Spain. ResultsTwo hundred and nine physicians from 88 centres responded to the survey. Ninety percent were specialists in gastrointestinal medicine and 69% worked in a tertiary centre. The majority (64.4%) do not routinely use scales to measure pain. When choosing a drug, experience in its use was the most important factor. The most commonly prescribed initial treatments are: combination of paracetamol and metamizole (53.5%), paracetamol alone (19.1%) and metamizole alone (17.4%). As rescue: meperidine (54.8%), tramadol (17.8%), morphine chloride (17.8%) and metamizole (11.5%). Continuous perfusion is used in 8.2% of initial treatments. Physicians with >10 years of service use more metamizole as monotherapy (50%), while residents and attending physicians with <10 years of service prescribe it in combination with paracetamol (85%). If progression is needed, morphine chloride and meperidine are mainly used. The speciality of the respondent, the size of the work centre and the unit/service where the patients were admitted did not influence the analgesia prescribed. Satisfaction with pain management reached 7.8/10 (SD 0.98). ConclusionIn our setting, metamizole and paracetamol are the most commonly used analgesics as initial pain treatment in acute pancreatitis, and meperidine is the most commonly used rescue analgesic.

The Value of Jejunal Tube in the Treatment of Severe Acute Pancreatitis

The Value of Jejunal Tube in the Treatment of Severe Acute Pancreatitis

Interleukin-22 Alleviates Caerulein-Induced Acute Pancreatitis by Activating AKT/mTOR Pathway.

Acute pancreatitis (AP) is one of the most common acute abdominal disorders; due to the lack of specific treatment, the treatment of acute pancreatitis, especially serious acute pancreatitis (SAP), is difficult and challenging. We will observe the changes of Interleukin -22 levels in acute pancreatitis animal models, and explore the mechanism of Interleukin -22 in acute pancreatitis. This study aims to assess the potential protective effect of Interleukin -22 on caerulein-induced acute pancreatitis and to explore its mechanism. Blood levels of amylase and lipase and Interleukin -22 were assessed in mice with acute pancreatitis. In animal model and cell model of caerulein-induced acute pancreatitis, the mRNA levels of P62 and Beclin-1 were determined using PCR, and the protein expression of P62, LC3-II, mTOR, AKT, p-mTOR, and p-AKT were evaluated through Western blot analysis. Interleukin -22 administration reduced blood amylase and lipase levels and mitigated tissue damage in acute pancreatitis mice model. Interleukin -22 inhibited the relative mRNA levels of P62 and Beclin-1, and the Interleukin -22 group showed a decreased protein expression of LC3-II and P62 and the phosphorylation of the AKT/mTOR pathway. Furthermore, we obtained similar results in the cell model of acute pancreatitis. This study suggests that Interleukin -22 administration could alleviate pancreatic damage in caerulein-induced acute pancreatitis. This effect may result from the activation of the AKT/mTOR pathway, leading to the inhibition of autophagy. Consequently, Interleukin -22 shows potential as a treatment.

Laparoscopic necrosectomy for acute necrotizing pancreatitis: mesocolon-preserving approach and outcomes.

The surgical treatment of acute necrotizing pancreatitis has significantly evolved in recent years with the advent of enhanced imaging techniques and minimally invasive surgery. Various minimally invasive techniques, such as video-assisted retroperitoneal debridement (VARD) and endoscopic transmural necrosectomy (ETN), have been employed in the management of acute necrotizing pancreatitis and are often part of step-up approaches. However, almost all reported step-up approaches only employ a fixed minimally invasive technique prior to open surgery. In contrast, we implemented different minimally invasive techniques during the treatment of acute pancreatitis based on the extent of pancreatic necrosis. For acute necrotizing pancreatitis of the pancreatic bed with or without extension into the left retroperitoneum, we performed mesocolon-preserving laparoscopic necrosectomy for debridment. The quantitative indication for pancreatic debridment in our institute has been described previously. For acute necrotizing pancreatitis of the pancreatic bed with or without extension into the left retroperitoneum, mesocolon-preserving laparoscopic necrosectomy was performed for debridment. To safeguard the mesocolon, the pancreatic bed was entered via the gastrocolic ligament, and the left retroperitoneum was accessed via the lateral peritoneal attachments of the descending colon. Of the 77 patients requiring pancreatic debridment, 41 patients were deemed suitable for mesocolon-preserving laparoscopic necrosectomy by multiple disciplinary team and informed consent was acquired. Of these 41 patients, 27 underwent percutaneous drainage, 10 underwent transluminal drainage, and 2 underwent transluminal necrosectomy prior to laparoscopic necrosectomy. Two patients (4.88%) died of sepsis, three patients (7.32%) required further laparotomic necrosectomy, and five patients (12.20%) required additional percutaneous drainage for residual infection. Three patients (7.32%) experienced duodenal fistula, all of which were cured through non-surgical treatments. Nineteen patients (46.34%) developed pancreatic fistula that persisted for over 3weeks, with 17 being successfully treated non-surgically. The remaining two patients had pancreatic fistulas that lasted over 3months; an internal drainage procedure has been planned for them. No patient developed colonic fistula. Mesocolon-preserving laparoscopic necrosectomy proved to be safe and effective in selected patients. It can serve as a supplementary procedure for step-up approaches or as an alternative to other debridment procedures such as VARD, ETN, and laparotomic necrosectomy.

Corticosteroids to Reduce Inflammation in Severe Pancreatitis (CRISP) protocol and statistical analysis plan: a prospective, multicentre, double-blind, randomized, placebo controlled clinical trial

IntroductionAcute pancreatitis is a common disease which, in its severe form, is associated with significant morbidity and mortality. Currently, there is no specific therapy known to attenuate organ failure in severe pancreatitis and treatment consists primarily of supportive care. Corticosteroids have been shown to be beneficial in disease processes associated with systemic inflammation and could potentially improve outcomes in severe acute pancreatitis. MethodsThe Corticosteroids to Reduce Inflammation in Severe Pancreatitis (CRISP) trial is a multi-centre, double-blind, randomized, placebo-controlled clinical trial that aims to determine the impact of corticosteroids versus placebo on organ injury in patients with severe acute pancreatitis. Patients are randomized to receive 100 mg of hydrocortisone parenterally versus matching placebo every 8 h for 3 days. Clinical and laboratory data are collected at the time of study enrollment, at 24, 48 and 72 h. The primary end-point for the trial is the difference in 72-h change in the Sequential Organ Failure Assessment (SOFA) score between hydrocortisone and placebo groups. Additional key secondary outcomes include ventilator free days and 28-day mortality. DiscussionThis study will add to the evidence base in the treatment of severe acute pancreatitis. The results will inform clinical practice and future studies in the field.Trial registration numberThe trial is registered on clinicaltrials.gov (NCT05160506). It was posted on December 16th, 2021. The study protocol was approved by the Beth Israel Deaconess Medical Center Committee on Clinical Investigation (CCI) (protocol 2021 P-000803).

Pyrazole derivative Z10 ameliorates acute pancreatitis by inhibiting the ERK/Ddt pathway

Acute pancreatitis (AP) can lead to death; however, there is no specific treatment for AP. Screening of drugs for AP treatment is rarely performed. Compounds were screened in a primary pancreatic acinar cell and peritoneal macrophage coculture system. Compounds were used in vitro and in vivo. Compound targets were predicted and validated. Among the 18 nitrogen-containing heterocycles, Z10 was shown to decrease the cerulein plus lipopolysaccharide (CL)–induced secretion of both acinar digestive enzymes and macrophage cytokines. Z10 was also shown to ameliorate CL-induced or sodium taurocholate–induced AP in mice. Proteomics analysis and enzyme linked immunosorbent assay (ELISA) revealed that Z10 decreased the levels of D-dopachrome tautomerase (Ddt) within macrophages and those in the extracellular milieu under CL treatment. Z10 also decreased Ddt expression in AP mice. Moreover, exogenous Ddt induced cytokine and digestive enzyme secretion, which could be inhibited by Z10. Ddt knockdown inhibited CL-induced cytokine secretion. Medium from CL-treated macrophages induced the release of amylase by acinar cells, and Ddt knockdown medium decreased amylase secretion. The target of Z10 was predicted to be ERK2. Z10 increased the thermostability of ERK1/2 but not ERK1 K72A/ERK2 K52A. The docking poses of ERK1 and ERK2 with Z10 were similar. Z10 inhibited ERK1/2 phosphorylation, and Ddt levels and cytokines were regulated by ERK1/2 during AP. Additionally, Z10 could not further inhibit cytokines under ERK1/2 knockdown with CL. Thus, this study revealed that Z10-mediated ERK1/2 inhibition decreased Ddt expression and secretion by macrophages. Ddt inhibition decreased cytokine release and digestive enzyme secretion.

Elimination of intracellular Ca2+ overload by BAPTA‑AM liposome nanoparticles: A promising treatment for acute pancreatitis.

Calcium overload, a notable instigator of acute pancreatitis (AP), induces oxidative stress and an inflammatory cascade, subsequently activating both endogenous and exogenous apoptotic pathways. However, there is currently lack of available pharmaceutical interventions to alleviate AP by addressing calcium overload. In the present study, the potential clinical application of liposome nanoparticles (LNs) loaded with 1,2‑bis(2‑aminophenoxy)ethane‑N,N,N',N'‑tetraacetic acid tetrakis (acetoxymethyl ester) (BAPTA‑AM), acell‑permeant calcium chelator, was investigated as a therapeutic approach for the management of AP. To establish the experimental models invitro, AR42J cells were exposed to high glucose/sodium oleate (HGO) to induce necrosis, and invivo, intra‑ductal taurocholate (TC) infusion was used to induce AP. The findings of the present study indicated that the use of BAPTA‑AM‑loaded LN (BLN) effectively and rapidly eliminated excessive Ca2+ and reactive oxygen species, suppressed mononuclear macrophage activation and the release of inflammatory cytokines, and mitigated pancreatic acinar cell apoptosis and necrosis induced by HGO. Furthermore, the systemic administration of BLN demonstrated promising therapeutic potential in the rat model of AP. Notably, BLN significantly enhanced the survival rates of rats subjected to the TC challenge, increasing from 37.5to75%. This improvement was attributed to the restoration of pancreatic function, as indicated by improved blood biochemistry indices and alleviation of pancreatic lesions. The potential therapeutic efficacy of BLN in rescuing patients with AP is likely attributed to its capacity to inhibit oxidative stress, prevent premature activation of zymogens and downregulate the expression of TNF‑α, IL‑6 and cathepsin B. Thus, BLN demonstrated promising value as a novel therapeutic approach for promptly alleviating the burden of intracellular Ca2+ overload in patients with AP.

Recent Treatment Strategies for Acute Pancreatitis.

Acute pancreatitis (AP) is a leading gastrointestinal disease that causes hospitalization. Initial management in the first 72 h after the diagnosis of AP is pivotal, which can influence the clinical outcomes of the disease. Initial management, including assessment of disease severity, fluid resuscitation, pain control, nutritional support, antibiotic use, and endoscopic retrograde cholangiopancreatography (ERCP) in gallstone pancreatitis, plays a fundamental role in AP treatment. Recent updates for fluid resuscitation, including treatment goals, the type, rate, volume, and duration, have triggered a paradigm shift from aggressive hydration with normal saline to goal-directed and non-aggressive hydration with lactated Ringer's solution. Evidence of the clinical benefit of early enteral feeding is becoming definitive. The routine use of prophylactic antibiotics is generally limited, and the procalcitonin-based algorithm of antibiotic use has recently been investigated to distinguish between inflammation and infection in patients with AP. Although urgent ERCP (within 24 h) should be performed for patients with gallstone pancreatitis and cholangitis, urgent ERCP is not indicated in patients without cholangitis. The management approach for patients with local complications of AP, particularly those with infected necrotizing pancreatitis, is discussed in detail, including indications, timing, anatomical considerations, and selection of intervention methods. Furthermore, convalescent treatment, including cholecystectomy in gallstone pancreatitis, lipid-lowering medications in hypertriglyceridemia-induced AP, and alcohol intervention in alcoholic pancreatitis, is also important for improving the prognosis and preventing recurrence in patients with AP. This review focuses on recent updates on the initial and convalescent management strategies for AP.

Network pharmacology-based investigation and experimental validation of the therapeutic potential and molecular mechanism of Danshen Chuanxiongqin injection in acute pancreatitis.

Danshen Chuanxiong Injection (DCI) has demonstrated significant clinical efficacy in the treatment of acute pancreatitis (AP); however, the precise molecular mechanisms underlying its therapeutic effects remain incompletely understood. In this study, we employed network pharmacology analysis to comprehensively investigate the active components, potential targets, and signaling pathways involved in DCI-mediated treatment of AP. We utilized the mouse pancreatic acinar cell line 266-6 to establish an cholecystokinin (CCK)-induced AP cell injury model and evaluated cell viability using the Cell counting kit-8 assay. Western blotting and quantitative PCR were employed to determine the expression levels of key target proteins and genes. Network pharmacology analysis identified a total of 144 active components and 430 potential targets within DCI. By integrating data from public databases, we identified 762 AP-related genes. Among these, we identified 93 potential targets that may be involved in the therapeutic effects of DCI for AP. These targets were significantly enriched in biological processes such as oxidative stress, regulation of cytokine production, leukocyte migration, and the TNF signaling pathway. Molecular docking studies revealed a high binding affinity between the active components and the key targets AKT1 and NFKBA, indicative of potential interaction. Additionally, CCK-induced acinar cell injury led to upregulation of AKT1, NFKBA, and P53 proteins, as well as TNF, IL6, and MMP9 genes. Conversely, treatment with DCI dose-dependently attenuated CCK-induced acinar cell injury and restored the expression levels of the aforementioned proteins and genes. Overall, this study provides a comprehensive understanding of the molecular mechanisms underlying the therapeutic effects of DCI in the treatment of AP. Our findings confirm the protective effect of DCI against CCK-induced acinar cell injury and its regulation of key targets.

Intravenous Hemin, a potential heme oxygenase-1 activator, does not protect from post-ERCP acute pancreatitis in humans: Results of a randomized multicentric multinational placebo-controlled trial

ObjectiveHemin, a heme oxygenase 1 activator has shown efficacy in the prevention and treatment of acute pancreatitis in mouse models. We conducted a randomized controlled trial (RCT) to assess the protective effect of Hemin administration to prevent post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) in patients at risk. MethodsIn this multicenter, multinational, placebo-controlled, double-blind RCT, we assigned patients at risk for PEP to receive a single intravenous dose of Hemin (4 mg/kg) or placebo immediately after ERCP. Patients were considered to be at risk on the basis of validated patient- and/or procedure-related risk factors. Neither rectal NSAIDs nor pancreatic stent insertion were allowed in randomized patients. The primary outcome was the incidence of PEP. Secondary outcomes included lipase elevation, mortality, safety, and length of stay. ResultsA total of 282 of the 294 randomized patients had complete follow-up. Groups were similar in terms of clinical, laboratory, and technical risk factors for PEP. PEP occurred in 16 of 142 patients (11.3%) in the Hemin group and in 20 of 140 patients (14.3%) in the placebo group (p = 0.48). Incidence of severe PEP reached 0.7% and 4.3% in the Hemin and placebo groups, respectively (p = 0.07). Significant lipase elevation after ERCP did not differ between groups. Length of hospital stay, mortality and severe adverse events rates were similar between groups. ConclusionWe failed to detect large improvements in PEP rate among participants at risk for PEP who received IV hemin immediately after the procedure compared to placebo. Trial registration numberClinicalTrials.gov number, NCT01855841).

Health Literacy Needs of Acute Pancreatitis Patients During the Diagnosis and Treatment Process Under the Lens of the Timing It Right Theory: A Qualitative Study.

The incidence and recurrence rate of acute pancreatitis (AP) continues to increase worldwide. The risk of AP attack and recurrence is closely related to the patient's health literacy. Previous studies have shown that AP patients had low levels of health literacy. Understanding patients' experience in AP's diagnosis and treatment process and their health literacy needs might significantly improve their health status. This study aims to understand the experience of acute pancreatitis (AP) patients in the diagnostic and treatment process and explore their health literacy needs at various phases of this process. This study utilized a qualitative approach based on Timing It Right theory. A purposive sampling strategy was employed to select 31 participants diagnosed with AP at various phases of the diagnosis and treatment process. These patients were selected from the Pancreatitis Treatment Centers of two tertiary hospitals in Eastern China. Subsequently, semi-structured in-depth interviews were conducted with the selected participants. The qualitative data was analyzed using the Colaizzi's method. The themes of AP patients' experiences and health literacy needs at various phases of the diagnosis and treatment process were presented as follows. 1. Diagnosis phase: inability to obtain disease information, psychological support seeking, and change unhealthy lifestyle; 2. Hospitalization phase: disease treatment information needs and medical professionals' healthcare. 3. Discharge Preparation phase: fear of recurrence, individualized healthy lifestyle instruction. 4. Home Recovery phase: self-management, continuous healthcare needs, and family support. AP patients' HL needs and health-related problems vary during the diagnosis and treatment process. Medical professionals should comprehend AP patients' changing needs and individual differences, provide continuous healthcare, and involve families in patient management. These factors support patients' long-term self-management and preserve their overall health.