Acute Pancreatitis Research Articles

Retracted] Ginsenoside Rg3 ameliorates acute pancreatitis by activating the NRF2/HO‑1‑mediated ferroptosis pathway

Retracted] Ginsenoside Rg3 ameliorates acute pancreatitis by activating the NRF2/HO‑1‑mediated ferroptosis pathway

Rationale and design of the SHASTA-3 and SHASTA-4 studies: randomized, double-blind, placebo-controlled, phase 3 studies of plozasiran in patients with severe hypertriglyceridemia

Abstract Severe hypertriglyceridemia (sHTG) confers an increased risk of atherosclerotic cardiovascular disease (ASCVD) and acute pancreatitis (AP). sHTG-associated AP is a substantial source of morbidity, mortality, reduced quality of life and financial burden to health care systems. Currently available therapeutic approaches for sHTG are often insufficient to reduce triglyceride (TG) levels and prevent AP. Plozasiran, an investigational siRNA therapeutic, inhibits hepatic production of apolipoprotein C3 (APOC3), a key regulator of lipoprotein lipase-mediated TG metabolism and clearance. In a phase 2 study of sHTG patients [TG ≥500 mg/dL (≥5.65 mmol/L)], plozasiran demonstrated durable reductions in TG levels of up to -80%, 12 weeks after the last dose, and decreased TG below 500 mg/dL (5.65 mmol/L), a threshold of increased risk for AP in most participants. The SHASTA-3 and SHASTA-4 trials will evaluate safety and efficacy of plozasiran, including AP rates, in patients with sHTG. SHASTA-3 and SHASTA-4 are phase 3, randomized, double-blind, placebo-controlled, multi-center trials. Key inclusion criteria are prior sHTG and fasting TG ≥500 mg/dL (≥5.65 mmol/L), at screening. Key exclusion criteria include use of any hepatocyte targeted siRNA treatments that target lipids and/or TGs within 1 year (except inclisiran at least 4 weeks prior to enrollment), siRNA or ASO within 60 days, known FCS diagnosis, and AP within 4 weeks of screening. 700 adults with sHTG will be enrolled in these two trials in several sites across multiple countries. Patients will be randomized 2:1 to receive 4 quarterly subcutaneous injections of plozasiran 25 mg or matching placebo over a 1-year double-blinded period, followed by post-treatment evaluation or entry into the open-label extension study. The randomization will be stratified based on TG levels (≥880 mg/dL vs <880 mg/dL [≥ vs <10 mmol/L]) and prior history of AP, within 5 years of screening. The primary efficacy endpoint of the studies is placebo-adjusted percent change in fasting TG from baseline to month 12 with plozasiran. Secondary endpoints include percent change in fasting TG from baseline to month 10 compared to placebo, percent of patients achieving fasting TGs of <500 mg/dL (<5.65 mmol/L) and TGs of <150 mg/dL (<1.69 mmol/L) at month 10 and 12 compared to placebo, and event rate of adjudicated abdominal clinical events including ER visits and hospitalization for abdominal pain attributed to HTG and events of documented pancreatitis. The effect of plozasiran on other lipids and lipoproteins, inflammatory biomarkers, and liver fat content using magnetic resonance imaging-proton density fat fraction will be assessed. Adjudicated major adverse cardiovascular event rates, safety and tolerability will be assessed. SHASTA-3 and SHASTA-4 are designed to determine whether the quarterly-dosed APOC3 siRNA plozasiran, added to standard of care, safely reduces TG levels and the rate of AP in patients with sHTG.

Transition of patients with familial chylomicronaemia syndrome from volanesorsen to olezarsen: safety and pharmacokinetic results

Abstract Background Familial chylomicronaemia syndrome (FCS) is a rare genetic disorder of lipoprotein lipase deficiency resulting in severe hypertriglyceridaemia and pancreatitis risk. Volanesorsen is a weekly-injected antisense oligonucleotide (ASO) designed to degrade APOC3 mRNA that is approved as an adjunct to diet to treat FCS in the EU, UK, and Brazil. Olezarsen is an investigational monthly-injected ASO-GalNAC3 conjugate also designed to degrade APOC3 mRNA, but directed to hepatocytes, resulting in more potency and less systemic exposure and making it a potential alternative to volanesorsen for FCS. Purpose This interim analysis of an open-label phase 3 trial evaluated olezarsen safety and pharmacokinetics in patients (pts) with FCS previously treated with volanesorsen. Methods Adults with FCS with prior volanesorsen treatment, or actively participating in an expanded access programme (US and Canada), started olezarsen 80 mg by subcutaneous injection every 4 weeks after a minimum washout of 6 weeks. Historical volanesorsen laboratory and safety data were unavailable. The primary objective was to assess safety from changes vs baseline in platelet count, liver enzymes, and renal function; bleeding events; and adverse events. Pharmacokinetic measurements included plasma volanesorsen and olezarsen concentrations. Immunogenicity was assessed by measuring anti-drug antibodies (Abs). Results Of 24 pts enrolled, the majority were female (n=13; 54.2%) and White (n=21; 87.5%), with mean age of 49.1 years; 20 (83.3%) had genetically and 4 (16.7%) clinically validated FCS, all had history of acute pancreatitis (or symptoms suggestive of pancreatitis requiring hospitalisation or emergency room/urgent care visit; mean, 3.4 episodes within 5 years) and 5 (20.8%) of thrombocytopaenia. Time since last volanesorsen dose was 42—1118 days. Baseline fasting triglyceride (median [interquartile range (IQR)], 18.6 [9.6,34.0] mmol/L [1648 (852,3007) mg/dL]; mean [standard deviation (SD)], 25.5 [20.5] mmol/L [2256 (1812) mg/dL]) and apolipoprotein C-III (median [IQR], 0.2 [0.1,0.4] g/L [16.1 (12.4,39.0) mg/dL]; mean [SD], 0.3 [0.2] g/L [25.9 (19.5) mg/dL]) levels were elevated. During a mean (SD) of 329 (95) days of olezarsen 80 mg treatment, no pts experienced hepatic failure, renal impairment, major bleeding events, or platelet count below the prespecified threshold of 50,000 mm³ (Table 1). Olezarsen levels at trough were elevated during the first 3 months, mainly due to residual volanesorsen levels in pts with washout <90 days (Figure 1). Eleven (45.8%) pts had treatment-emergent anti-olezarsen Abs, of whom 5 (20.8%) had anti-volanesorsen Abs, with no impact on safety or efficacy; pts with vs without anti-drug Abs had higher olezarsen trough levels (mean, 4.4–7.8 ng/mL vs 1.1 ng/mL). Conclusions In this interim analysis, olezarsen was safe and well tolerated in pts with FCS previously treated with volanesorsen after a minimum washout of 6 weeks.

Endoscopic diagnosis and treatment of recurrent acute pancreatitis after pancreaticojejunostomy: A case report

Endoscopic diagnosis and treatment of recurrent acute pancreatitis after pancreaticojejunostomy: A case report

Minocycline-Induced Acute Pancreatitis With Cyst Formation in a Young Man

Minocycline-Induced Acute Pancreatitis With Cyst Formation in a Young Man

The molecular mechanism of PLD2-mediated regulation of apoptosis and cell edema in pancreatic cells via the Nrf2/NF-κB pathway

This study aimed to elucidate the molecular mechanisms by which PLD2 controls apoptosis and edema in pancreatic cells via the Nrf2/NF-κB pathway. AR42J rat pancreatic cells were treated with 10 nM mitomycin to create an in vitro pancreatitis model (model group), with a control group receiving phosphate-buffered saline. Cells were transfected with a PLD2 overexpression plasmid using Lipofectamine 3000, forming the PLD2 overexpression group. PLD2 protein expression was assessed by Western blotting, and TNF-α, IL-6, and IL-10 levels were measured by RT-qPCR. Nrf2/NF-κB protein expressions were also analyzed. Apoptosis and necrosis were evaluated using Annexin V-FITC/PI staining and the LDH release test. Cell edema was assessed by cell volume, ion content, and membrane damage. Western blotting was used to analyze pan-apoptosis-related proteins. PLD2 expression was lower in the model group compared to controls (P < 0.05) but higher in the PLD2 overexpression group (P < 0.05). TNF-α, IL-6, and IL-10 levels were elevated in the model group (P < 0.05) and reduced in the PLD2 overexpression group (P < 0.05). Nrf2 expression decreased in the model group but increased with PLD2 overexpression (P < 0.05). NF-κB expression increased in the model group but decreased with PLD2 overexpression (P < 0.05). Apoptosis and necrosis rates were higher in the model group (P < 0.05) but lower in the PLD2 overexpression group (P < 0.05). Cell volume, Na + content, and LDH release increased in the model group (P < 0.05) but decreased with PLD2 overexpression (P < 0.05). RIPK1 expression decreased in the model group (P < 0.05) but increased with PLD2 overexpression (P < 0.05). CASP8, FADD, and ZBP1 levels were higher in the model group (P < 0.05) and reduced with PLD2 overexpression (P < 0.05). PLD2 exerts a protective effect in acute pancreatitis by activating Nrf2 and inhibiting NF-κB, reducing apoptosis, cell swelling, and membrane damage. This highlights potential therapeutic targets for pancreatic inflammation.

Angiotensin-(1-7) improves intestinal microbiota disturbances and modulates fecal metabolic aberrations in acute pancreatitis.

Acute pancreatitis (AP) is a serious health problem that dysregulates intestinal microbiota. Angiotensin (Ang)-(1-7) plays a protective role in the intestinal barrier in AP, but its effect on intestinal microbiota remains clear. To investigate the impact of Ang-(1-7) on AP-induced intestinal microbiota disorder and metabolites. We collected blood and fecal samples from 31 AP patients within 48 h after admission to the hospital, including 11 with mild AP (MAP), 14 with moderately severe AP (MSAP), six with severe AP (SAP). Mice were divided into four groups: control, AP, AP + Ang-(1-7) via tail vein injection, and AP + Ang-(1-7) via oral administration. The samples of mice were collected 12 h after AP. Pancreatic and intestinal histopathology scores were analyzed using the Schmidt and Chiu scores. Fecal microbiota and metabolites analysis was performed via 16S rDNA sequencing and nontargeted metabolomics analysis, respectively. In patients, the abundance of beneficial bacteria (Negativicutes) decreased and pathogenic bacteria (Clostridium bolteae and Ruminococcus gnavus) increased in SAP compared with MAP. Ang-(1-7) levels were associated with changes in the microbiota. There were differences in the intestinal microbiota between control and AP mice. Ang-(1-7) attenuated intestinal microbiota dysbiosis in AP mice, reflecting in the increase in beneficial bacteria (Odoribacter and Butyricimonas) than AP, as well as pancreatic and intestinal injuries. Oral administration of Ang-(1-7) reversing AP-induced decreases in metabolisms: secondary bile acids, emodin, and naringenin. Ang-(1-7) may improve intestinal microbiota dysbiosis and modulate fecal metabolites in AP, thereby reducing the damage of AP.

Systematic review of treatments for the gastrointestinal manifestations of systemic lupus erythematosus

ObjectivesTo comprehensively assess and present the evidence for treatments used in the management of the gastrointestinal manifestations of SLE. MethodsA systematic search of the literature from January 1990 to June 2022 was performed using the following databases: MEDLINE, EMBASE, PubMed and Cochrane. Key words relating to the gastrointestinal system, SLE, and treatment were used. Where there was sufficient evidence for the treatment of a manifestation, we excluded case series with <10 cases and case reports. However, for rarer manifestations with insufficient higher-level evidence, smaller case series and case reports were included. ResultsA total of 29 studies including 767 patients were included in the review; six cohort studies, 11 case-control studies, and 11 case series. Specific gastrointestinal manifestations included enteritis (5 studies), mesenteric vasculitis (3 studies), acute pancreatitis (5 studies), chronic pancreatitis (1 study), intestinal pseudo-obstruction (IPO) (2 studies), hepatitis (4 studies), protein-losing enteropathy (PLE) (6 studies), acute acalculous cholecystitis (2 studies), and Budd-Chiari Syndrome (1 study). Evidence for the treatment of Ascites (13 case reports), peritonitis (3 case reports), and miscellaneous GI manifestations (11 case reports) are included as a supplemental file. Most studies demonstrated a benefit from pulsed intravenous methylprednisolone (IVMP) in severe or life-threatening manifestations, and oral prednisolone for less severe manifestations. However, the quality of evidence was low, with a high risk of bias in all studies. ConclusionThis review highlights the need for standardised disease definitions and terminology, as well as consideration of including gastrointestinal manifestations in disease scoring systems. There is a significant need for high-quality clinical trials in the treatment of the gastrointestinal manifestations of SLE, which will likely need to be multi-centre. We hope that this review will promote awareness of the gastrointestinal manifestations of SLE, and serve as a practical guide for evidence-based treatment.

Anlotinib plus TQB2450, a PD-L1 Antibody, in Patients with Advanced Alveolar Soft Part Sarcoma: a single-arm, phase 2 trial.

Alveolar soft part sarcoma (ASPS) is an ultra-rare soft-tissue sarcoma with a high rate of metastasis and no established treatment. This study aimed to explore the efficacy and safety of anlotinib (a tyrosine-kinase inhibitor) and TQB2450 (a PD-L1 inhibitor) in ASPS patients. This single-arm, phase 2 study evaluated the efficacy of TQB2450, an anti-programmed death ligand 1 (PD-L1) agent, combined with anlotinib, a TKI, in adults with advanced ASPS. TQB2450 was given intravenously (1,200 mg) on day 1, and anlotinib (12 mg/day) was taken orally from day 1 to day 14 every 3 weeks. The primary endpoint was overall response rate, with secondary endpoints including duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Lymphocyte infiltration and tertiary lymphoid structure (TLS) were also analyzed as potential prognostic biomarkers. The study enrolled 29 patients, with 28 evaluable (one withdrew due to acute pancreatitis). An objective response was achieved in 82.1% of patients, including 4 complete and 19 partial responses. The median time to response was 2.8 months, and the DOR was not reached, with an estimated median PFS of 35.2 months. Grade 3-4 treatment-related adverse events occurred in 44.8% of patients, with no study-related deaths. Responders had a higher proportion of TLS area, density, and CD20-positive immune cells. The combination of anlotinib and TQB2450 is effective and tolerable in ASPS patients. TLS may serve as a prognostic biomarker, meriting further investigation.

Role of Sphingosine-1-Phosphate Signaling Pathway in Pancreatic Diseases

Sphingosine-1-phosphate (S1P) is a sphingolipid metabolic product produced via the phosphorylation of sphingosine by sphingosine kinases (SPHKs), serving as a powerful modulator of various cellular processes through its interaction with S1P receptors (S1PRs). Currently, this incompletely understood mechanism in pancreatic diseases including pancreatitis and pancreatic cancer, largely limits therapeutic options for these disorders. Recent evidence indicates that S1P significantly contributes to pancreatic diseases by modulating inflammation, promoting pyroptosis in pancreatic acinar cells, regulating the activation of pancreatic stellate cells, and affecting organelle functions in pancreatic cancer cells. Nevertheless, no review has encapsulated these advancements. Thus, this review compiles information about the involvement of S1P signaling in exocrine pancreatic disorders, including acute pancreatitis, chronic pancreatitis, and pancreatic cancer, as well as prospective treatment strategies to target S1P signaling for these conditions. The insights presented here possess the potential to offer valuable guidance for the implementation of therapies targeting S1P signaling in various pancreatic diseases.

Feeding Intolerance—A Key Factor in the Management of Acute Pancreatitis: A Review

Feeding Intolerance—A Key Factor in the Management of Acute Pancreatitis: A Review

Lipid metabolic profiling and diagnostic model development for hyperlipidemic acute pancreatitis

Lipid metabolic profiling and diagnostic model development for hyperlipidemic acute pancreatitis

Relationship of Crohn’s disease and acute pancreatitis in pediatric practice: literature review

Inflammatory bowel diseases (IBD) are a certain group of pathologic conditions of the gastrointestinal tract (GIT), including Crohn’s disease (CD) and ulcerative colitis (UC). In the modern world, vigilance for these diseases is growing, because their characteristic feature is the involvement of other organs in the pathological inflammatory process, as well as the development of local and systemic complications. As a rule, in children CCD occurs mainly at the age of 12-16 years. Recently, the attention of the medical world has been drawn to the issue of extraintestinal manifestations of CD. Pathological manifestations associated with lesions of the skin and mucous membranes, eyes, bone and joint system, pancreas, negatively affect both physical and psychological health of the child. Such pathology associated with pancreatic malfunction, such as acute pancreatitis (AP) often occurs in patients with inflammatory bowel disease and is one of the main causes of hospitalization for diseases of the digestive system. According to statistics, the incidence ranges from 15 to 40 cases per 100,000 per year in European countries. According to the Gastroenterological Society, there are different variations in the course of acute pancreatitis, whether occurring in patients with IBS due to the disease itself or as a side effect of drug therapy. However, IBD patients are at increased risk of developing both acute and chronic pancreatitis. In this review, we consider the relationship and mutual influence of these two pathologies.

Association Between Body Composition Measured by Artificial Intelligence and Long-Term Sequelae After Acute Pancreatitis.

The clinical utility of body composition in the development of complications of acute pancreatitis (AP) remains unclear. We aimed to describe the associations between body composition and the recurrence of AP. We performed a retrospective study of patients hospitalized with AP at three tertiary care centers. Patients with computer tomography (CT) imaging of the abdomen at admission were included. A previously validated and fully automated abdominal segmentation algorithm was used for body composition analysis. Hospitalization for a recurrent episode of AP was the primary endpoint. Secondary endpoints included the development of chronic pancreatitis (CP) or diabetes mellitus (DM) in patients who were evaluated. Cox Proportional Hazards regression was used. From a total of 347 patients, 89 (25.6%) were hospitalized for recurrent AP (median time: 219days). Thirty-four of 112 patients (30.4%) developed CP (median time: 311days) and 22 of 88 (25.0%) developed DM (median time: 1104days). After adjusting for age, male sex, first episode of AP, BUN, and severity of AP, we found that obesity, body mass index, alcohol pancreatitis, and gallstone pancreatitis were significantly associated with a recurrent episode of AP. Body composition was not associated with recurrent AP. In unadjusted analysis, subcutaneous adipose tissue (SAT) (HR 0.87 per 10 cm2, p = 0.002) was associated with CP. Skeletal muscle (SM) mass approached significance for CP (p = 0.0546). Intermuscular adipose tissue (IMAT) (HR 1.45 per 5 cm2, p = 0.0264) was associated with DM. Body composition was not associated with having a recurrent AP. At follow-up, 30% and 25% of evaluated patients developed CP and DM, respectively. A higher SAT and IMAT were associated with a lower incidence of CP and higher incidence of DM, respectively.

Psoas Muscle Index and Density as Prognostic Predictors in Patients Hospitalized with Acute Pancreatitis

Background: Early prognostication of acute pancreatitis (AP) patients for those at high risk of complications during hospitalization can facilitate clinical decision-making. Sarcopenia has been proven to be a risk factor for poor prognosis in patients with AP. We aimed to evaluate the association between the muscle parameters measured in computed tomography (CT) and the clinical outcomes of hospitalized patients with AP. Methods: A total of 132 consecutive patients hospitalized between 1 January 2015 and 31 December 2021 for AP with a valid CT scan were analyzed. The first CT conducted during hospitalization was analyzed for psoas muscle area (PMA), index (PMI), and density (PMD) at the L3 vertebral level. The main adverse outcomes indicating a worse prognosis were the development of extrapancreatic complications, infections, ICU transfer, in-hospital mortality, and hospitalization length. Results: The lowest tertile of PMI, as a surrogate for sarcopenia, was significantly correlated with increased rates of extrapancreatic complications, infections, and longer hospitalizations. It was additionally correlated with a worse CT severity index. The results for PMA and PMD also showed worse outcomes, largely mirroring the results for PMI. Although in-hospital mortality was relatively low, none of the patients died in the highest tertile of PMI. A clear cutoff with sufficient predictive capability could not be found. Conclusions: A low psoas muscle index can serve as an additional potential predictive marker for more severe disease and worse outcomes in hospitalized acute pancreatitis patients. More studies are needed to determine its combination with existing prediction tools.

Incidence rate of hemorrhagic fever with renal syndrome complicated with acute pancreatitis: a meta-analysis

BackgroundAcute pancreatitis (AP) is a rare but serious complication in patients diagnosed with hemorrhagic fever with renal syndrome (HFRS). When AP complicates HFRS, the clinical outcome significantly worsens and the risk of mortality increases. However, the incidence of AP in HFRS patients and its associated mortality risk remain unclear. To address this knowledge gap, we conducted a meta-analysis to determine the AP incidence rate in HFRS patients and assess the impact of AP on mortality in these patients.MethodsWe systematically searched seven databases (PubMed, Web of Science, EMBase, Sinomed, Chinese National Knowledge Infrastructure, WanFang Data, and Chongqing VIP) for relevant studies on HFRS complicated by AP. The studies were selected using predefined inclusion and exclusion criteria based on the Population, Intervention, Comparison, Outcome, and Study design principle. Two independent reviewers screened the studies, and the quality of the included studies was assessed using the Agency for Healthcare Research and Quality and the Newcastle-Ottawa Evaluation Scale (NOS).ResultsIn total, 11 studies, encompassing 1,218 HFRS patients, met the inclusion criteria. The overall incidence of HFRS complicated by AP was 8.5% (95% CI for r 5.9–11.1%). The HFRS patients with AP had a significantly higher risk of mortality than those without AP (OR = 3.668, 95% CI for OR 1.112–12.031). No statistically significant differences were observed in the subgroup and meta-regression analyses.ConclusionAlthough the incidence of AP in HFRS patients is not high, it significantly increases the risk of mortality in these patients. Future large-scale prospective studies are required to further validate these findings.

Multiparametric quantitative MRI of healthy adult pancreas: correlations with gender and age

BackgroundThe pancreas plays an important role in the nutrition and metabolism of the whole body. Many disease processes including obesity, diabetes mellitus (DM), acute or chronic pancreatitis, and pancreatic carcinoma result in abnormality of pancreas morphology and function. Magnetic resonance imaging (MRI) provides quantitative parameters including T1, T2, and apparent diffusion coefficient (ADC) values for evaluating normal and abnormal pancreas. Based on the normal range of these quantitative parameters, pancreatic abnormality could be detected early. However, the range and the relationship of T1, T2, and ADC values with gender and age groups using the same dataset have not been explored.PurposeTo establish the ranges of MRI tissue and functional parameters, including T1, T2, and ADC values, in healthy adult pancreas and their correlations with gender, subregion, and age.Materials and methodsThe T1, T2, and ADC values of healthy pancreas in 86 adults were measured using a 3.0-T MRI scanner. The average T1, T2, and ADC values were obtained in the whole pancreas and subregions (head, neck, body, and tail). Their correlations with gender and age were investigated.ResultsThe T1, T2, and ADC values of the whole pancreas from all subjects were 870.07 ± 61.86 ms, 44.07 ± 6.14 ms, and 1.072 ± 0.212 × 10−3 mm2/s, respectively. T2 values were significantly different between genders (P &amp;lt; 0.05). No significant differences were found between subregions. The T1, T2, and ADC values differed significantly among the age groups (P &amp;lt; 0.05). The T1 value revealed a moderately positive correlation, while the T2 and ADC values displayed negative correlations with age (r = 0.31, −0.45, and −0.39, respectively). The combination of T1, T2, and ADC values achieved the highest AUC value and showed a significant difference compared to T1, T2, and ADC values alone in predicting age older than 45 years.ConclusionThis study established the normal ranges of T1, T2, and ADC. We found that T2 is different between men and women, and T1, T2, and ADC are age-dependent. These results could be useful for quantitative MRI of pancreatic disease.

Clinical and Financial Validation of the International Study Group for Pancreatic Surgery (ISGPS) Definition of Post-Pancreatectomy Acute Pancreatitis (PPAP): International Multicenter Prospective Study.

To validate the ISGPS definition and grading system of PPAP after pancreatoduodenectomy (PD). In 2022, the International Study Group for Pancreatic Surgery (ISGPS) defined post-pancreatectomy acute pancreatitis (PPAP) and recommended a prospective validation of its diagnostic criteria and grading system. This was a prospective, international, multicenter study including patients undergoing PD at 17 referral pancreatic centers across Europe, Asia, Oceania, and the United States. PPAP diagnosis required the following three parameters: (1) postoperative serum hyperamylasemia /hyperlipasemia (POH) persisting on postoperative days 1 and 2, (2) radiologic alterations consistent with PPAP, and (3) a clinically relevant deterioration in the patient's condition. To validate the grading system, clinical and economic parameters were analyzed across all grades. Among 2902 patients undergoing PD, 7.5% (n=218) developed PPAP (6.3% grade B and 1.2% grade C). POH occurred in 24.1% of patients. Hospital stay was associated with PPAP grades (No POH/PPAP 10 days (IQR 7-17) days, grade B 22 days (IQR 15-34) days, and grade C 43 days (IQR 27-54) days; P<0.001), as well as intensive care unit admission (No POH/PPAP 5.4%, grade B 12.6%, grade C 82.9%; P<0.010), and hospital readmission rates (No POH/PPAP 7.3%, grade B 16.1%, grade C 18.5%; P<0.05). Costs of grade B and C PPAP were 2 and 11 times greater than uncomplicated clinical course, resp. (P<0.001). This first prospective, international validation study of the ISGPS definition and grading system for PPAP highlighted the relevant clinical and financial implications of this condition. These results stress the importance of routine screening for PPAP in patients undergoing PD.

Genetic Variability in the CPA1 Gene and Its Impact on Acute Pancreatitis Risk: New Insights from a Large-Scale Study.

Acute pancreatitis (AP) is a common and potentially lethal disease. Over the last 10 years, AP has become one of the most important healthcare problems. On a global scale, the incidence has increased by 63% over the last 20 years. AP is usually caused by gallstones and excessive alcohol consumption and genetic factors play an important role in the development of inflammation. Recent studies involving the CPA1 mutations are ambiguous and dependent on the population studied. In this study, the variability of the CPA1 gene in patients with AP was analyzed. Genetic material was isolated from the blood of 301 patients with AP and 184 healthy individuals. Identification of the variants in exons 5, 6, 8, and 9 with introns was performed using molecular biology methods. Mutations were identified by comparison to the reference sequence (NM_001868.4). Statistical analysis included the identification of mutations correlating with the risk of AP, the etiology of inflammation, and family history. Several novel mutations in the CPA1 gene have been identified, along with a high degree of variability within the coding region of the carboxypeptidase gene. A correlation between mutations CPA1:c.1072 + 84del; c.987 + 57G>A and increased risk of developing AP was found. Two protective mutations, CPA1:c.625A>T, c.1072 + 94del, were identified. The CPA1 gene is characterized by high sequence variability and regions in which mutations lead to an increased risk of developing AP. Single or co-occurring mutations of the CPA1 gene can significantly affect the risk of developing AP.

The clinical value of serum creatinine to bilirubin ratio in predicting the severity and prognosis of acute pancreatitis.

Bilirubin (BIL) and creatinine (Cr) have been used as potential early predictors of the severity of many diseases. A recent study found that the Cr to BIL ratio (CTR) was more sensitive and specific than either serum Cr or BIL alone. Our research focused on the clinical significance of CTR in evaluating the severity and prognosticating outcomes of acute pancreatitis (AP) in patients. Patients diagnosed with AP at the First Affiliated Hospital of Guangdong Pharmaceutical University between July 1, 2016, and December 31, 2020 were included. The analysis then focused on examining the relationship between CTR levels and the severity of the illness, the occurrence of complications, and the prognosticating outcomes for individuals diagnosed with AP. A total of 286 AP patients were enrolled. Multivariate regression analyses showed that patients with AP with increased CTR levels had a poorer disease (easier to develop severe AP); higher Ranson, and Acute Physiology and Chronic Health Evaluation (APACHE-II) scores; higher incidence of organ failure (acute heart failure, acute kidney injury and acute myocardial infarction ); and leading to a worse prognosis characterized more by frequent use of vasoactive and diuretic agents. When CTR &gt;14.05, AP patients had increased occurrence of AHF and AKI, higher 30-day all-cause mortality rates, more frequently using vasoactive agent and diuretic agent. Besides, the disease severity scores and hospital stays were markedly increased. Patients with AP who exhibit higher CTR levels tend to experience escalating disease severity, more complications, and a poorer outcome compared with those with lower CTR levels.