Severe Acute Pancreatitis Research Articles

Intra-abdominal pressure: a predictor of severity in acute pancreatitis

Background: Acute pancreatitis is a multisystem disease which has an unpredictable course. The major consequence of severe acute pancreatitis is usually intra-abdominal hypertension. So, abdominal compartment syndrome occurs with serve increase in intra-abdominal pressure (IAP) with organ failure. If conservative measures fail, some early interventional procedures have to be performed to reduce mortality in those patients. Methods: The ethics committee clearance was obtained. The study included 50 patients who were admitted in our institution with acute pancreatitis (diagnosed based on clinical, radiological, biochemical parameters) from December 2022 to August 2023. Intravesical route was used to measure IAP and it was performed by bladder catheterization using a Foley's catheter which was then connected with a three-way stopcock, which further attached with a water manometer and on that same day APACHE scores was calculated, compared and analyzed. Results: IAP was >25 cm H2O in 48% of patients and 28% of patients developed MODS and they did not survive. The mean IAP among the survivors was 13.56 cm H2O and in non-survivors it was 24.94 cm H2O. Correlation studies between IAP & the clinical severity of acute pancreatitis was significant (p<0.05). Conclusions: IAP seems to be a simple, reliable and single mortality predictor and helps to assess organ failure in acute pancreatitis and it also well correlates with other pancreatic prognostic scores. It also serves as a selective prognostic marker in acute pancreatitis and found to have a direct correlation between IAP and clinical severity of acute pancreatitis.

Usefulness of Dynamic Assessment of Clinical and Laboratory Factors in Severe Acute Pancreatitis.

Background/Objectives: Early identification of patients at risk of developing severe acute pancreatitis (SAP) is still an issue. Dynamic assessment of clinical and laboratory parameters within the first 48 h of admission may offer valuable insights into the prediction of unfavorable outcomes such as SAP and death. Methods: A prospective observational study was conducted on a cohort of patients admitted for AP at a tertiary referral hospital. Clinical and laboratory data were collected on admission and at 48 h. Patients were classified based on the Revised Atlanta classification. Logistic regression analysis was performed to identify independent risk factors for SAP. Likelihood ratios and post-test probabilities were calculated to assess the clinical usefulness of predictive markers. Results: 227 patients were included, with biliary etiology being the most common and a prevalence of SAP and death of 10.7% and 5.7%, respectively. BISAP ≥ 2 on admission, presence of SIRS after 48 h, rise in heart rate over 20 bpm, and any increase in BUN after 48 h were independent risk factors for SAP. The combination of these factors increased the post-test probability of SAP and death, with BISAP ≥ 2 combined with the presence of SIRS after 48 h showing the highest probability (82% and 73%, respectively). Conclusions: Dynamic assessment of BUN, heart rate, and SIRS within the first 48 h of admission can aid in predicting the development of SAP and death in patients with AP. These findings underscore the importance of continuous monitoring, although multicenter studies are warranted to refine predictive models for SAP.

IDH2-NADPH pathway protects against acute pancreatitis via suppressing acinar cell ferroptosis.

Acute pancreatitis (AP) is associated with acinar cell death and inflammatory responses. Ferroptosis is characterized by an overwhelming lipid peroxidation downstream of metabolic dysfunction, in which NADPH-related redox systems have been recognized as the mainstay in ferroptosis control. Nevertheless, it remains unknown how ferroptosis is regulated in AP and whether we can target it to restrict AP development. Metabolomics were applied to explore changes in metabolic pathways in pancreatic acinar cells (PACs) in AP. Using wild-type and Ptf1aCreERT2/+IDH2fl/fl mice, AP was induced by caerulein and sodium taurocholate (NaT). IDH2 overexpressing adenovirus was constructed for infection of PACs. Mice or PACs were pretreated with inhibitors of FSP1 or glutathione reductase. Pancreatitis severity, acinar cell injury, mitochondrial morphological changes and pancreatic lipid peroxidation were analysed. Unsaturated fatty acid biosynthesis and the tricarboxylic acid cycle pathways were significantly altered in PACs during AP. Inhibition of ferroptosis reduced mitochondrial damage, lipid peroxidation and the severity of AP. During AP, the NADPH abundance and IDH2 expression were decreased. Acinar cell-specific deletion of IDH2 exacerbated acinar cell ferroptosis and pancreatic injury. Pharmacological inhibition of NADPH-dependent GSH/GPX4 and FSP1/CoQ10 pathways abolished the protective effect of IDH2 overexpression on ferroptosis in acinar cells. CoQ10 supplementation attenuated experimental pancreatitis via inhibiting acinar cell ferroptosis. We identified the IDH2-NADPH pathway as a novel regulator in protecting against AP via restricting acinar cell ferroptosis. Targeting the pathway and its downstream may shed light on AP treatment.

Enhancing predictive accuracy in hypertriglyceridemia-induced acute pancreatitis: Role of red cell distribution width and prospective studies.

This letter addresses the study titled "Red cell distribution width: A predictor of the severity of hypertriglyceridemia-induced acute pancreatitis" by Lv et al published in the World Journal of Experimental Medicine. The study offers a valuable analysis of red cell distribution width (RDW) as a predictive marker for persistent organ failure in patients with hypertriglyceridemia-induced acute pancreatitis. The study results suggest that RDW, combined with the Bedside Index for Severity in Acute Pancreatitis score, could enhance the predictive accuracy for severe outcomes. Further investigation into the role of RDW in different severities of acute pancreatitis is recommended. Additionally, the need for large-scale and multicenter prospective studies to validate these findings is emphasized.

ACUTE PANCREATITIS: IS THERE ANY RELATIONSHIP BETWEEN HEMATOCRIT AND SEVERITY OF THE DISEASE?

Introduction. Acute pancreatitis (AP) is one of the unsolved clinical problems in the practice of modern gastroenterology, surgery, and emergency medicine, which does not lose its relevance even with the advent of modern and high-tech diagnostic and therapeutic solutions. The failure of modern methods to diagnose and stratify the severity of the disease in the early stages after hospitalization of patients lead to the loss of precious time at the beginning of resuscitation measures in severe forms of AP. The aim. To assess the presence and strength of the correlation between hematocrit count and the severity of AP on the first day of the disease. Materials and methods. Polychoric analysis and receiver operating characteristic (ROC) analysis were used to assess the association and predictive value of hematocrit with the severity of AP. Only patients who arrived at the hospital within 24 hours of the onset of the disease were included in the study. Results. The correlation coefficient φ2 between hematocrit (at the reference value of 45%) and severity of AP is 0.34. The coefficient of mutual conjugation of K. Pearson (C) is equal to 0.5 which indicates the presence of a relationship between the hematocrit count and the severity of AP. After conducting the ROC analysis, it was determined that with the isolated use of hematocrit indicator provided its value of > 44.4%, almost 70% of patients were diagnosed with severe AP; almost 90% of patients with a hematocrit level of £ 44.4% did not have severe AP. Also, due to the rather high values of the indicators of the prognostic capacity of the ROC analysis, it is possible to state about the presence of prognostic significance of hematocrit indicator for severe AP within the first day from the onset of the disease. Conclusions. Thus, the hematocrit number has a significant relationship with the severity of AP when calculated during the first day from the onset of the disease, which makes it promising for building systems of stratification of the severity of AP earlier than suggested by revised Atlanta criteria.

Renalase peptides reduce pancreatitis severity in mice.

Acute pancreatitis, an acute inflammatory injury of the pancreas, lacks a specific treatment. The circulatory protein renalase is produced by the kidney and other tissues and has potent anti-inflammatory and prosurvival properties. Recombinant renalase can reduce the severity of mild cerulein pancreatitis; the activity is contained in a conserved 20 aa renalase site (RP220). Here, we investigated the therapeutic effects of renalase on pancreatitis using two clinically relevant models of acute pancreatitis. The ability of peptides containing the RP220 site to reduce injury in a 1-day post-endoscopic retrograde cholangiopancreatography (ERCP) and a 2-day severe cerulein induced in mice was examined. The initial dose of renalase peptides was given either prophylactically (before) or therapeutically (after) the initiation of the disease. Samples were collected to determine early pancreatitis responses (tissue edema, plasma amylase, active zymogens) and later histologic tissue injury and inflammatory changes. In both preclinical models, renalase peptides significantly reduced histologic damage associated with pancreatitis, especially inflammation, necrosis, and overall injury. Quantifying inflammation using specific immunohistochemical markers demonstrated that renalase peptides significantly reduced overall bone marrow-derived inflammation and neutrophils and macrophage populations in both models. In the severe cerulein model, administering a renalase peptide with or without pretreatment significantly reduced injury. Pancreatitis and renalase peptide effects appeared to be the same in female and male mice. These studies suggest renalase peptides that retain the anti-inflammatory and prosurvival properties of recombinant renalase can reduce the severity of acute pancreatitis and might be attractive candidates for therapeutic development.NEW & NOTEWORTHY Renalase is a secretory protein. The prosurvival and anti-inflammatory effects of the whole molecule are contained in a 20 aa renalase site (RP220). Systemic treatment with peptides containing this renalase site reduced the severity of post-endoscopic retrograde cholangiopancreatography (ERCP) and severe cerulein pancreatitis in mouse models.

Gut microbiota-melatonin signaling axis in acute pancreatitis: Revealing the impact of gut health on pancreatic inflammation and disease severity in a case-control study.

Acute pancreatitis (AP), a severe inflammatory condition affecting the pancreas requires investigation into its predictors. Melatonin, a compound with anti-inflammatory and antioxidant properties, has shown promise in managing AP. Additionally, the gut microbiota, a community of microorganisms residing in the intestines has been linked to AP development. This study aims to explore the correlation between melatonin and gut microbiota in predicting AP severity. This study involved 199 participants, with 99 diagnosed with AP and 100 serving as healthy controls. The AP patients were categorized into 2 groups based on the severity of their condition: mild AP (MAP) and severe AP (SAP). Serum melatonin levels were measured on Days 1, 3, and 5 of hospitalization, and gut microbiota composition was examined via 16S rRNA gene sequencing. Other parameters were evaluated, such as the Acute Physiology and Chronic Health Evaluation (APACHE) score, Ranson, and Acute Gastrointestinal Injury (AGI) scores. Melatonin levels were significantly lower in subjects with severe AP compared those with mild AP (18.2 ng/mL vs 32.2 ng/mL, P = .001), and melatonin levels decreased significantly in patients with AP on Days 3 and 5. The study also revealed that individuals with AP exhibited a significantly altered gut microbiota composition compared to control individuals, with a lower Shannon index and higher Simpson index. The AUCs for Simpson index and F/B ratio were significantly higher than those for other biomarkers, indicating that these gut microbiota markers may also be useful for AP prediction. The study proposes that there is a relationship between melatonin levels and the dynamics of gut microbiota profiles in relation to the severity of AP. As a result, the severity of the disease can be assessed by assessing the levels of serum melatonin and gut microbiota profiles.

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, whereas 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.NEW & NOTEWORTHY Chymotrypsins defend the pancreas against the inflammatory disorder pancreatitis by degrading harmful trypsinogen. This study demonstrates that mice devoid of pancreatic chymotrypsins are phenotypically normal but become sensitized to secretagogue hyperstimulation and exhibit increased intrapancreatic trypsin activation, more severe acute pancreatitis, and rapid progression to chronic pancreatitis. The observations confirm and extend the essential role of chymotrypsins in pancreas health.

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

PurposeThere 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.MethodsElderly 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).ResultsA 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.ConclusionWe 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.

Fistuloclysis in the nutritional management of a enteroatmospheric fistula: case report and literature review

Introduction: The open abdomen (OA) strategy has been widely adopted as a life-saving intervention in critically ill patients. Initially described as part of the damage control surgery in trauma practice, OA techniques have since further expanded its indications, being successfully adapted to many non-trauma emergent surgical conditions, including abdominal compartment syndrome, severe acute pancreatitis, vascular diseases, and peritonitis/intra-abdominal sepsis. Case Report: This report presents a successful application of this technique in the management of a high-output enteroatmospheric fistula following abdominal complications in a trauma patient. Final considerations: Fistuloclysis is a promising modality for the nutritional support of complex cases of enteroatmospheric fistula in OA patients that also align with the recent efforts to ensure enteral nutrition whenever feasible. Besides its advantages over prolonged exclusive parenteral nutrition in terms of morbidity and costs, the improvement in bowel mucosal trophism is critical for the definitive reconstructive surgery. Future clinical guidelines may encourage the use of fistuloclysis as a safe and effective alternative method for the management of these challenging cases.

From pancreas to lungs: The role of immune cells in severe acute pancreatitis and acute lung injury.

Severe acute pancreatitis (SAP) is a potentially lethal inflammatory pancreatitis condition that is usually linked to multiple organ failure.When it comes to SAP, the lung is the main organ that is frequently involved. Many SAP patients experience respiratory failure following an acute lung injury (ALI). Clinicians provide insufficient care for compounded ALIsince the underlying pathophysiology is unknown. The mortality rate of SAP patients is severely impacted by it. The study aims to provide insight into immune cells, specifically their roles and modifications during SAP and ALI, through a comprehensive literature review. The emphasis is on immune cells as a therapeutic approach for treating SAP and ALI. Immune cells play an important role in the complicated pathophysiology ofSAP and ALI by maintaining the right balance of pro- and anti-inflammatory responses. Immunomodulatory drugs now in the market have low thepeutic efficacy because they selectively target one immune cell while ignoring immune cell interactions. Accurate management of dysregulated immune responses is necessary. A critical initial step is precisely characterizing the activity of the immune cells during SAP and ALI. Given the increasing incidence of SAP, immunotherapy is emerging as a potential treatment option for these patients. Interactions among immune cells improve our understanding of the intricacy of concurrent ALI in SAP patients. Acquiring expertise in these domains will stimulate the development of innovative immunomodulation therapies that will improve the outlook for patients with SAP and ALI.

Using Acidosis as a Surrogate for or Supplement to the Bedside Index of Severity in Acute Pancreatitis Scoring Prediction System Has a Nonsignificant Effect.

Currently, risk stratification calculators for acute pancreatitis (AP) can at best predict acute pancreatitis mortality at 12 hours from the presentation. Given the severe morbidity associated with AP, the identification of additional prognostic indicators, which may afford earlier prediction in length of stay (LOS) and mortality, is desired. Metabolic acidosis can be a prognostic marker for the severity of AP, and venous bicarbonate can reliably and accurately be substituted for arterial base deficit to detect metabolic acidosis. Since serum bicarbonate, anion gap (AG), and corrected AG (CAG) are routinely obtained upon presentation to the emergency department and often daily in the hospital, we conducted a retrospective analysis of 443 patients, evaluating if venous bicarbonate could predict the severity of pancreatitis as well as mortality, admission to the ICU, ICU LOS, and hospital LOS. The inclusion of venous bicarbonate, AG, and CAGin the first 12 hours only slightly improved the predictive capabilities of the Bedside Index for Severity in Acute Pancreatitis (BISAP) score for these secondary outcomes. None of our incorporations of acidemia improved severity predictions more than the BISAP alone. Adding CAG to BISAP scoring had the largest effect on predicting ICU admission and hospital LOS (area under the curve (AUC): 1.12 (confidence interval (CI) 95%: 1.06-1.19), p <.001 and AUC1.02 (CI 95%1.01-1.04), p <.001; respectively). ICU LOS was not impacted by the addition of AG, CAG, or venous bicarbonate. In-hospital death (n=12) was too small to be determined.

Evaluation of Red Cell Distribution Width and Its Ratio to Total Serum Calcium as Predictors of Severity in Acute Pancreatitis.

Acute pancreatitis (AP) is a potentially fatal condition that varies in its severity at presentation. It's crucial to recognize patients with a higher likelihood of severe outcomes to enhance their prognosis by promptly providing medical or endoscopic treatment and admitting them to a specialized intensive care unit (ICU). Despite the various scoring systems and methods, there is no reliable instrument to assess the severity of AP at its presentation. Red cell distribution width (RDW) and serum calcium levels are inexpensive markers readily available upon admission that can be used to anticipate the severity of AP. An observational cross-sectional study was carried out on 85 patients admitted to a referral hospital. The AP patients were categorized into two groups: those with mild AP (MAP) and those with moderately severe/severe AP (MSAP/SAP). RDW was assessed in all patients upon admission and at the 24-hour mark. Among the 85 AP patients, 55 were diagnosed with MAP, while 17 had MSAP and 13 had SAP. The mean serum calcium levels were notably lower in patients with MSAP/SAP compared to MAP. Additionally, the modified Marshall (MM) score, bedside index for severity in acute pancreatitis (BISAP) index, RDW at 0 hours and 24 hours, and RDW/total serum calcium (RDW/TSC) ratio were significantly higher in patients with MSAP/SAP than in MAP. The BISAP index, followed by MM, emerged as the most reliable predictors of severity, with RDW/TSC also showing strong predictive value. RDW/TSC demonstrated superior predictive ability for AP severity when compared to RDW measured at admission and at 24 hours. However, no individual parameter was identified as an independent significant predictor of AP. Red cell distribution width and RDW/TSC ratio are comparable to BISAP index as predictors of severity in AP. They offer a cost-effective and readily accessible means to forecast AP severity upon admission, facilitating prompt intervention at the outset.

Comparing prognostic scoring systems in acute pancreatitis: Bedside Index of Severity in Acute Pancreatitis, WL, and Chinese Simple Scoring System Scores.

Several scoring systems are used to predict prognosis in acute pancreatitis (AP), but their predictive success varies. This study compares the validity of the commonly used Bedside Index of Severity in AP (BISAP) score with the newly developed WL score and the Chinese Simple Scoring System (CSSS) score in predicting mortality and unfavorable prognostic outcomes in AP patients. This retrospective descriptive study included all AP patients presenting to the emergency department from June 2, 2019, to June 2, 2022. Patient demographics, vital signs, laboratory values, and imaging findings were recorded, and WL, CSSS, and BISAP scores were calculated. The effectiveness of these scores in predicting adverse outcomes and mortality was compared. Among 357 patients, 53.2% were male, with a median age of 62 years (interquartile range: 48-75). Area under the curve (AUC) values for 7-day outcomes were 0.956 for WL, 0.759 for CSSS, and 0.871 for BISAP; for 30-day outcomes, AUC values were 0.941 for WL, 0.823 for CSSS, and 0.901 for BISAP; and for poor prognostic outcomes, AUC values were 0.792 for WL, 0.769 for CSSS, and 0.731 for BISAP. In AP patients, WL, CSSS, and BISAP scores are effective predictors of unfavorable prognosis and mortality. WL score outperforms the CSSS and BISAP scores in predicting 7-day and 30-day mortality and poor prognosis. After WL, BISAP is the second-best system for predicting mortality. For predicting unfavorable prognoses, CSSS is the second-best system after WL. The simplicity of calculating the WL score based on four laboratory parameters makes it a preferable choice.

A Prospective Observational Study on the Clinical Spectrum of Acute Pancreatitis in the Department of General Medicine in a Tertiary Care Hospital

ABSTRACT Background: Acute pancreatitis (AP) is an inflammatory disorder of the pancreas, which can be life-threatening. It is characterized by sudden-onset abdominal pain, elevated pancreatic enzymes, and potential involvement of multiple organs. Materials and Methods: We conducted a prospective observational study over a 6-month period. A total of 121 subjects were included, comprising 116 males (95.87%) and 5 females (4.13%). Most subjects fell within the age group of 26–35 (36.36%). Alcohol emerged as a major etiological factor, accounting for 101 cases (83.4%). Results: During the first 4 weeks of admission, patients developed various complications such as acute fluid collection (43.13%), ascites (33.33%), gastrointestinal disturbances (15.6%), necrotizing pancreatitis (5.88%) and pleural effusion (5.88%). Conclusion: Abdominal pain was the most common clinical manifestation across all age groups. We assessed severity using the Bedside Index of Severity in AP scoring scale and Ranson’s scoring scale, with the majority of subjects classified as being at mild risk. In addition, serum lipase proved to be an accurate biomarker for diagnosing AP. Interestingly, the alleviation of abdominal pain was independent of pancreatin administration.

1193 Could Acute Severe Pancreatitis Have Caused These Oesophageal Strictures?

1193 Could Acute Severe Pancreatitis Have Caused These Oesophageal Strictures?

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

ObjectivesWe 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. MethodsPost-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. ResultsIn 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. ConclusionsThe degree of necrosis in LEPP assessed using early CECT of SAP was a better predictor of mortality than the extent of pancreatic inflammation.

Construction and validation of a rat model of acute necrotizing pancreatitis-associated intestinal injury.

Acute pancreatitis (AP) is an acute inflammatory reaction of the pancreatic tissue, which involves auto-digestion, edema, hemorrhage, and necrosis. AP can be categorized into mild, moderately severe, and severe AP, with severe pancreatitis also referred to as acute necrotizing pancreatitis (ANP). ANP is characterized by the accumulation of necrotic material in the peritoneal cavity. This can result in intestinal injury. However, the mechanism of ANP-associated intestinal injury remains unclear. We established an ANP-associated intestinal injury rat model (ANP-IR model) by injecting pancreatitis-associated ascites fluid (PAAF) and necrotic pancreatic tissue at various proportions into the triangular area formed by the left renal artery and ureter. The feasibility of the ANP-IR model was verified by comparing the similar changes in indicators of intestinal inflammation and barrier function between the two rat models. In addition, we detected changes in apoptosis levels and YAP protein expression in the ileal tissues of rats in each group and validated them in vitro in rat epithelial crypt cells (IEC-6) to further explore the potential injury mechanisms of ANP-associated intestinal injury. We also collected clinical data from patients with ANP to validate the effects of PAAF and pancreatic necrosis on intestinal injury. Our findings offer a theoretical basis for restricting the buildup of peritoneal necrosis in individuals with ANP, thus promoting the restoration of intestinal function and enhancing treatment efficacy. The use of the ANP-IR model in further studies can help us better understand the mechanism and treatment of ANP-associated intestinal injury.NEW & NOTEWORTHY We constructed a rat model of acute necrotizing pancreatitis-associated intestinal injury and verified its feasibility. In addition, we identified the mechanism by which necrotic pancreatic tissue and pancreatitis-associated ascites fluid (PAAF) cause intestinal injury through the HIPPO signaling pathway.

Nutritional parameters following first episode of pediatric acute pancreatitis

Acute pancreatitis (AP) carries the risk of subsequent nutritional deficiencies. The prevalence of these deficiencies following a single episode of AP in children is unknown. We aimed to determine prevalence of anthropometric and laboratory-based measures of nutritional status in children following their first (index) admission for AP. Prospective observational cohort study of patients ≤21 years of age with first episode of confirmed AP. Anthropometric and laboratory values were obtained at time of AP onset and at follow up time points of 3 and 12 months (m) post AP. AP attack was classified as either: mild, moderately severe or severe (which were combined in one group (SAP)). 181 patients met criteria and were followed prospectively with 52% male, a median age of 13.7 years (IQR 9.4-16.0) and median Body Mass Index (BMI) Z-score of 0.6 (IQR -0.5, 1.6). Most patients had mild AP (140, 77%), with 23% meeting criteria for moderate or severe (41/181). 6 (3%) had diabetes mellitus (DM) predating AP and were excluded from further analysis. BMI Z-score remained stable during the follow up period. 13% of patients developed pre-DM or DM at 3m or 12m. Nearly one third of patients had low ferritin at 3m (29%) or 12m (29%). At 12m, 8% of patients had Vitamin A deficiency. 6% of patients had low Vitamin E levels at 3m and 5% at 12m. Over half of patients at both 3m and 12m had 25 OH Vitamin D insufficiency or deficiency (56% and 56%). Prolonged International Normalized Ratio (INR) (>1.3) was seen in 9% of patients at 12m. Very low albumin (<3.5g/dL) was found in 24% of patients at 3m and 18% at 12m (Table1). Patients with very low albumin at 3m were younger (median 10.7 vs. 14.2 years, p=0.04), however sex, BMI Z-score and AP severity were not associated with albumin level. Although BMI Z-score did not differ between the groups, those with SAP had a significant decrease in BMI Z-score from first attack compared to mild AP at 3m (-0.4 vs. 0.0, p=0.0002, Figure2). At 3m, Vitamin E deficiency in SAP versus mild AP was found in 20% vs 2% (p=0.04) and SAP had a lower median hematocrit (35.8 vs. 37.6, p=0.046). There were no other laboratory significant differences at 3m in mild versus SAP groups. At 12m, those with SAP were more likely to have pre-DM or DM compared to mild AP (31% vs. 7%, p=0.002). No other significant laboratory differences occurred at 12m. After the first AP attack patients experience nutritional deficiencies, including ferritin, all fat-soluble vitamins, and low albumin. SAP is associated with a decrease in BMI Z-score, increased prevalence of vitamin E deficiency at 3m, and an increase in pre-diabetes and diabetes at 12m. Serial monitoring of vitamin and mineral values post AP is warranted and further prospective studies are needed.

Immune markers of severe acute pancreatitis.

Acute pancreatitis is a common acute inflammatory disorder of the pancreas, and its incidence has been increasing worldwide. Approximately 10% of acute pancreatitis progresses to severe acute pancreatitis (SAP), which carries significant morbidity and mortality. Disordered immune response to pancreatic injury is regarded as a key event that mediates systemic injury in SAP. In this article, we review recent developments in immune biomarkers of SAP and future directions for research. Given the importance of the NLRP3-inflammasome pathway in mediating systemic inflammatory response syndrome and systemic injury, recent studies have investigated associations of SAP with systemic levels of activators of NLRP3, such as the damage associated molecular patterns (DAMPs) for the first time in human SAP. For example, circulating levels of histones, mitochondrial DNAs, and cell free DNAs have been associated with SAP. A panel of mechanistically relevant immune markers (e.g., panel of Angiopoeitin-2, hepatocyte growth factor, interleukin-8 (IL-8), resistin and sTNF-α R1) carried higher predictive accuracies than existing clinical scores and individual immune markers. Of the cytokines with established relevance to SAP pathogenesis, phase 2 trials of immunotherapies, including tumor necrosis factor (TNF)-alpha inhibition and stimulation of IL-10 production, are underway to determine if altering the immunologic response can reduce the severity of acute pancreatitis (AP). Circulating systemic levels of various DAMPs and a panel of immune markers that possibly reflect activities of different pathways that drive SAP appear promising as predictive biomarkers for SAP. But larger multicenter studies are needed for external validation. Studies investigating immune cellular pathways driving SAP using immunophenotyping techniques are scarce. Interdisciplinary efforts are also needed to bring some of the promising biomarkers to the bedside for validation and testing for clinical utility. Studies investigating the role of and characterization of altered gut-lymph and gut-microbiota in severe AP are needed.