Identifying novel acute pancreatitis sub-phenotypes using total serum calcium trajectories.

BACKGROUND: Acute pancreatitis (AP) has heterogeneous clinical features, and identifying clinically relevant sub-phenotypes is useful. We aimed to identify novel sub-phenotypes in hospitalized AP patients using longitudinal total serum calcium (TSC) trajectories. METHODS: AP patients had at least two TSC measurements during the first 24 h of hospitalization in the US-based critical care database (Medical Information Mart for Intensive Care-III (MIMIC-III) and MIMIC-IV were included. Group-based trajectory modeling was used to identify calcium trajectory phenotypes, and patient characteristics and treatment outcomes were compared between the phenotypes. RESULTS: A total of 4518 admissions were included in the analysis. Four TSC trajectory groups were identified: "Very low TSC, slow resolvers" (n = 65; 1.4% of the cohort); "Moderately low TSC" (n = 559; 12.4%); "Stable normal-calcium" (n = 3875; 85.8%); and "Fluctuating high TSC" (n = 19; 0.4%). The "Very low TSC, slow resolvers" had the lowest initial, maximum, minimum, and mean TSC, and highest SOFA score, creatinine and glucose level. In contrast, the "Stable normal-calcium" had the fewest ICU admission, antibiotic use, intubation and renal replace treatment. In adjusted analysis, significantly higher in-hospital mortality was noted among "Very low TSC, slow resolvers" (odds ratio [OR], 7.2; 95% CI, 3.7 to 14.0), "moderately low TSC" (OR, 5.0; 95% CI, 3.8 to 6.7), and "Fluctuating high TSC" (OR, 5.6; 95% CI, 1.5 to 20.6) compared with the "Stable normal-calcium" group. CONCLUSIONS: We identified four novel sub-phenotypes of patients with AP, with significant variability in clinical outcomes. Not only the absolute TSC levels but also their trajectories were significantly associated with in-hospital mortality.

Molecular Patterns in Acute Pancreatitis Reflect Generalizable Endotypes of the Host Response to Systemic Injury in Humans.

OBJECTIVE: Acute Pancreatitis (AP) is sudden onset pancreas inflammation that causes systemic injury with a wide and markedly heterogeneous range of clinical consequences. Here, we hypothesized that this observed clinical diversity corresponds to diversity in molecular subtypes that can be identified in clinical and multiomics data. SUMMARY BACKGROUND DATA: Observational cohort study. n = 57 for the discovery cohort (clinical, transcriptomics, proteomics, and metabolomics data) and n = 312 for the validation cohort (clinical and metabolomics data). METHODS: We integrated coincident transcriptomics, proteomics, and metabolomics data at serial time points between admission to hospital and up to 48 hours after recruitment from a cohort of patients presenting with acute pancreatitis. We systematically evaluated 4 different metrics for patient similarity using unbiased mathematical, biological, and clinical measures of internal and external validity.We next compared the AP molecular endotypes with previous descriptions of endotypes in a critically ill population with acute respiratory distress syndrome (ARDS). RESULTS: Our results identify 4 distinct and stable AP molecular endotypes. We validated our findings in a second independent cohort of patients with AP.We observed that 2 endotypes in AP recapitulate disease endotypes previously reported in ARDS. CONCLUSIONS: Our results show that molecular endotypes exist in AP and reflect biological patterns that are also present in ARDS, suggesting that generalizable patterns exist in diverse presentations of critical illness.

Validation of the Modified Determinant-Based Classification for Patients With Acute Pancreatitis in Intensive Care Medicine.

OBJECTIVES: To validate the Modified Determinant-Based Classification (MDBC) system, and compare it with the Revised Atlanta Classification (RAC) and the Determinant-Based Classification (DBC). METHODS: Prospective observational research was conducted in 35 international intensive care units, on patients with acute pancreatitis, and at least 1 organ failure (OF). Patient classification according to the MDBC was as follows: group 1 (transient OF, without local complications [LCs]), group 2 (transient OF and LC), group 3 (persistent OF, without LC), and group 4 (persistent OF and LC). RESULTS: A total of 316 patients were enrolled (mortality of 25.6%). In group 1, patients presented with low mortality (3.31%) and low morbidity (13.68%); in group 2, low mortality (5.26%) and moderate morbidity (55.56%); in group 3, high mortality (32.18%) and moderate morbidity (54.24%); and in group 4, high mortality (53.93%) and high morbidity (97.56%). The area under the receiver operator characteristic curve for mortality was 0.80 (95% confidence interval [CI], 0.75-0.84), with significant differences in comparison to RAC (0.76; 95% CI, 0.70-0.80) and DBC (0.79; 95% CI, 0.74-0.83) (P < 0.01). CONCLUSIONS: The MDBC identified 4 groups with differentiated clinical evolutions. Its tiered mortality rating provided it with better discriminatory power than the DBC and the RAC.

Groove pancreatitis has a spectrum of severity and can be managed conservatively.

BACKGROUND & AIMS: The natural history of groove pancreatitis is incompletely characterized. Published literature suggests a high rate of surgery. We describe the short- and long-term outcomes in a cohort of patients with groove pancreatitis treated at our institution. METHODS: Medical records of patients hospitalized in the University of Pittsburgh Medical Center system from 2000 to 2014 and diagnosed with groove pancreatitis based on imaging were retrospectively reviewed. Clinical presentation and outcomes during index admission and follow-up were recorded. RESULTS: Forty-eight patients with groove pancreatitis were identified (mean age 53.2 years, 79% male). Seventy-one percent were alcohol abusers and an equal number were cigarette smokers. Prior histories of acute and chronic pancreatitis were noted in 30 (62.5%) and 21 (43.8%), respectively. Forty-four (91.7%) met criteria for acute pancreatitis during their index admission. Alcohol was the most common etiology (68.8%). No patient experienced organ failure. The most frequent imaging findings were fat stranding in the groove (83.3%), duodenal wall thickening (52.1%), and soft tissue mass/thickening in the groove (50%). Over a mean follow-up of 5.0 years, seven (14.6%) required a pancreas-related surgery. Patients had a high burden of pancreatitis-related readmissions (68.8%, 69.4/100 patient-years). Incident diabetes and chronic pancreatitis were diagnosed in 5 (13.9% of patients at risk) and 8 (29.6% of patients at risk) respectively. CONCLUSIONS: Groove pancreatitis has a wide spectrum of severity; most patients have mild disease. These patients have a high burden of readmissions and progression to chronic pancreatitis. A small minority requires surgical intervention.

Pancreas Divisum Increases the Risk of Recurrent Acute Pancreatitis in Patients with rs12338 Polymorphism in the Cathepsin B Gene.

OBJECTIVES: Pancreas divisum (PD) as a cause of pancreatitis has been debated. In this study, we report the association of multiple gene polymorphisms on the risk of RAP in the presence of PD. DESIGN: We enrolled 687 individuals (167 IRAP, 276 ICP, and 244 unrelated healthy controls) from May 2015 to September 2016. Patients were divided into those with/without PD. Associations between the significantly prevalent SNPs and IRAP/ICP in the presence of PD were evaluated. Clinical data were analyzed using Mann-Whitney U/Chi-square test. Effect size of association of SNPs with IRAP/ICP was expressed as odds ratio (OR) (95% CI). Gene-gene interaction was assessed by transheterozygosity analyses. Bonferroni-corrected two-tailed "p" value of ≤ 0.01 was considered statistically significant. RESULTS: Thirty-three (19.8%) and 82 (29.7%) patients with IRAP and ICP, respectively, had PD. Among the patients with IRAP, duration of disease was significantly shorter in those with PD compared to those without (mean [95% CI] duration: 1.6 (1.3-1.9) vs 2.7 (2.3-3.1) years; p = 0.005). There were no differences in gender, race, and diabetes among patients with/without PD in IRAP/ICP groups. Mean (95% CI) pancreatic duct diameter (mm) was significantly higher in the presence of PD in patients with both IRAP [1.6 (1.4-1.9) v/s 1.29 (1.2-1.4); p = 0.03)] and ICP [5.2 (4.5-5.9) v/s 4.5 (3.9-5.1); p = 0.02]. CTSB (rs12338) polymorphisms were significantly associated with IRAP [OR (95% CI) 2.44 (1.41-4.22); p = 0.001] among patients with PD. No association was observed with ICP. Transheterozygosity analysis did not show any significant associations of combination of SNPs with IRAP in the presence of PD. CONCLUSION: Risk of RAP due to PD increases in patients with rs12338 polymorphism in the cathepsin B gene.

Pancreatitis aguda. Diagnóstico y enfrentamiento inicial en la práctica clínica / Acute pancreatitis. Diagnosis and initial approach in clinical practice

Acute pancreatitis is a prevalent disease, with variable clinical course: several patients recover quickly and uneventfully, while others require treatment in critical care units with long hospital stay and even with a considerable mortality. The patient's symptoms, laboratory tests and radiological images allow diagnosis without major difficulties. However, early identification of more severe cases can be difficult, and it determines the adequate selection of the hospitalization unit and the quick initiation of the appropriate therapy. In this paper we give some practical treatment guidelines for the everyday clinical practice: immediate severity stratification, fluid replacement and pain control. Early enteral nutrition, monitorization of severe cases in critical care units, adequate therapeutic but no prophylactic use of antibiotics assures the best treatment results. (AU)

Outcomes and risk factors for ERCP-related complications in a predominantly black urban population.

OBJECTIVE: There is a lack of literature on postendoscopic retrograde cholangiopancreatography (ERCP) complications in predominantly black urban populations of low socioeconomic status. The aim of this study was to determine the incidence and predictors of post-ERCP complications in this patient population. DESIGN: Retrospective review of ERCP cases performed at two hospitals from 2007 to 2017 was performed. The categories of complications evaluated were overall complications, severe or fatal complications, pancreatitis, bleeding, infection, perforation and cardiopulmonary events. Predictors of complications were determined by univariate analysis. RESULTS: A total of 1079 ERCP procedures were reviewed. There were 106 complications (9.8%). Twenty-one were severe (1.9%) and 20 were fatal (1.9%). Both post-ERCP pancreatitis (PEP) and post-ERCP bleeding occurred in 18 patients (1.7%) each. Risk factors for overall complications were male sex (OR 1.54), ASA grade IV or V (OR 2.19), prior history of PEP (OR 6.98) and pancreatic duct stent placement (OR 2.75). Those who were ASA grade III or lower (OR 0.4) or who underwent biliary stone extraction (OR 0.62) had fewer complications. PEP was more likely in those with a prior history of PEP (OR 37.6). Those with a suspected or known biliary duct stone had less frequent pancreatitis (OR 0.32). Post-ERCP bleeding was more likely in the presence of cholangitis (OR 8.72). CONCLUSION: Outcomes of ERCP in a predominantly black urban population demonstrate a lower incidence of PEP and all-cause mortality compared with historical data reported in the general population. Potential risk factors for post-ERCP complications were identified but require larger studies for validation.

The Severity of Acute Pancreatitis According to Modified Balthazar Classification in Patients With Pancreatic Cancer.

OBJECTIVE: Although acute pancreatitis (AP) is a self-limited disease under supportive and medical treatment, it can have life-threatening potential in some patients. Results of studies reporting outcomes of AP-associated pancreatic malignancy are controversial. The aim of this study was to evaluate the severity and prognosis of pancreatic cancer (PC)-related AP by modified Balthazar score. METHODS: A total of 354 patients hospitalized and followed up in our clinic between 2013 and 2019 were included in the study. Demographic data of all patients were recorded. The etiology of all cases was determined. According to the etiology, the cases were divided into 2 groups: AP related to pancreatic malignancy and AP due to nonmalignant causes. The patients underwent computed tomography of the abdomen within the first 12 hours of admission and after 3 to 7 days. Patients were evaluated and classified by modified Balthazar classification. RESULTS: Malignancy-related AP was detected in 18 (5.1%) patients. A total of 336 cases (94.9%) were related to nonmalignant causes. There was no statistically significant difference in the severity of AP in both groups at admission and after 3 days (p > 0.05). The changes (regression, progression, or no change) in the disease severity at the first and the subsequent imaging were examined. There was no significant relationship between the 2 groups (p > 0.05). CONCLUSION: AP may be the clinical manifestation of PC or PC may induce AP in various ways. It was shown that the underlying malignancy did not adversely affect the severity and course of AP.

Pancreatic and biliary tract involvement in IgG4-related disease.

The diagnosis and treatment of pancreatic and biliary tract involvement in IgG4 disease can be challenging for physicians. A French series shows that the pancreas is the most frequently involved organ in systemic IgG4 disease. Pancreatitis may be found in more than 50% of patients with IgG4 disease and the biliary tract is involved in one third. Pancreatic or biliary involvement may be isolated, metachronous or synchronous of other IgG4-related organ injuries. Pancreatitis related to IgG4 disease is called autoimmune pancreatitis (AIP) type 1. The diagnosis is mainly suspected in the presence of symptoms and morphological features. Changes observed on conventional imaging are not typical and are usually similar to lesions observed in autoimmune pancreatitis type 2. AIP type 1 can also sometimes have a clinical or morphological presentation that mimics pancreatic cancer, especially pseudo-tumoral forms, associated with obstructive jaundice, weight loss and fatigue. Thus, the first challenge is to confirm the diagnosis of autoimmune pancreatitis and to exclude cancer. The AIP type must then be determined to decide on the most appropriate treatment.

Reporting of acute pancreatitis by radiologists-time for a systematic change with structured reporting template.

Acute pancreatitis has a wide array of imaging presentations. Various classifications have been used in the past to standardize the terminology and reduce confusing and redundant terms. We aim to review the historical and current classifications of acute pancreatitis and propose a new reporting template which can improve communication between various medical teams by use of appropriate terminology and structured radiology template. The standardized reporting template not only conveys the most important imaging findings in a simplified yet comprehensive way but also allows structured data collection for future research and teaching purposes.

Classification, Severity Assessment, and Prevention of Recurrences in Acute Pancreatitis.

BACKGROUND: Acute pancreatitis is a common disease, the incidence of which is 75-100/100,000/year in Finland. The worldwide incidence of acute pancreatitis is increasing. The identified mildcases usually show rapid recovery with conservative treatment allowing early discharge. Severe cases need early intensive care to reduce the risk of serious complications such as multi-organ failure. The revised Atlanta classification of acute pancreatitis was introduced in 2012-2013. A recurrent acute pancreatitis is defined as two or more well-documented separate attacks of acute pancreatitis with complete resolution in between. Alcoholic pancreatitis is the most common recurrent acute pancreatitis type. METHODS: In this review current severity classifications and literature on the prevention of recurrent acute pancreatitis are analyzed. RESULTS: The severity of the disease is classified as mild, moderately severe, and severe acute pancreatitis. Novel entities include acute peripancreatic fluid collections in mild acute pancreatitis and acute necrotic collections in necrotizing acute pancreatitis lesser than 4 weeks after the onset and pancreatic pseudocyst in mild acute pancreatitis and walled-off necrosis in necrotizing acute pancreatitis more than 4 weeks after the onset of the disease. After the first attack of alcohol-induced acute pancreatitis, 46% of the patients develop at least one recurrence within 10- to 20-year follow-up. With repeated intervention against alcohol consumption, it is possible to reduce the recurrences. Removing the gall bladder after biliary pancreatitis is the key preventing recurrences. In mild cases, even during the index admission; in severe cases, it is recommended to wait until the inflammatory changes have resolved. Of total, 59% of the idiopathic pancreatitis had sludge of stones in the gall bladder. In other etiologies, addressing the etiological factor may prevent recurrent acute pancreatitis. CONCLUSIONS: This review describes current use of novel severity classifications and also different possibilities to prevent recurrent acute pancreatitis with different etiologies including idiopathic.

Acute pancreatitis: an update on the revised Atlanta classification.

Acute pancreatitis (AP) is the most common gastrointestinal disease resulting in hospitalization in the United States with reports of over 270,000 hospitalizations and costs up to 2.6 billion dollars per year. AP is highly variable in disease course and outcome. Established in 1992, the original Atlanta classification system aimed to categorize the wide spectrum of AP by creating consensus-based terminology for AP types, severity, and complications. Though the original system standardized terminology, certain terms and definitions (i.e. pancreatic abscess) were unclear and often misused. The 2012 revised Atlanta classification (RAC) system updated terms, clarified definitions, and incorporated the medical community's improved understanding of the physiology of AP. The resulting RAC effectively defined the morphologic types of pancreatitis, provided a more standardized system for disease severity grading, further classified the local retroperitoneal complications, and established objective measures to describe this highly variable but common disease. This review provides an update on the recent literature evaluating the RAC, discusses both the strengths and shortcomings of the RAC system (including problematic interobserver agreement), and considers improvements for future classification systems.

CT imaging, classification, and complications of acute pancreatitis.

Acute pancreatitis is an increasingly common condition and can result in significant morbidity and mortality. Contrast enhanced computed tomography (CECT) is the primary initial imaging modality in the characterization of acute pancreatitis. In this article, we provide sample CECT technical acquisition parameters for pancreatic imaging. We also review the classification systems for acute pancreatitis and give examples of common and uncommon complications of acute pancreatitis.

Emerging imaging techniques for acute pancreatitis.

Acute pancreatitis (AP) is caused by acute inflammation of the pancreas and adjacent tissue and is a common source of abdominal pain. The current CT and MRI evaluation of AP is mostly based on morphologic features. Recent advances in image acquisition and analysis offer the opportunity to go beyond morphologic features. Advanced MR techniques such as diffusion-weighted imaging, as well as T1 and T2 mapping, can potentially quantify signal changes reflective of underlying tissue abnormalities. Advanced analytic techniques such as radiomics and artificial neural networks (ANNs) offer the promise of uncovering imaging biomarkers that can provide additional classification and prognostic information. The purpose of this article is to review recent advances in imaging acquisition and analytic techniques in the evaluation of AP.

Role of extrapancreatic necrosis volume in determining early prognosis in patients with acute pancreatitis.

PURPOSE: This study aims to evaluate the capacity of the clinical and radiological findings and the extrapancreatic necrotic tissue volume in early (2-6 days) computerized tomography (CT) images of patients diagnosed with AP to predict reliably the temporary or permanent organ failure and other local or systemic complications due to pancreatitis. MATERIALS AND METHODS: Adult patients who were diagnosed with AP based on Revised Atlanta classification and underwent abdomen CT scans between May 2015 and May 2018 were examined retrospectively. Extrapancreatic necrosis volume was compared to various clinical parameters that indicate the prognosis of AP such as C-reactive protein (CRP) at 48-72th h, organ failure, infection, requirement for percutaneous or surgical intervention, length of hospital stay, and mortality, and to various imaging-based scoring systems such as the computerized tomography severity index (CTSI) and the modified CTSI (mCTSI). The receiver operating characteristic (ROC) curve was used to estimate the optimal threshold for predicting clinical prognosis. RESULTS: Extrapancreatic necrosis volume had moderate positive correlation with length of hospital stay (p = 0.0001) and CRP (at 48-72th h) (p = 0.0001) and strong positive correlation with CTSI (p = 0.0001), mCTSI (p = 0.0001), and white blood cell count (p = 0.0001). CONCLUSION: Extrapancreatic necrosis volume was found to be particularly better in predicting organ failure and infection compared to the imaging-based scoring systems (Balthazar, CTSI, and mCTSI) and the laboratory-based scoring systems (CRP at 48-72th h).

Endoscopic intervention in pancreatitis: perspectives from a gastroenterologist.

The last decade has seen a dramatic paradigm shift for the treatment of pancreatitis and its related complications away from surgery to minimally invasive endoscopic approaches. In this review, we provide an overview of the indications, techniques and outcomes of endoscopic interventions in the management of acute and chronic pancreatitis. Emphasis is placed on drainage of pancreatic pseudocysts and treatment of pain in chronic pancreatitis.

Plasma D-Dimer Level Is an Early Predictor of Severity of Acute Pancreatitis Based on 2012 Atlanta Classification.

BACKGROUND Acute pancreatitis (AP) is a common digestive disorder. Its management depends on the severity; therefore, it is essential to stratify AP patients early. D-dimer, a coagulation indicator, appears to be associated with the pathogenesis of AP. The aim of this study was to evaluate D-dimer as an early predictor of the severity of AP. MATERIAL AND METHODS This was a single-center retrospective study of 1260 patients diagnosed based on the revised Atlanta classification. Only patients hospitalized within 24 h of onset were included, and 334 patients were enrolled. Blood was collected at admission and 3 times within 48 h of admission. Values at admission and average of the 3 blood samples were evaluated by univariate and multivariate analyses. Furthermore, the area under the receiver-operating characteristic curve (AUC) was used to estimate the validity of the predictor and to define optimal cut-off points for prediction. RESULTS We found that 53.3% of the patients had mild AP (MAP), 24.3% had moderately severe AP (MSAP), and 22.4% had severe AP (SAP). D-dimer at admission and the average D-dimer could distinguish MAP patients from MSAP and SAP patients, with cut-off values of 3.355 mg/L and 4.868 mg/L, respectively. No difference in the parameters at admission was observed in multivariate analysis in distinguishing SAP from MSAP, but the average D-dimer level was significantly different with a cut-off value of 7.268 mg/L by comparing Ranson score, APACHE II score, and D-dimer level. CONCLUSIONS The average value of D-dimer levels could be used as a predictor of severity of AP. In general, patients with an average D-dimer level <4.868 could be diagnosed with MAP, >7.268 would develop into SAP, and between 4.868 and 7.268 would be MSAP.

A comparison of the BISAP score and Amylase and BMI (CAB) score versus for predicting severe acute pancreatitis.

BACKGROUND AND AIMS: Early prediction of severe acute pancreatitis (SAP)would be helpful for triaging patients to the appropriate level of care and intervention. The aim of this study is to compare the performance of the Change in Amylase And Body mass index (CAB) score and BISAP score for predicting SAP. PATIENTS AND METHODS: A total of 406 with AP were enrolled. The age, gender, body mass index(BMI), blood urea nitrogen determined at the time of admission and serum amylase determined on day 1 and day 2 after hospitalization were collected and analyzed statistically. RESULTS: Multivariable analysis confirmed that blood urea nitrogen (OR 1.06; 95%CI 1.03-1.09) and percentage change in amylase day 2 (OR 0.75; 95%CI 0.65-0.87) were independently associated with development of SAP. No statistically significant association was observed between BMI (OR 1.04; 95%CI 0.951.13) and severity of acute pancreatitis. The area under the receiver operating characteristic curve for Body mass index (BMI), percentage change in amylase day 2, BISAP score and CAB score were 0.57±0.05, 0.68±0.04, 0.84±0.03 and0.53±0.05, respectively. CONCLUSION: BISAP is more accurate for predicting the severity of acute pancreatitis than the CAB score.