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Item Dynamic changes in the pancreatitis activity scoring system during hospital course in a multicenter, prospective cohort(Wiley, 2021) Paragomi, Pedram; Tuft, Marie; Pothoulakis, loannis; Singh, Vikesh K.; Stevens, Tyler; Nawaz, Haq; Easler, Jeffrey J.; Thakkar, Shyam; Cote, Gregory A.; Lee, Peter J.; Akshintala, Venkata; Kamal, Ayesha; Gougol, Amir; Evans Phillips, Anna; Machicado, Jorge D.; Whitcomb, David C.; Greer, Phil J.; Buxbaum, James L.; Hart, Phil; Conwell, Darwin; Tang, Gong; Wu, Bechien U.; Papachristou, Georgios I.; Medicine, School of MedicineBackground and aim: The primary aim was to validate the Pancreatitis Activity Scoring System (PASS) in a multicenter prospectively ascertained acute pancreatitis (AP) cohort. Second, we investigated the association of early PASS trajectories with disease severity and length of hospital stay (LOS). Methods: Data were prospectively collected through the APPRENTICE consortium (2015-2018). AP severity was categorized based on revised Atlanta classification. Delta PASS (ΔPASS) was calculated by subtracting activity score from baseline value. PASS trajectories were compared between severity subsets. Subsequently, the cohort was subdivided into three LOS subgroups as short (S-LOS): 2-3 days; intermediate (I-LOS): 3-7 days; and long (L-LOS): ≥7 days. The generalized estimating equations model was implemented to compare PASS trajectories. Results: There were 434 subjects analyzed including 322 (74%) mild, 86 (20%) moderately severe, and 26 (6%) severe AP. Severe AP subjects had the highest activity levels and the slowest rate of decline in activity (P = 0.039). Focusing on mild AP, L-LOS subjects (34%) had 28 points per day slower decline; whereas, S-LOS group (13%) showed 34 points per day sharper decrease compared with I-LOS (53%; P < 0.001). We noticed an outlier subset with a median admission-PASS of 466 compared with 140 in the rest. Morphine equivalent dose constituted 80% of the total PASS in the outliers (median morphine equivalent dose score = 392), compared with only 25% in normal-range subjects (score = 33, P value < 0.001). Conclusions: This study highlighted that PASS can quantify AP activity. Significant differences in PASS trajectories were found both in revised Atlanta classification severity and LOS groups, which can be harnessed in AP monitoring/management (ClincialTrials.gov number, NCT03075618).Item Incidence and risk factors of oral feeding intolerance in acute pancreatitis: Results from an international, multicenter, prospective cohort study(Wiley, 2021-02) Pothoulakis, Ioannis; Nawaz, Haq; Paragomi, Pedram; Jeong, Kwonho; Talukdar, Rupjyoti; Kochhar, Rakesh; Goenka, Mahesh Kumar; Gulla, Aiste; Singh, Vikesh K.; Gonzalez, Jose A.; Ferreira, Miguel; Barbu, Sorin T.; Stevens, Tyler; Gutierrez, Silvia C.; Zarnescu, Narcis O.; Capurso, Gabriele; Easler, Jeffrey; Triantafyllou, Konstantinos; Pelaez-Luna, Mario; Thakkar, Shyam; Ocampo, Carlos; de-Madaria, Enrique; Wu, Bechien U.; Cote, Gregory A.; Abebe, Kaleab; Tang, Gong; Lahooti, Ali; Phillips, Anna E.; Papachristou, Georgios I.; Medicine, School of MedicineBackground: Inability to advance to an oral diet, or oral feeding intolerance, is a common complication in patients with acute pancreatitis associated with worse clinical outcomes. The factors related to oral feeding intolerance are not well studied. Objective: We aimed to determine the incidence and risk factors of oral feeding intolerance in acute pancreatitis. Methods: Patients were prospectively enrolled in the Acute Pancreatitis Patient Registry to Examine Novel Therapies in Clinical Experience, an international acute pancreatitis registry, between 2015 and 2018. Oral feeding intolerance was defined as worsening abdominal pain and/or vomiting after resumption of oral diet. The timing of the initial feeding attempt was stratified based on the day of hospitalization. Multivariable logistic regression was performed to assess for independent risk factors/predictors of oral feeding intolerance. Results: Of 1233 acute pancreatitis patients included in the study, 160 (13%) experienced oral feeding intolerance. The incidence of oral feeding intolerance was similar irrespective of the timing of the initial feeding attempt relative to hospital admission day (p = 0.41). Patients with oral feeding intolerance were more likely to be younger (45 vs. 50 years of age), men (61% vs. 49%), and active alcohol users (44% vs. 36%). They also had higher blood urea nitrogen (20 vs. 15 mg/dl; p < 0.001) and hematocrit levels (41.7% vs. 40.5%; p = 0.017) on admission; were more likely to have a nonbiliary acute pancreatitis etiology (69% vs. 51%), systemic inflammatory response syndrome of 2 or greater on admission (49% vs. 35%) and at 48 h (50% vs. 26%), develop pancreatic necrosis (29% vs. 13%), moderate to severe acute pancreatitis (41% vs. 24%), and have a longer hospital stay (10 vs. 6 days; all p < 0.04). The adjusted analysis showed that systemic inflammatory response syndrome of 2 or greater at 48 h (odds ratio 3.10; 95% confidence interval 1.83-5.25) and a nonbiliary acute pancreatitis etiology (odds ratio 1.65; 95% confidence interval 1.01-2.69) were independent risk factors for oral feeding intolerance. Conclusion: Oral feeding intolerance occurs in 13% of acute pancreatitis patients and is independently associated with systemic inflammatory response syndrome at 48 h and a nonbiliary etiology.Item Introduction and Validation of a Novel Acute Pancreatitis Digital Tool: Interrogating Large Pooled Data From 2 Prospectively Ascertained Cohorts(Wolters Kluwer, 2020) Paragomi, Pedram; Spagnolo, Daniel M.; Breze, Cameron R.; Gougol, Amir; Talukdar, Rupjyoti; Kochhar, Rakesh; Goenka, Mahesh Kumar; Gulla, Aiste; Gonzalez, Jose A.; Singh, Vikesh K.; Ferreira, Miguel; Stevens, Tyler; Barbu, Sorin T.; Nawaz, Haq; Gutierrez, Silvia C.; Zarnescu, Narcis O.; Archibugi, Livia; Easler, Jeffrey J.; Triantafyllou, Konstantinos; Pelaez-Luna, Mario; Thakkar, Shyam; Ocampo, Carlos; de-Madaria, Enrique; Cote, Gregory A.; Wu, Bechien U.; Pothoulakis, Ioannis; Haupt, Mark; Whitcomb, David C.; Papachristou, Georgios I.; Medicine, School of MedicineObjectives: Acute pancreatitis (AP) is a sudden onset, rapidly evolving inflammatory response with systemic inflammation and multiorgan failure (MOF) in a subset of patients. New highly accurate clinical decision support tools are needed to allow local doctors to provide expert care. Methods: Ariel Dynamic Acute Pancreatitis Tracker (ADAPT) is a digital tool to guide physicians in ordering standard tests, evaluate test results and model progression using available data, propose emergent therapies. The accuracy of the severity score calculators was tested using 2 prospectively ascertained Acute Pancreatitis Patient Registry to Examine Novel Therapies in Clinical Experience cohorts (pilot University of Pittsburgh Medical Center, n = 163; international, n = 1544). Results: The ADAPT and post hoc expert-calculated AP severity scores were 100% concordant in both pilot and international cohorts. High-risk criteria of all 4 severity scores at admission were associated with moderately-severe or severe AP and MOF (both P < 0.0001) and prediction of no MOF was 97.8% to 98.9%. The positive predictive value for MOF was 7.5% to 14.9%. Conclusions: The ADAPT tool showed 100% accuracy with AP predictive metrics. Prospective evaluation of ADAPT features is needed to determine if additional data can accurately predict and mitigate severe AP and MOF.Item The Modified Pancreatitis Activity Scoring System Shows Distinct Trajectories in Acute Pancreatitis: An International Study(Elsevier, 2022) Paragomi, Pedram; Hinton, Alice; Pothoulakis, Ioannis; Talukdar, Rupjyoti; Kochhar, Rakesh; Goenka, Mahesh K.; Gulla, Aiste; Gonzalez, Jose A.; Singh, Vikesh K.; Bogado, Miguel Ferreira; Stevens, Tyler; Barbu, Sorin T.; Nawaz, Haq; Gutierrez, Silvia C.; Zarnescu, Narcis; Archibugi, Livia; Easler, Jeffrey J.; Triantafyllou, Konstantinos; Peláez-Luna, Mario; Thakkar, Shyam; Ocampo, Carlos; de-Madaria, Enrique; Cote, Gregory A.; Lee, Peter J.; Krishna, Somashekar; Lara, Luis F.; Han, Samuel; Wu, Bechien U.; Papachristou, Georgios I.; Medicine, School of MedicineBackground & aims: The aims of this study were to: (1) assess the performance of the Pancreatitis Activity Scoring System (PASS) in a large intercontinental cohort of patients with acute pancreatitis (AP); and (2) investigate whether a modified PASS (mPASS) yields a similar predictive accuracy and produces distinct early trajectories between severity subgroups. Methods: Data was prospectively collected through the Acute Pancreatitis Patient Registry to Examine Novel Therapies In Clinical Experience (APPRENTICE) consortium (2015-2018) involving 22 centers from 4 continents. AP severity was categorized per the revised Atlanta classification. PASS trajectories were compared between the three severity groups using the generalized estimating equations model. Four mPASS models were generated by modifying the morphine equivalent dose (MED), and their trajectories were compared. Results: A total of 1393 subjects were enrolled (median age, 49 years; 51% males). The study cohort included 950 mild (68.2%), 315 (22.6%) moderately severe, and 128 (9.2%) severe AP. Mild cases had the lowest PASS at each study time point (all P < .001). A subset of patients with outlier admission PASS values was identified. In the outlier group, 70% of the PASS variation was attributed to the MED, and 66% of these patients were from the United States centers. Among the 4 modified models, the mPASS-1 (excluding MED from PASS) demonstrated high performance in predicting severe AP with an area under the receiver operating characteristic curve of 0.88 (vs area under the receiver operating characteristic of 0.83 in conventional PASS) and produced distinct trajectories with distinct slopes between severity subgroups (all P < .001). Conclusion: We propose a modified model by removing the MED component, which is easier to calculate, predicts accurately severe AP, and maintains significantly distinct early trajectories.Item Mortality in acute pancreatitis with persistent organ failure is determined by the number, type, and sequence of organ systems affected(Wiley, 2021-03) Machicado, Jorge D.; Gougol, Amir; Tan, Xiaoqing; Gao, Xiaotian; Paragomi, Pedram; Pothoulakis, Ioannis; Talukdar, Rupjyoti; Kochhar, Rakesh; Goenka, Mahesh K.; Gulla, Aiste; Gonzalez, Jose A.; Singh, Vikesh K.; Ferreira, Miguel; Stevens, Tyler; Barbu, Sorin T.; Nawaz, Haq; Gutierrez, Silvia C.; Zarnescu, Narcis O.; Capurso, Gabriele; Easler, Jeffrey J.; Triantafyllou, Konstantinos; Pelaez-Luna, Mario; Thakkar, Shyam; Ocampo, Carlos; de-Madaria, Enrique; Cote, Gregory A.; Wu, Bechien U.; Conwell, Darwin L.; Hart, Phil A.; Tang, Gong; Papachristou, Georgios I.; Medicine, School of MedicineBackground: Persistent organ failure (POF) is the strongest determinant of mortality in acute pancreatitis (AP). There is a paucity of data regarding the impact of different POF attributes on mortality and the role of different characteristics of systemic inflammatory response syndrome (SIRS) in the risk of developing POF. Objective: We aimed to assess the association of POF dynamic features with mortality and SIRS characteristics with POF. Methods: We studied 1544 AP subjects prospectively enrolled at 22 international centers (APPRENTICE consortium). First, we estimated the association of onset, duration, and maximal score of SIRS with POF. Then, we evaluated the risk of mortality based on POF onset, duration, number, type, and sequence of organs affected. Analyses were adjusted for potential confounders. Results: 58% had SIRS, 11% developed POF, and 2.5% died. Early SIRS, persistent SIRS, and maximal SIRS score ≥ 3 were independently associated with higher risk of POF (p < 0.05). Mortality risk in POF was higher with two (33%, odds ratio [OR] = 10.8, 3.3-34.9) and three (48%, OR = 20.2, 5.9-68.6) organs failing, in comparison to single POF (4%). In subjects with multiple POF, mortality was higher when the cardiovascular and respiratory systems failed first or concurrently as compared to when the renal system failed first or concurrently with other organ (p < 0.05). In multivariate regression model, the number and sequence of organs affected in POF were associated with mortality (p < 0.05). Onset and duration of POF had no impact mortality. Conclusion: In AP patients with POF, the risk of mortality is influenced by the number, type, and sequence of organs affected. These results are useful for future revisions of AP severity classification systems.Item Obesity and alcoholic etiology as risk factors for multisystem organ failure in acute pancreatitis: Multinational study(Wiley, 2023) Lee, Peter J.; Lahooti, Ali; Culp, Stacey; Boutsicaris, Andrew; Holovach, Phillip; Wozniak, Kayla; Lahooti, Ila; Paragomi, Pedram; Hinton, Alice; Pothoulakis, Ioannis; Talukdar, Rupjyoti; Kochhar, Rakesh; Goenka, Mahesh K.; Gulla, Aiste; Gonzalez, Jose A.; Singh, Vikesh; Bogado, Miguel Ferreira; Stevens, Tyler; Babu, Sorin Traian; Nawaz, Haq; Gutierrez, Silvia Cristina; Zarnescu, Narcis; Capurso, Gabriele; Easler, Jeffrey; Triantafyllou, Konstantinos; Luna, Mario Peláez; Thakkar, Shyam; Ocampo, Carlos; de-Madaria, Enrique; Cote, Gregory A.; Wu, Bechien U.; Hart, Phil A.; Krishna, Somashekar G.; Lara, Luis; Han, Samuel; Papachristou, Georgios I.; Medicine, School of MedicineBackground: Multisystem organ failure (MSOF) is the most important determinant of mortality in acute pancreatitis (AP). Obesity and alcoholic etiology have been examined as potential risk factors for MSOF, but prior studies have not adequately elucidated their independent effects on the risk of MSOF. Objective: We aimed to determine the adjusted effects of body mass index (BMI) and alcoholic etiology on the risk of MSOF in subjects with AP. Methods: A prospective observational study of 22 centers from 10 countries was conducted. Patients admitted to an APPRENTICE consortium center with AP between August 2015 and January 2018 were enrolled. Multivariable logistic regression was used to estimate the adjusted effects of BMI, etiology, and other relevant covariates on the risk of MSOF. Models were stratified by sex. Results: Among 1544 AP subjects, there was a sex-dependent association between BMI and the risk of MSOF. Increasing BMI was associated with increased odds of MSOF in males (OR 1.10, 95% confidence interval [CI] 1.04-1.15) but not in females (OR 0.98, 95% CI 0.90-1.1). Male subjects with AP, whose BMIs were 30-34 and >35 kg/m2 , had odds ratios of 3.78 (95% CI 1.62-8.83) and 3.44 (95% CI 1.08-9.99), respectively. In females, neither higher grades of obesity nor increasing age increased the risk of MSOF. Alcoholic etiology was independently associated with increased odds of MSOF compared with non-alcohol etiologies (OR 4.17, 95% CI 2.16-8.05). Conclusion: Patients with alcoholic etiology and obese men (but not women) are at substantially increased risk of MSOF in AP.Item The Relationship Between Pre-existing Diabetes Mellitus and the Severity of Acute Pancreatitis: Report From a Large International Registry(Elsevier, 2022) Paragomi, Pedram; Papachristou, Georgios I.; Jeong, Kwonho; Hinton, Alice; Pothoulakis, Ioannis; Talukdar, Rupjyoti; Kochhar, Rakesh; Goenka, Mahesh K.; Gulla, Aiste; Gonzalez, Jose A.; Singh, Vikesh K.; Bogado, Miguel Ferreira; Stevens, Tyler; Barbu, Sorin T.; Nawaz, Haq; Gutierrez, Silvia C.; Zarnescu, Narcis; Archibugi, Livia; Easler, Jeffrey J.; Triantafyllou, Konstantinos; Peláez-Luna, Mario; Thakkar, Shyam; Ocampo, Carlos; de-Madaria, Enrique; Cote, Gregory A.; Wu, Bechien U.; Lee, Peter J.; Hart, Phil A.; Conwell, Darwin L.; Toledo, Frederico G. S.; Yadav, Dhiraj; Medicine, School of MedicineBackground/objectives: The relationship between pre-existing diabetes mellitus (DM) and acute pancreatitis (AP) severity has not been established. We assessed the impact of pre-existing DM on AP severity in an international, prospectively ascertained registry. Methods: APPRENTICE registry prospectively enrolled 1543 AP patients from 22 centers across 4 continents (8 US, 6 Europe, 5 Latin America, 3 India) between 2015 and 2018, and collected detailed clinical information. Pre-existing DM was defined a diagnosis of DM prior to AP admission. The primary outcome was AP severity defined by the Revised Atlanta Classification (RAC). Secondary outcomes were development of systemic inflammatory response syndrome (SIRS) or intensive care unit (ICU) admission. Results: Pre-existing DM was present in 270 (17.5%) AP patients, of whom 252 (93.3%) had type 2 DM. Patients with pre-existing DM were significantly (p < 0.05) older (55.8 ± 16 vs. 48.3 ± 18.7 years), more likely to be overweight (BMI 29.5 ± 7 vs. 27.2 ± 6.2), have hypertriglyceridemia as the etiology (15% vs. 2%) and prior AP (33 vs. 24%). Mild, moderate, and severe AP were noted in 66%, 23%, and 11% of patients, respectively. On multivariable analysis, pre-existing DM did not significantly impact AP severity assessed by the RAC (moderate-severe vs. mild AP, OR = 0.86, 95% CI 0.63-1.18; severe vs. mild-moderate AP, OR = 1.05, 95% CI, 0.67-1.63), development of SIRS, or the need for ICU admission. No interaction was noted between DM status and continent. Conclusion: About one in 5 patients with AP have pre-existing DM. Once confounding risk factors are considered, pre-existing DM per se is not a risk factor for severe AP.Item Worldwide Variations in Demographics, Management, and Outcomes of Acute Pancreatitis(Elsevier, 2019) Matta, Bassem; Gougol, Amir; Gao, Xiaotian; Reddy, Nageshwar; Talukdar, Rupiyoti; Kochhar, Rakesh; Goenka, Mahesh Kumar; Gulla, Aiste; Gonzalez, Jose A.; Singh, Vikesh K.; Ferreira, Miguel; Stevens, Tyler; Barbu, Sorin T.; Nawaz, Haq; Gutierrez, Silvia C.; Zarnescu, Narcis O.; Capurso, Gabriele; Easler, Jeffrey; Triantafyllou, Konstantinos; Pelaez-Luna, Mario; Thakkar, Shyam; Ocampo, Carlos; de-Madaria, Enrique; Cote, Gregory A.; Wu, Bechien U.; Paragomi, Pedram; Pothoulakis, Ioannis; Tang, Gong; Papachristou, Georgios I.; Medicine, School of MedicineBackground & Aims Few studies have compared regional differences in acute pancreatitis. We analyzed data from an international registry of patients with acute pancreatitis to evaluate geographic variations in patient characteristics, management, and outcomes. Methods We collected data from the APPRENTICE registry of patients with acute pancreatitis, which obtains information from patients in Europe (6 centers), India (3 centers), Latin America (5 centers), and North America (8 centers) using standardized questionnaires. Our final analysis included 1,612 patients with acute pancreatitis (median age, 49 years; 53% male, 62% white) enrolled from August 2015 through January 2018. Results Biliary (45%) and alcoholic acute pancreatitis (21%) were the most common etiologies. Based on the revised Atlanta classification, 65% of patients developed mild disease, 23% moderate, and 12% severe. The mean age of patients in Europe (58 years) was older than mean age for all 4 regions (46 years) and a higher proportion of patients in Europe had comorbid conditions (73% vs 50% overall). The predominant etiology of acute pancreatitis in Latin America was biliary (78%), whereas alcohol-associated pancreatitis accounted for the highest proportion of acute pancreatitis cases in India (45%). Pain was managed with opioid analgesics in 93% of patients in North America versus 27% of patients in the other 3 regions. Cholecystectomies were performed at the time of hospital admission for most patients in Latin America (60% vs 15% overall). A higher proportion of European patients with severe acute pancreatitis died during the original hospital stay (44%) compared with the other 3 regions (15%). Conclusions We found significant variation in demographics, etiologies, management practices, and outcomes of acute pancreatitis worldwide.