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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 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 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 Rationale and Design for the Diabetes RElated to Acute Pancreatitis and Its Mechanisms (DREAM) Study: A Prospective Cohort Study From the Type 1 Diabetes in Acute Pancreatitis Consortium (T1DAPC)(Wolters Kluwer, 2022) Hart, Phil A.; Papachristou, Georgios I.; Park, Walter G.; Dyer, Anne-Marie; Chinchilli, Vernon M.; Afghani, Elham; Akshintala, Venkata S.; Andersen, Dana K.; Buxbaum, James L.; Conwell, Darwin L.; Dungan, Kathleen M.; Easler, Jeffrey J.; Fogel, Evan L.; Greenbaum, Carla J.; Kalyani, Rita R.; Korc, Murray; Kozarek, Richard; Laughlin, Maren R.; Lee, Peter J.; Maranki, Jennifer L.; Pandol, Stephen J.; Evans Phillips, Anna; Serrano, Jose; Singh, Vikesh K.; Speake, Cate; Tirkes, Temel; Toledo, Frederico G. S.; Trikudanathan, Guru; Vege, Santhi Swaroop; Wang, Ming; Yazici, Cemal; Zaheer, Atif; Forsmark, Christopher E.; Bellin, Melena D.; Yadav, Dhiraj; Type 1 Diabetes in Acute Pancreatitis Consortium (T1DAPC); Medicine, School of MedicineAcute pancreatitis (AP) is a disease characterized by an acute inflammatory phase followed by a convalescent phase. Diabetes mellitus (DM) was historically felt to be a transient phenomenon related to acute inflammation; however, it is increasingly recognized as an important late and chronic complication. There are several challenges that have prevented precisely determining the incidence rate of DM after AP and understanding the underlying mechanisms. The DREAM (Diabetes RElated to Acute Pancreatitis and its Mechanisms) Study is a prospective cohort study designed to address these and other knowledge gaps to provide the evidence needed to screen for, prevent, and treat DM after AP. In the following article, we summarize literature regarding the epidemiology of DM after AP and provide the rationale and an overview of the DREAM study.Item Recruitment and Retention Strategies for the Diabetes RElated to Acute Pancreatitis and Its Mechanisms Study: From the Type 1 Diabetes in Acute Pancreatitis Consortium(Wolters Kluwer, 2022) Yazici, Cemal; Dyer, Anne-Marie; Conwell, Darwin L.; Afghani, Elham; Andersen, Dana K.; Basina, Marina; Bellin, Melena D.; Boone, Leslie R.; Casu, Anna; Easler, Jeffrey J.; Greenbaum, Carla J.; Hart, Phil A.; Jeon, Christie Y.; Lee, Peter J.; Meier, Shelby; Papachristou, Georgios I.; Raja-Khan, Nazia T.; Saeed, Zeb I.; Serrano, Jose; Yadav, Dhiraj; Fogel, Evan L.; Type 1 Diabetes in Acute Pancreatitis Consortium (T1DAP); Medicine, School of MedicineRecruitment and retention of patients with acute pancreatitis (AP) in clinical studies can be challenging. While some obstacles are similar to other clinical conditions, some are unique to AP. Identifying potential barriers early and developing targeted solutions can help optimize recruitment and retention in AP studies. Such preemptive and detailed planning can help prospective, longitudinal studies focusing on exocrine and endocrine complications of AP in accurately measuring outcomes. This manuscript highlights the challenges in recruitment and retention strategies in AP studies and reviews available resources to create opportunities to address them. We describe the multifaceted approach used by the Recruitment and Retention Committee of the Type 1 Diabetes in Acute Pancreatitis Consortium (T1DAPC), which builds upon earlier experiences to develop a recruitment and retention plan for the DREAM (Diabetes RElated to Acute pancreatitis and its Mechanisms) study.Item Standard Operating Procedures for Biospecimen Collection, Processing, and Storage: From the Type 1 Diabetes in Acute Pancreatitis Consortium(Wolters Kluwer, 2022) Wasserfall, Clive; Dyer, Anne-Marie; Speake, Cate; Andersen, Dana K.; Baab, Kendall Thomas; Bellin, Melena D.; Broach, James R.; Campbell-Thompson, Martha; Chinchilli, Vernon M.; Lee, Peter J.; Park, Walter G.; Pratley, Richard E.; Saloman, Jami L.; Sims, Emily K.; Tang, Gong; Yadav, Dhiraj; Yazici, Cemal; Conwell, Darwin L.; Type 1 Diabetes in Acute Pancreatitis Consortium (T1DAPC); Pediatrics, School of MedicineDifferences in methods for biospecimen collection, processing, and storage can yield considerable variability and error. Therefore, best practices for standard operating procedures are critical for successful discovery, development, and validation of disease biomarkers. Here, we describe standard operating procedures developed for biospecimen collection during the DREAM (Diabetes RElated to Acute pancreatitis and its Mechanisms) Study within the Type 1 Diabetes in Acute Pancreatitis Consortium (T1DAPC). Notably these protocols were developed using an integrative process based on prior consortium experience and with input from working groups with expertise in immunology, pancreatitis and diabetes. Publication and adoption consistent biospecimen protocols will inform future studies and allow for better comparisons across different metabolic research efforts.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.