Efstratios Koutroumpakis

Elevated Serum Triglycerides are Independently Associated With Persistent Organ Failure in Acute Pancreatitis

Objectives:Hypertriglyceridemia (HTG) represents a major health problem with prevalence exceeding 30% in the U.S. The present study aims to assess the effect of elevated serum triglyceride (TG) levels on the severity of acute pancreatitis (AP).Methods:Prospectively enrolled AP patients were categorized into normal, mild, moderate, and severe/very severe categories based on their TG levels and compared in respect to demographics, comorbidities, and clinical outcomes. Multivariate analysis determined whether elevated TG levels were independently associated with persistent organ failure.Results:Two hundred and one out of 400 AP patients had serum TGs measured within 72 h of presentation, of which 115 had normal TG levels and 86 HTG (20 mild, 41 moderate, and 25 severe/very severe). Patients with HTG were of younger age (44 vs. 52 years), predominantly male (65% vs. 45%), obese (57% vs. 34%), diabetic (38% vs. 17%), and developed more frequently persistent organ failure (40% vs. 17%) compared with those with normal TGs (P<0.02). The rate of persistent organ failure increased proportionally with HTG severity grades (17% when normal TGs, 30% in mild, 39% in moderate, and 48% in severe/very severe HTG, Ptrend<0.001). On multivariate analysis controlling for age, gender, body mass index, diabetes, and alcohol etiology, moderate HTG (odds ratio (OR), 2.6; P=0.04) and severe/very severe HTG (OR, 4.9; P=0.009) were independently associated with persistent organ failure.Conclusions:Elevated serum TGs in AP patients are independently and proportionally correlated with persistent organ failure regardless of etiology. TG-mediated lipotoxicity may be an attractive target to design novel interventions for severe AP.

Admission hematocrit and rise in blood urea nitrogen at 24 h outperform other laboratory markers in predicting persistent organ failure and pancreatic necrosis in acute pancreatitis: A post hoc analysis of three large prospective databases

OBJECTIVES:Predicting severe acute pancreatitis (AP) remains a challenge. The present study compares admission blood urea nitrogen (BUN), hematocrit, and creatinine, as well as changes in their levels over 24 h, aiming to determine the most accurate laboratory test for predicting persistent organ failure and pancreatic necrosis.METHODS:Clinical data of 1,612 AP patients, enrolled prospectively in three independent cohorts (University of Pittsburgh, Brigham and Women’s Hospital, Dutch Pancreatitis Study Group), were abstracted. The predictive accuracy of the studied laboratories was measured using area under the receiver-operating characteristic curve (AUC) analysis. A pooled analysis was conducted to determine their impact on the risk for persistent organ failure and pancreatic necrosis. Finally, a classification tree was developed on the basis of the most accurate laboratory parameters.RESULTS:Admission hematocrit ≥44% and rise in BUN at 24 h were the most accurate in predicting persistent organ failure (AUC: 0.67 and 0.71, respectively) and pancreatic necrosis (0.66 and 0.67, respectively), outperforming the other laboratory parameters and the acute physiology and chronic health evaluation-II score. In a pooled analysis, admission hematocrit ≥44% and rise in BUN at 24 h were associated with an odds ratio of 3.54 and 5.84 for persistent organ failure, and 3.11 and 4.07, respectively, for pancreatic necrosis. In addition, the classification tree illustrated that when both admission hematocrit was ≥44% and BUN levels increased at 24 h, the rates of persistent organ failure and pancreatic necrosis reached 53.6% and 60.3%, respectively.CONCLUSIONS:Admission hematocrit ≥44% and rise in BUN at 24 h may be the optimal predictive tools in clinical practice among existing laboratory parameters and scoring systems.

The Influence of Anti-tumor Necrosis Factor Agents on Hemoglobin Levels of Patients with Inflammatory Bowel Disease.

Background:Anti–tumor necrosis factor (TNF) agents are an important component of inflammatory bowel disease (IBD) treatment, but data on their influence on anemia, a frequent complication of IBD, are limited. The aim of this study was to evaluate the effect of anti-TNF agents on hemoglobin (Hb) levels in a large IBD cohort. Methods:Prospectively collected demographic, clinical, laboratory, and treatment data from IBD patients who started anti-TNF treatment at a tertiary referral center during the years 2010 to 2012 were analyzed. Follow-up data including disease activity scores (Harvey–Bradshaw index or ulcerative colitis activity index), quality of life scores (short IBD questionnaire) completed at each visit, and laboratory data were analyzed. Data from the year of anti-TNF initiation (yr 0) to the following year (yr 1) were compared. Results:A total of 430 IBD patients (324 with Crohns disease, 51.6% females) started anti-TNF treatment. The prevalence of anemia and median Hb levels did not change between years 0 and 1. Median short IBD questionnaire was significantly improved at year 1 (P = 0.002). IBD patients with anemia had significantly higher median Hb levels at year 1 compared with year 0 (P = 0.0009). Hematopoietic response (increase of Hb ≥2 g/dL) was observed in only 33.6% of the 134 anemic IBD patients, despite iron replacement being administered in 126 anemic patients (oral, 77%). Improvement in Hb levels was independently significantly correlated with change of C-reactive protein levels (P = 0.04) and immunomodulator use (P = 0.03). Conclusions:Anemia remains a significant manifestation of IBD 1 year after treatment with anti-TNF agents.

Clinical Profile and Natural Course in a Large Cohort of Patients With Hypertriglyceridemia and Pancreatitis.

Goals: To report the clinical profile and natural course in a large series of patients with hypertriglyceridemia (HTG) and acute pancreatitis (AP). Background: The natural history of HTG-related pancreatitis is poorly defined. Study: Medical records of 121 patients with serum triglycerides (TG) levels of ≥500 mg/dL suffering 225 attacks of AP between January 2001 to August 2013 treated at the University of Pittsburgh Medical Center were retrospectively studied. Structured data were collected on initial presentation and long-term outcomes (mean follow-up 64.7±42.8 mo). AP severity was classified using Revised Atlanta Classification. Results: Most patients were young-middle aged (mean 44±12.7 y), male (70%), white (78%), and had sentinel AP (63%). Peak serum TG recorded was ≥1000 mg/dL in 48%. At least 1 secondary risk factor (diabetes, high-risk drinking, obesity, offending medications) was present in the majority (78%). Sentinel AP attack varied in severity between mild (41%), moderate (26%), and severe (33%). Recurrent AP attacks occurred in 32%, often in patients with poorly controlled diabetes, alcoholism, and TG levels. A cumulative increase in prevalence of pancreatic and/or peripancreatic necrosis was observed, with 45% patients having it at some time during observation. Local complications were higher in patients with serum TG ≥1000 mg/dL. Chronic pancreatitis was noted in 16.5% patients (new-onset in 9%). Conclusions: Patients with HTG-related pancreatitis have a high prevalence of secondary risk factors. Frequent recurrences in them are usually due to poor control of secondary factors or TG. Serum TG ≥1000 mg/dL increases the risk of local complications. A subset can have or develop chronic pancreatitis.

Five-Year Period Prevalence and Characteristics of Anemia in a Large US Inflammatory Bowel Disease Cohort.

Background: Anemia is a common manifestation of inflammatory bowel disease (IBD), but its prevalence in the United States is not well defined. Aim of this study was to determine the prevalence and characteristics of anemia in IBD patients who were followed in a US referral center. Materials and Methods: Demographic, clinical, laboratory, and treatment data from a prospective, consented longitudinal IBD registry between the years 2009 and 2013 were analyzed. Disease activity was evaluated using Harvey-Bradshaw index in Crohn’s disease (CD) and ulcerative colitis (UC) activity index in UC as well as C-reactive protein and erythrocyte sedimentation rate. Anemia was defined based on the World Health Organization criteria. Results: A total of 1821 IBD patients (1077 with CD, 744 with UC, median age 43.8 y, 51.9% female) were included. The 5-year period prevalence of anemia in IBD patients was 50.1%, (CD: 53.3% vs. UC: 44.7%, P=0.001). In multivariate logistic regression analysis, anemia was associated with surgery for IBD [odds ratio (OR)=2.77; 95% confidence interval (CI), 2.21-3.48; P<0.0001], female gender (OR=1.29; 95% CI, 1.04-1.61; P=0.02), C-reactive protein (OR=1.26; 95% CI, 1.16-1.37; P<0.0001), erythrocyte sedimentation rate (OR=1.02; 95% CI, 1.01-1.03; P=0.0002), and use of biologics (OR=2.00; 95% CI, 1.58-2.52; P=0.0001) or immunomodulators (OR=1.51; 95% CI, 1.21-1.87; P=0.0003). Iron replacement therapy was administered to 46.8% of the anemic patients. Conclusion: Anemia has a high period prevalence in IBD patients followed at a tertiary center. Anemia is more common in CD than in UC, is associated with disease activity, and in current practice is undertreated.

Isolated Peripancreatic Necrosis in Acute Pancreatitis Is Infrequent and Leads to Severe Clinical Course Only When Extensive: A Prospective Study From a US Tertiary Center.

Goals: To explore the diagnostic challenges, management, and clinical outcomes of patients with isolated peripancreatic necrosis (PPN), with emphasis on the extent of involvement, and compare them to pancreatic necrosis (PN). Background: PPN, a relatively new term, has been included as a separate entity in the Revised Atlanta Classification. Study: Clinical data of recruited acute pancreatitis patients were recorded prospectively. Contrast-enhanced computed tomographic scans were reviewed by expert radiologists blinded to clinical outcomes. Results: In total, 271 of the 400 acute pancreatitis patients underwent contrast-enhanced computed tomography, of which 29 (11%) had PPN (14: limited; 15: extensive) and 124 (46%) PN (40: <30%, 16: 30% to 50%, 68: >50% of parenchyma). Patients with PPN were similar to PN in age (56 y), gender (55% male), and body mass index (29 kg/m2). Nutritional support was provided in 18 (62%) patients with PPN and 97 (78%) with PN (P=0.12). Drainage/debridement was required in 2 patients (7%) with PPN and 64 (53%) with parenchymal necrosis (P<0.001). Persistent organ failure rates did not differ significantly (34% vs. 51%, P=0.17), but hospital stay was shorter in patients with PPN (15 vs. 20 d, P=0.05). Limited PPN required no intervention and had similar persistent organ failure rates and hospitalization length with interstitial pancreatitis (both P≥0.12). Extensive PPN mainly developed in patients with persistent organ failure (60%) and rarely required drainage (2/15). Conclusions: PPN prevalence was lower than PN with a ratio of 1:4. PPN rarely required intervention. Utilizing the extent of involvement has the potential to classify PPN and PN with escalating clinical significance and guide management.

Acute pancreatitis patient registry to examine novel therapies in clinical experience (APPRENTICE): an international, multicenter consortium for the study of acute pancreatitis

Background We have established a multicenter international consortium to better understand the natural history of acute pancreatitis (AP) worldwide and to develop a platform for future randomized clinical trials. Methods The AP patient registry to examine novel therapies in clinical experience (APPRENTICE) was formed in July 2014. Detailed web-based questionnaires were then developed to prospectively capture information on demographics, etiology, pancreatitis history, comorbidities, risk factors, severity biomarkers, severity indices, health-care utilization, management strategies, and outcomes of AP patients. Results Between November 2015 and September 2016, a total of 20 sites (8 in the United States, 5 in Europe, 3 in South America, 2 in Mexico and 2 in India) prospectively enrolled 509 AP patients. All data were entered into the REDCap (Research Electronic Data Capture) database by participating centers and systematically reviewed by the coordinating site (University of Pittsburgh). The approaches and methodology are described in detail, along with an interim report on the demographic results. Conclusion APPRENTICE, an international collaboration of tertiary AP centers throughout the world, has demonstrated the feasibility of building a large, prospective, multicenter patient registry to study AP. Analysis of the collected data may provide a greater understanding of AP and APPRENTICE will serve as a future platform for randomized clinical trials.

An international multicenter study of early intravenous fluid administration and outcome in acute pancreatitis

Aims Early aggressive fluid resuscitation in acute pancreatitis is frequently recommended but its benefits remain unproven. The aim of this study was to determine the outcomes associated with early fluid volume administration in the emergency room (FVER) in patients with acute pancreatitis. Methods A four-center retrospective cohort study of 1010 patients with acute pancreatitis was conducted. FVER was defined as any fluid administered from the time of arrival to the emergency room to 4 h after diagnosis of acute pancreatitis, and was divided into tertiles: nonaggressive (<500 ml), moderate (500 to 1000 ml), and aggressive (>1000 ml). Results Two hundred sixty-nine (26.6%), 427 (42.3%), and 314 (31.1%) patients received nonaggressive, moderate, and aggressive FVER respectively. Compared with the nonaggressive fluid group, the moderate group was associated with lower rates of local complications in univariable analysis, and interventions, both in univariable and multivariable analysis (adjusted odds ratio (95% confidence interval): 0.37 (0.14–0.98)). The aggressive resuscitation group was associated with a significantly lower need for interventions, both in univariable and multivariable analysis (adjusted odds ratio 0.21 (0.05–0.84)). Increasing fluid administration categories were associated with decreasing hospital stay in univariable analysis. Conclusions Early moderate to aggressive FVER was associated with lower need for invasive interventions.

Patients With Sentinel Acute Pancreatitis of Alcoholic Etiology Are at Risk for Organ Failure and Pancreatic Necrosis: A Dual-Center Experience.

Objectives To assess the relationship between alcoholic etiology, tobacco use, and severe acute pancreatitis (AP). Methods Smoking and alcohol exposure were recorded upon admission in a cohort of patients with AP within the United States. Patients with first, “sentinel” attack of AP were identified for analysis. Associations between alcohol, smoking, and severe AP were validated in an independent cohort of patients from Spain. Results US cohort (n = 222): Thirty-five percent developed organ failure (OF), 35% pancreatic necrosis (PNec), and 7% died. OF (54% vs 33%, P = 0.03), PNec (62% vs 31%, P = 0.006), intensive care unit admission (58% vs 36%, P = 0.03), and length of stay (LOS) (20 vs 8 days, P = 0.007) were greater in alcoholic when compared to other etiologies. Spanish cohort (n = 366): Similar differences in outcomes were also found with between alcoholic and nonalcoholic etiologies: OF (24% vs 8%, P = 0.001), PNec (38% vs 14%, P < 0.001), intensive care unit admission (20% vs 3%, P < 0.001), and LOS (17 vs 11 days, P = 0.04). Multivariable analysis confirmed alcoholic etiology to be independently associated with OF and PNec in both cohorts. Conclusions Alcoholic etiology is independently associated with OF and PNec in patients with sentinel AP and is important when evaluating risk for severe disease in AP.

Which Patients with Mild Acute Pancreatitis Require Prolonged Hospitalization

Objectives:In our experience, a subset of mild acute pancreatitis (AP) patients, as defined by the Revised Atlanta Classification, has longer than expected hospitalization. Our aims are to report the prevalence of patients with mild AP who have a prolonged length of stay (LOS), evaluate the etiology, thoroughly phenotype, and finally compare this subset to those with expected LOS.Methods:Patients admitted with AP from 2003 to 2015 were prospectively enrolled into this cohort study. LOS ≥8 days was considered as prolonged LOS. Data on demographics, clinical and laboratory variables, management, and outcomes was both prospectively and retrospectively collected. Continuous variables were compared using the nonparametric t-test (Wilcoxons test) and categorical variables using the Pearson’s χ2 test.Results:Among 231 enrolled mild AP patients, 46 (20%) had a prolonged LOS (≥8 days). The main determinants of prolonged LOS included ongoing pancreatitis-related symptoms (n=31, 67.4%) and performance of cholecystectomy (n=11, 23.9%). When compared to patients with expected LOS (<8 days, n=185), patients with prolonged LOS due to ongoing symptoms (n=31) were more likely to have systemic inflammatory response syndrome at 48 h from admission (37% vs. 13.4%, P<0.001), a prolonged fasting period (6.6 vs. 2.8 days, P<0.001), and need for nutritional support (30% vs. 1.6%, P<0.001).Conclusions:About 20% of patients with mild AP have a longer than expected hospital stay, mostly attributed to ongoing pancreatitis-related symptoms. An early decision (at 72 h) for enteral nutrition support in these patients needs to be explored so as to shorten hospitalization and reduce cost of care.