Peter Junwoo Lee

Thirty-Day Readmission Predicts 1-Year Mortality in Acute Pancreatitis

Objectives There is limited knowledge of the prognostic indicators after hospital discharge after acute pancreatitis (AP). The aim was to determine risk factors for mortality after discharge in patients admitted with AP. Methods A retrospective cohort study was conducted, including consecutive patients with AP admitted to the Cleveland Clinic between 2007 and 2011. Clinical data, mortality status, and the date of death were collected. Univariable and multivariable Cox regression was performed to determine variables significantly associated with mortality within a year of discharge. Results Three hundred thirty-one patients were included in the study, current to July 2012. After a mean follow-up of 20 months, 41 subjects (12.4%) died after discharge from the hospital. Thirty-three (10.0%) died within a year after discharge. In univariable analyses, higher Charlson Comorbidity Index, blood urea nitrogen > 20 on admission, higher Bedside Index of Severity in Acute Pancreatitis scores, longer length of stay, and readmission within 30 days were associated with a higher hazard of mortality. In the multivariable analysis, subjects who were readmitted within 30 days had a 4.5 times higher hazard of dying within a year than those who were not readmitted (hazard ratio, 4.5; 95% confidence interval, 2.2–9.1). Conclusion A higher Charlson Comorbidity Index, early readmission, and longer hospitalization predict a higher 1-year mortality after AP.

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.

Decreased Severity in Recurrent Versus Initial Episodes of Acute Pancreatitis.

Objectives The comparative outcomes of initial versus recurrent acute pancreatitis (AP) have not been clearly established. Aim The aim was to compare the clinical outcomes of those with an initial episode of AP to those with recurrent AP stratified by the number of prior episodes. Methods This retrospective cohort study included consecutive patients with AP admitted to the Cleveland Clinic between 2008 and 2011. The odds of severe AP, multisystem organ failure, ICU admission, new local complications, elevated blood urea nitrogen and bedside index for severity in acute pancreatitis score, systemic inflammatory response syndrome, and mortality were compared using univariable and multivariable logistic regression. Results Two hundred and ninety two patients were included, of which 213 (72%) were admitted on their initial AP episode. Mortality in patients experiencing first episode was 4.7%, compared to 0% in patients with recurrent attack of pancreatitis (P = 0.047). Prior episodes of AP were found to be protective against multisystem organ failure (odds ratio, 0.14 for each prior episode; confidence interval, 0.01–0.76) and intensive care unit admission (0.24, confidence interval, 0.06–0.91), adjusting for potential confounding factors such as transfer status and obesity. Conclusions Patients presenting with recurrent AP may be at decreased risk of a clinically severe course and incur decreased mortality.

Association of Statins With Decreased Acute Pancreatitis Severity: A Propensity Score Analysis

Background: Statins possess anti-inflammatory properties and have a protective effect in certain inflammatory conditions; however, their effect on the natural history of pancreatitis is unknown. Aim: The aim of this study is to assess the effect of statin exposure on the severity of pancreatitis and incidence of organ failure using a propensity-matched approach. Methods: A historical cohort study was conducted of adult patients with acute pancreatitis (AP) admitted in the Cleveland Clinic Health System between 2007 and 2014. All medication, clinical, and outcomes data were extracted from the electronic medical record. Factors that influence statin use were included in a propensity model to minimize selection bias. Patients on and off statins were matched (1:1) based on the propensity score to simulate a randomized controlled trial. Measured outcomes included pancreatitis severity (Revised Atlanta Classification), incidence of multisystem organ failure (MSOF), new MSOF, acute necrosis, and death. Additional surrogate markers of severity included hospital length of stay, Bedside Index of Severity of Acute Pancreatitis (BISAP), and presence of SIRS. Results: A total of 110 subjects taking a statin at admission were matched with 210 subjects not on a statin. Known baseline factors that may influence statin use and severity of pancreatitis were evenly matched between the 2 groups. Patients on a statin were less likely to develop MSOF, severe AP and necrosis. Although less in-hospital death occurred in the statin group when compared to nonusers, the difference was not statistically significant (2% vs. 4%; P=0.38). Conclusions: Statin use is associated with decreased severity of AP observed as reduction in both overall MSOF incidence and new MSOF. Prospective randomized controlled trials are needed to determine the efficacy of statin drugs in the treatment of AP.

Characterization of long-term prognosis in acute pancreatitis: An explorative analysis

BACKGROUND/OBJECTIVES Severity classification systems of acute pancreatitis (AP) assess inpatient morbidity and mortality without predicting outpatient course of AP. To provide appropriate outpatient care, determinants of long-term prognosis must also be identified. The aim of this study was to define clinical groups that carry long-term prognostic significance in AP. METHODS A retrospective study that included patients admitted with AP was conducted. Determinants of long-term prognosis were extracted: These included Revised Atlanta and Determinant Based Classification (RAC), Charlson Comorbidity Index (CCI), Modified CT Severity Index (MCTSI), etiology, and local complications (LCs). Seven surrogates of morbidity up to 1 year after discharge were also collected and subsequently imputed into a clustering algorithm. The algorithm was set to produce three categories and multinomial regression analysis was performed. RESULTS 281 patients were included. The incidences of morbidity endpoints were similar among the 3 RAC categories. Three clusters were identified that carried long-term prognostic significance. Each cluster was given a name to reflect prognosis. The limited AP had the best prognosis and included patients without LCs with a low co-morbidity burden. The brittle AP had a low co-morbidity burden and high MCTSI (LCs 94%). It ran a very morbid course but had excellent survival. The high-risk AP had the worst prognosis with the highest mortality rate (28%). They had a high co-morbidity burden without local complications. CONCLUSION Categories that carry long-term prognostic significance in AP have been developed. This study could help formulate appropriate follow-up and ultimately improve AP outcomes.

Preoperative biliary drainage in resectable pancreatic cancer: a systematic review and network meta-analysis

BACKGROUND Controversy remains about the best pre-operative management of jaundice in patients with resectable pancreatic head cancer (RPC) undergoing planned pancreaticoduodenectomy (PD). OBJECTIVE The aim of this study was to compare rates of post-operative complications in patients undergoing four pre-operative approaches (POA): preoperative biliary drainage with plastic stent (PBD-PS), metal stent (PBD-MS), and percutaneous transhepatic drain (PBD-PT), or no pre-operative biliary drainage (NPBD). METHOD A study was included in the systematic review if it assessed the effects of PBD on post-operative outcomes in jaundiced patients with RPC. Endpoints were the rate of any post-operative complication, wound infection, intra-abdominal infection and post-operative bleeding. A network meta-analysis (NMA) was performed to rank the POAs from the best to worst, for each outcome. RESULTS Thirty-two studies were included in the systematic review. Ten out of 32 studies included in the systematic review reported at least one of the 4 outcomes of interest and thus were used for NMA. The calculated odds ratios and P-scores ranked NPBD as the best approach. There was insufficient evidence to determine the best modality of PBD among PBD-PS, PBD-MS and PBD-PT. CONCLUSIONS No preoperative biliary drainage may be the best management of preoperative jaundice in patients with RPC before PD. Further studies are needed to determine the best modality in patients that need PBD.

Reply to: Yang et al, Clinical Features of Recurrent Acute Pancreatitis

the number of AP attacks. Furthermore, another difference between our study and the studies by Lee et al and other researchers was that hyperlipidemiawas the most common etiology of RAP in our study. However, this might be attributed to the varieties among different ethnicities and lifestyles. One retrospective study in 4 general hospitals of China conducted by Huang et al from January 1990 to December 2005 revealed that the incidence of hyperlipidemia-induced acute pancreatitis (HLAP) had been significantly increasing during the past 15 years. The severity of HLAP was markedly higher than acute biliary pancreatitis, with a higher recurrence rate. Another Chinese study by Zeng et al also indicated that the severity of APwas related to the plasma triglyceride (TG) level in patients with acute biliary pancreatitis. Patients with moderately high TG level [TG level, ≥2.26 mmol/L (200 mg/mL)] had a higher risk of developing severe acute pancreatitis. Furthermore, patients were more likely to develop severe acute pancreatitis when their TG level reached 5.65 mmol/L (500 mg/mL) or higher and at a higher risk of organ dysfunction (especially ARDS). Up to now, the pathogenesis of HLAP still has not been well studied. The most well-accepted theory proposed by Havel is that lipoproteins can be hydrolyzed into free fatty acids by pancreatic enzymes. Free fatty acids, which act as a key pathogenic factor that damage the function of platelet and vascular endothelium, could induce pancreatic ischemia and acinar cell injury. In addition, the high-viscosity plasma caused by hyperlipidemia could also lead to pancreatic ischemia and acidosis. Furthermore, specific genemutations, including cystic fibrosis transmembrane conductance regulator and tumor necrosis factor promoter may also correlate to HLAP and might be its independent risk factors. In summary, the work of Lee et al highlighted the underlying correlation between severity and number of AP attacks in patients with RAP. However, our study showed quite different results on the etiology and disease severity of the patients with RAP in our center. This might be attributed to the difference in recurrence rate and etiology between our patients and those of Lee et al; further studies recruiting more patients from different regions and ethnicities may be needed. We welcome more voices on these questions in the purpose of providing a better understanding and more basis for clinical work.

Positive predictive value of ICD-9 discharge diagnosis of acute pancreatitis

Acute pancreatitis (AP) is a disease with a rising incidence that causes considerable morbidity and, in its most severe form, high mortality. Research to investigate risk factors and treatment outcomes in AP use administrative databases for case finding, usually based on the International Classification of Diseases, Ninth Revision (ICD-9) 577.0; however, in a recent systematic review, the positive predictive value (PPV) for ICD-9 code 577.0 ranged from 40% to 75%, revealing low to moderate PPV and specificity. A single-center retrospective cohort study was conducted in our institution to determine the PPVof ICD-9 code (577.0) for primary discharge diagnosis of AP to derive an algorithm for improved PPVand specificity. We also compared the accuracy of the discharge diagnosis based on the admitting service (internal medicine vs gastroenterology vs surgery). A manual chart review was conducted of consecutive patients admitted through the emergency department between January 1, 2010, and December 31, 2011, with a primary discharge diagnosis of ICD-9 577.0 assigned by the admitting physician. The ICD-9 code discharge diagnosis was compared with the American College of Gastroenterology guidelines definition, which is made based on 2 of the following criteria: (1) abdominal pain characteristic of AP, (2) serum amylase and/or lipase level 3 times the upper limit of normal, and (3) characteristic findings of AP on computed tomographic scan or ultrasound. For encounters that did not fulfill the criteria for AP, the data were collected on alternative diagnoses. Finally, a new algorithm was tested that included ICD-9 code of 577.0 plus the presence of a serum lipase level 3 times the upper limit of normal. The PPV of ICD-9 code (577.0) for primary discharge diagnosis of AP was calculated as the percentage of true AP cases out of all patients with a diagnosis of ICD-9 577.0. The PPV of the new algorithm was calculated as the percentage of true AP cases out of all patients with primary discharge diagnosis of ICD-9 577.0 and serum lipase level 3 times the upper limit of normal. The results of our study are shown in Table 1. Low to moderate PPVof 67% for ICD-9 577.0 was observed for the discharge diagnosis of AP. No significant difference was found in the accuracy of discharge diagnosis among the different admitting services. The implication is that studies relying on ICD-9 discharge diagnosis for case finding will include a large number of patients who did not truly have AP. This misclassification will result in difficulty in interpreting the studies and applying them to the care of patients with AP. We tested an improved method for identifying ‘‘true’’ AP cases for research purposes, which was to filter the billinggenerated list using elevated lipase level. This was accomplished by cross-matching the billing and laboratory databases, preserving the automated and quick case finding needed for large epidemiological studies. The new algorithm demonstrated improved PPV and specificity. The tradeoff was a lower sensitivity, which we find acceptable. Based on limited data, it seems that ICD-10 may improve the identification of AP. A nationwide study validating the ICD-10 coding for AP in the Swedish Patient Register found a PPV of 83%. In conclusion, our validation of the ICD-9 577.0 primary discharge diagnosis of AP showed a low to moderate PPV, which improved with a new and improved algorithm of ICD-9 code plus lipase levels. The authors declare no conflict of interest.