|
1
|
Chen WJ, Su QY, Zhong M, Zheng YJ, Wang XF, Qu HP, Mao EQ, Yang ZT, Chen EZ, Chen Y. Establishment and validation of a prediction model for acute kidney injury in moderate severe and severe acute pancreatitis patients. Eur J Med Res 2025; 30:187. [PMID: 40108645 PMCID: PMC11924734 DOI: 10.1186/s40001-025-02394-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2024] [Accepted: 02/18/2025] [Indexed: 03/22/2025] Open
Abstract
PURPOSE This study aimed to develop a nomogram for predicting acute kidney injury (AKI) in patients with moderate severe acute pancreatitis (MSAP) and severe acute pancreatitis (SAP). METHODS This study enrolled a total of 1,077 patients with MSAP and SAP, categorizing them into three groups: training (n = 646), internal validation (n = 278), and external validation (n = 153). In the training cohort, logistic regression analysis identified independent predictors of AKI in patients with MSAP and SAP. A nomogram was developed based on these independent predictors. The model's performance was assessed using the receiver operating characteristics (ROC) curve, precision-recall (PR) curve, calibration curve, and decision curve analysis (DCA). RESULTS The incidence rates of AKI in the training set, internal validation set, and external validation set were 32.82%, 32.01%, and 27.45%, respectively. Independent predictors of AKI in patients with MSAP and SAP included: shock index (odds ratio [OR] = 7.42, 95% confidence interval [CI] 2.18-25.19), blood urea nitrogen (OR = 1.32, 95% CI 1.22-1.43), uric acid (OR = 1.002, 95% CI 1.000-1.003), serum calcium (OR = 0.38, 95% CI 0.18-0.79), triglycerides (OR = 1.02, 95% CI 1.004-1.041), hematocrit > 0.5 (OR = 3.24, 95% CI 1.10-9.59), serum sodium < 135 mmol/L (OR = 2.01, 95% CI 1.15-3.49), creatine kinase isoenzyme > 4 ng/mL (OR = 2.61, 95% CI 1.48-4.61), and thrombin time < 14 s (OR = 2.83, 95% CI 1.28-6.27). In the training, internal validation, and external validation sets, the areas under the ROC curves for the nomogram were 0.841, 0.789, and 0.853, respectively. Similarly, the areas under the PR curves were 0.807, 0.733, and 0.770. The calibration curves demonstrated that the predicted outcomes were well-aligned with the actual results. The decision curve analysis (DCA) indicated that the model had satisfactory clinical applicability. CONCLUSIONS Nine indicators have been identified as independent predictors of AKI in patients with MSAP and SAP. The developed nomogram exhibits robust predictive capability and shows promise for clinical application.
Collapse
Affiliation(s)
- Wen-Jie Chen
- Department of Emergency, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Ruijin 2# Road No. 197, Shanghai, 200025, China
| | - Qin-Yue Su
- Department of Emergency, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Ruijin 2# Road No. 197, Shanghai, 200025, China
- Department of Critical Care Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College, Beijing, China
| | - Ming Zhong
- Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Yan-Jun Zheng
- Department of Emergency, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Ruijin 2# Road No. 197, Shanghai, 200025, China
| | - Xiao-Feng Wang
- Department of Emergency, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Ruijin 2# Road No. 197, Shanghai, 200025, China
| | - Hong-Ping Qu
- Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - En-Qiang Mao
- Department of Emergency, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Ruijin 2# Road No. 197, Shanghai, 200025, China
| | - Zhi-Tao Yang
- Department of Emergency, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Ruijin 2# Road No. 197, Shanghai, 200025, China
| | - Er-Zhen Chen
- Department of Emergency, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Ruijin 2# Road No. 197, Shanghai, 200025, China.
- Shanghai Institute of Aviation Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
| | - Ying Chen
- Department of Emergency, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Ruijin 2# Road No. 197, Shanghai, 200025, China.
- Department of Emergency and Critical Care Medicine, Ruijin Hospital Wuxi Branch, Shanghai Jiao Tong University School of Medicine, Wuxi, China.
| |
Collapse
|
|
2
|
Gu K, Wang Q. Establishment and Validation of a Dynamic Nomogram for Persistent Organ Failure in Acute Biliary Pancreatitis: A Retrospective Study. J Inflamm Res 2024; 17:8513-8530. [PMID: 39534058 PMCID: PMC11556325 DOI: 10.2147/jir.s489044] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2024] [Accepted: 10/26/2024] [Indexed: 11/16/2024] Open
Abstract
Purpose The objective of this study was to create a predictive model for the onset of persistent organ failure (POF) in individuals suffering from acute biliary pancreatitis (ABP) by utilizing indicators observed within 24 hours of hospital admission. Early detection of high-risk POF patients is crucial for clinical decision-making. Patients and Methods Clinical data and laboratory indicators within 24 hours of admission from ABP patients diagnosed at The First Affiliated Hospital of Wenzhou Medical University between January 1, 2016, and January 1, 2024 were collected and retrospectively analyzed. The Least Absolute Shrinkage and Selection Operator (LASSO) regression and multivariate logistic regression (stepwise regression) methods were employed to identify variables for constructing the prediction model. The prediction model's performance was evaluated using the area under the curve (AUC), calibration curve, and decision curve analysis (DCA). It was compared with other scoring systems such as SIRS, BISAP, APACHE II, CTSI, and MCTSI. Additionally, a web-based calculator was created to simplify the calculation process. Results Out of 324 ABP patients, 25 developed POF. Initial screening identified 18 variables; through LASSO regression and multivariable logistic regression analysis, five variables including BMI, Hb, ALB, Ca, and LIP were determined as independent predictors of POF. According to these factors to build prediction model, draw the nomogram. The AUC's receiver operating characteristic curve analysis demonstrated a significantly higher value in comparison to other scoring systems. Calibration curve and DCA show that the established model to predict the accuracy of POF is higher, clinical decision of net benefit is also higher. A network calculator utilizing this predictive model was developed. Conclusion A predictive model incorporating five risk indicators has been established exhibiting high discriminatory power and accuracy which aids in early identification of ABP patients at risk for developing POF. This holds significant value in guiding clinical decision-making.
Collapse
Affiliation(s)
- Kaier Gu
- Medical Intensive Care Unit, Shaoxing Maternity and Child Health Care Hospital, Shaoxing, Zhejiang Province, People’s Republic of China
- Maternity and Child Health Care Affiliated Hospital, Shaoxing University, Shaoxing, Zhejiang Province, People’s Republic of China
| | - Qianchun Wang
- Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, People’s Republic of China
| |
Collapse
|
|
3
|
Takano T, Yule DI. Neuronal and hormonal control of Ca 2+ signalling in exocrine glands: insight from in vivo studies. J Physiol 2024; 602:3341-3350. [PMID: 38847391 PMCID: PMC11250672 DOI: 10.1113/jp285461] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2024] [Accepted: 05/14/2024] [Indexed: 07/17/2024] Open
Abstract
Fluid and enzyme secretion from exocrine glands is initiated by Ca2+ signalling in acinar cells and is activated by external neural or hormonal signals. A wealth of information has been derived from studies in acutely isolated exocrine cells but Ca2+ signalling has until recently not been studied in undisrupted intact tissue in live mice. Our in vivo observations using animals expressing genetically encoded Ca2+ indicators in specific cell types in exocrine glands revealed both similarities to and differences from the spatiotemporal characteristics previously reported in isolated cells. These in vivo studies facilitate further understanding of how both neuronal and hormonal input shapes Ca2+ signalling events in a physiological setting and how these signals are translated into the stimulation of fluid secretion and exocytosis.
Collapse
Affiliation(s)
- Takahiro Takano
- Department of Pharmacology and Physiology, University of Rochester, Rochester, NY 14526, USA
| | - David I. Yule
- Department of Pharmacology and Physiology, University of Rochester, Rochester, NY 14526, USA
| |
Collapse
|
|
4
|
Lin Y, Liu Y, Lin Q, Wang M, Jiang P, Mao K, Chen F, Ding J, Li D. Development and Validation of a Nomogram for Predicting the Severity of the First Episode of Hyperlipidemic Acute Pancreatitis. J Inflamm Res 2024; 17:3211-3223. [PMID: 38800592 PMCID: PMC11122203 DOI: 10.2147/jir.s459258] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2024] [Accepted: 05/07/2024] [Indexed: 05/29/2024] Open
Abstract
Purpose Early detection of hyperlipidemic acute pancreatitis (HLAP) with exacerbation tendency is crucial for clinical decision-making and improving prognosis. The aim of this study was to establish a reliable model for the early prediction of HLAP severity. Patients and Methods A total of 225 patients with first-episode HLAP who were admitted to Fujian Medical University Union Hospital from June 2012 to June 2023 were included. Patients were divided into mild acute pancreatitis (MAP) or moderate-severe acute pancreatitis and severe acute pancreatitis (MSAP+SAP) groups. Independent predictors for progression to MSAP or SAP were identified through univariate analysis and least absolute shrinkage and selection operator regression. A nomogram was established through multivariate logistic regression analysis to predict this progression. The calibration, receiver operating characteristic(ROC), and clinical decision curves were employed to evaluate the model's consistency, differentiation, and clinical applicability. Clinical data of 93 patients with first-episode HLAP who were admitted to the First Affiliated Hospital of Fujian Medical University from October 2015 to October 2022 were collected for external validation. Results White blood cell count, lactate dehydrogenase, albumin, serum creatinine, serum calcium, D-Dimer were identified as independent predictors for progression to MSAP or SAP in patients with HLAP and used to establish a predictive nomogram. The internally verified Harrell consistency index (C-index) was 0.908 (95% CI 0.867-0.948) and the externally verified C-index was 0.950 (95% CI 0.910-0.990). The calibration, ROC, and clinical decision curves showed this nomogram's good predictive ability. Conclusion We have established a nomogram that can help identify HLAP patients who are likely to develop MSAP or SAP at an early stage, with high discrimination and accuracy.
Collapse
Affiliation(s)
- Yongxu Lin
- Department of Gastroenterology, Fujian Medical University Union Hospital, Fuzhou, People’s Republic of China
- Fujian Clinical Research Center for Digestive System Tumors and Upper Gastrointestinal Diseases, Fuzhou, People’s Republic of China
| | - Yaling Liu
- Department of Gastroenterology, the First Affiliated Hospital, Fujian Medical University, Fuzhou, People’s Republic of China
| | - Qiuyan Lin
- Department of Gastroenterology, Fujian Medical University Union Hospital, Fuzhou, People’s Republic of China
- Fujian Clinical Research Center for Digestive System Tumors and Upper Gastrointestinal Diseases, Fuzhou, People’s Republic of China
| | - Mingrong Wang
- Department of Gastroenterology, Fujian Medical University Union Hospital, Fuzhou, People’s Republic of China
- Fujian Clinical Research Center for Digestive System Tumors and Upper Gastrointestinal Diseases, Fuzhou, People’s Republic of China
| | - Pingying Jiang
- Department of Gastroenterology, Fujian Medical University Union Hospital, Fuzhou, People’s Republic of China
- Fujian Clinical Research Center for Digestive System Tumors and Upper Gastrointestinal Diseases, Fuzhou, People’s Republic of China
| | - Kaiyi Mao
- Department of Gastroenterology, Fujian Medical University Union Hospital, Fuzhou, People’s Republic of China
- Fujian Clinical Research Center for Digestive System Tumors and Upper Gastrointestinal Diseases, Fuzhou, People’s Republic of China
| | - Fenglin Chen
- Department of Gastroenterology, Fujian Medical University Union Hospital, Fuzhou, People’s Republic of China
- Fujian Clinical Research Center for Digestive System Tumors and Upper Gastrointestinal Diseases, Fuzhou, People’s Republic of China
| | - Jian Ding
- Department of Gastroenterology, the First Affiliated Hospital, Fujian Medical University, Fuzhou, People’s Republic of China
| | - Dan Li
- Department of Gastroenterology, Fujian Medical University Union Hospital, Fuzhou, People’s Republic of China
- Fujian Clinical Research Center for Digestive System Tumors and Upper Gastrointestinal Diseases, Fuzhou, People’s Republic of China
| |
Collapse
|
|
5
|
Chan MJ, Hsieh CY, Su YJ, Huang CC, Huang WH, Weng CH, Yen TH, Hsu CW. Giant Pancreatic Pseudocyst after Coronary Artery Bypass Graft in a Hemodialysis Patient: A Case Report. Clin Pract 2023; 13:1236-1243. [PMID: 37887087 PMCID: PMC10605616 DOI: 10.3390/clinpract13050111] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2023] [Revised: 09/27/2023] [Accepted: 09/29/2023] [Indexed: 10/28/2023] Open
Abstract
End-stage renal disease (ESRD) patients have a high prevalence of coronary artery disease, and coronary artery bypass graft (CABG) is one of the essential treatments. ESRD patients undergoing CABG surgery have an increased risk of postoperative complications, including acute pancreatitis. Here, we present the unique case of an exceptionally large pancreatic pseudocyst caused by pancreatitis in an ESRD patient after CABG surgery. A 45-year-old male with ESRD under maintenance hemodialysis received CABG surgery for significant coronary artery disease. Two weeks later, he experienced worsening abdominal pain and a palpable mass was noticed in the epigastric region. Computer tomography revealed an unusually large pseudocyst measuring 21 × 17 cm in the retroperitoneum due to necrotizing pancreatitis. The patient underwent percutaneous cystic drainage, and the symptoms were significantly improved without surgical intervention. Factors such as prolonged cardiopulmonary bypass time, postoperative hypotension, and intradialytic hypotension appeared to have contributed to the development of severe pancreatitis in this case. This report highlights the rarity of a giant pancreatic pseudocyst in an ESRD patient after CABG surgery and emphasizes the importance of vigilant postoperative care.
Collapse
Affiliation(s)
- Ming-Jen Chan
- Department of Nephrology, Clinical Poison Center, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan City 333423, Taiwan; (M.-J.C.); (C.-Y.H.); (C.-C.H.); (W.-H.H.); (C.-H.W.); (T.-H.Y.)
- School of Medicine, College of Medicine, Chang Gung University, Taoyuan City 333323, Taiwan
- Graduate Institute of Clinical Medical Science, College of Medicine, Chang Gung University, Taoyuan City 333323, Taiwan
| | - Chun-Yih Hsieh
- Department of Nephrology, Clinical Poison Center, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan City 333423, Taiwan; (M.-J.C.); (C.-Y.H.); (C.-C.H.); (W.-H.H.); (C.-H.W.); (T.-H.Y.)
- School of Medicine, College of Medicine, Chang Gung University, Taoyuan City 333323, Taiwan
| | - Yi-Jiun Su
- Division of Hematology-Oncology, Department of Internal Medicine, Linkou Chang Gung Memorial Hospital, Taoyuan City 333423, Taiwan;
| | - Chien-Chang Huang
- Department of Nephrology, Clinical Poison Center, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan City 333423, Taiwan; (M.-J.C.); (C.-Y.H.); (C.-C.H.); (W.-H.H.); (C.-H.W.); (T.-H.Y.)
| | - Wen-Hung Huang
- Department of Nephrology, Clinical Poison Center, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan City 333423, Taiwan; (M.-J.C.); (C.-Y.H.); (C.-C.H.); (W.-H.H.); (C.-H.W.); (T.-H.Y.)
- School of Medicine, College of Medicine, Chang Gung University, Taoyuan City 333323, Taiwan
| | - Cheng-Hao Weng
- Department of Nephrology, Clinical Poison Center, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan City 333423, Taiwan; (M.-J.C.); (C.-Y.H.); (C.-C.H.); (W.-H.H.); (C.-H.W.); (T.-H.Y.)
- School of Medicine, College of Medicine, Chang Gung University, Taoyuan City 333323, Taiwan
| | - Tzung-Hai Yen
- Department of Nephrology, Clinical Poison Center, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan City 333423, Taiwan; (M.-J.C.); (C.-Y.H.); (C.-C.H.); (W.-H.H.); (C.-H.W.); (T.-H.Y.)
- School of Medicine, College of Medicine, Chang Gung University, Taoyuan City 333323, Taiwan
| | - Ching-Wei Hsu
- Department of Nephrology, Clinical Poison Center, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan City 333423, Taiwan; (M.-J.C.); (C.-Y.H.); (C.-C.H.); (W.-H.H.); (C.-H.W.); (T.-H.Y.)
- School of Medicine, College of Medicine, Chang Gung University, Taoyuan City 333323, Taiwan
| |
Collapse
|
|
6
|
Li B, Wu W, Liu A, Feng L, Li B, Mei Y, Tan L, Zhang C, Tian Y. Establishment and Validation of a Nomogram Prediction Model for the Severe Acute Pancreatitis. J Inflamm Res 2023; 16:2831-2843. [PMID: 37449283 PMCID: PMC10337691 DOI: 10.2147/jir.s416411] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2023] [Accepted: 07/01/2023] [Indexed: 07/18/2023] Open
Abstract
Background Severe acute pancreatitis (SAP) can progress to lung and kidney dysfunction, and blood clotting within 48 hours of its onset, and is associated with a high mortality rate. The aim of this study was to establish a reliable diagnostic prediction model for the early stage of severe pancreatitis. Methods The clinical data of patients diagnosed with acute pancreatitis from October 2017 to June 2022 at the Shangluo Central Hospital were collected. The risk factors were screened by least absolute shrinkage and selection operator (LASSO) regression analysis. A novel nomogram model was then established by multivariable logistic regression analysis. Results The data of 436 patients with acute pancreatitis, 45 (10.3%) patients had progressed to SAP. Through univariate and LASSO regression analyses, the neutrophils (P <0.001), albumin (P < 0.001), blood glucose (P < 0.001), serum calcium (P < 0.001), serum creatinine (P < 0.001), blood urea nitrogen (P < 0.001) and procalcitonin (P = 0.005) were identified as independent predictive factors for SAP. The nomogram built on the basis of these factors predicted SAP with sensitivity of 0.733, specificity of 0.9, positive predictive value of 0.458 and negative predictive value of 0.967. Furthermore, the concordance index of the nomogram reached 0.889 (95% CI, 0.837-0.941), and the area under the curve (AUC) in receiver operating characteristic curve (ROC) analysis was significantly higher than that of the APACHEII and ABISAP scoring systems. The established model was validated by plotting the clinical decision curve analysis (DCA) and clinical impact curve (CIC). Conclusion We established a nomogram to predict the progression of early acute pancreatitis to SAP with high discrimination and accuracy.
Collapse
Affiliation(s)
- Bo Li
- Department of Pancreatic Surgery, Shangluo Center Hospital, Shangluo, Shaanxi, 726000, People’s Republic of China
| | - Weiqing Wu
- Department of Pancreatic Surgery, Shangluo Center Hospital, Shangluo, Shaanxi, 726000, People’s Republic of China
| | - Aijun Liu
- Department of Pancreatic Surgery, Shangluo Center Hospital, Shangluo, Shaanxi, 726000, People’s Republic of China
| | - Lifeng Feng
- Department of Pancreatic Surgery, Shangluo Center Hospital, Shangluo, Shaanxi, 726000, People’s Republic of China
| | - Bin Li
- Department of Pancreatic Surgery, Shangluo Center Hospital, Shangluo, Shaanxi, 726000, People’s Republic of China
| | - Yong Mei
- Department of Pancreatic Surgery, Shangluo Center Hospital, Shangluo, Shaanxi, 726000, People’s Republic of China
| | - Li Tan
- Department of Pancreatic Surgery, Shangluo Center Hospital, Shangluo, Shaanxi, 726000, People’s Republic of China
| | - Chaoyang Zhang
- Department of Ultrasound Medicine, Shangluo Center Hospital, Shangluo, Shaanxi, 726000, People’s Republic of China
| | - Yangtao Tian
- Department of Pancreatic Surgery, Shangluo Center Hospital, Shangluo, Shaanxi, 726000, People’s Republic of China
| |
Collapse
|
|
7
|
Son RG, Kandasamy B, Bowden T, Azzam RK, Oakes SA, Philipson LH, Greeley SAW. Acute Recurrent Pancreatitis in a Child With INS-Related Monogenic Diabetes and a Heterozygous Pathogenic CFTR Mutation. J Endocr Soc 2023; 7:bvac182. [PMID: 36655002 PMCID: PMC9836200 DOI: 10.1210/jendso/bvac182] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2022] [Indexed: 12/15/2022] Open
Abstract
Given the close anatomical and physiological links between the exocrine and endocrine pancreas, diseases of 1 compartment often affect the other through mechanisms that remain poorly understood. Pancreatitis has been associated with both type 1 and type 2 diabetes, but its association with monogenic diabetes is unknown. Patients heterozygous for pathogenic CFTR variants are cystic fibrosis carriers and have been reported to have an increased risk of acute pancreatitis. We describe a 12-year-old patient with monogenic neonatal diabetes due to a pathogenic heterozygous paternally inherited mutation of the insulin gene (INS), c.94 G > A (p.Gly32Ser), who experienced 3 recurrent episodes of acute pancreatitis over 7 months in conjunction with poor glycemic control, despite extensive efforts to improve glycemic control in the past 4 years. Intriguingly, the maternal side of the family has an extensive history of adult-onset pancreatitis consistent with autosomal dominant inheritance and the proband is heterozygous for a maternally inherited, CFTR variant c.3909C > G (p.Asn1303Lys). Paternally inherited monogenic neonatal diabetes may have promoted earlier age-of-onset of pancreatitis in this pediatric patient compared to maternal relatives with adult-onset acute pancreatitis. Further study is needed to clarify how separate pathophysiologies associated with INS and CFTR mutations influence interactions between the endocrine and exocrine pancreas.
Collapse
Affiliation(s)
- Rachel G Son
- Pritzker School of Medicine, University of Chicago, Chicago, IL, USA
| | - Balamurugan Kandasamy
- Department of Medicine/Kovler Diabetes Center, University of Chicago, Chicago, IL, USA
| | - Tiana Bowden
- Kovler Diabetes Center, University of Chicago, Chicago, IL, USA
| | - Ruba K Azzam
- Section of Pediatric Gastroenterology and Hepatology, University of Chicago, Chicago, IL, USA
| | - Scott A Oakes
- Department of Pathology, University of Chicago, Chicago, IL, USA
| | - Louis H Philipson
- Department of Medicine/Kovler Diabetes Center, University of Chicago, Chicago, IL, USA
| | - Siri Atma W Greeley
- Section of Pediatric and Adult Endocrinology, Diabetes and Metabolism, University of Chicago, Chicago, IL, USA
| |
Collapse
|
|
8
|
Baraf L, Averbuch NS, Carmon L, Szalat A, Sukenik-Halevy R, Fraenkel M. Expanding the phenotype of familial hypocalciuric hypercalcemia type 3: Case report and review of the literature. JOURNAL OF CLINICAL AND TRANSLATIONAL ENDOCRINOLOGY CASE REPORTS 2022. [DOI: 10.1016/j.jecr.2022.100137] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
|
|
9
|
Lai Q, Wei W, He Y, Cheng T, Han T, Cao Y. A Rapid Prognostic Score Based on Bedside Arterial Blood Gas Analysis (ABG) Established for Predicting 60-Day Adverse Outcomes in Patients with Acute Pancreatitis in the Emergency Department. J Inflamm Res 2022; 15:5337-5346. [PMID: 36131781 PMCID: PMC9484575 DOI: 10.2147/jir.s381438] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2022] [Accepted: 08/29/2022] [Indexed: 12/02/2022] Open
Abstract
Objective To establish a rapid and concise prognosis scoring system for pancreatitis in the emergency department based on bedside arterial blood gas analysis (ABG). Methods A single-center, retrospective cohort study was used to establish the new scoring system, and a validation group was used to verify it. The primary endpoint was 60-day death, and secondary endpoints were 28-day death, admission to the intensive care unit (AICU), requirement for mechanical ventilation (MV) and persistent organ failure (POF). Receiver operating characteristic (ROC) curves was drawn to validate the predictive value of the new scoring system. The performance of the new scoring system was compared with that of conventional predictive scoring. Results 443 patients were in the derivation group and 217 patients in the validation group, of which 27 and 25 died during follow-up. A total of 443 patients in the derivation group, 27 of whom died during the follow-up period. Multivariate regression analysis showed that mental status, hematocrit (HCT), base excess (BE) and Serum ionic calcium (Ca2+) were independent risk factors for 60-day mortality of pancreatitis, and they were used to create a new scoring system (MHBC). In the derivation and validation, the ability of MHBC (AUC= 0.922, 0.773, respectively) to predict 60-day mortality from pancreatitis was no less than that of APACHE II (AUC= 0.838, 0.748, respectively) and BISAP (AUC= 0.791, 0.750, respectively), while, MHBC is more quickly and concisely than APACHE II and BISAP. Compared with MHBC less than or equal to 2, when MHBC is greater than 2, the 28-day mortality, 60-day mortality and the incidence of AICU, MV and POF increased significantly (P <0.001). Conclusion The MHBC can quickly and concisely evaluate the 60-day mortality, 28-day mortality, and the incidence of AICU, MV and POF of patients with acute pancreatitis in the emergency department.
Collapse
Affiliation(s)
- Qiang Lai
- Emergency Department, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.,Laboratory of Emergency Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.,Disaster Medical Center, Sichuan University, Chengdu, Sichuan, People's Republic of China
| | - Wei Wei
- Emergency Department, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.,Laboratory of Emergency Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.,Disaster Medical Center, Sichuan University, Chengdu, Sichuan, People's Republic of China
| | - Yarong He
- Emergency Department, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.,Laboratory of Emergency Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.,Disaster Medical Center, Sichuan University, Chengdu, Sichuan, People's Republic of China
| | - Tao Cheng
- Emergency Department, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.,Laboratory of Emergency Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.,Disaster Medical Center, Sichuan University, Chengdu, Sichuan, People's Republic of China
| | - Tianyong Han
- Emergency Department, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.,Laboratory of Emergency Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.,Disaster Medical Center, Sichuan University, Chengdu, Sichuan, People's Republic of China
| | - Yu Cao
- Emergency Department, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.,Laboratory of Emergency Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.,Disaster Medical Center, Sichuan University, Chengdu, Sichuan, People's Republic of China
| |
Collapse
|
|
10
|
Effect of Admission Serum Calcium Levels and Length of Stay in Patients with Acute Pancreatitis: Data from the MIMIC-III Database. Emerg Med Int 2022; 2022:4275283. [PMID: 35769519 PMCID: PMC9236806 DOI: 10.1155/2022/4275283] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2022] [Accepted: 06/03/2022] [Indexed: 11/17/2022] Open
Abstract
Objective. We retrospectively investigated the effect of admission serum calcium levels on length of stay (LOS) in patients hospitalized with acute pancreatitis (AP). Methods. Clinical data for 3156 patients diagnosed with AP were obtained from the Multiparametric Intelligent Monitoring in Intensive Care III (MIMIC-III) database. Restricted cubic spline curve (RCS) functions of dose-response analysis curves and logistic regression analysis were used to analyze the relationship between admission serum calcium levels and the LOS. Results. All patients were divided into 2 groups (<8.5 mg/dl group and ≥8.5 mg/dl group) based on RCS analysis. RCS showed a significant nonlinear negative correlation between blood calcium levels and the LOS (
). In addition, compared with patients with blood calcium <8.5 mg/dl, multivariate logistic regression analysis showed that patients with blood calcium ≥8.5 mg/dl had a reduced risk of the LOS >2 days (aOR = 0.653; 95% CI 0.507–0.842;
), a reduced risk of the LOS >5 days (aOR = 0.589; 95% CI 0.503–0.689;
), and a reduced risk of the LOS >7 days (aOR = 0.515; 95% CI 0.437–0.609;
). And similar results were found in the subgroup analysis. Conclusion. Our findings suggest that low blood calcium increases the LOS in patients with AP. More attention is needed for patients with combined low blood calcium levels (<8.5 mg/dl) in hospitalized AP patients.
Collapse
|
|
11
|
Establishment of Early Multi-Indicator Prediction Models of Moderately Severe Acute Pancreatitis and Severe Acute Pancreatitis. Gastroenterol Res Pract 2022; 2022:5142473. [PMID: 35419053 PMCID: PMC9001090 DOI: 10.1155/2022/5142473] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Revised: 03/03/2022] [Accepted: 03/14/2022] [Indexed: 12/23/2022] Open
Abstract
Background It is critical to accurately identify patients with severe acute pancreatitis (SAP) and moderately SAP (MSAP) in a timely manner. The study was done to establish two early multi-indicator prediction models of MSAP and SAP. Methods Clinical data of 469 patients with acute pancreatitis (AP) between 2015 and 2020, at the First Affiliated Hospital of Fujian Medical University, and between 2012 and 2020, at the Affiliated Union Hospital of Fujian Medical University, were retrospectively analyzed. The unweighted predictive score (unwScore) and weighted predictive score (wScore) for MSAP and SAP were derived using logistic regression analysis and were compared with four existing systems using receiver operating characteristic curves. Results Seven prognostic indicators were selected for incorporation into models, including white blood cell count, lactate dehydrogenase, C-reactive protein, triglyceride, D-dimer, serum potassium, and serum calcium. The cut-offs of the unwScore and wScore for predicting severity were set as 3 points and 0.513 points, respectively. The unwScore (AUC = 0.854) and wScore (AUC = 0.837) were superior to the acute physiology and chronic health evaluation II score (AUC = 0.526), the bedside index for severity in AP score (AUC = 0.766), and the Ranson score (AUC = 0.693) in predicting MSAP and SAP, which were equivalent to the modified computed tomography severity index score (AUC = 0.823). Conclusions The unwScore and wScore have good predictive value for MSAP and SAP, which could provide a valuable clinical reference for management and treatment.
Collapse
|
|
12
|
Yu XQ, Deng HB, Liu Y, Qu C, Duan ZH, Tong ZH, Liu YX, Li WQ. Serum magnesium level as a predictor of acute kidney injury in patients with acute pancreatitis. World J Clin Cases 2021; 9:10899-10908. [PMID: 35047600 PMCID: PMC8678854 DOI: 10.12998/wjcc.v9.i35.10899] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Revised: 09/03/2021] [Accepted: 10/31/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Decreased serum magnesium (Mg2+) is commonly seen in critically ill patients. Hypomagnesemia is significantly more frequent in patients with severe acute pancreatitis. Acute kidney injury (AKI) in patients with acute pancreatitis (AP) is associated with an extremely high mortality. The association underlying serum Mg2+ and AKI in AP has not been elucidated.
AIM To explore the association between serum Mg2+ on admission and AKI in patients with AP.
METHODS A retrospective observational study was conducted in a cohort of patients (n = 233) with AP without any renal injury before admission to our center from August 2015 to February 2019. Demographic characteristics on admission, severity score, laboratory values and in-hospital mortality were compared between patients with and without AKI.
RESULTS A total of 233 patients were included for analysis, including 85 with AKI. Compared to patients without AKI, serum Mg2+ level was significantly lower in patients with AKI at admission [OR = 6.070, 95%CI: 3.374-10.921, P < 0.001]. Multivariate logistic analysis showed that lower serum Mg2+ was an independent risk factor for AKI [OR = 8.47, 95%CI: 3.02-23.72, P < 0.001].
CONCLUSION Our analysis indicates that serum Mg2+ level at admission is independently associated with the development of AKI in patients with AP and may be a potential prognostic factor.
Collapse
Affiliation(s)
- Xian-Qiang Yu
- Medical School, Southeast University, Nanjing 210009, Jiangsu Province, China
| | - Hong-Bin Deng
- Department of Critical Care Medicine, Nanjing Medical University, Nanjing 210002, Jiangsu Province, China
| | - Yang Liu
- Department of Critical Care Medicine, Nanjing University, Nanjing 210002, Jiangsu Province, China
| | - Cheng Qu
- Department of Critical Care Medicine, Nanjing University, Nanjing 210002, Jiangsu Province, China
| | - Ze-Hua Duan
- Department of Critical Care Medicine, Nanjing University, Nanjing 210002, Jiangsu Province, China
| | - Zhi-Hui Tong
- Department of Critical Care Medicine, General Hospital of Eastern Theater Command, Nanjing 210002, Jiangsu Province, China
| | - Yu-Xiu Liu
- Department of Critical Care Medicine, General Hospital of Eastern Theater Command, Nanjing 210002, Jiangsu Province, China
| | - Wei-Qin Li
- Medical School, Southeast University, Nanjing 210009, Jiangsu Province, China
- Department of Critical Care Medicine, General Hospital of Eastern Theater Command, Nanjing 210002, Jiangsu Province, China
| |
Collapse
|
|
13
|
Lou J, Yang X, Shan W, Jin Z, Ding J, Hu Y, Liao Q, Du Q, Xie R, Xu J. Effects of calcium‑permeable ion channels on various digestive diseases in the regulation of autophagy (Review). Mol Med Rep 2021; 24:680. [PMID: 34318907 DOI: 10.3892/mmr.2021.12319] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2020] [Accepted: 05/07/2021] [Indexed: 12/09/2022] Open
Abstract
Autophagy is a process of degradation and catabolism in cells. By removing damaged or dysfunctional organelles, autophagy interacts with the ubiquitin‑proteasome degradation system to jointly regulate cell function and energy homeostasis. Since autophagy plays a key role in physiology, disorders of the autophagy mechanism are associated with various diseases. Therefore, thorough understanding of the autophagy regulatory mechanism are crucially important in the diagnosis and treatment of diseases. To date, ion channels may affect the development and treatment of diseases by regulating autophagy, especially calcium‑permeable ion channels, in the process of digestive system diseases. However, the mechanism by which calcium ions and their channels regulate autophagy is still poorly understood, thus emphasizing the need for further research in this field. The present review intends to discuss the association, mechanism and application of calcium ions, their channels and autophagy in the occurrence and development of digestive system diseases.
Collapse
Affiliation(s)
- Jun Lou
- Department of Gastroenterology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563003, P.R. China
| | - Xiaoxu Yang
- Department of Gastroenterology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563003, P.R. China
| | - Weixi Shan
- Department of Gastroenterology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563003, P.R. China
| | - Zhe Jin
- Department of Gastroenterology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563003, P.R. China
| | - Jianhong Ding
- Department of Gastroenterology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563003, P.R. China
| | - Yanxia Hu
- Department of Gastroenterology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563003, P.R. China
| | - Qiushi Liao
- Department of Gastroenterology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563003, P.R. China
| | - Qian Du
- Department of Gastroenterology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563003, P.R. China
| | - Rui Xie
- Department of Gastroenterology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563003, P.R. China
| | - Jingyu Xu
- Department of Gastroenterology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563003, P.R. China
| |
Collapse
|
|
14
|
Wu Q, Wang J, Qin M, Yang H, Liang Z, Tang G. Accuracy of conventional and novel scoring systems in predicting severity and outcomes of acute pancreatitis: a retrospective study. Lipids Health Dis 2021; 20:41. [PMID: 33906658 PMCID: PMC8080352 DOI: 10.1186/s12944-021-01470-4] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Accepted: 04/20/2021] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND Recently, several novel scoring systems have been developed to evaluate the severity and outcomes of acute pancreatitis. This study aimed to compare the effectiveness of novel and conventional scoring systems in predicting the severity and outcomes of acute pancreatitis. METHODS Patients treated between January 2003 and August 2020 were reviewed. The Ranson score (RS), Glasgow score (GS), bedside index of severity in acute pancreatitis (BISAP), pancreatic activity scoring system (PASS), and Chinese simple scoring system (CSSS) were determined within 48 h after admission. Multivariate logistic regression was used for severity, mortality, and organ failure prediction. Optimum cutoffs were identified using receiver operating characteristic curve analysis. RESULTS A total of 1848 patients were included. The areas under the curve (AUCs) of RS, GS, BISAP, PASS, and CSSS for severity prediction were 0.861, 0.865, 0.829, 0.778, and 0.816, respectively. The corresponding AUCs for mortality prediction were 0.693, 0.736, 0.789, 0.858, and 0.759. The corresponding AUCs for acute respiratory distress syndrome prediction were 0.745, 0.784, 0.834, 0.936, and 0.820. Finally, the corresponding AUCs for acute renal failure prediction were 0.707, 0.734, 0.781, 0.868, and 0.816. CONCLUSIONS RS and GS predicted severity better than they predicted mortality and organ failure, while PASS predicted mortality and organ failure better. BISAP and CSSS performed equally well in severity and outcome predictions.
Collapse
Affiliation(s)
- Qing Wu
- Department of Gastroenterology, the Second Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Jie Wang
- Department of Gastroenterology, the Second Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Mengbin Qin
- Department of Gastroenterology, the Second Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Huiying Yang
- Department of Gastroenterology, the First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Zhihai Liang
- Department of Gastroenterology, the First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Guodu Tang
- Department of Gastroenterology, the First Affiliated Hospital of Guangxi Medical University, Nanning, China.
| |
Collapse
|
|
15
|
Tsai WH, Lee CC, Cheng SP, Zeng YH. Hyperparathyroidism presenting as hyperemesis and acute pancreatitis in pregnancy: A case report. Medicine (Baltimore) 2021; 100:e25451. [PMID: 33832152 PMCID: PMC8036029 DOI: 10.1097/md.0000000000025451] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2020] [Accepted: 12/08/2020] [Indexed: 01/05/2023] Open
Abstract
RATIONALE Nausea and vomiting are common in the early period of pregnancy and rarely seen as an overture to pancreatitis. PATIENT CONCERNS Here, we describe a 31-year-old pregnant woman who presented with progressive nausea and vomiting followed by severe epigastric pain. Biochemical data and sonographic features confirmed the occurrence of acute pancreatitis. Accompanying electrolyte abnormalities included hypercalcemia and hypokalemia. Her condition stabilized following medical treatment, but hypercalcemia persisted despite intravenous fluids and furosemide administration. DIAGNOSES A diagnosis of primary hyperparathyroidism was made based on the elevated parathyroid hormone level and urinary calcium-to-creatinine clearance ratio. INTERVENTIONS Localization study with neck ultrasonography indicated left inferior parathyroid adenoma. She underwent parathyroidectomy successfully and made an uneventful recovery. OUTCOMES At 37 weeks of gestation, she had a serum calcium level of 8.8 mg/dL and normal parathyroid hormone of 28.55 pg/mL. A healthy baby weighing 3180 g was delivered smoothly with no clinical nor biochemical evidence of hypocalcemia. LESSONS Although primary hyperparathyroidism during pregnancy is usually asymptomatic, patients may present with atypical manifestations such as hyperemesis and pancreatitis. Proper diagnosis and timely intervention are crucial to minimizing potential hazards to both mother and fetus.
Collapse
Affiliation(s)
- Wen-Hsuan Tsai
- Division of Endocrinology and Metabolism, Department of Internal Medicine MacKay Memorial Hospital, Taipei
| | - Chun-Chuan Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine MacKay Memorial Hospital, Taipei
- Department of Medicine, MacKay Medical College, New Taipei City
| | - Shih-Ping Cheng
- Department of Surgery, MacKay Memorial Hospital, Taipei, Taiwan ROC
| | - Yi-Hong Zeng
- Division of Endocrinology and Metabolism, Department of Internal Medicine MacKay Memorial Hospital, Taipei
- Department of Medicine, MacKay Medical College, New Taipei City
| |
Collapse
|
|
16
|
Zhang X, Xin G, Li S, Wei Z, Ming Y, Yuan J, Wen E, Xing Z, Yu K, Li Y, Zhang J, Zhang B, Niu H, Huang W. Dehydrocholic Acid Ameliorates Sodium Taurocholate-Induced Acute Biliary Pancreatitis in Mice. Biol Pharm Bull 2021; 43:985-993. [PMID: 32475920 DOI: 10.1248/bpb.b20-00021] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Acute biliary pancreatitis (ABP) with a high mortality rate is an incurable digestive system disease induced by abnormal bile acid regurgitation due to the biliary obstruction. Dehydrocholic acid (DA) alleviates the severity of cholestatic hepatitis related to biliary inflammation, suggesting DA is potential to develop for the incurable ABP management. Here we identified DA potency and explored the underlying mechanism in ABP. Our data showed that DA administration not only reduced typically clinicopathological parameters including serum levels of amylase and lipase but also suppressed pancreatic tissue edema, necrosis and trypsin activation in ABP mice. We also found that DA significantly reduced the necrosis of pancreatic acinar cells induced by sodium taurocholate (NaT). Further experimental data showed the significant inhibitions of DA on mitochondrial membrane potential depolarization, ATP exhaustion, calcium overload and reactive oxygen species (ROS) erupted in acinar cells induced by NaT, indicating DA could avert acinar cell death through protecting the mitochondrial function, scavenging excessive oxidative stress and balancing calcium. The comprehensive study found DA elevated the expression of transcription factor EB (TFEB) in vitro thus to increase the functional lysosome content. Indeed, DA decreased the Microtubule-associated protein light chain 3 (LC3) II/I ratio as well as ubiquitin-binding protein p62 and Parkin expressions in vivo and in vitro, revealing autophagy restoration maybe through the improvement of TFEB-mediated lysosome biogenesis. These data indicate that DA improves ABP through the mitochondrial protection, antioxidant ability enhancement and autophagy recovery. In conclusion, our study proposes a potential therapy strategy for the incurable ABP.
Collapse
Affiliation(s)
- Xiaoyu Zhang
- Laboratory of Ethnopharmacology, West China School of Pharmacy, West China Hospital, West China Medical School, Sichuan University
| | - Guang Xin
- Laboratory of Ethnopharmacology, West China School of Pharmacy, West China Hospital, West China Medical School, Sichuan University
| | - Shiyi Li
- Laboratory of Ethnopharmacology, West China School of Pharmacy, West China Hospital, West China Medical School, Sichuan University
| | - Zeliang Wei
- Laboratory of Ethnopharmacology, West China School of Pharmacy, West China Hospital, West China Medical School, Sichuan University
| | - Yue Ming
- Laboratory of Ethnopharmacology, West China School of Pharmacy, West China Hospital, West China Medical School, Sichuan University
| | - Jiyan Yuan
- Laboratory of Ethnopharmacology, West China School of Pharmacy, West China Hospital, West China Medical School, Sichuan University
| | - E Wen
- Laboratory of Ethnopharmacology, West China School of Pharmacy, West China Hospital, West China Medical School, Sichuan University
| | - Zhihua Xing
- Laboratory of Ethnopharmacology, West China School of Pharmacy, West China Hospital, West China Medical School, Sichuan University
| | - Kui Yu
- Laboratory of Ethnopharmacology, West China School of Pharmacy, West China Hospital, West China Medical School, Sichuan University
| | - Youping Li
- Laboratory of Ethnopharmacology, West China School of Pharmacy, West China Hospital, West China Medical School, Sichuan University
| | - Junhua Zhang
- Tianjin University of Traditional Chinese Medicine
| | - Boli Zhang
- Laboratory of Ethnopharmacology, West China School of Pharmacy, West China Hospital, West China Medical School, Sichuan University.,Tianjin University of Traditional Chinese Medicine
| | - Hai Niu
- Laboratory of Ethnopharmacology, West China School of Pharmacy, West China Hospital, West China Medical School, Sichuan University
| | - Wen Huang
- Laboratory of Ethnopharmacology, West China School of Pharmacy, West China Hospital, West China Medical School, Sichuan University
| |
Collapse
|
|
17
|
Kroner PT, Mareth K, Raimondo M, Lee DD, Alsaad A, Aslam N, Abader P, Wadei HM. Acute Pancreatitis in Advanced Chronic Kidney Disease and Kidney Transplant Recipients: Results of a US Nationwide Analysis. Mayo Clin Proc Innov Qual Outcomes 2019; 3:160-168. [PMID: 31193877 PMCID: PMC6543454 DOI: 10.1016/j.mayocpiqo.2019.03.006] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
Abstract
Objective To study the prevalence, etiology, and outcome of acute pancreatitis (AP) in kidney transplant and stage 5 chronic kidney disease (CKD) populations in comparison to a non-CKD cohort. Patients and Methods Using the Nationwide Inpatient Sample database, we identified patients with acute pancreatitis as the primary discharge diagnosis, after which propensity scores were used to create 2 cohorts of patients: 1 with CKD (n=13,425) and 1 without CKD (n=13,425). The CKD group was subsequently subdivided into dialysis-independent stage 5 CKD (n=690), dialysis-dependent stage 5 CKD (n=11,415), and kidney transplant recipients (n=1320). Patients younger than 18 years old, those who received a kidney transplant during the incident admission, and pancreas transplant recipients were excluded. Results The adjusted odds ratios (ORs) of AP were comparable between the no CKD, stage 5 CKD, and kidney transplant populations. Adjusted inpatient mortality was highest in patients with dialysis-dependent stage 5 CKD (OR, 2.72; 95% CI, 2.2-3.3; P<.01), followed by kidney transplant recipients (OR, 2.29; 95% CI, 1.12-4.51; P=.02), compared to the non-CKD group. Patients with stage 5 CKD experienced higher rates of shock and intensive care unit admission and had more prolonged and costly hospitalizations than the non-CKD group (P<.01 for all). Hypercalcemia was the most common cause of AP in both dialysis-dependent and dialysis-independent patients with stage 5 CKD, while viral and drug-induced pancreatitis were more prevalent in the transplant recipients. Conclusion Despite comparable adjusted prevalence of AP among the stage 5 CKD, transplant, and non-CKD populations, mortality, morbidity, and resource utilization were higher in the patients with stage 5 CKD and transplant recipients. Hypercalcemia is the most common cause of AP in the stage 5 CKD population irrespective of dialysis requirement.
Collapse
Key Words
- AP, acute pancreatitis
- CCI, Charlson Comorbidity Index
- CKD, chronic kidney disease
- CKD5, stage 5 CKD
- ERCP, endoscopic retrograde cholangiopancreatography
- ESRD, end-stage renal disease
- ICD-9-CM, International Classification of Diseases, Ninth Revision, Clinical Modification
- ICU, intensive care unit
- NIS, Nationwide Inpatient Sample
- OR, odds ratio
- US, ultrasonography
Collapse
Affiliation(s)
- Paul T Kroner
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL
| | - Karl Mareth
- Department of Medicine, Mayo Clinic, Jacksonville, FL
| | - Massimo Raimondo
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL
| | - David D Lee
- Department of Transplantation, Mayo Clinic, Jacksonville, FL
| | - Ali Alsaad
- Department of Medicine, Mayo Clinic, Jacksonville, FL
| | - Nabeel Aslam
- Division of Nephrology and Hypertension, Mayo Clinic, Jacksonville, FL
| | - Peter Abader
- Department of Transplantation, Mayo Clinic, Jacksonville, FL
| | - Hani M Wadei
- Department of Transplantation, Mayo Clinic, Jacksonville, FL.,Division of Nephrology and Hypertension, Mayo Clinic, Jacksonville, FL
| |
Collapse
|
|
18
|
The Management of Resistant Hypercalcaemia Secondary to Cancer of Unknown Primary and Presenting with Pancreatitis. REPORTS 2019. [DOI: 10.3390/reports2020013] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
We present a 31-year-old female who presented to the general surgical take with epigastric pain associated with a raised amylase and corrected calcium on admission. Computed tomography confirmed acute pancreatitis and also demonstrated a 15 cm liver tumour. She was subsequently diagnosed with cancer of unknown primary with liver metastases. The patient’s pancreatitis symptoms improved with conservative management, but her calcium proved quite resistant to basic measures. Further input was sought from the medical on-call endocrinology and oncology teams to help manage this patient’s hypercalcaemia, which included pamidronate, zolendronate, and denusomab, but ultimately it only improved significantly following chemotherapy. This case to our knowledge is the only one of its kind and highlights the importance of early multidisciplinary team involvement across specialties to help manage complex patients.
Collapse
|
|
19
|
Luaces-Regueira M, Castiñeira-Alvariño M, Castro-Manzanares M, Campos-Toimil M, Domínguez-Muñoz JE. Pathophysiological Events Associated With Pancreatitis in Response to Tobacco: An In Vitro Comparative Study With Ethanol in Primary Acinar Cell Culture. Pancreas 2019; 47:1304-1311. [PMID: 30286014 DOI: 10.1097/mpa.0000000000001180] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
OBJECTIVES The aim of this study was to comparatively analyze the effects of different concentrations of cigarette smoke condensate (CSC, a standardized tobacco extract) and ethanol on intracellular enzyme activation, cell necrosis, alteration of cytosolic calcium concentration ([Ca]c), and amylase secretion in pancreatic acinar cells. METHODS The effects of CSC (1 μg/mL to 0.4 mg/mL) and ethanol (10-100 mM) on intracellular enzyme activity, cell necrosis, and [Ca]c were measured by fluorescence assays in isolated pancreatic acinar cells. Amylase secretion was evaluated by spectrophotometry. Supramaximal concentrations of cholecystokinin (10-100 nM) were used as positive control. RESULTS Neither CSC nor ethanol induced trypsin or elastase activation. Both CSC (0.1-0.4 mg/mL) and ethanol (10-75 mM) significantly increased [Ca]c. Amylase secretion was increased only in CSC-treated cells (0.3 and 0.4 mg/mL). After 60 minutes, CSC (0.3 and 0.4 mg/mL) significantly increased acinar cell necrosis at a similar percentage to that induced by cholecystokinin. Ethanol did not induce any significant cell necrosis. CONCLUSIONS Cigarette smoke condensate induces acinar cell injury and increases [Ca]c and amylase secretion, independently of intracellular enzyme activation, suggesting that tobacco could induce several main early events of pancreatitis in pancreatic acinar cells. However, ethanol only induces increases [Ca]c, having no effect on cell injury, amylase secretion, or intracellular enzyme activation.
Collapse
Affiliation(s)
| | | | - María Castro-Manzanares
- CD Pharma, Center for Research in Molecular Medicine and Chronic Diseases, University of Santiago de Compostela, Santiago de Compostela, Spain
| | - Manuel Campos-Toimil
- CD Pharma, Center for Research in Molecular Medicine and Chronic Diseases, University of Santiago de Compostela, Santiago de Compostela, Spain
| | | |
Collapse
|
|
20
|
Research Progress on the Relationship Between Acute Pancreatitis and Calcium Overload in Acinar Cells. Dig Dis Sci 2019; 64:25-38. [PMID: 30284136 DOI: 10.1007/s10620-018-5297-8] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2018] [Accepted: 09/01/2018] [Indexed: 02/07/2023]
Abstract
Acute pancreatitis is a human disease with multiple causes that leads to autodigestion of the pancreas. There is sufficient evidence to support the key role of sustained increase in cytosolic calcium concentrations in the early pathogenesis of the disease. To clarify the mechanism of maintaining calcium homeostasis in the cell and pathological processes caused by calcium overload would help to research directly targeted therapeutic agents. We will specifically review the following: intracellular calcium homeostasis and regulation, the occurrence of calcium overload in acinar cells, the role of calcium overload in the pathogenesis of AP, the treatment strategy proposed for calcium overload.
Collapse
|
|
21
|
Zhou J, Qin M, Wang H, He J, Fu H, Shi H, Liang Z, Tang G. Cav 1.2 and Cav 2.2 expression is regulated by different endogenous ghrelin levels in pancreatic acinar cells during acute pancreatitis. Int J Mol Med 2018; 41:2909-2916. [PMID: 29436604 DOI: 10.3892/ijmm.2018.3490] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2016] [Accepted: 02/07/2018] [Indexed: 11/05/2022] Open
Abstract
Ghrelin influences pancreatic endocrine and exocrine functions, regulates intracellular calcium [Ca2+]i levels, and has an anti-inflammatory role in acute pancreatitis. This study investigated the role of endogenous ghrelin in the expression of Cav 1.2 (L-type of Ca2+ channel) and Cav 2.2 (N-type of Ca2+ channel) in acute pancreatitis. For this purpose, acute edematous pancreatitis (AEP) and acute necrotizing pancreatitis (ANP) rat models were established. Cav 1.2 and Cav 2.2 expression was assessed by immunohistochemistry in the pancreatic tissues of rats; ghrelin, interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) serum levels were detected using ELISA. Next, in AR42J cells with either knock-out or overexpression of ghrelin, Cav 1.2 and Cav 2.2 expression was examined using western blot analysis, and intracellular calcium [Ca2+]i was detected with confocal microscopy. In this study, the ghrelin serum level was highest in the ANP group and was higher in the AEP group than the normal group. Expression of Cav 1.2 and Cav 2.2 in the ANP and AEP groups was higher than in the respective control groups. The serum IL-1β and TNF-α levels were significantly higher in the ANP group compared to the other groups. Cav 1.2 and Cav 2.2 expression and [Ca2+]i decreased in ghrelin knockdown AR42J cells but increased in ghrelin overexpressing cells. In conclusion, Cav 1.2 and Cav 2.2 expression increased in ANP. The [Ca2+]i level, which is mediated by Cav 1.2 and Cav 2.2 expression, is directly regulated by ghrelin in pancreatic acinar cells, and serum ghrelin levels may be involved in the severity of acute pancreatitis.
Collapse
Affiliation(s)
- Jie Zhou
- Department of Gastroenterology, The First Affiliated Hospital, Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Mengbin Qin
- Department of Gastroenterology, The First Affiliated Hospital, Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Huilin Wang
- Department of Gastroenterology, The First Affiliated Hospital, Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Jiaping He
- Department of Gastroenterology, The First Affiliated Hospital, Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Hongzong Fu
- Department of Gastroenterology, The First Affiliated Hospital, Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Huirong Shi
- Department of Gastroenterology, The First Affiliated Hospital, Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Zhihai Liang
- Department of Gastroenterology, The First Affiliated Hospital, Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Guodu Tang
- Department of Gastroenterology, The First Affiliated Hospital, Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| |
Collapse
|
|
22
|
Peng T, Peng X, Huang M, Cui J, Zhang Y, Wu H, Wang C. Serum calcium as an indicator of persistent organ failure in acute pancreatitis. Am J Emerg Med 2017; 35:978-982. [PMID: 28291705 DOI: 10.1016/j.ajem.2017.02.006] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2016] [Accepted: 02/03/2017] [Indexed: 02/06/2023] Open
Abstract
AIM Decreased level of serum calcium was commonly seen in critical illness. Hypocalcemia was significantly more frequent in patients with severe form of acute pancreatitis (AP), and a negative correlation was observed between endotoxemia and serum calcium in AP. AP patients with persistent organ failure (POF) show an extremely high mortality. The association underlying calcium and POF in AP has not been characterized. METHODS We conducted a retrospective cohort study of adult patients who presented within 72hours from symptom onset of AP at our center between January 2014 and May 2015. Demographic parameters on admission, organ failure assessment, laboratory data and in-hospital mortality were compared between patients with and without POF. Uni-and multi-variate logistic regression analyses were utilized to evaluated the predictive ability of serum calcium. RESULTS A total of 128 consecutive AP patients, including 29 with POF, were included. Compared to patients without POF, patients with POF showed a significantly lower value of serum calcium on admission (2.11±0.46 vs. 1.55±0.36mmol/L, P<0.001). After multivariate logistic analysis, serum calcium remained an independent risk factor for POF (Hazard ratio 0.21, 95% confident interval: 0.08-0.58; P=0.002). A calcium value of 1.97mmol/L predicted POF with an area under the curve (AUC) of 0.888, a sensitivity with 89.7% and specificity with 74.8%, respectively. CONCLUSION Our results indicate that serum calcium on admission is independently associated with POF in AP and may serve as a potential prognostic factor.
Collapse
Affiliation(s)
- Tao Peng
- Pancreatic Disease Institute, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, People's Republic of China
| | - Xin Peng
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, People's Republic of China
| | - Min Huang
- Pancreatic Disease Institute, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, People's Republic of China
| | - Jing Cui
- Pancreatic Disease Institute, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, People's Republic of China
| | - Yushun Zhang
- Pancreatic Disease Institute, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, People's Republic of China.
| | - Heshui Wu
- Pancreatic Disease Institute, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, People's Republic of China
| | - Chunyou Wang
- Pancreatic Disease Institute, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, People's Republic of China
| |
Collapse
|
|
23
|
Gariepy CE, Heyman MB, Lowe ME, Pohl JF, Werlin SL, Wilschanski M, Barth B, Fishman DS, Freedman SD, Giefer MJ, Gonska T, Himes R, Husain SZ, Morinville VD, Ooi CY, Schwarzenberg SJ, Troendle DM, Yen E, Uc A. Causal Evaluation of Acute Recurrent and Chronic Pancreatitis in Children: Consensus From the INSPPIRE Group. J Pediatr Gastroenterol Nutr 2017; 64:95-103. [PMID: 27782962 PMCID: PMC5191966 DOI: 10.1097/mpg.0000000000001446] [Citation(s) in RCA: 56] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECTIVES Acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP) have been diagnosed in children at increasing rates during the past decade. As pediatric ARP and CP are still relatively rare conditions, little quality evidence is available on which to base the diagnosis and determination of etiology. The aim of the study was to review the current state of the literature regarding the etiology of these disorders and to developed a consensus among a panel of clinically active specialists caring for children with these disorders to help guide the diagnostic evaluation and identify areas most in need of future research. METHODS A systematic review of the literature was performed and scored for quality, followed by consensus statements developed and scored by each individual in the group for level of agreement and strength of the supporting data using a modified Delphi method. Scores were analyzed for the level of consensus achieved by the group. RESULTS The panel reached consensus on 27 statements covering the definitions of pediatric ARP and CP, evaluation for potential etiologies of these disorders, and long-term monitoring. Statements for which the group reached consensus to make no recommendation or could not reach consensus are discussed. CONCLUSIONS This consensus helps define the minimal diagnostic evaluation and monitoring of children with ARP and CP. Even in areas in which we reached consensus, the quality of the evidence is weak, highlighting the need for further research. Improved understanding of the underlying cause will facilitate treatment development and targeting.
Collapse
Affiliation(s)
- Cheryl E. Gariepy
- Nationwide Children’s Hospital and The Ohio State University, Columbus, OH, USA
| | - Melvin B. Heyman
- University of California at San Francisco, San Francisco, CA, USA
| | - Mark E. Lowe
- Children’s Hospital of Pittsburgh of UPMC, Pittsburgh, PA, USA
| | | | | | | | - Bradley Barth
- University of Texas Southwestern Medical School, Dallas, TX, USA
| | | | | | | | | | - Ryan Himes
- Baylor College of Medicine, Houston, TX, USA
| | | | | | - Chee Y. Ooi
- University of New South Wales and Sydney Children’s Hospital Randwick Sydney, Australia
| | | | | | - Elizabeth Yen
- University of California at San Francisco, San Francisco, CA, USA
| | - Aliye Uc
- University of Iowa Children’s Hospital, Iowa City, IA, USA
| |
Collapse
|
|
24
|
Liu C, Yang W, Devidas M, Cheng C, Pei D, Smith C, Carroll WL, Raetz EA, Bowman WP, Larsen EC, Maloney KW, Martin PL, Mattano LA, Winick NJ, Mardis ER, Fulton RS, Bhojwani D, Howard SC, Jeha S, Pui CH, Hunger SP, Evans WE, Loh ML, Relling MV. Clinical and Genetic Risk Factors for Acute Pancreatitis in Patients With Acute Lymphoblastic Leukemia. J Clin Oncol 2016; 34:2133-40. [PMID: 27114598 DOI: 10.1200/jco.2015.64.5812] [Citation(s) in RCA: 66] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
PURPOSE Acute pancreatitis is one of the common causes of asparaginase intolerance. The mechanism is unknown, and genetic predisposition to asparaginase-induced pancreatitis has not been previously identified. METHODS To determine clinical risk factors for asparaginase-induced pancreatitis, we studied a cohort of 5,185 children and young adults with acute lymphoblastic leukemia, including 117 (2.3%) who were diagnosed with at least one episode of acute pancreatitis during therapy. A genome-wide association study was performed in the cohort and in an independent case-control group of 213 patients to identify genetic risk factors. RESULTS Risk factors associated with pancreatitis included genetically defined Native American ancestry (P < .001), older age (P < .001), and higher cumulative dose of asparaginase (P < .001). No common variants reached genome-wide significance in the genome-wide association study, but a rare nonsense variant rs199695765 in CPA2, encoding carboxypeptidase A2, was highly associated with pancreatitis (hazard ratio, 587; 95% CI, 66.8 to 5166; P = 9.0 × 10(-9)). A gene-level analysis showed an excess of additional CPA2 variants in patients who did versus those who did not develop pancreatitis (P = .001). Sixteen CPA2 single-nucleotide polymorphisms were associated (P < .05) with pancreatitis, and 13 of 24 patients who carried at least one of these variants developed pancreatitis. Biologic functions that were overrepresented by common variants modestly associated with pancreatitis included purine metabolism and cytoskeleton regulation. CONCLUSION Older age, higher exposure to asparaginase, and higher Native American ancestry were independent risk factors for pancreatitis in patients with acute lymphoblastic leukemia. Those who inherit a nonsense rare variant in the CPA2 gene had a markedly increased risk of asparaginase-induced pancreatitis.
Collapse
Affiliation(s)
- Chengcheng Liu
- Chengcheng Liu, Wenjian Yang, Cheng Cheng, Deqing Pei, Colton Smith, Sima Jeha, Ching-Hon Pui, William E. Evans, and Mary V. Relling, St Jude Children's Research Hospital; Scott C. Howard, University of Memphis, Memphis, TN; Meenakshi Devidas, University of Florida, Gainesville, FL; William L. Carroll, New York University Langone Medical Center, New York, NY; Elizabeth A. Raetz, University of Utah, Salt Lake City, UT; W. Paul Bowman, Cook Children's Hospital, Ft Worth; Naomi J. Winick, University of Texas Southwestern Medical Center, Dallas, TX; Eric C. Larsen, Maine Children's Cancer Program, Scarborough, ME; Kelly W. Maloney, University of Colorado Denver, Aurora, CO; Paul L. Martin, Duke University, Durham, NC; Leonard A. Mattano Jr, HARP Pharma Consulting, Mystic, CT; Elaine R. Mardis and Robert S. Fulton, The McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO; Deepa Bhojwani, Children's Hospital of Los Angeles, Los Angeles; Mignon L. Loh, University of California San Francisco Medical Center-Parnassus, San Francisco, CA; and Stephen P. Hunger, Children's Hospital of Philadelphia, Philadelphia, PA
| | - Wenjian Yang
- Chengcheng Liu, Wenjian Yang, Cheng Cheng, Deqing Pei, Colton Smith, Sima Jeha, Ching-Hon Pui, William E. Evans, and Mary V. Relling, St Jude Children's Research Hospital; Scott C. Howard, University of Memphis, Memphis, TN; Meenakshi Devidas, University of Florida, Gainesville, FL; William L. Carroll, New York University Langone Medical Center, New York, NY; Elizabeth A. Raetz, University of Utah, Salt Lake City, UT; W. Paul Bowman, Cook Children's Hospital, Ft Worth; Naomi J. Winick, University of Texas Southwestern Medical Center, Dallas, TX; Eric C. Larsen, Maine Children's Cancer Program, Scarborough, ME; Kelly W. Maloney, University of Colorado Denver, Aurora, CO; Paul L. Martin, Duke University, Durham, NC; Leonard A. Mattano Jr, HARP Pharma Consulting, Mystic, CT; Elaine R. Mardis and Robert S. Fulton, The McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO; Deepa Bhojwani, Children's Hospital of Los Angeles, Los Angeles; Mignon L. Loh, University of California San Francisco Medical Center-Parnassus, San Francisco, CA; and Stephen P. Hunger, Children's Hospital of Philadelphia, Philadelphia, PA
| | - Meenakshi Devidas
- Chengcheng Liu, Wenjian Yang, Cheng Cheng, Deqing Pei, Colton Smith, Sima Jeha, Ching-Hon Pui, William E. Evans, and Mary V. Relling, St Jude Children's Research Hospital; Scott C. Howard, University of Memphis, Memphis, TN; Meenakshi Devidas, University of Florida, Gainesville, FL; William L. Carroll, New York University Langone Medical Center, New York, NY; Elizabeth A. Raetz, University of Utah, Salt Lake City, UT; W. Paul Bowman, Cook Children's Hospital, Ft Worth; Naomi J. Winick, University of Texas Southwestern Medical Center, Dallas, TX; Eric C. Larsen, Maine Children's Cancer Program, Scarborough, ME; Kelly W. Maloney, University of Colorado Denver, Aurora, CO; Paul L. Martin, Duke University, Durham, NC; Leonard A. Mattano Jr, HARP Pharma Consulting, Mystic, CT; Elaine R. Mardis and Robert S. Fulton, The McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO; Deepa Bhojwani, Children's Hospital of Los Angeles, Los Angeles; Mignon L. Loh, University of California San Francisco Medical Center-Parnassus, San Francisco, CA; and Stephen P. Hunger, Children's Hospital of Philadelphia, Philadelphia, PA
| | - Cheng Cheng
- Chengcheng Liu, Wenjian Yang, Cheng Cheng, Deqing Pei, Colton Smith, Sima Jeha, Ching-Hon Pui, William E. Evans, and Mary V. Relling, St Jude Children's Research Hospital; Scott C. Howard, University of Memphis, Memphis, TN; Meenakshi Devidas, University of Florida, Gainesville, FL; William L. Carroll, New York University Langone Medical Center, New York, NY; Elizabeth A. Raetz, University of Utah, Salt Lake City, UT; W. Paul Bowman, Cook Children's Hospital, Ft Worth; Naomi J. Winick, University of Texas Southwestern Medical Center, Dallas, TX; Eric C. Larsen, Maine Children's Cancer Program, Scarborough, ME; Kelly W. Maloney, University of Colorado Denver, Aurora, CO; Paul L. Martin, Duke University, Durham, NC; Leonard A. Mattano Jr, HARP Pharma Consulting, Mystic, CT; Elaine R. Mardis and Robert S. Fulton, The McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO; Deepa Bhojwani, Children's Hospital of Los Angeles, Los Angeles; Mignon L. Loh, University of California San Francisco Medical Center-Parnassus, San Francisco, CA; and Stephen P. Hunger, Children's Hospital of Philadelphia, Philadelphia, PA
| | - Deqing Pei
- Chengcheng Liu, Wenjian Yang, Cheng Cheng, Deqing Pei, Colton Smith, Sima Jeha, Ching-Hon Pui, William E. Evans, and Mary V. Relling, St Jude Children's Research Hospital; Scott C. Howard, University of Memphis, Memphis, TN; Meenakshi Devidas, University of Florida, Gainesville, FL; William L. Carroll, New York University Langone Medical Center, New York, NY; Elizabeth A. Raetz, University of Utah, Salt Lake City, UT; W. Paul Bowman, Cook Children's Hospital, Ft Worth; Naomi J. Winick, University of Texas Southwestern Medical Center, Dallas, TX; Eric C. Larsen, Maine Children's Cancer Program, Scarborough, ME; Kelly W. Maloney, University of Colorado Denver, Aurora, CO; Paul L. Martin, Duke University, Durham, NC; Leonard A. Mattano Jr, HARP Pharma Consulting, Mystic, CT; Elaine R. Mardis and Robert S. Fulton, The McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO; Deepa Bhojwani, Children's Hospital of Los Angeles, Los Angeles; Mignon L. Loh, University of California San Francisco Medical Center-Parnassus, San Francisco, CA; and Stephen P. Hunger, Children's Hospital of Philadelphia, Philadelphia, PA
| | - Colton Smith
- Chengcheng Liu, Wenjian Yang, Cheng Cheng, Deqing Pei, Colton Smith, Sima Jeha, Ching-Hon Pui, William E. Evans, and Mary V. Relling, St Jude Children's Research Hospital; Scott C. Howard, University of Memphis, Memphis, TN; Meenakshi Devidas, University of Florida, Gainesville, FL; William L. Carroll, New York University Langone Medical Center, New York, NY; Elizabeth A. Raetz, University of Utah, Salt Lake City, UT; W. Paul Bowman, Cook Children's Hospital, Ft Worth; Naomi J. Winick, University of Texas Southwestern Medical Center, Dallas, TX; Eric C. Larsen, Maine Children's Cancer Program, Scarborough, ME; Kelly W. Maloney, University of Colorado Denver, Aurora, CO; Paul L. Martin, Duke University, Durham, NC; Leonard A. Mattano Jr, HARP Pharma Consulting, Mystic, CT; Elaine R. Mardis and Robert S. Fulton, The McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO; Deepa Bhojwani, Children's Hospital of Los Angeles, Los Angeles; Mignon L. Loh, University of California San Francisco Medical Center-Parnassus, San Francisco, CA; and Stephen P. Hunger, Children's Hospital of Philadelphia, Philadelphia, PA
| | - William L Carroll
- Chengcheng Liu, Wenjian Yang, Cheng Cheng, Deqing Pei, Colton Smith, Sima Jeha, Ching-Hon Pui, William E. Evans, and Mary V. Relling, St Jude Children's Research Hospital; Scott C. Howard, University of Memphis, Memphis, TN; Meenakshi Devidas, University of Florida, Gainesville, FL; William L. Carroll, New York University Langone Medical Center, New York, NY; Elizabeth A. Raetz, University of Utah, Salt Lake City, UT; W. Paul Bowman, Cook Children's Hospital, Ft Worth; Naomi J. Winick, University of Texas Southwestern Medical Center, Dallas, TX; Eric C. Larsen, Maine Children's Cancer Program, Scarborough, ME; Kelly W. Maloney, University of Colorado Denver, Aurora, CO; Paul L. Martin, Duke University, Durham, NC; Leonard A. Mattano Jr, HARP Pharma Consulting, Mystic, CT; Elaine R. Mardis and Robert S. Fulton, The McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO; Deepa Bhojwani, Children's Hospital of Los Angeles, Los Angeles; Mignon L. Loh, University of California San Francisco Medical Center-Parnassus, San Francisco, CA; and Stephen P. Hunger, Children's Hospital of Philadelphia, Philadelphia, PA
| | - Elizabeth A Raetz
- Chengcheng Liu, Wenjian Yang, Cheng Cheng, Deqing Pei, Colton Smith, Sima Jeha, Ching-Hon Pui, William E. Evans, and Mary V. Relling, St Jude Children's Research Hospital; Scott C. Howard, University of Memphis, Memphis, TN; Meenakshi Devidas, University of Florida, Gainesville, FL; William L. Carroll, New York University Langone Medical Center, New York, NY; Elizabeth A. Raetz, University of Utah, Salt Lake City, UT; W. Paul Bowman, Cook Children's Hospital, Ft Worth; Naomi J. Winick, University of Texas Southwestern Medical Center, Dallas, TX; Eric C. Larsen, Maine Children's Cancer Program, Scarborough, ME; Kelly W. Maloney, University of Colorado Denver, Aurora, CO; Paul L. Martin, Duke University, Durham, NC; Leonard A. Mattano Jr, HARP Pharma Consulting, Mystic, CT; Elaine R. Mardis and Robert S. Fulton, The McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO; Deepa Bhojwani, Children's Hospital of Los Angeles, Los Angeles; Mignon L. Loh, University of California San Francisco Medical Center-Parnassus, San Francisco, CA; and Stephen P. Hunger, Children's Hospital of Philadelphia, Philadelphia, PA
| | - W Paul Bowman
- Chengcheng Liu, Wenjian Yang, Cheng Cheng, Deqing Pei, Colton Smith, Sima Jeha, Ching-Hon Pui, William E. Evans, and Mary V. Relling, St Jude Children's Research Hospital; Scott C. Howard, University of Memphis, Memphis, TN; Meenakshi Devidas, University of Florida, Gainesville, FL; William L. Carroll, New York University Langone Medical Center, New York, NY; Elizabeth A. Raetz, University of Utah, Salt Lake City, UT; W. Paul Bowman, Cook Children's Hospital, Ft Worth; Naomi J. Winick, University of Texas Southwestern Medical Center, Dallas, TX; Eric C. Larsen, Maine Children's Cancer Program, Scarborough, ME; Kelly W. Maloney, University of Colorado Denver, Aurora, CO; Paul L. Martin, Duke University, Durham, NC; Leonard A. Mattano Jr, HARP Pharma Consulting, Mystic, CT; Elaine R. Mardis and Robert S. Fulton, The McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO; Deepa Bhojwani, Children's Hospital of Los Angeles, Los Angeles; Mignon L. Loh, University of California San Francisco Medical Center-Parnassus, San Francisco, CA; and Stephen P. Hunger, Children's Hospital of Philadelphia, Philadelphia, PA
| | - Eric C Larsen
- Chengcheng Liu, Wenjian Yang, Cheng Cheng, Deqing Pei, Colton Smith, Sima Jeha, Ching-Hon Pui, William E. Evans, and Mary V. Relling, St Jude Children's Research Hospital; Scott C. Howard, University of Memphis, Memphis, TN; Meenakshi Devidas, University of Florida, Gainesville, FL; William L. Carroll, New York University Langone Medical Center, New York, NY; Elizabeth A. Raetz, University of Utah, Salt Lake City, UT; W. Paul Bowman, Cook Children's Hospital, Ft Worth; Naomi J. Winick, University of Texas Southwestern Medical Center, Dallas, TX; Eric C. Larsen, Maine Children's Cancer Program, Scarborough, ME; Kelly W. Maloney, University of Colorado Denver, Aurora, CO; Paul L. Martin, Duke University, Durham, NC; Leonard A. Mattano Jr, HARP Pharma Consulting, Mystic, CT; Elaine R. Mardis and Robert S. Fulton, The McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO; Deepa Bhojwani, Children's Hospital of Los Angeles, Los Angeles; Mignon L. Loh, University of California San Francisco Medical Center-Parnassus, San Francisco, CA; and Stephen P. Hunger, Children's Hospital of Philadelphia, Philadelphia, PA
| | - Kelly W Maloney
- Chengcheng Liu, Wenjian Yang, Cheng Cheng, Deqing Pei, Colton Smith, Sima Jeha, Ching-Hon Pui, William E. Evans, and Mary V. Relling, St Jude Children's Research Hospital; Scott C. Howard, University of Memphis, Memphis, TN; Meenakshi Devidas, University of Florida, Gainesville, FL; William L. Carroll, New York University Langone Medical Center, New York, NY; Elizabeth A. Raetz, University of Utah, Salt Lake City, UT; W. Paul Bowman, Cook Children's Hospital, Ft Worth; Naomi J. Winick, University of Texas Southwestern Medical Center, Dallas, TX; Eric C. Larsen, Maine Children's Cancer Program, Scarborough, ME; Kelly W. Maloney, University of Colorado Denver, Aurora, CO; Paul L. Martin, Duke University, Durham, NC; Leonard A. Mattano Jr, HARP Pharma Consulting, Mystic, CT; Elaine R. Mardis and Robert S. Fulton, The McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO; Deepa Bhojwani, Children's Hospital of Los Angeles, Los Angeles; Mignon L. Loh, University of California San Francisco Medical Center-Parnassus, San Francisco, CA; and Stephen P. Hunger, Children's Hospital of Philadelphia, Philadelphia, PA
| | - Paul L Martin
- Chengcheng Liu, Wenjian Yang, Cheng Cheng, Deqing Pei, Colton Smith, Sima Jeha, Ching-Hon Pui, William E. Evans, and Mary V. Relling, St Jude Children's Research Hospital; Scott C. Howard, University of Memphis, Memphis, TN; Meenakshi Devidas, University of Florida, Gainesville, FL; William L. Carroll, New York University Langone Medical Center, New York, NY; Elizabeth A. Raetz, University of Utah, Salt Lake City, UT; W. Paul Bowman, Cook Children's Hospital, Ft Worth; Naomi J. Winick, University of Texas Southwestern Medical Center, Dallas, TX; Eric C. Larsen, Maine Children's Cancer Program, Scarborough, ME; Kelly W. Maloney, University of Colorado Denver, Aurora, CO; Paul L. Martin, Duke University, Durham, NC; Leonard A. Mattano Jr, HARP Pharma Consulting, Mystic, CT; Elaine R. Mardis and Robert S. Fulton, The McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO; Deepa Bhojwani, Children's Hospital of Los Angeles, Los Angeles; Mignon L. Loh, University of California San Francisco Medical Center-Parnassus, San Francisco, CA; and Stephen P. Hunger, Children's Hospital of Philadelphia, Philadelphia, PA
| | - Leonard A Mattano
- Chengcheng Liu, Wenjian Yang, Cheng Cheng, Deqing Pei, Colton Smith, Sima Jeha, Ching-Hon Pui, William E. Evans, and Mary V. Relling, St Jude Children's Research Hospital; Scott C. Howard, University of Memphis, Memphis, TN; Meenakshi Devidas, University of Florida, Gainesville, FL; William L. Carroll, New York University Langone Medical Center, New York, NY; Elizabeth A. Raetz, University of Utah, Salt Lake City, UT; W. Paul Bowman, Cook Children's Hospital, Ft Worth; Naomi J. Winick, University of Texas Southwestern Medical Center, Dallas, TX; Eric C. Larsen, Maine Children's Cancer Program, Scarborough, ME; Kelly W. Maloney, University of Colorado Denver, Aurora, CO; Paul L. Martin, Duke University, Durham, NC; Leonard A. Mattano Jr, HARP Pharma Consulting, Mystic, CT; Elaine R. Mardis and Robert S. Fulton, The McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO; Deepa Bhojwani, Children's Hospital of Los Angeles, Los Angeles; Mignon L. Loh, University of California San Francisco Medical Center-Parnassus, San Francisco, CA; and Stephen P. Hunger, Children's Hospital of Philadelphia, Philadelphia, PA
| | - Naomi J Winick
- Chengcheng Liu, Wenjian Yang, Cheng Cheng, Deqing Pei, Colton Smith, Sima Jeha, Ching-Hon Pui, William E. Evans, and Mary V. Relling, St Jude Children's Research Hospital; Scott C. Howard, University of Memphis, Memphis, TN; Meenakshi Devidas, University of Florida, Gainesville, FL; William L. Carroll, New York University Langone Medical Center, New York, NY; Elizabeth A. Raetz, University of Utah, Salt Lake City, UT; W. Paul Bowman, Cook Children's Hospital, Ft Worth; Naomi J. Winick, University of Texas Southwestern Medical Center, Dallas, TX; Eric C. Larsen, Maine Children's Cancer Program, Scarborough, ME; Kelly W. Maloney, University of Colorado Denver, Aurora, CO; Paul L. Martin, Duke University, Durham, NC; Leonard A. Mattano Jr, HARP Pharma Consulting, Mystic, CT; Elaine R. Mardis and Robert S. Fulton, The McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO; Deepa Bhojwani, Children's Hospital of Los Angeles, Los Angeles; Mignon L. Loh, University of California San Francisco Medical Center-Parnassus, San Francisco, CA; and Stephen P. Hunger, Children's Hospital of Philadelphia, Philadelphia, PA
| | - Elaine R Mardis
- Chengcheng Liu, Wenjian Yang, Cheng Cheng, Deqing Pei, Colton Smith, Sima Jeha, Ching-Hon Pui, William E. Evans, and Mary V. Relling, St Jude Children's Research Hospital; Scott C. Howard, University of Memphis, Memphis, TN; Meenakshi Devidas, University of Florida, Gainesville, FL; William L. Carroll, New York University Langone Medical Center, New York, NY; Elizabeth A. Raetz, University of Utah, Salt Lake City, UT; W. Paul Bowman, Cook Children's Hospital, Ft Worth; Naomi J. Winick, University of Texas Southwestern Medical Center, Dallas, TX; Eric C. Larsen, Maine Children's Cancer Program, Scarborough, ME; Kelly W. Maloney, University of Colorado Denver, Aurora, CO; Paul L. Martin, Duke University, Durham, NC; Leonard A. Mattano Jr, HARP Pharma Consulting, Mystic, CT; Elaine R. Mardis and Robert S. Fulton, The McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO; Deepa Bhojwani, Children's Hospital of Los Angeles, Los Angeles; Mignon L. Loh, University of California San Francisco Medical Center-Parnassus, San Francisco, CA; and Stephen P. Hunger, Children's Hospital of Philadelphia, Philadelphia, PA
| | - Robert S Fulton
- Chengcheng Liu, Wenjian Yang, Cheng Cheng, Deqing Pei, Colton Smith, Sima Jeha, Ching-Hon Pui, William E. Evans, and Mary V. Relling, St Jude Children's Research Hospital; Scott C. Howard, University of Memphis, Memphis, TN; Meenakshi Devidas, University of Florida, Gainesville, FL; William L. Carroll, New York University Langone Medical Center, New York, NY; Elizabeth A. Raetz, University of Utah, Salt Lake City, UT; W. Paul Bowman, Cook Children's Hospital, Ft Worth; Naomi J. Winick, University of Texas Southwestern Medical Center, Dallas, TX; Eric C. Larsen, Maine Children's Cancer Program, Scarborough, ME; Kelly W. Maloney, University of Colorado Denver, Aurora, CO; Paul L. Martin, Duke University, Durham, NC; Leonard A. Mattano Jr, HARP Pharma Consulting, Mystic, CT; Elaine R. Mardis and Robert S. Fulton, The McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO; Deepa Bhojwani, Children's Hospital of Los Angeles, Los Angeles; Mignon L. Loh, University of California San Francisco Medical Center-Parnassus, San Francisco, CA; and Stephen P. Hunger, Children's Hospital of Philadelphia, Philadelphia, PA
| | - Deepa Bhojwani
- Chengcheng Liu, Wenjian Yang, Cheng Cheng, Deqing Pei, Colton Smith, Sima Jeha, Ching-Hon Pui, William E. Evans, and Mary V. Relling, St Jude Children's Research Hospital; Scott C. Howard, University of Memphis, Memphis, TN; Meenakshi Devidas, University of Florida, Gainesville, FL; William L. Carroll, New York University Langone Medical Center, New York, NY; Elizabeth A. Raetz, University of Utah, Salt Lake City, UT; W. Paul Bowman, Cook Children's Hospital, Ft Worth; Naomi J. Winick, University of Texas Southwestern Medical Center, Dallas, TX; Eric C. Larsen, Maine Children's Cancer Program, Scarborough, ME; Kelly W. Maloney, University of Colorado Denver, Aurora, CO; Paul L. Martin, Duke University, Durham, NC; Leonard A. Mattano Jr, HARP Pharma Consulting, Mystic, CT; Elaine R. Mardis and Robert S. Fulton, The McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO; Deepa Bhojwani, Children's Hospital of Los Angeles, Los Angeles; Mignon L. Loh, University of California San Francisco Medical Center-Parnassus, San Francisco, CA; and Stephen P. Hunger, Children's Hospital of Philadelphia, Philadelphia, PA
| | - Scott C Howard
- Chengcheng Liu, Wenjian Yang, Cheng Cheng, Deqing Pei, Colton Smith, Sima Jeha, Ching-Hon Pui, William E. Evans, and Mary V. Relling, St Jude Children's Research Hospital; Scott C. Howard, University of Memphis, Memphis, TN; Meenakshi Devidas, University of Florida, Gainesville, FL; William L. Carroll, New York University Langone Medical Center, New York, NY; Elizabeth A. Raetz, University of Utah, Salt Lake City, UT; W. Paul Bowman, Cook Children's Hospital, Ft Worth; Naomi J. Winick, University of Texas Southwestern Medical Center, Dallas, TX; Eric C. Larsen, Maine Children's Cancer Program, Scarborough, ME; Kelly W. Maloney, University of Colorado Denver, Aurora, CO; Paul L. Martin, Duke University, Durham, NC; Leonard A. Mattano Jr, HARP Pharma Consulting, Mystic, CT; Elaine R. Mardis and Robert S. Fulton, The McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO; Deepa Bhojwani, Children's Hospital of Los Angeles, Los Angeles; Mignon L. Loh, University of California San Francisco Medical Center-Parnassus, San Francisco, CA; and Stephen P. Hunger, Children's Hospital of Philadelphia, Philadelphia, PA
| | - Sima Jeha
- Chengcheng Liu, Wenjian Yang, Cheng Cheng, Deqing Pei, Colton Smith, Sima Jeha, Ching-Hon Pui, William E. Evans, and Mary V. Relling, St Jude Children's Research Hospital; Scott C. Howard, University of Memphis, Memphis, TN; Meenakshi Devidas, University of Florida, Gainesville, FL; William L. Carroll, New York University Langone Medical Center, New York, NY; Elizabeth A. Raetz, University of Utah, Salt Lake City, UT; W. Paul Bowman, Cook Children's Hospital, Ft Worth; Naomi J. Winick, University of Texas Southwestern Medical Center, Dallas, TX; Eric C. Larsen, Maine Children's Cancer Program, Scarborough, ME; Kelly W. Maloney, University of Colorado Denver, Aurora, CO; Paul L. Martin, Duke University, Durham, NC; Leonard A. Mattano Jr, HARP Pharma Consulting, Mystic, CT; Elaine R. Mardis and Robert S. Fulton, The McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO; Deepa Bhojwani, Children's Hospital of Los Angeles, Los Angeles; Mignon L. Loh, University of California San Francisco Medical Center-Parnassus, San Francisco, CA; and Stephen P. Hunger, Children's Hospital of Philadelphia, Philadelphia, PA
| | - Ching-Hon Pui
- Chengcheng Liu, Wenjian Yang, Cheng Cheng, Deqing Pei, Colton Smith, Sima Jeha, Ching-Hon Pui, William E. Evans, and Mary V. Relling, St Jude Children's Research Hospital; Scott C. Howard, University of Memphis, Memphis, TN; Meenakshi Devidas, University of Florida, Gainesville, FL; William L. Carroll, New York University Langone Medical Center, New York, NY; Elizabeth A. Raetz, University of Utah, Salt Lake City, UT; W. Paul Bowman, Cook Children's Hospital, Ft Worth; Naomi J. Winick, University of Texas Southwestern Medical Center, Dallas, TX; Eric C. Larsen, Maine Children's Cancer Program, Scarborough, ME; Kelly W. Maloney, University of Colorado Denver, Aurora, CO; Paul L. Martin, Duke University, Durham, NC; Leonard A. Mattano Jr, HARP Pharma Consulting, Mystic, CT; Elaine R. Mardis and Robert S. Fulton, The McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO; Deepa Bhojwani, Children's Hospital of Los Angeles, Los Angeles; Mignon L. Loh, University of California San Francisco Medical Center-Parnassus, San Francisco, CA; and Stephen P. Hunger, Children's Hospital of Philadelphia, Philadelphia, PA
| | - Stephen P Hunger
- Chengcheng Liu, Wenjian Yang, Cheng Cheng, Deqing Pei, Colton Smith, Sima Jeha, Ching-Hon Pui, William E. Evans, and Mary V. Relling, St Jude Children's Research Hospital; Scott C. Howard, University of Memphis, Memphis, TN; Meenakshi Devidas, University of Florida, Gainesville, FL; William L. Carroll, New York University Langone Medical Center, New York, NY; Elizabeth A. Raetz, University of Utah, Salt Lake City, UT; W. Paul Bowman, Cook Children's Hospital, Ft Worth; Naomi J. Winick, University of Texas Southwestern Medical Center, Dallas, TX; Eric C. Larsen, Maine Children's Cancer Program, Scarborough, ME; Kelly W. Maloney, University of Colorado Denver, Aurora, CO; Paul L. Martin, Duke University, Durham, NC; Leonard A. Mattano Jr, HARP Pharma Consulting, Mystic, CT; Elaine R. Mardis and Robert S. Fulton, The McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO; Deepa Bhojwani, Children's Hospital of Los Angeles, Los Angeles; Mignon L. Loh, University of California San Francisco Medical Center-Parnassus, San Francisco, CA; and Stephen P. Hunger, Children's Hospital of Philadelphia, Philadelphia, PA
| | - William E Evans
- Chengcheng Liu, Wenjian Yang, Cheng Cheng, Deqing Pei, Colton Smith, Sima Jeha, Ching-Hon Pui, William E. Evans, and Mary V. Relling, St Jude Children's Research Hospital; Scott C. Howard, University of Memphis, Memphis, TN; Meenakshi Devidas, University of Florida, Gainesville, FL; William L. Carroll, New York University Langone Medical Center, New York, NY; Elizabeth A. Raetz, University of Utah, Salt Lake City, UT; W. Paul Bowman, Cook Children's Hospital, Ft Worth; Naomi J. Winick, University of Texas Southwestern Medical Center, Dallas, TX; Eric C. Larsen, Maine Children's Cancer Program, Scarborough, ME; Kelly W. Maloney, University of Colorado Denver, Aurora, CO; Paul L. Martin, Duke University, Durham, NC; Leonard A. Mattano Jr, HARP Pharma Consulting, Mystic, CT; Elaine R. Mardis and Robert S. Fulton, The McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO; Deepa Bhojwani, Children's Hospital of Los Angeles, Los Angeles; Mignon L. Loh, University of California San Francisco Medical Center-Parnassus, San Francisco, CA; and Stephen P. Hunger, Children's Hospital of Philadelphia, Philadelphia, PA
| | - Mignon L Loh
- Chengcheng Liu, Wenjian Yang, Cheng Cheng, Deqing Pei, Colton Smith, Sima Jeha, Ching-Hon Pui, William E. Evans, and Mary V. Relling, St Jude Children's Research Hospital; Scott C. Howard, University of Memphis, Memphis, TN; Meenakshi Devidas, University of Florida, Gainesville, FL; William L. Carroll, New York University Langone Medical Center, New York, NY; Elizabeth A. Raetz, University of Utah, Salt Lake City, UT; W. Paul Bowman, Cook Children's Hospital, Ft Worth; Naomi J. Winick, University of Texas Southwestern Medical Center, Dallas, TX; Eric C. Larsen, Maine Children's Cancer Program, Scarborough, ME; Kelly W. Maloney, University of Colorado Denver, Aurora, CO; Paul L. Martin, Duke University, Durham, NC; Leonard A. Mattano Jr, HARP Pharma Consulting, Mystic, CT; Elaine R. Mardis and Robert S. Fulton, The McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO; Deepa Bhojwani, Children's Hospital of Los Angeles, Los Angeles; Mignon L. Loh, University of California San Francisco Medical Center-Parnassus, San Francisco, CA; and Stephen P. Hunger, Children's Hospital of Philadelphia, Philadelphia, PA
| | - Mary V Relling
- Chengcheng Liu, Wenjian Yang, Cheng Cheng, Deqing Pei, Colton Smith, Sima Jeha, Ching-Hon Pui, William E. Evans, and Mary V. Relling, St Jude Children's Research Hospital; Scott C. Howard, University of Memphis, Memphis, TN; Meenakshi Devidas, University of Florida, Gainesville, FL; William L. Carroll, New York University Langone Medical Center, New York, NY; Elizabeth A. Raetz, University of Utah, Salt Lake City, UT; W. Paul Bowman, Cook Children's Hospital, Ft Worth; Naomi J. Winick, University of Texas Southwestern Medical Center, Dallas, TX; Eric C. Larsen, Maine Children's Cancer Program, Scarborough, ME; Kelly W. Maloney, University of Colorado Denver, Aurora, CO; Paul L. Martin, Duke University, Durham, NC; Leonard A. Mattano Jr, HARP Pharma Consulting, Mystic, CT; Elaine R. Mardis and Robert S. Fulton, The McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO; Deepa Bhojwani, Children's Hospital of Los Angeles, Los Angeles; Mignon L. Loh, University of California San Francisco Medical Center-Parnassus, San Francisco, CA; and Stephen P. Hunger, Children's Hospital of Philadelphia, Philadelphia, PA.
| |
Collapse
|
|
25
|
A prospective cohort study on the association between coffee drinking and risk of non-gallstone-related acute pancreatitis. Br J Nutr 2016; 115:1830-4. [PMID: 26987519 DOI: 10.1017/s0007114516000866] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Only one previous study has examined the association between coffee consumption and risk of acute pancreatitis, and it found a reduced risk for alcohol-related episodes among high consumers of coffee. Therefore, we examined (1) the association between coffee consumption and risk of non-gallstone-related acute pancreatitis and (2) whether this association was modified by alcohol intake. Data were obtained from two prospective cohorts, the Cohort of Swedish Men and the Swedish Mammography Cohort, including 76 731 men and women (born 1914-1952). Coffee consumption was assessed at baseline with a FFQ, and the cohorts were followed up between 1998 and 2012 via linkage to national health registries. Hazard ratios were estimated using Cox models, with adjustment for potential confounding factors. During 1 035 881 person-years of total follow-up, 383 cases (246 in men and 137 in women) of incident non-gallstone-related acute pancreatitis were identified. Overall, and irrespective of whether a categorical or a continuous exposure model was used, we observed no association between coffee consumption and risk of non-gallstone-related acute pancreatitis (e.g. the multivariable-adjusted hazard ratio for each 1 cup/d increase in coffee consumption was 0·97; 95 % CI 0·92, 1·03). There was no evidence of effect modification by alcohol intake (P interaction=0·77). In conclusion, coffee consumption was not associated with risk of non-gallstone-related acute pancreatitis in this large prospective cohort study. Because of the limited number of epidemiological studies and their conflicting results, further research is needed to elucidate this potential association.
Collapse
|
|
26
|
Abstract
Acute pancreatitis, an inflammatory disorder of the pancreas, is the leading cause of admission to hospital for gastrointestinal disorders in the USA and many other countries. Gallstones and alcohol misuse are long-established risk factors, but several new causes have emerged that, together with new aspects of pathophysiology, improve understanding of the disorder. As incidence (and admission rates) of acute pancreatitis increase, so does the demand for effective management. We review how to manage patients with acute pancreatitis, paying attention to diagnosis, differential diagnosis, complications, prognostic factors, treatment, and prevention of second attacks, and the possible transition from acute to chronic pancreatitis.
Collapse
Affiliation(s)
- Paul Georg Lankisch
- Department of General Internal Medicine and Gastroenterology, Clinical Centre of Lüneburg, Lüneburg, Germany.
| | - Minoti Apte
- Pancreatic Research Group, South Western Sydney Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia; Ingham Institute for Applied Medical Research, Liverpool Hospital, Liverpool, NSW, Australia
| | - Peter A Banks
- Division of Gastroenterology, Hepatology, and Endoscopy, Harvard Medical School, and Brigham and Women's Hospital, Boston, MA, USA
| |
Collapse
|
|
27
|
Zhou P, Chang L, Zhang XH, Chen YD, Feng XL, Deng L, Wang JD. Correlation between expression of 1 α -hydroxylase and hypocalcaemia in rats with severe pancreatitis. ASIAN PAC J TROP MED 2015; 8:386-91. [PMID: 26003599 DOI: 10.1016/s1995-7645(14)60349-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022] Open
Abstract
OBJECTIVE To investigate the essential biochemical indices like 1 -hydroxylase and hypocalcaemia in the rats with severe acute pancreatitis and explore the correlation between them. METHODS A total of 120 SPF grade Wistar male rats which were in similar physiological status were selected and randomly divided into two groups: sham group (SO group) and severe acute pancreatitis group (SAP group). Then they were divided into 1 h, 3 h, 6 h, and 12 h subgroups according to the killing time. The severe acute pancreatitis model was established by retrograde injection of 5% sodium taurocholate. Serum calcium, serum creatinine, serum urea nitrogen and serum amylase were measured at different time. Serum 1, 25 dihydroxy vitamin D3 level was determined by enzyme linked immunosorbentassay. The expression of 1-hydroxylase protein in the kidney tissue was determined with Western blotting and immunohistochemistry to observe its location. The pathologic features of the kidney tissue section was observed under light microscope and submicroscopic structure of the proximal convoluted tubule epithelial cell was observed under transmission electron microscope. RESULTS Compared with the SO group, rats in the SAP group showed continuous pathological injury as time went by. There was significant increase in serum creatinine, serum urea nitrogen and serum amylase in SAP group compared with the SO group 1, 3, 6, 12 hours after the operation (P<0.05). There was significant decrease in serum calcium and 1, 25 dihydroxy vitamin D3 3, 6, 12 hours after the operation (P<0.05). It also showed that the expression of the 1-hydroxylase protein in kidney tissues was upregulated at 1 h, 3 h and decreased at 6 h, 12 h compared with the SO group. The serum calcium, 1, 25 dihydroxy vitamin D3 and the expression of the 1-hydroxylase protein in kidney tissues of the SAP group showed sustaining decrease. Western blotting showed positive correlation between the 1-hydroxylase expression and serum calcium at 3 h, 6 h and 12 h (r=0.976, P<0.001; r=0.948, P<0.001; r=0.742, P=0.001) and also positive correlation between the 1-hydroxylase expression and serum 1, 25 dihydroxy vitamin D3 at 1 h, 3 h, 6 h and 12 h (r=0.935, P<0.001; r=0.952, P<0.001; r=0.917, P<0.001; r=0.874, P<0.001). CONCLUSIONS At the early stage of the kidney injury, the expression of 1-hydroxylase in the kidney tissue is reduced with the progress of the disease and the decrease in its activity has a correlation with the hypocalcaemia.
Collapse
Affiliation(s)
- Ping Zhou
- Academy of Medical Sciences in Sichuan Province; ICU Department, Sichuan Province People's Hospital, Chengdu 610072, China
| | - Li Chang
- Academy of Medical Sciences in Sichuan Province; ICU Department, Sichuan Province People's Hospital, Chengdu 610072, China
| | - Xiao-Hong Zhang
- Academy of Medical Sciences in Sichuan Province; ICU Department, Sichuan Province People's Hospital, Chengdu 610072, China
| | - You-Dai Chen
- Academy of Medical Sciences in Sichuan Province; ICU Department, Sichuan Province People's Hospital, Chengdu 610072, China
| | - Xuan-Lin Feng
- Academy of Medical Sciences in Sichuan Province; ICU Department, Sichuan Province People's Hospital, Chengdu 610072, China
| | - Lei Deng
- Academy of Medical Sciences in Sichuan Province; ICU Department, Sichuan Province People's Hospital, Chengdu 610072, China
| | - Jian-Dong Wang
- Academy of Medical Sciences in Sichuan Province; ICU Department, Sichuan Province People's Hospital, Chengdu 610072, China.
| |
Collapse
|
|
28
|
Sun X, Huang X, Zhao R, Chen B, Xie Q. Meta-analysis: Tobacco smoking may enhance the risk of acute pancreatitis. Pancreatology 2015; 15:286-94. [PMID: 25804129 DOI: 10.1016/j.pan.2015.03.001] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2014] [Revised: 02/13/2015] [Accepted: 03/02/2015] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIM Questions remain unclear about the association of smoking status and the development of acute pancreatitis (AP). We performed a meta-analysis of observational studies explore this association. METHODS A computerized literature search was performed in MEDLINE and EMBASE through November 30, 2014. We also searched the reference lists of pertinent articles. We used a random-effects model to calculate the summary relative risks (SRRs) and their corresponding 95% confidence intervals (CIs). RESULTS A total of 3690 incident cases of AP included 12 observational studies (6 case-control and 6 prospective cohort/nested case-control studies) were identified. Compared with never smokers, the summary RR estimates were 1.54 (95% CI, 1.31-1.80) for ever smokers, 1.71 (95% CI, 1.37-2.14) for current smokers, and 1.21 (95% CI, 1.02-1.43) for former smokers. Smoking is found to be a potential risk factor for alcohol use, idiopathic factors and drugs related AP, but not for gallstone related AP, in the ever and current smokers. A dose-response effect of tobacco use on the risk was ascertained: current smokers had a 40% (95% CI, 30%-51%) increased risk of AP for every additional 10 cigarettes per day. CONCLUSION The present analysis suggests that smokers have an elevated risk of AP development. Further studies, however, are warranted before definitive conclusions can be drawn.
Collapse
Affiliation(s)
- Xiaobing Sun
- Department of Internal Medicine, The Second People's Hospital of Nantong, Nantong, Jiangsu 226002, China.
| | - Xiaoquan Huang
- Department of Internal Medicine, The Second People's Hospital of Nantong, Nantong, Jiangsu 226002, China
| | - Ruifeng Zhao
- Department of Internal Medicine, The Second People's Hospital of Nantong, Nantong, Jiangsu 226002, China
| | - Beibei Chen
- Department of Internal Medicine, The Second People's Hospital of Nantong, Nantong, Jiangsu 226002, China
| | - Qin Xie
- Department of Internal Medicine, The Second People's Hospital of Nantong, Nantong, Jiangsu 226002, China
| |
Collapse
|
|
29
|
Di Ciaula A, Portincasa P. Fat, epigenome and pancreatic diseases. Interplay and common pathways from a toxic and obesogenic environment. Eur J Intern Med 2014; 25:865-73. [PMID: 25457435 DOI: 10.1016/j.ejim.2014.10.012] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2014] [Revised: 10/08/2014] [Accepted: 10/10/2014] [Indexed: 02/07/2023]
Abstract
The worldwide obesity epidemic is paralleled by a rise in the incidence of pancreatic disorders ranging from "fatty" pancreas to pancreatitis and cancer. Body fat accumulation and pancreatic dysfunctions have common pathways, mainly acting through insulin resistance and low-grade inflammation, frequently mediated by the epigenome. These mechanisms are affected by lifestyle and by the toxic effects of fat and pollutants. An early origin is common, starting in pediatric age or during the fetal life in response to nutritional factors, endocrine disruptor chemicals (EDCs) or parental exposure to toxics. A "fatty pancreas" is frequent in obese and is able to induce pancreatic damage. The fat is a target of EDCs and of the cytotoxic/mutagenic effects of heavy metals, and is the site of bioaccumulation of lipophilic and persistent pollutants related with insulin resistance and able to promote pancreatic cancer. Increased Body Mass Index (BMI) can act as independent risk factor for a more severe course of acute pancreatitis and obesity is also a well-known risk factor for pancreatic cancer, that is related with BMI, insulin resistance, and duration of exposure to the toxic effects of fat and/or of environmental pollutants. All these mechanisms involve gene-environment interactions through epigenetic factors, and might be manipulated by primary prevention measures. Further studies are needed, pointing to better assess the interplays of modifiable factors on both obesity and pancreatic diseases, and to verify the efficacy of primary prevention strategies involving lifestyle and environmental exposure to toxics.
Collapse
Affiliation(s)
| | - Piero Portincasa
- Department of Biomedical Sciences and Human Oncology, Clinica Medica "A. Murri", University of Bari Medical School, Bari, Italy.
| |
Collapse
|
|
30
|
Li J, Zhou R, Zhang J, Li ZF. Calcium signaling of pancreatic acinar cells in the pathogenesis of pancreatitis. World J Gastroenterol 2014; 20:16146-16152. [PMID: 25473167 PMCID: PMC4239501 DOI: 10.3748/wjg.v20.i43.16146] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2014] [Revised: 06/09/2014] [Accepted: 07/11/2014] [Indexed: 02/07/2023] Open
Abstract
Pancreatitis is an increasingly common and sometimes severe disease that lacks a specific therapy. The pathogenesis of pancreatitis is still not well understood. Calcium (Ca2+) is a versatile carrier of signals regulating many aspects of cellular activity and plays a central role in controlling digestive enzyme secretion in pancreatic acinar cells. Ca2+ overload is a key early event and is crucial in the pathogenesis of many diseases. In pancreatic acinar cells, pathological Ca2+ signaling (stimulated by bile, alcohol metabolites and other causes) is a key contributor to the initiation of cell injury due to prolonged and global Ca2+ elevation that results in trypsin activation, vacuolization and necrosis, all of which are crucial in the development of pancreatitis. Increased release of Ca2+ from stores in the intracellular endoplasmic reticulum and/or increased Ca2+ entry through the plasma membrane are causes of such cell damage. Failed mitochondrial adenosine triphosphate (ATP) production reduces re-uptake and extrusion of Ca2+ by the sarco/endoplasmic reticulum Ca2+-activated ATPase and plasma membrane Ca2+-ATPase pumps, which contribute to Ca2+ overload. Current findings have provided further insight into the roles and mechanisms of abnormal pancreatic acinar Ca2+ signals in pancreatitis. The lack of available specific treatments is therefore an objective of ongoing research. Research is currently underway to establish the mechanisms and interactions of Ca2+ signals in the pathogenesis of pancreatitis.
Collapse
|
|
31
|
Hung WY, Abreu Lanfranco O. Contemporary review of drug-induced pancreatitis: A different perspective. World J Gastrointest Pathophysiol 2014; 5:405-415. [PMID: 25400984 PMCID: PMC4231505 DOI: 10.4291/wjgp.v5.i4.405] [Citation(s) in RCA: 70] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2014] [Revised: 06/17/2014] [Accepted: 07/29/2014] [Indexed: 02/06/2023] Open
Abstract
Although gallstone and alcohol use have been considered the most common causes of acute pancreatitis, hundreds of frequently prescribed medications are associated with this disease state. The true incidence is unknown since there are few population based studies available. The knowledge of drug induced acute pancreatitis is limited by the availability and the quality of the evidence as the majority of data is extrapolated from case reports. Establishing a definitive causal relationship between a drug and acute pancreatitis poses a challenge to clinicians. Several causative agent classification systems are often used to identify the suspected agents. They require regular updates since new drug induced acute pancreatitis cases are reported continuously. In addition, infrequently prescribed medications and herbal medications are often omitted. Furthermore, identification of drug induced acute pancreatitis with new medications often requires accumulation of post market case reports. The unrealistic expectation for a comprehensive list of medications and the multifactorial nature of acute pancreatitis call for a different approach. In this article, we review the potential mechanisms of drug induced acute pancreatitis and provide the perspective of deductive reasoning in order to allow clinicians to identify potential drug induced acute pancreatitis with limited data.
Collapse
|
|
32
|
An F, Zhan Q, Xia M, Jiang L, Lu G, Huang M, Guo J, Liu S. From moderately severe to severe hypertriglyceridemia induced acute pancreatitis: circulating miRNAs play role as potential biomarkers. PLoS One 2014; 9:e111058. [PMID: 25365448 PMCID: PMC4218837 DOI: 10.1371/journal.pone.0111058] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2014] [Accepted: 09/18/2014] [Indexed: 12/27/2022] Open
Abstract
The incidence of hypertriglyceridemia induced acute pancreatitis (HTAP) continues to rise in China. It has systemic complications and high mortality, making the early assessment of the severity of this disease even more important. Circulating microRNAs (miRNAs) could be novel, non-invasive biomarkers for disease progression judgment. This study aimed to identify the potential role of serum miRNAs as novel biomarkers of HTAP progression. HTAP patients were divided into two groups: moderately severe (HTMSAP) and severe (HTSAP), healthy people were used as control group. The serum miRNA expression profiles of these three groups were determined by microarray and verified by qRT-PCR. The functions and pathways of the targeted genes of deregulated miRNAs were predicted, using bioinformatics analysis; miRNA-mRNA network was generated. Moreover, the correlation between miR-181a-5p and pancreatitis metabolism related substances were studied and the serum concentration of inflammatory cytokines and miRNAs at different time points during the MSAP and SAP were investigated, respectively. Finally, the receiver operating characteristic (ROC) curve of miRNAs was studied. Significant changes in the serum concentration of the following miRNAs of HTAP patients (P<0.05) were discovered: miR24-3p, 361-5p, 1246, and 222-3p (constantly upregulated), and 181a-5p (constantly downregulated) (P<0.05). Bioinformatics analysis predicted that 13 GOs and 36 pathways regulated by overlap miRNAs were involved in glucose, fat, calcium (Ca++), and insulin metabolism (P<0.001). miRNA-mRNA network revealed that the overlap miRNAs targeted genes participating in pancreas metabolism and miR-181a-5p, the only downregulated miRNA, had good negative correlation with triglyceride (TG), total cholesterol (TC), and fast blood glucose (FBG), but a positive correlation with Ca++. When compared with inflammatory cytokines, the changes of all five overlap miRNAs were more stable. It was found that when used for evaluating the progression of HTAP, miRNAs showed good AUC. These data suggested that serum miRNAs have the potential to be excellent HTAP biomarkers.
Collapse
Affiliation(s)
- Fangmei An
- Department of Gastroenterology, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu, China
- * E-mail: (FA); (SL)
| | - Qiang Zhan
- Department of Gastroenterology, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu, China
- Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Min Xia
- Department of Gastroenterology, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu, China
| | - Lisha Jiang
- Department of Gastroenterology, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu, China
| | - Guoming Lu
- Department of Gastroenterology, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu, China
| | - Mindan Huang
- Department of Gastroenterology, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu, China
| | - Jizhong Guo
- Department of Gastroenterology, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu, China
| | - Side Liu
- Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
- * E-mail: (FA); (SL)
| |
Collapse
|
|
33
|
Kang R, Lotze MT, Zeh HJ, Billiar TR, Tang D. Cell death and DAMPs in acute pancreatitis. Mol Med 2014; 20:466-77. [PMID: 25105302 PMCID: PMC4277549 DOI: 10.2119/molmed.2014.00117] [Citation(s) in RCA: 110] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2014] [Accepted: 08/04/2014] [Indexed: 12/18/2022] Open
Abstract
Cell death and inflammation are key pathologic responses of acute pancreatitis (AP), the leading cause of hospital admissions for gastrointestinal disorders. It is becoming increasingly clear that damage-associated molecular pattern molecules (DAMPs) play an important role in the pathogenesis of AP by linking local tissue damage to systemic inflammation syndrome. Endogenous DAMPs released from dead, dying or injured cells initiate and extend sterile inflammation via specific pattern recognition receptors. Inhibition of the release and activity of DAMPs (for example, high mobility group box 1, DNA, histones and adenosine triphosphate) provides significant protection against experimental AP. Moreover, increased serum levels of DAMPs in patients with AP correlate with disease severity. These findings provide novel insight into the mechanism, diagnosis and management of AP. DAMPs might be an attractive therapeutic target in AP.
Collapse
Affiliation(s)
- Rui Kang
- Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America
| | - Michael T Lotze
- Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America
| | - Herbert J Zeh
- Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America
| | - Timothy R Billiar
- Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America
| | - Daolin Tang
- Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America
| |
Collapse
|
|
34
|
Inman KS, Francis AA, Murray NR. Complex role for the immune system in initiation and progression of pancreatic cancer. World J Gastroenterol 2014; 20:11160-11181. [PMID: 25170202 PMCID: PMC4145756 DOI: 10.3748/wjg.v20.i32.11160] [Citation(s) in RCA: 107] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2013] [Revised: 01/27/2014] [Accepted: 04/16/2014] [Indexed: 02/06/2023] Open
Abstract
The immune system plays a complex role in the development and progression of pancreatic cancer. Inflammation can promote the formation of premalignant lesions and accelerate pancreatic cancer development. Conversely, pancreatic cancer is characterized by an immunosuppressive environment, which is thought to promote tumor progression and invasion. Here we review the current literature describing the role of the immune response in the progressive development of pancreatic cancer, with a focus on the mechanisms that drive recruitment and activation of immune cells at the tumor site, and our current understanding of the function of the immune cell types at the tumor. Recent clinical and preclinical data are reviewed, detailing the involvement of the immune response in pancreatitis and pancreatic cancer, including the role of specific cytokines and implications for disease outcome. Acute pancreatitis is characterized by a predominantly innate immune response, while chronic pancreatitis elicits an immune response that involves both innate and adaptive immune cells, and often results in profound systemic immune-suppression. Pancreatic adenocarcinoma is characterized by marked immune dysfunction driven by immunosuppressive cell types, tumor-promoting immune cells, and defective or absent inflammatory cells. Recent studies reveal that immune cells interact with cancer stem cells and tumor stromal cells, and these interactions have an impact on development and progression of pancreatic ductal adenocarcinoma (PDAC). Finally, current PDAC therapies are reviewed and the potential for harnessing the actions of the immune response to assist in targeting pancreatic cancer using immunotherapy is discussed.
Collapse
|
|
35
|
Association of admission serum calcium levels and in-hospital mortality in patients with acute ST-elevated myocardial infarction: an eight-year, single-center study in China. PLoS One 2014; 9:e99895. [PMID: 24926660 PMCID: PMC4057419 DOI: 10.1371/journal.pone.0099895] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2014] [Accepted: 05/19/2014] [Indexed: 01/23/2023] Open
Abstract
OBJECTIVE The relationship between admission serum calcium levels and in-hospital mortality in patients with acute ST-segment elevation myocardial infarction (STEMI) has not been well definitively explored. The objective was to assess the predictive value of serum calcium levels on in-hospital mortality in STEMI patients. METHODS From 2003 to 2010, 1431 consecutive STEMI patients admitted to the First Affiliated Hospital of Nanjing Medical University were enrolled in the present study. Patients were stratified according to quartiles of serum calcium from the blood samples collected in the emergency room after admission. Between the aforementioned groups,the baseline characteristics, in-hospital management, and in-hospital mortality were analyzed. The association of serum calcium level with in-hospital mortality was calculated by a multivariable Cox regression analysis. RESULTS Among 1431 included patients, 79% were male and the median age was 65 years (range, 55-74). Patients in the lower quartiles of serum calcium, as compared to the upper quartiles of serum calcium, were older, had more cardiovascular risk factors, lower rate of emergency revascularization,and higher in-hospital mortality. According to univariate Cox proportional analysis, patients with lower serum calcium level (hazard ratio 0.267, 95% confidence interval 0.164-0.433, p<0.001) was associated with higher in-hospital mortality. The result of multivariable Cox proportional hazard regression analyses showed that the Killip's class≥3 (HR = 2.192, p = 0.026), aspartate aminotransferase (HR = 1.001, p<0.001), neutrophil count (HR = 1.123, p<0.001), serum calcium level (HR = 0.255, p = 0.001), and emergency revascularization (HR = 0.122, p<0.001) were significantly and independently associated with in-hospital mortality in STEMI patients. CONCLUSIONS Serum calcium was an independent predictor for in-hospital mortality in patients with STEMI. This widely available serum biochemical index may be incorporated into the current established risk stratification model of STEMI patients. Further studies are required to determine the actual mechanism and whether patients with hypocalcaemia could benefit from calcium supplement.
Collapse
|
|
36
|
Kim MY, Chung CY, Kim JS, Myung DS, Cho SB, Park CH, Kim Y, Joo YE. Parathyroid cyst presenting as acute pancreatitis: report of a case. Chonnam Med J 2014; 49:125-8. [PMID: 24400215 PMCID: PMC3881208 DOI: 10.4068/cmj.2013.49.3.125] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2013] [Revised: 05/24/2013] [Accepted: 06/07/2013] [Indexed: 12/27/2022] Open
Abstract
We report the first case of hypercalcemia-induced acute pancreatitis caused by a functioning parathyroid cyst in a 67-year-old man. Laboratory investigation revealed increased serum amylase and lipase, increased serum ionized calcium and parathyroid hormone (PTH) levels, and decreased serum phosphate, indicating pancreatitis and primary hyperparathyroidism (PHPT). Abdominal computed tomography (CT) revealed mild swelling of the pancreatic head with peri-pancreatic fat infiltration and fluid collection around the pancreatic tail. Ultrasonography and CT of the neck showed a cystic lesion at the inferior portion of the left thyroid gland, suggesting a parathyroid cyst. There was no evidence of parathyroid adenoma by 99mTc sestamibi scintigraphy. PHPT caused by a functioning parathyroid cyst was suspected. The patient underwent surgical resection of the functioning parathyroid cyst owing to his prolonged hypercalcemia. At 3 weeks after the operation, his serum levels of PTH, total calcium, ionized calcium, inorganic phosphate, amylase, and lipase were normalized. At the follow-up examinations, he has remained asymptomatic.
Collapse
Affiliation(s)
- Mi-Young Kim
- Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea
| | - Cho-Yun Chung
- Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea
| | - Jong-Sun Kim
- Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea
| | - Dae-Seong Myung
- Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea
| | - Sung-Bum Cho
- Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea
| | - Chang-Hwan Park
- Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea
| | - Young Kim
- Department of Pathology, Chonnam National University Medical School, Gwangju, Korea
| | - Young-Eun Joo
- Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea
| |
Collapse
|
|
37
|
Weber H, Jonas L, Wakileh M, Krüger B. Beneficial effect of the bioflavonoid quercetin on cholecystokinin-induced mitochondrial dysfunction in isolated rat pancreatic acinar cells. Can J Physiol Pharmacol 2013; 92:215-25. [PMID: 24593786 DOI: 10.1139/cjpp-2013-0112] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
The pathogenesis of acute pancreatitis (AP) is still poorly understood. Thus, a reliable pharmacological therapy is currently lacking. In recent years, an impairment of the energy metabolism of pancreatic acinar cells, caused by Ca(2+)-mediated depolarization of the inner mitochondrial membrane and a decreased ATP supply, has been implicated as an important pathological event. In this study, we investigated whether quercetin exerts protection against mitochondrial dysfunction. Following treatment with or without quercetin, rat pancreatic acinar cells were stimulated with supramaximal cholecystokinin-8 (CCK). CCK caused a decrease in the mitochondrial membrane potential (MMP) and ATP concentration, whereas the mitochondrial dehydrogenase activity was significantly increased. Quercetin treatment before CCK application exerted no protection on MMP but increased ATP to a normal level, leading to a continuous decrease in the dehydrogenase activity. The protective effect of quercetin on mitochondrial function was accompanied by a reduction in CCK-induced changes to the cell membrane. Concerning the molecular mechanism underlying the protective effect of quercetin, an increased AMP/ATP ratio suggests that the AMP-activated protein kinase system may be activated. In addition, quercetin strongly inhibited CCK-induced trypsin activity. The results indicate that the use of quercetin may be a therapeutic strategy for reducing the severity of AP.
Collapse
Affiliation(s)
- Heike Weber
- a Institute of Clinical Chemistry and Laboratory Medicine, University of Rostock, Ernst-Heydemann-Straße 6, 18057 Rostock, Germany
| | | | | | | |
Collapse
|
|
38
|
Wu L, Cai B, Liu X, Cai H. Emodin attenuates calcium overload and endoplasmic reticulum stress in AR42J rat pancreatic acinar cells. Mol Med Rep 2013; 9:267-72. [PMID: 24190079 DOI: 10.3892/mmr.2013.1773] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2013] [Accepted: 10/25/2013] [Indexed: 01/13/2023] Open
Abstract
The aim of the present study was to investigate the protective effects of emodin against calcium overload and endoplasmic reticulum (ER) stress in an acute pancreatitis model in vitro. AR42J rat pancreatic acinar cells treated with cerulein (10(‑7) M) and lipoplysaccharide (LPS; 10 mg/l) were used to mimic acute pancreatitis in vitro. The amylase activity in cellular lysates and culture media was detected by spectrophotometry. The level of cytosolic calcium was measured by laser confocal microscopy. Cell apoptosis and necrosis were examined by flow cytometry. Reverse transcription‑polymerase chain reaction was used to determine the mRNA expression of ER chaperone immunoglobulin‑binding protein (Bip) and downstream molecules, including protein kinase‑like ER kinase (PERK), activation transcription factor 6 (ATF6) and inositol‑requiring protein 1 (IRE1). The results showed that emodin significantly reduced the expression and release of amylase, attenuated calcium overload and decreased the mRNA expression of Bip, PERK, ATF6 and IRE1 which was significantly elevated in AR42J cells treated with cerulein and LPS. Emodin also reduced cell apoptosis and necrosis. Therefore, the results of the present study indicate that emodin protects against AR42J cell injury caused by cerulein and LPS. These effects may be associated with reduced calcium overload and inhibited ER stress responses.
Collapse
Affiliation(s)
- Li Wu
- National First-Class Key Discipline for Science of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, P.R. China
| | | | | | | |
Collapse
|
|
39
|
Ma B, Wu L, Lu M, Gao B, Qiao X, Sun B, Xue D, Zhang W. Differentially expressed kinase genes associated with trypsinogen activation in rat pancreatic acinar cells treated with taurolithocholic acid 3-sulfate. Mol Med Rep 2013; 7:1591-6. [PMID: 23467886 DOI: 10.3892/mmr.2013.1355] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2012] [Accepted: 02/27/2013] [Indexed: 11/05/2022] Open
Abstract
Trypsinogen activation is the initial factor involved in the development of all types of acute pancreatitis (AP) and has been suggested to be regulated by protein kinases. In the present study, AR42J rat pancreatic acinar cells were treated with taurolithocholic acid 3-sulfate (TLC-S), and trypsinogen activation was detected with bis-(CBZ-L-isoleucyl-L-prolyl-L-arginine amide) dihydrochloride (BZiPAR) staining and flow cytometry. Differentially expressed protein kinase genes were screened by Gene Chip analysis, and the functions of these kinases were analyzed. A significantly increased activation of trypsinogen in AR42J cells following treatment with TLC-S was observed. A total of 22 differentially expressed protein kinase genes were found in the TLC-S group, among which 19 genes were upregulated and 3 were downregulated. Based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, kinase genes of the same KEGG pathways were connected to create a network through signaling pathways, and 10 nodes of kinases were identified, which were mitogen-activated protein kinase (Mapk)8, Mapk14, Map2k4, interleukin-1 receptor-associated kinase 3 (Irak3), ribosomal protein S6 kinase, 90 kDa, polypeptide 2 (Rps6ka2), protein kinase C, alpha (Prkca), v-yes-1 Yamaguchi sarcoma viral related oncogene homolog (Lyn), protein tyrosine kinase 2 beta (Ptk2b), p21 protein (Cdc42/Rac)-activated kinase 4 (Pak4) and FYN oncogene related to SRC, FGR, YES (Fyn). The interactions between signaling pathways were further analyzed and a network was created. MAPK and calcium signaling pathways were found to be located at the center of the network. Thus, protein kinases constitute potential drug targets for AP treatment.
Collapse
Affiliation(s)
- Biao Ma
- Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, PR China
| | | | | | | | | | | | | | | |
Collapse
|