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Zhao B, Sun W, Wang Y, Ma L, Gui M, Li J, Yu X, Qi X, Ning N, Sun S, Li M, Yao Y, Ni T, He J, Yang Z, Chen Y, Sheng H, Shen M, Li J, Huang J, Mao E. High-dose intravenous vitamin C reduce C-reactive protein levels, fluid retention, and APACHE II scores in patients with moderately severe acute pancreatitis: a prospective, randomized, double-blinded, placebo-controlled study. Ann Intensive Care 2025; 15:30. [PMID: 40091112 PMCID: PMC11911288 DOI: 10.1186/s13613-025-01437-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2024] [Accepted: 01/13/2025] [Indexed: 03/19/2025] Open
Abstract
BACKGROUND The aim of this study was to investigate whether high-dose intravenous vitamin C (HDIVC) could decrease the mortality rate within 28 days among patients moderately severe acute pancreatitis (MSAP) and severe acute pancreatitis (SAP). METHODS In this randomized, placebo-controlled trial, patients diagnosed with predicted MSAP or SAP within 72 h of symptom onset were enrolled to receive either a vitamin C infusion (200 mg/kg/24 h) or a matched placebo for 7 days. The primary outcome was 28-day mortality. RESULTS 212 adults including 155 MSAP and 57 SAP were enrolled from September 2019 to June 2023. The trial was terminated prematurely due to a lower than expected 28-day mortality rate which showed no difference between the HDIVC and Control group (3/109 vs. 4/103, unadjusted OR: 0.70, 95% CI, 0.15-3.21, p = 0.647). Among patients with MSAP, the HDIVC group exhibited a more pronounced reduction in C-reactive protein levels compared to the Control group (Day0 to Day3, median 72 mg/L vs. 46 mg/L, p = 0.003; Day0 to Day7, median 168 mg/L vs. 121 mg/L, p = 0.013); The volume of fluid retention was lower in the HDIVC group compared to the Control group (Day0-Day1, median 676.5 ml vs. 1130 ml, P = 0.04; Day0-Day2, median 511 ml vs. 1290 ml, P = 0.02; Day0-Day3, median 692 ml vs. 1534 ml, P = 0.04). The APACHE II scores reduction from Day0 to Day7 was significantly greater in the HDIVC group in APACHE II scores (median change of 3 vs. 2, P = 0.01). No significant difference was observed among patients with SAP. CONCLUSION HDIVC did not significantly reduce 28-day mortality in MSAP and SAP patients. While it showed potential benefits in reducing CRP, fluid retention, and APACHE II scores in MSAP patients, these effects may not be directly related to the study drug, and no similar changes were observed in SAP patients. TRIAL REGISTRATION ChiCTR.org.cn, ChiCTR1900022022. Registered March 21 2019, https//www.chictr.org.cn/showproj.html?proj=37,106 .
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Affiliation(s)
- Bing Zhao
- Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, P. R. China
| | - Wenwu Sun
- Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, P. R. China
- Department of Emergency Medicine, Daping Hospital, State Key Laboratory of Trauma and Chemical Poisoning, Army Medical University, Chongqing, 400042, China
| | - Yihui Wang
- Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, P. R. China
| | - Li Ma
- Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, P. R. China
| | - Menglu Gui
- Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, P. R. China
| | - Jiaoyan Li
- Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, P. R. China
| | - Xianxian Yu
- Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, P. R. China
| | - Xing Qi
- Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, P. R. China
| | - Ning Ning
- Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, P. R. China
| | - Silei Sun
- Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, P. R. China
| | - Mengjiao Li
- Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, P. R. China
| | - Yi Yao
- Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, P. R. China
| | - Tongtian Ni
- Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, P. R. China
| | - Juan He
- Department of Pharmacy, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, P. R. China
| | - Zhitao Yang
- Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, P. R. China
| | - Ying Chen
- Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, P. R. China
| | - Huiqiu Sheng
- Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, P. R. China
| | - Meihua Shen
- National Center for Translational Medicine (Shanghai) SHU Branch, Shanghai University, Shanghai, PR China.
- Department of Critical Care Unit, Shanghai Provincial CorpsHospital, Chinese People's Armed Police Forces, Shanghai, PR China.
| | - Jian Li
- Clinical Research Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, P. R. China.
| | - Jun Huang
- Department of Cardiovascular Medicine, State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Shanghai Institute of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, P. R. China.
| | - Enqiang Mao
- Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, P. R. China.
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Cai Y, Yang F, Huang X. Oxidative stress and acute pancreatitis (Review). Biomed Rep 2024; 21:124. [PMID: 39006508 PMCID: PMC11240254 DOI: 10.3892/br.2024.1812] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2024] [Accepted: 06/06/2024] [Indexed: 07/16/2024] Open
Abstract
Acute pancreatitis (AP) is a common inflammatory disorder of the exocrine pancreas that causes severe morbidity and mortality. Although the pathophysiology of AP is poorly understood, a substantial body of evidence suggests some critical events for this disease, such as dysregulation of digestive enzyme production, cytoplasmic vacuolization, acinar cell death, edema formation, and inflammatory cell infiltration into the pancreas. Oxidative stress plays a role in the acute inflammatory response. The present review clarified the role of oxidative stress in the occurrence and development of AP by introducing oxidative stress to disrupt cellular Ca2+ balance and stimulating transcription factor activation and excessive release of inflammatory mediators for the application of antioxidant adjuvant therapy in the treatment of AP.
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Affiliation(s)
- Yongxia Cai
- Department of Emergency Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310016, P.R. China
| | - Feng Yang
- Department of Emergency Medicine, The First People's Hospital of Wuyi County, Jinhua, Zhejiang 321200, P.R. China
| | - Xizhu Huang
- Department of Emergency Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310016, P.R. China
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Sun JK, Lv C, Gao L, Mao W, Li W, Ke L. Nutrition therapy in critically ill patients with severe acute pancreatitis. Nutr Clin Pract 2024; 39:271-280. [PMID: 38357829 DOI: 10.1002/ncp.11135] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2023] [Revised: 01/17/2024] [Accepted: 01/19/2024] [Indexed: 02/16/2024] Open
Abstract
A significant proportion of patients (10%-20%) with acute pancreatitis develop severe acute pancreatitis characterized by pancreatic necrosis, systemic inflammation, and organ failure, commonly requiring intensive care unit (ICU) admission. In this specific population, nutrition therapy is more challenging than that in the general ICU population, primarily because of inevitable gastrointestinal involvement by pancreatic inflammation. In this review, we discussed several key aspects of nutrition therapy in this population, including key pathophysiology that may impede nutrition therapy, the timing and implementation of enteral nutrition and parenteral nutrition, the importance of specific nutrient supplements, and the long-term outcomes that may be addressed by nutrition therapy.
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Affiliation(s)
- Jia-Kui Sun
- Department of Critical Care Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Cheng Lv
- Department of Critical Care Medicine, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu Province, China
- Research Institute of Critical Care Medicine and Emergency Rescue At, Nanjing University, Nanjing, Jiangsu Province, China
| | - Lin Gao
- Department of Critical Care Medicine, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu Province, China
- Research Institute of Critical Care Medicine and Emergency Rescue At, Nanjing University, Nanjing, Jiangsu Province, China
| | - Wenjian Mao
- Department of Critical Care Medicine, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu Province, China
- Research Institute of Critical Care Medicine and Emergency Rescue At, Nanjing University, Nanjing, Jiangsu Province, China
| | - Weiqin Li
- Department of Critical Care Medicine, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu Province, China
- Research Institute of Critical Care Medicine and Emergency Rescue At, Nanjing University, Nanjing, Jiangsu Province, China
| | - Lu Ke
- Department of Critical Care Medicine, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu Province, China
- Research Institute of Critical Care Medicine and Emergency Rescue At, Nanjing University, Nanjing, Jiangsu Province, China
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Rykina-Tameeva N, Samra JS, Sahni S, Mittal A. Non-Surgical Interventions for the Prevention of Clinically Relevant Postoperative Pancreatic Fistula-A Narrative Review. Cancers (Basel) 2023; 15:5865. [PMID: 38136409 PMCID: PMC10741911 DOI: 10.3390/cancers15245865] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2023] [Revised: 12/06/2023] [Accepted: 12/12/2023] [Indexed: 12/24/2023] Open
Abstract
Clinically relevant postoperative pancreatic fistula (CR-POPF) is the leading cause of morbidity and mortality after pancreatic surgery. Post-pancreatectomy acute pancreatitis (PPAP) has been increasingly understood as a precursor and exacerbator of CR-POPF. No longer believed to be the consequence of surgical technique, the solution to preventing CR-POPF may lie instead in non-surgical, mainly pharmacological interventions. Five databases were searched, identifying eight pharmacological preventative strategies, including neoadjuvant therapy, somatostatin and its analogues, antibiotics, analgesia, corticosteroids, protease inhibitors, miscellaneous interventions with few reports, and combination strategies. Two further non-surgical interventions studied were nutrition and fluids. New potential interventions were also identified from related surgical and experimental contexts. Given the varied efficacy reported for these interventions, numerous opportunities for clarifying this heterogeneity remain. By reducing CR-POPF, patients may avoid morbid sequelae, experience shorter hospital stays, and ensure timely delivery of adjuvant therapy, overall aiding survival where prognosis, particularly in pancreatic cancer patients, is poor.
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Affiliation(s)
- Nadya Rykina-Tameeva
- Faculty of Medicine and Health, University of Sydney, Camperdown, NSW 2050, Australia
- Kolling Institute of Medical Research, University of Sydney, St Leonards, NSW 2065, Australia
| | - Jaswinder S. Samra
- Faculty of Medicine and Health, University of Sydney, Camperdown, NSW 2050, Australia
- Upper GI Surgical Unit, Royal North Shore Hospital, St Leonards, NSW 2065, Australia
- Upper GI Surgical Unit, North Shore Private Hospital, St Leonards, NSW 2065, Australia
- Australian Pancreatic Centre, St Leonards, NSW 2065, Australia
| | - Sumit Sahni
- Faculty of Medicine and Health, University of Sydney, Camperdown, NSW 2050, Australia
- Kolling Institute of Medical Research, University of Sydney, St Leonards, NSW 2065, Australia
- Australian Pancreatic Centre, St Leonards, NSW 2065, Australia
| | - Anubhav Mittal
- Faculty of Medicine and Health, University of Sydney, Camperdown, NSW 2050, Australia
- Upper GI Surgical Unit, Royal North Shore Hospital, St Leonards, NSW 2065, Australia
- Upper GI Surgical Unit, North Shore Private Hospital, St Leonards, NSW 2065, Australia
- Australian Pancreatic Centre, St Leonards, NSW 2065, Australia
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Sun W, Zhao B, Li J, Wang Y, Qi X, Ning N, Sun S, Li M, Yao Y, Ni T, Ma L, He J, Huang J, Yang Z, Chen Y, Sheng H, Mao E. Effect of high-dose intravenous vitamin C therapy on the prognosis in patients with moderately severe and severe acute pancreatitis: protocol of a prospective, randomized, double-blinded, placebo-controlled study. Front Med (Lausanne) 2023; 10:1278167. [PMID: 38020102 PMCID: PMC10665842 DOI: 10.3389/fmed.2023.1278167] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2023] [Accepted: 10/16/2023] [Indexed: 12/01/2023] Open
Abstract
Introduction Acute pancreatitis is a common gastrointestinal disease. The mortality of patients affected by severe acute pancreatitis (SAP) remains high. It is unclear whether high-dose intravenous vitamin C (HDIVC) therapy could improve the prognosis of these patients. The current prospective, randomized, double-blinded, placebo-controlled study will explore the effect of high-dose intravenous vitamin C therapy on the prognosis in patients with moderately severe and severe acute pancreatitis. Methods and design A total of 418 participants with moderately severe and severe acute pancreatitis who meet the eligible criteria will be randomly assigned in a 1:1 ratio to receive treatment with HDIVC (200 mg/kg/24 h) or placebo (saline) for a period of 7 days. The primary outcome is 28-day mortality in these patients. The secondary outcomes include organ functions and interventions, laboratory tests, healthcare, and 90-day mortality. Ethics and dissemination This protocol was approved by the institutional ethics board of the Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China (Registration Number: 2019-90). The report of the study will be published in peer-reviewed journals and presented at conferences, both nationally and internationally. Clinical trial registration Chinese Clinical Trial Registry (ChiCTR1900022022). Version 1.5.
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Affiliation(s)
- Wenwu Sun
- Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Bing Zhao
- Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jiaoyan Li
- Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yihui Wang
- Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xing Qi
- Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Ning Ning
- Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Silei Sun
- Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Mengjiao Li
- Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yi Yao
- Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Tongtian Ni
- Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Li Ma
- Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Juan He
- Department of Pharmacy, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jun Huang
- Department of Cardiovascular Medicine, State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Shanghai Institute of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zhitao Yang
- Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Ying Chen
- Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Huiqiu Sheng
- Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Enqiang Mao
- Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Wang SQ, Jiao W, Zhang J, Zhang JF, Tao YN, Jiang Q, Yu F. Ulinastatin in the treatment of severe acute pancreatitis: A single-center randomized controlled trial. World J Clin Cases 2023; 11:4601-4611. [PMID: 37469723 PMCID: PMC10353502 DOI: 10.12998/wjcc.v11.i19.4601] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2023] [Revised: 05/16/2023] [Accepted: 06/02/2023] [Indexed: 06/30/2023] Open
Abstract
BACKGROUND Severe acute pancreatitis (AP) is one of the most common diseases of the gastrointestinal tract and carries a significant financial burden with high disability and mortality. There are no effective drugs in the clinical management of severe AP, and there is an absence of evidence-based medicine concerning the treatment of severe AP.
AIM To explore whether ulinastatin (UTI) can improve the outcome of severe AP.
METHODS The present research included patients who were hospitalized in intensive critical care units (ICUs) after being diagnosed with severe AP. Patients received UTI (400000 IU) or placebos utilizing computer-based random sequencing (in a 1:1 ratio). The primary outcome measures were 7-d mortality, clinical efficacy, inflammatory response, coagulation function, infection, liver function, renal function, and drug-related adverse effects were evaluated.
RESULTS A total of 181 individuals were classified into two groups, namely, the placebo group (n = 90) and the UTI group (n = 91). There were no statistically significant differences in baseline clinical data between the two groups. The 7-d mortality and clinical efficacy in the UTI group were remarkably improved compared with those in the placebo group. UTI can protect against hyperinflammation and improve coagulation dysfunction, infection, liver function, and renal function. UTI patients had markedly decreased hospital stays and hospitalization expenditures compared with the placebo group.
CONCLUSION The findings from the present research indicated that UTI can improve the clinical outcomes of patients with severe AP and has fewer adverse reactions.
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Affiliation(s)
- Su-Qin Wang
- Department of General Surgery, The 904th Hospital of Joint Logistic Support Force, Wuxi 214044, Jiangsu Province, China
| | - Wei Jiao
- Department of Nursing, The 904th Hospital of Joint Logistic Support Force, Wuxi 214044, Jiangsu Province, China
| | - Jing Zhang
- Department of Nursing, The 904th Hospital of Joint Logistic Support Force, Wuxi 214044, Jiangsu Province, China
| | - Ju-Fen Zhang
- Department of Neurosurgery, The 904th Hospital of Joint Logistic Support Force, Wuxi 214044, Jiangsu Province, China
| | - Yun-Na Tao
- Department of Neurosurgery, The 904th Hospital of Joint Logistic Support Force, Wuxi 214044, Jiangsu Province, China
| | - Qing Jiang
- Department of General Surgery, The 904th Hospital of Joint Logistic Support Force, Wuxi 214044, Jiangsu Province, China
| | - Feng Yu
- Department of General Surgery, The 904th Hospital of Joint Logistic Support Force, Wuxi 214044, Jiangsu Province, China
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Vázquez-Frias R, Rivera-Suazo Y, Aguayo-Elorriaga A, Alfaro-Bolaños J, Argüello-Arévalo G, Cadena-León J, Chávez-Sáenz J, Consuelo-Sánchez A, Cruz-Romero E, Espinosa-Saavedra D, Espriu-Ramírez M, Flores-Calderón J, González-Ortiz B, Hernández-Rosiles V, Ignorosa-Arellano K, Jaramillo-Esparza C, Lozano-Hernández F, Larrosa-Haro A, Leal-Quiroga U, Macias-Flores J, Martínez-Leo B, Martínez-Vázquez A, Mendoza-Tavera N, Pacheco-Sotelo S, Reyes-Apodaca M, Sánchez-Ramírez C, Sifuentes-Vela C, Sosa-Arce M, Zárate-Mondragón F. Consenso de la Asociación Mexicana de Gastroenterología sobre el diagnóstico y tratamiento de pancreatitis aguda en niñas, niños y adolescentes. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO 2023; 88:267-281. [DOI: 10.1016/j.rgmx.2023.04.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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Vázquez-Frias R, Rivera-Suazo Y, Aguayo-Elorriaga AK, Alfaro-Bolaños JE, Argüello-Arévalo GA, Cadena-León JF, Chávez-Sáenz JA, Consuelo-Sánchez A, Cruz-Romero EV, Espinosa-Saavedra D, Espriu-Ramírez MX, Flores-Calderón J, González-Ortiz B, Hernández-Rosiles V, Ignorosa-Arellano KR, Jaramillo-Esparza CM, Lozano-Hernández FR, Larrosa-Haro A, Leal-Quiroga U, Macias-Flores JA, Martínez-Leo BA, Martínez-Vázquez A, Mendoza-Tavera NMJ, Pacheco-Sotelo S, Reyes-Apodaca M, Sánchez-Ramírez CA, Sifuentes-Vela CA, Sosa-Arce M, Zárate-Mondragón FE. The Asociación Mexicana de Gastroenterología consensus on the diagnosis and treatment of acute pancreatitis in children and adolescents. REVISTA DE GASTROENTEROLOGIA DE MEXICO (ENGLISH) 2023; 88:267-281. [PMID: 37336694 DOI: 10.1016/j.rgmxen.2023.04.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/15/2023] [Accepted: 04/12/2023] [Indexed: 06/21/2023]
Abstract
Acute pancreatitis (AP) and recurrent acute pancreatitis (RAP) are conditions, whose incidence is apparently on the rise. Despite the ever-increasing evidence regarding the management of AP in children and adults, therapeutic actions that could potentially affect having a poor prognosis in those patients, especially in the pediatric population, continue to be carried out. Therefore, the Asociación Mexicana de Gastroenterología convened a group of 24 expert pediatric gastroenterologists from different institutions and areas of Mexico, as well as 2 pediatric nutritionists and 2 specialists in pediatric surgery, to discuss different aspects of the epidemiology, diagnosis, and treatment of AP and RAP in the pediatric population. The aim of this document is to present the consensus results. Different AP topics were addressed by 6 working groups, each of which reviewed the information and formulated statements considered pertinent for each module, on themes involving recommendations and points of debate, concerning diagnostic or therapeutic approaches. All the statements were presented and discussed. They were then evaluated through a Delphi process, with electronic and anonymous voting, to determine the level of agreement on the statements. A total of 29 statements were formulated, all of which reached above 75% agreement in the first round of voting.
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Affiliation(s)
- R Vázquez-Frias
- Departamento de Gastroenterología y Nutrición, Hospital Infantil de México Federico Gómez, Instituto Nacional de Salud, Mexico City, Mexico.
| | - Y Rivera-Suazo
- Hospital Star Médica Infantil Privado, Mexico City, Mexico
| | - A K Aguayo-Elorriaga
- Hospital Pediátrico Coyoacán, Secretaría de Salud de la Ciudad de México, Mexico City, Mexico
| | - J E Alfaro-Bolaños
- Servicio de Gastroenterología, Centro Médico Nacional 20 de Noviembre, ISSSTE, Mexico City, Mexico
| | | | - J F Cadena-León
- Departamento de Gastroenterología y Nutrición, Instituto Nacional de Pediatría, Mexico City, Mexico
| | | | - A Consuelo-Sánchez
- Departamento de Gastroenterología y Nutrición, Hospital Infantil de México Federico Gómez, Instituto Nacional de Salud, Mexico City, Mexico
| | - E V Cruz-Romero
- Servicio de Cirugía, Centro Médico Naval, Mexico City, Mexico
| | - D Espinosa-Saavedra
- Departamento de Gastroenterología, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico
| | - M X Espriu-Ramírez
- Servicio de Gastroenterología Pediátrica, Hospital General de Cancún Dr. Jesús Kumate Rodríguez, Cancún, Quintana Roo, Mexico
| | - J Flores-Calderón
- Departamento de Gastroenterología, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico
| | - B González-Ortiz
- Departamento de Gastroenterología, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico
| | - V Hernández-Rosiles
- Departamento de Gastroenterología y Nutrición, Hospital Infantil de México Federico Gómez, Instituto Nacional de Salud, Mexico City, Mexico
| | - K R Ignorosa-Arellano
- Departamento de Gastroenterología y Nutrición, Instituto Nacional de Pediatría, Mexico City, Mexico
| | - C M Jaramillo-Esparza
- Departamento de Gastroenterología y Endoscopia Pediátrica, Hospital Ángeles Universidad, Mexico City, Mexico
| | - F R Lozano-Hernández
- Servicio de Gastroenterología Pediátrica, Centro Médico Naval, Mexico City, Mexico
| | - A Larrosa-Haro
- Instituto de Nutrición Humana, Centro Universitario de Ciencias de la Salud, Departamento de Reproducción Humana Crecimiento y Desarrollo Infantil, Universidad de Guadalajara, Guadalajara, Jalisco, Mexico
| | - U Leal-Quiroga
- Servicio de Gastroenterología, Christus Muguerza Hospital Sur, Monterrey, Nuevo León, Mexico
| | - J A Macias-Flores
- Departamento de Gastroenterología, Hospital Infantil de Especialidades de Chihuahua, Chihuahua, Chihuahua, Mexico
| | - B A Martínez-Leo
- Hospital Pediátrico Moctezuma, Secretaría de Salud de la Ciudad de México, Mexico City, Mexico
| | - A Martínez-Vázquez
- Departamento de Gastroenterología y Nutrición Pediátrica, Hospital para el Niño Poblano, Puebla, Puebla, Mexico
| | | | - S Pacheco-Sotelo
- Servicio de Gastroenterología y Nutrición Pediátrica, UMAE, Hospital de Pediatría, Centro Médico Nacional de Occidente, Instituto Mexicano de Seguro Social, Guadalajara, Jalisco, Mexico
| | - M Reyes-Apodaca
- Programa de Maestría y Doctorado en Ciencias Médicas, Odontológicas y de la Salud, Universidad Nacional Autónoma de México, Mexico City, Mexico
| | | | | | - M Sosa-Arce
- Departamento de Gastroenterología, Centro Médico Nacional La Raza, Instituto Mexicano del Seguro Social, Mexico City, Mexico
| | - F E Zárate-Mondragón
- Departamento de Gastroenterología y Nutrición, Instituto Nacional de Pediatría, Mexico City, Mexico
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Sadeghi A, Jafari-Moghaddam R, Ataei S, Asadiafrooz M, Abbasinazari M. Role of vitamin C and rectal indomethacin in preventing and alleviating post-endoscopic retrograde cholangiopancreatography pancreatitis: a clinical study. Clin Endosc 2023; 56:214-220. [PMID: 37013392 PMCID: PMC10073861 DOI: 10.5946/ce.2022.165] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2022] [Accepted: 06/27/2022] [Indexed: 04/05/2023] Open
Abstract
BACKGROUND/AIMS This study aimed to determine whether vitamin C in addition to indomethacin decreases the occurrence and severity of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) occurrence and severity. METHODS This randomized clinical trial included patients undergoing ERCP. The participants were administered either rectal indomethacin (100 mg) plus an injection of vitamin C (500 mg) or rectal indomethacin (100 mg) alone just before ERCP. The primary outcomes were PEP occurrence and severity. The secondary amylase and lipase levels were determined after 24 hours. RESULTS A total of 344 patients completed the study. Based on intention-to-treat analysis, the PEP rates were 9.9% for indomethacin plus vitamin C plus indomethacin and 15.7% for indomethacin alone. Regarding the per-protocol analysis, the PEP rates were 9.7% and 15.7% in the combination and indomethacin arms, respectively. There was a remarkable difference between the two arms in PEP occurrence and severity on intention-to-treat and per-protocol analyses (p=0.034 and p=0.031, respectively). The post-ERCP lipase and amylase concentrations were lower in the combination arm than in the indomethacin alone arm (p=0.034 and p=0.029, respectively). CONCLUSION Vitamin C injection in addition to rectal indomethacin reduced PEP occurrence and severity.
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Affiliation(s)
- Amir Sadeghi
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Rana Jafari-Moghaddam
- Department of Clinical Pharmacy, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Sara Ataei
- Department of Clinical Pharmacy, School of Pharmacy, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Mahboobe Asadiafrooz
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Abbasinazari
- Department of Clinical Pharmacy, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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10
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Hey-Hadavi J, Velisetty P, Mhatre S. Trends and recent developments in pharmacotherapy of acute pancreatitis. Postgrad Med 2022; 135:334-344. [PMID: 36305300 DOI: 10.1080/00325481.2022.2136390] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
Acute pancreatitis (AP), a complex inflammatory disease of the pancreas, is associated with increased morbidity and mortality. Currently, no specific therapies are approved for its treatment, and management is primarily based on supportive care. Despite enhanced understanding of AP pathogenesis, patients remain at significant risk owing to a lack of targeted drug treatments. Therefore, there is an urgent need for effective pharmacological therapeutic measures which may inhibit the early systemic inflammation, thereby preventing subsequent organ failure. This narrative review summarizes the available treatment options for AP and highlights the potential drug classes and pharmacologic therapies including those under clinical development. Although, several therapies targeting different aspects of AP pathogenesis have been investigated, some therapies with promising preclinical activity have been rendered ineffective in clinical trials. Other novel drug classes or molecules including dabigatran (anticoagulant), ulinastatin (protease inhibitor), infliximab (monoclonal antibody), spautin-A41 (autophagy inhibitor), and CM4620-Injectible Emulsion (calcium channel inhibitor) await further clinical assessment. Alternative treatment options using stem cells and nanoparticles are also being explored and may hold promise for AP therapy. However, challenges for exploring targeted treatment approaches include disease complexity, timing of therapeutic intervention, and establishing appropriate clinical endpoints. Understanding the role of specific biomarkers may help in identifying appropriate targets for drug discovery and facilitate determining relevant clinical study endpoints to monitor disease severity and progression, thereby aiding in design of more precise therapies with improved clinical outcomes.
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11
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Zheng X, Zhao J, Wang S, Hu L. Research Progress of Antioxidant Nanomaterials for Acute Pancreatitis. Molecules 2022; 27:7238. [PMID: 36364064 PMCID: PMC9658789 DOI: 10.3390/molecules27217238] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Revised: 10/16/2022] [Accepted: 10/21/2022] [Indexed: 08/30/2023] Open
Abstract
Acute pancreatitis (AP) is a complex inflammatory disease caused by multiple etiologies, the pathogenesis of which has not been fully elucidated. Oxidative stress is important for the regulation of inflammation-related signaling pathways, the recruitment of inflammatory cells, the release of inflammatory factors, and other processes, and plays a key role in the occurrence and development of AP. In recent years, antioxidant therapy that suppresses oxidative stress by scavenging reactive oxygen species has become a research highlight of AP. However, traditional antioxidant drugs have problems such as poor drug stability and low delivery efficiency, which limit their clinical translation and applications. Nanomaterials bring a brand-new opportunity for the antioxidant treatment of AP. This review focuses on the multiple advantages of nanomaterials, including small size, good stability, high permeability, and long retention effect, which can be used not only as effective carriers of traditional antioxidant drugs but also directly as antioxidants. In this review, after first discussing the association between oxidative stress and AP, we focused on summarizing the literature related to antioxidant nanomaterials for the treatment of AP and highlighting the effects of these nanomaterials on the indicators related to oxidative stress in pathological states, aiming to provide references for follow-up research and promote clinical application.
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Affiliation(s)
- Xiaoyi Zheng
- Ningxia Medical University, Postgraduate Training Base in Shanghai Gongli Hospital, Pudong New Area, No. 219 Miao Pu Road, Shanghai 200135, China
- Department of Gastroenterology, Changhai Hospital, Naval Medical University, No. 168 Changhai Road, Shanghai 200433, China
| | - Jiulong Zhao
- Department of Gastroenterology, Changhai Hospital, Naval Medical University, No. 168 Changhai Road, Shanghai 200433, China
| | - Shige Wang
- School of Materials and Chemistry, University of Shanghai for Science and Technology, No. 516 Jungong Road, Shanghai 200093, China
| | - Lianghao Hu
- Department of Gastroenterology, Changhai Hospital, Naval Medical University, No. 168 Changhai Road, Shanghai 200433, China
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12
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Tusa NV, Abuelo A, Levy NA, Gandy JC, Langlois DK, Cridge H. Peripheral biomarkers of oxidative stress in dogs with acute pancreatitis. J Vet Intern Med 2022; 36:1958-1965. [PMID: 36086902 DOI: 10.1111/jvim.16535] [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: 05/01/2022] [Accepted: 08/22/2022] [Indexed: 12/01/2022] Open
Abstract
BACKGROUND Oxidative stress is considered a pathomechanism of acute pancreatitis (AP), but no studies have extensively characterized oxidant status in dogs with naturally-occurring AP. HYPOTHESIS OR OBJECTIVES Evaluate measures of oxidant status in dogs with AP and explore whether these measures correlate with AP severity. ANIMALS Fifteen dogs with AP and 9 control dogs. METHODS Prospective, controlled observational study. Plasma reactive metabolite (RM) concentrations, antioxidant potential (AOP), and urinary F2 isoprostane concentrations were measured in AP dogs and healthy controls. Severity of AP was assessed by length of hospitalization and 3 disease severity indices: canine acute pancreatitis severity (CAPS), modified canine activity index (M-CAI), and the acute patient physiologic and laboratory evaluation score (APPLEfull ). RESULTS Reactive metabolite (RM) concentrations (median, 65 relative fluorescent units [RFU]/μL; range, 20-331 RFU/μL) and RM:AOP (median, 7; range, 4-109) were higher in AP dogs than healthy controls (median RM, 25 RFU/μL; range, 16-41 RFU/μL; median RM:AOP, 4; range, 2-7; P < .001 for both comparisons). Reactive metabolite (rS = 0.603, P = .08) and RM:AOP (rS = 0.491, P = .06) were not correlated with the duration of hospitalization or disease severity indices evaluated. However, disease severity indices did not predict mortality in our study. Normalized urine 2,3-dinor-8-iso-prostaglandin F2α concentrations were correlated with C-reactive protein (CRP; rS = 0.491, P = .03), canine specific pancreatic lipase (Spec cPL; rS = 0.746, P = .002), and CAPS (rS = 0.603, P = .02). CONCLUSIONS AND CLINICAL IMPORTANCE Oxidant status is altered in dogs with naturally occurring AP, but the clinical relevance of this finding is unknown.
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Affiliation(s)
- Nicole V Tusa
- Department of Small Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan, USA
| | - Angel Abuelo
- Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan, USA
| | - Nyssa A Levy
- Department of Small Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan, USA
| | - Jeffery C Gandy
- Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan, USA
| | - Daniel K Langlois
- Department of Small Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan, USA
| | - Harry Cridge
- Department of Small Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan, USA
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13
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Cridge H, Lim SY, Algül H, Steiner JM. New insights into the etiology, risk factors, and pathogenesis of pancreatitis in dogs: Potential impacts on clinical practice. J Vet Intern Med 2022; 36:847-864. [PMID: 35546513 PMCID: PMC9151489 DOI: 10.1111/jvim.16437] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2022] [Revised: 04/08/2022] [Accepted: 04/12/2022] [Indexed: 12/11/2022] Open
Abstract
While most cases of pancreatitis in dogs are thought to be idiopathic, potential risk factors are identified. In this article we provide a state‐of‐the‐art overview of suspected risk factors for pancreatitis in dogs, allowing for improved awareness and detection of potential dog‐specific risk factors, which might guide the development of disease prevention strategies. Additionally, we review important advances in our understanding of the pathophysiology of pancreatitis and potential areas for therapeutic manipulation based thereof. The outcome of pathophysiologic mechanisms and the development of clinical disease is dependent on the balance between stressors and protective mechanisms, which can be evaluated using the critical threshold theory.
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Affiliation(s)
- Harry Cridge
- Department of Small Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan, USA
| | - Sue Yee Lim
- Gastrointestinal Laboratory, Department of Small Animal Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, Texas, USA
| | - Hana Algül
- Gastrointestinal Cancer and Inflammatory Research Laboratory, Technical University of Munich, Munich, Germany
| | - Jörg M Steiner
- Gastrointestinal Laboratory, Department of Small Animal Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, Texas, USA
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14
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Ladd AM, Conwell D, Burroughs TE, Satish M. Prior Exposure to Nonsteroidal Anti-inflammatory Drugs Reduces the Rate of Organ Failure and In-Hospital Mortality in Acute Pancreatitis. Am J Med 2022; 135:471-477.e1. [PMID: 34793751 DOI: 10.1016/j.amjmed.2021.10.020] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2021] [Revised: 10/04/2021] [Accepted: 10/13/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND Nonsteroidal anti-inflammatory drugs (NSAIDs) have been linked recently to a lower expression of pro-inflammatory cytokines in humans with acute pancreatitis. Because it is unclear if this effect results in clinical benefits, the aim of this study was to determine if prior NSAID exposure improves immediate clinical outcomes. METHODS Retrospective medical record review of adult patients admitted with acute pancreatitis. Cases were extracted from a national Veterans Affairs database using International Classification of Diseases, Ninth Revision codes. Prior NSAIDs use was determined through pharmacy data claims. The rates of acute kidney injury, respiratory failure, cardiovascular failure, and in-hospital mortality were compared between those with prior NSAID use (AP+NSAID) and those without it (AP-NSAID) using univariate and multivariate analysis. RESULTS A total of 31,340 patients were identified: 28,364 AP+NSAID and 2976 AP-NSAID. The median age was 60 years, 68% were white, and the median hospital stay was 4 days. Approximately 2% of patients died during the hospitalization. After adjusting for demographics and other covariates, patients in the AP+NSAID arm had lower rates of acute kidney injury, P = .0002), cardiovascular failure (P = .025), any organ failure (P ≤ .0001), and in-hospital mortality (P < .0001). CONCLUSION Prior use of NSAIDs is associated with a lower incidence of organ failure and in-hospital mortality in adult patients with acute pancreatitis. The role of NSAIDs as therapeutic agents in this condition should be evaluated in interventional trials.
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Affiliation(s)
- Antonio Mendoza Ladd
- Department of Internal Medicine, Division of Gastroenterology, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, Texas.
| | - Darwin Conwell
- Division of Gastroenterology, Hepatology and Nutrition. The Ohio State Universtiy Wexner Medical Center, Columbus, Ohio
| | - Thomas E Burroughs
- Saint Louis University Center for Health Outcomes Research, St. Louis, Missouri
| | - Munigala Satish
- Saint Louis University Center for Health Outcomes Research, St. Louis, Missouri
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15
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Rasch S, Sancak S, Erber J, Wießner J, Schulz D, Huberle C, Algül H, Schmid RM, Lahmer T. Influence of extracorporeal cytokine adsorption on hemodynamics in severe acute pancreatitis: Results of the matched cohort pancreatitis cytosorbents inflammatory cytokine removal (PACIFIC) study. Artif Organs 2022; 46:1019-1026. [PMID: 35182395 DOI: 10.1111/aor.14195] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2021] [Revised: 01/02/2022] [Accepted: 01/24/2022] [Indexed: 02/06/2023]
Abstract
BACKGROUND Outcome of severe acute pancreatitis (SAP) highly depends on the degree of systemic inflammation and organ failure. Although treatment approaches targeting the inflammatory cascade have failed in pancreatitis, recent studies suggest that extracorporeal cytokine adsorption effectively reduces concentrations of pro-inflammatory cytokines and potentially improves the outcome of sepsis. METHODS Sixteen patients with SAP, presenting within 7 days upon onset of pain, an APACHE-II score of ≥10 and ≥1 marker of poor prognosis, received 2 consecutive 24-h treatments with CytoSorb® extracorporeal cytokine adsorption (intervention group). Hemodynamics, organ failure, and mortality were compared with an APACHE-II score-matched retrospective control group of 32 patients. RESULTS The primary objective (20% decrease in the vasopressor dependency index or 20% increase in the cardiac index) was reached in 68.8% of the intervention and 28.1% of the control patients (p = 0.007), respectively. The cytokine adsorption significantly reduced IL-6 (-1998 pg/ml, p = 0.005) serum levels and resulted in stable CRP (p = 0.101) and decreased PCT (p = 0.003) levels in contrast to increased CRP (p = 0.014) and stable PCT levels (p = 0.695) in the control group. While mortality and improvement of respiratory failure were similar in both groups, renal failure significantly improved (change of KDIGO classification 72 h postcytokine adsorption [-1 vs. 0, p = 0.005]) and the SOFA score significantly decreased (day 5: -1.8 ± 2.0 vs. 1 ± 3.8, p = 0.013) in the intervention group. CONCLUSION Cytokine adsorption might be an effective treatment option to stabilize hemodynamics in SAP. It decreases levels of the pro-inflammatory marker IL-6 and stabilizes organ function according to serial SOFA score assessments.
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Affiliation(s)
- Sebastian Rasch
- Department of Internal Medicine II, Technical University of Munich, School of Medicine, University Hospital rechts der Isar, Munich, Germany
| | - Sengül Sancak
- Department of Internal Medicine II, Technical University of Munich, School of Medicine, University Hospital rechts der Isar, Munich, Germany
| | - Johanna Erber
- Department of Internal Medicine II, Technical University of Munich, School of Medicine, University Hospital rechts der Isar, Munich, Germany
| | - Johannes Wießner
- Department of Internal Medicine II, Technical University of Munich, School of Medicine, University Hospital rechts der Isar, Munich, Germany
| | - Dominik Schulz
- Department of Internal Medicine II, Technical University of Munich, School of Medicine, University Hospital rechts der Isar, Munich, Germany
| | - Christina Huberle
- Department of Internal Medicine II, Technical University of Munich, School of Medicine, University Hospital rechts der Isar, Munich, Germany
| | - Hana Algül
- Department of Internal Medicine II, Technical University of Munich, School of Medicine, University Hospital rechts der Isar, Munich, Germany.,Comprehensive Cancer Center Munich CCCM (TUM), Technical University of Munich, School of Medicine, University Hospital rechts der Isar, Munich, Germany
| | - Roland M Schmid
- Department of Internal Medicine II, Technical University of Munich, School of Medicine, University Hospital rechts der Isar, Munich, Germany
| | - Tobias Lahmer
- Department of Internal Medicine II, Technical University of Munich, School of Medicine, University Hospital rechts der Isar, Munich, Germany
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16
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Pădureanu V, Florescu D, Pădureanu R, Ghenea A, Gheonea D, Oancea C. Role of antioxidants and oxidative stress in the evolution of acute pancreatitis (Review). Exp Ther Med 2022; 23:197. [PMID: 35126700 PMCID: PMC8794551 DOI: 10.3892/etm.2022.11120] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2021] [Accepted: 10/29/2021] [Indexed: 11/06/2022] Open
Affiliation(s)
- Vlad Pădureanu
- Department of Internal Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Dan Florescu
- Department of Gastroenterology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Rodica Pădureanu
- Department of Internal Medicine, Emergency Clinical County Hospital of Craiova, 200642 Craiova, Romania
| | - Alice Ghenea
- Department of Bacteriology‑Virology‑Parasitology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Dan Gheonea
- Department of Gastroenterology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Carmen Oancea
- Department of Analytical Chemistry, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
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17
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Moyer KA, Szabo FK, Preda E, Gal L. Pharmacological Management of Acute and Chronic Pancreatitis. COMPREHENSIVE PHARMACOLOGY 2022:286-301. [DOI: 10.1016/b978-0-12-820472-6.00132-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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18
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Cecire J, Adams K, Pham H, Pang T, Burnett D. Pharmacological prevention of post-operative pancreatitis: systematic review and meta-analysis of randomized controlled trials on animal studies. ANZ J Surg 2021; 92:1338-1346. [PMID: 34936178 DOI: 10.1111/ans.17417] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2021] [Revised: 11/23/2021] [Accepted: 11/24/2021] [Indexed: 11/30/2022]
Abstract
BACKGROUND Postoperative pancreatic fistula (POPF) remains a significant complication of pancreatic resection with recent evidence showing a strong association between post-operative pancreatitis and subsequent development of POPF. Incidence and severity of pancreatitis following endoscopic therapy has been effectively reduced with indomethacin prophylaxis, however further agents require evaluation. We present a systematic literature review and meta-analysis of the prophylactic treatment with corticosteroids or n-acetyl cysteine (NAC) of induced pancreatitis in rodent models. METHODS A systematic literature search was conducted using Pubmed, Medline, Embase and Cochrane library to identify eligible randomized control trials (RCT) involving animal models that examined NAC or corticosteroids. The primary outcome was the subsequent effect on serum amylase and IL-6 and the histopathological markers of severity such as pancreatic oedema and necrosis. RESULTS Four RCTs (n = 178) met inclusion criteria examining NAC and eight RCTs (n = 546) examining corticosteroid agents (dexamethasone, hydrocortisone, methylprednisolone). Prophylactic administration of all corticosteroid agents showed a net effect in favour of reducing markers of severity of pancreatitis. NAC showed a significant reduction in severity of amylase and necrosis. CONCLUSION The RCTs examined suggest that prophylactic administration of corticosteroid agents and NAC can reduce the severity of pancreatitis as indicated by histopathologic markers, serum amylase and IL-6 levels.
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Affiliation(s)
- Jack Cecire
- Surgical Innovations Unit, Westmead Hospital, Sydney, New South Wales, Australia
| | - Kristian Adams
- Surgical Innovations Unit, Westmead Hospital, Sydney, New South Wales, Australia
| | - Helen Pham
- Surgical Innovations Unit, Westmead Hospital, Sydney, New South Wales, Australia.,Western Clinical School, Faculty of Medical and Health Sciences, The University of Sydney, Sydney, New South Wales, Australia.,Department of Hepatobiliary, Pancreatic/Upper Gastrointestinal Surgery, Westmead Hospital, Sydney, New South Wales, Australia
| | - Tony Pang
- Surgical Innovations Unit, Westmead Hospital, Sydney, New South Wales, Australia.,Western Clinical School, Faculty of Medical and Health Sciences, The University of Sydney, Sydney, New South Wales, Australia.,Department of Hepatobiliary, Pancreatic/Upper Gastrointestinal Surgery, Westmead Hospital, Sydney, New South Wales, Australia
| | - David Burnett
- Department of Surgery, John Hunter Hospital, Newcastle, New South Wales, Australia
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19
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Gao L, Chong E, Pendharkar S, Phillips A, Ke L, Li W, Windsor JA. The Challenges and Effects of Ascorbic Acid Treatment of Acute Pancreatitis: A Systematic Review and Meta-Analysis of Preclinical and Clinical Studies. Front Nutr 2021; 8:734558. [PMID: 34765629 PMCID: PMC8576576 DOI: 10.3389/fnut.2021.734558] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2021] [Accepted: 09/22/2021] [Indexed: 12/22/2022] Open
Abstract
Background: Oxidative stress has been implicated in the pathogenesis of acute pancreatitis (AP), and ascorbic acid (AA), as an important endogenous antioxidant substance, has been shown to reduce AP severity in preclinical studies. However, the effects of AA supplementation in clinical settings remain controversial. Methods: PubMed, EMBASE, MEDLINE, and SCOPUS databases were searched, and both preclinical and clinical studies were included. For clinical trials, the primary outcome was incidence of organ failure, and for preclinical studies, the primary outcome was histopathological scores of pancreatic injuries. Results: Meta-analysis of clinical trials showed that compared with controls, AA administration did not reduce the incidence of organ failure or mortality during hospitalization but was associated with significantly reduced length of hospital stay. Meta-analysis of preclinical studies showed that AA supplementation reduced pancreatic injury, demonstrated as decreased histological scores and serum amylase, lipase levels. Conclusion: AA administration has no effect on survival or organ failure in patients with AP but may reduce the length of hospital stay. However, the evidence to date remains sparse, scattered, and of suboptimal quality, making it difficult to draw any firm conclusion on the clinical benefits of AA in AP.
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Affiliation(s)
- Lin Gao
- Department of Critical Care Medicine, Center of Severe Acute Pancreatitis (CSAP), Jinling Hospital, Medical School of Nanjing University, Nanjing, China.,Applied Surgery and Metabolism Laboratory, School of Biological Sciences, University of Auckland, Auckland, New Zealand
| | - Eric Chong
- Faculty of Medical and Health Sciences, Surgical and Translational Research Centre, School of Medicine, University of Auckland, Auckland, New Zealand
| | - Sayali Pendharkar
- Faculty of Medical and Health Sciences, Surgical and Translational Research Centre, School of Medicine, University of Auckland, Auckland, New Zealand
| | - Anthony Phillips
- Applied Surgery and Metabolism Laboratory, School of Biological Sciences, University of Auckland, Auckland, New Zealand.,Faculty of Medical and Health Sciences, Surgical and Translational Research Centre, School of Medicine, University of Auckland, Auckland, New Zealand
| | - Lu Ke
- Department of Critical Care Medicine, Center of Severe Acute Pancreatitis (CSAP), Jinling Hospital, Medical School of Nanjing University, Nanjing, China
| | - Weiqin Li
- Department of Critical Care Medicine, Center of Severe Acute Pancreatitis (CSAP), Jinling Hospital, Medical School of Nanjing University, Nanjing, China
| | - John Albert Windsor
- Applied Surgery and Metabolism Laboratory, School of Biological Sciences, University of Auckland, Auckland, New Zealand.,Faculty of Medical and Health Sciences, Surgical and Translational Research Centre, School of Medicine, University of Auckland, Auckland, New Zealand
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20
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Vitamin C in Critically Ill Patients: An Updated Systematic Review and Meta-Analysis. Nutrients 2021; 13:nu13103564. [PMID: 34684565 PMCID: PMC8539952 DOI: 10.3390/nu13103564] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2021] [Revised: 10/03/2021] [Accepted: 10/04/2021] [Indexed: 12/25/2022] Open
Abstract
Background: Vitamin C is a water-soluble antioxidant vitamin. Oxidative stress and its markers, along with inflammatory markers, are high during critical illness. Due to conflicting results of the published literature regarding the efficacy of vitamin C in critically ill patients, and especially the concerns for nephrotoxicity raised by some case reports, this meta-analysis was carried out to appraise the evidence and affirmation regarding the role of vitamin C in critically ill patients. Methods: We searched the database thoroughly to collect relevant studies that assessed intravenous vitamin C use in critically ill patients published until 25 February 2021. We included randomized controlled trials and observational studies with 20 or more critically ill patients who have received intravenous ascorbic acid (vitamin C). After screening 18,312 studies from different databases, 53 were included in our narrative synthesis, and 48 were included in the meta-analysis. We used the Covidence software for screening of the retrieved literature. Review Manager (RevMan) 5.4 was used for the pooling of data and Odds Ratios (OR) and Mean difference (MD) as measures of effects with a 95% confidence interval to assess for explanatory variables. Results: Pooling data from 33 studies for overall hospital mortality outcomes using a random-effect model showed a 19% reduction in odds of mortality among the vitamin C group (OR, 0.81; 95% CI, 0.66–0.98). Length of hospital stay (LOS), mortality at 28/30 days, ICU mortality, new-onset AKI and Renal Replacement Therapy (RRT) for AKI did not differ significantly across the two groups. Analysis of data from 30 studies reporting ICU stay disclosed 0.76 fewer ICU days in the vitamin C group than the placebo/standard of care (SOC) group (95% CI, −1.34 to −0.19). This significance for shortening ICU stay persisted even when considering RCTs only in the analysis (MD, −0.70; 95% CI, −1.39 to −0.02). Conclusion: Treatment of critically ill patients with intravenous vitamin C was relatively safe with no significant difference in adverse renal events and decreased in-hospital mortality. The use of vitamin C showed a significant reduction in the length of ICU stays in critically ill patients.
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21
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Impact of platelet-rich plasma versus selenium in ameliorating induced toxicity in rat testis: histological, immunohistochemical, and molecular study. Cell Tissue Res 2021; 385:223-238. [PMID: 33791879 DOI: 10.1007/s00441-021-03439-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2020] [Accepted: 02/18/2021] [Indexed: 10/21/2022]
Abstract
This study was conducted on forty adult rats divided into four groups: Group I (control) that is divided into subgroups A, B, and C and Group II (methotrexate (MTX)-treated); the rats were injected intraperitoneally with MTX at a dose of 1 mg/kg/week, for 8 weeks. Group III (MTX-Se co-treated) was injected with MTX like Group II plus an oral administration of selenium at a dose of 10 μg/kg b.w/day, for 8 weeks. Group IV (MTX-PRP co-treated), rats were injected intraperitoneally with MTX like Group II plus platelet-rich plasma (PRP) injection under the scrotum, three times with 2-week intervals (volume-0.1 ml per injection) and euthanized after 8 weeks. Histological, immunohistochemical, and genetic expression using qPCR and western blotting technique were conducted. There was improvement in histological structure of testes in most specimens of Group IV. The latter group revealed a significant decrease in Bax and an increase in Bcl-2. The regeneration of testicular tissue was more observed in Group IV as measured by an increase in mean number of PCNA. Moreover, Group IV revealed an increased genetic level of FSCN3, GCNF, UBQLN3, and DAZL. Both MTX-Se and MTX-PRP have an anti-inflammatory effect as measured by a reduction in NF-κb. The anti-oxidative effect of selenium and PRP was noticed by a decrease in the level of the iNos and an increase in eNos protein and the autophagy marker LC3. PRP has ameliorative effects on induced rat testicular toxicity as evaluated by morphological changes and confirmed by immunohistochemical reactions, genetic expression, and western blotting analyses including oxidative and anti- oxidative markers.
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Cyclic Voltammetry in Biological Samples: A Systematic Review of Methods and Techniques Applicable to Clinical Settings. SIGNALS 2021. [DOI: 10.3390/signals2010012] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Oxidative stress plays a pivotal role in the pathogenesis of many diseases, but there is no accurate measurement of oxidative stress or antioxidants that has utility in the clinical setting. Cyclic Voltammetry is an electrochemical technique that has been widely used for analyzing redox status in industrial and research settings. It has also recently been applied to assess the antioxidant status of in vivo biological samples. This systematic review identified 38 studies that used cyclic voltammetry to determine the change in antioxidant status in humans and animals. It focusses on the methods for sample preparation, processing and storage, experimental setup and techniques used to identify the antioxidants responsible for the voltammetric peaks. The aim is to provide key information to those intending to use cyclic voltammetry to measure antioxidants in biological samples in a clinical setting.
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Astaxanthin and Coenzyme Q10 are not synergistic against oxidative damage in cerulein-induced acute pancreatitis. JOURNAL OF SURGERY AND MEDICINE 2021. [DOI: 10.28982/josam.756220] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
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Haber PS, Kortt NC. Alcohol use disorder and the gut. Addiction 2021; 116:658-667. [PMID: 32511812 DOI: 10.1111/add.15147] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2020] [Revised: 04/14/2020] [Accepted: 06/02/2020] [Indexed: 02/07/2023]
Abstract
Acute and chronic gastrointestinal problems are common in the setting of excessive alcohol use, and excessive alcohol use is associated with injury to all parts of the gastrointestinal tract. There is mounting evidence of gastrointestinal injury and increased cancer risk even from moderate alcohol consumption. The major causes of alcohol-related morbidity and mortality within the gastrointestinal system are liver disease, pancreatitis and gastrointestinal cancer. Other alcohol-related intestinal dysfunction is common but not life-threatening, leading to diarrhoea, malabsorption and nutritional deficiencies. This review describes non-neoplastic and neoplastic alcohol-related disorders of the gastrointestinal tract, omitting the liver, which has been reviewed elsewhere.
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Affiliation(s)
- Paul S Haber
- Royal Prince Alfred Hospital, Camperdown, NSW, 2050, Australia.,University of Sydney, Sydney, NSW, 2050, Australia
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Yang X, Yao L, Fu X, Mukherjee R, Xia Q, Jakubowska MA, Ferdek PE, Huang W. Experimental Acute Pancreatitis Models: History, Current Status, and Role in Translational Research. Front Physiol 2020; 11:614591. [PMID: 33424638 PMCID: PMC7786374 DOI: 10.3389/fphys.2020.614591] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2020] [Accepted: 11/30/2020] [Indexed: 02/05/2023] Open
Abstract
Acute pancreatitis is a potentially severe inflammatory disease that may be associated with a substantial morbidity and mortality. Currently there is no specific treatment for the disease, which indicates an ongoing demand for research into its pathogenesis and development of new therapeutic strategies. Due to the unpredictable course of acute pancreatitis and relatively concealed anatomical site in the retro-peritoneum, research on the human pancreas remains challenging. As a result, for over the last 100 years studies on the pathogenesis of this disease have heavily relied on animal models. This review aims to summarize different animal models of acute pancreatitis from the past to present and discuss their main characteristics and applications. It identifies key studies that have enhanced our current understanding of the pathogenesis of acute pancreatitis and highlights the instrumental role of animal models in translational research for developing novel therapies.
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Affiliation(s)
- Xinmin Yang
- Department of Integrated Traditional Chinese Medicine and Western Medicine, Sichuan Provincial Pancreatitis Center and West China-Liverpool Biomedical Research Center, West China Hospital, Sichuan University, Chengdu, China
| | - Linbo Yao
- Department of Integrated Traditional Chinese Medicine and Western Medicine, Sichuan Provincial Pancreatitis Center and West China-Liverpool Biomedical Research Center, West China Hospital, Sichuan University, Chengdu, China
| | - Xianghui Fu
- Division of Endocrinology and Metabolism, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China
| | - Rajarshi Mukherjee
- Liverpool Pancreatitis Research Group, Liverpool University Hospitals National Health Service Foundation Trust and Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, United Kingdom
| | - Qing Xia
- Department of Integrated Traditional Chinese Medicine and Western Medicine, Sichuan Provincial Pancreatitis Center and West China-Liverpool Biomedical Research Center, West China Hospital, Sichuan University, Chengdu, China
| | | | - Pawel E. Ferdek
- Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland
| | - Wei Huang
- Department of Integrated Traditional Chinese Medicine and Western Medicine, Sichuan Provincial Pancreatitis Center and West China-Liverpool Biomedical Research Center, West China Hospital, Sichuan University, Chengdu, China
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Superoxide Dismutase Predicts Persistent Circulation Failure and Mortality in the Early Stage of Acute Pancreatitis. Dig Dis Sci 2020; 65:3551-3557. [PMID: 31997054 DOI: 10.1007/s10620-020-06069-w] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2019] [Accepted: 01/11/2020] [Indexed: 12/13/2022]
Abstract
OBJECTIVES Oxidative stress is an important event in the pathogenesis of acute pancreatitis. Superoxide dismutase is a major antioxidant enzyme in the body. The aim of this study was to investigate the changes in superoxide dismutase activity early in the onset of acute pancreatitis and its value in predicting the risk of organ failure and mortality. METHODS Data for 2549 patients hospitalized from 2013 to 2017 were extracted from the prospective database, and we selected 854 adult patients who were admitted within 24 h of disease onset with complete data. Serum superoxide dismutase activities on the first, second, and third days of hospital admission for patients with different severities, organ failure, and mortality were compared. The areas under the curve for the prediction of organ failure, pancreatic necrosis, and mortality were estimated using receiver operating characteristic curves. RESULTS Among the 854 adult patients, superoxide dismutase activities were significantly different among patients with mild acute pancreatitis, moderately severe acute pancreatitis, and severe acute pancreatitis (P = 0.005). Superoxide dismutase activity was significantly decreased in patients with persistent renal failure (77.8 ± 37.2), persistent circulatory failure (66.2 ± 14.9), and mortality (64.3 ± 16.0). The accuracy of superoxide dismutase with regard to predicting persistent circulatory failure and mortality was high, and the areas under the receiver operating characteristic curves were 0.83 and 0.84, respectively. CONCLUSIONS Superoxide dismutase activity was negatively correlated with the severity and clinical outcome of AP. Superoxide dismutase activity is highly accurate at predicting persistent circulation failure and mortality in the early stage of AP.
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Özbeyli D, Gürler EB, Buzcu H, Çilingir-Kaya ÖT, Çam ME, Yüksel M. Astaxanthin alleviates oxidative damage in acute pancreatitis via direct antioxidant mechanisms. TURKISH JOURNAL OF GASTROENTEROLOGY 2020; 31:706-712. [PMID: 33169708 DOI: 10.5152/tjg.2020.19520] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND/AIMS Astaxanthin (ATX) is a naturally occurring carotenoid and a potent antioxidant. Various anti-inflammatory effects of ATX have been examined. We aimed to investigate the protective effect of ATX and its mechanism in a cerulein-induced acute pancreatitis rat model. MATERIALS AND METHODS The rats were randomized into 2 main groups as control (C) and acute pancreatitis group (AP). AP group was subsequently divided into subgroups as AP+vehicle (AP), AP+ATX, and ATX+peroxisome proliferator-activated receptor-alpha antagonist GW6471 (ATX+GW) groups. To induce AP, the rats were administered cerulein (50 µg/kg, intraperitonally [ip]) at 1 hour intervals, whereas the C group received saline. The AP group was treated with vehicle olive oil, ATX 40 mg/kg/orally, or GW6471 and ATX (GW1 mg/kg/ip; ATX; 40 mg/kg/peroral). Treatments were administered after the 1st cerulein injection. At the 7th hour after the final injection, the rats were killed and the pancreatic tissue was used for the determination of malondialdehyde (MDA), glutathione (GSH), and myeloperoxidase (MPO) activities and luminol-lucigenin chemiluminescence levels. Serum amylase, lipase, and histopathological analyses were performed. RESULTS Elevated serum lipase and amylase levels in the vehicle-treated AP group (p<0.01) decreased in the ATX and ATX+GW groups (p<0.05). In the AP groups, GSH was reduced and MDA, MPO, luminol, and lucigenin levels were increased (p<0.05-0.001). ATX reversed these changes (p<0.05-0.001). The vehicle-treated group revealed significant severe cytoplasmic degeneration and vacuolization, whereas ATX ameliorated these destructions. GW6471 did not abolish the positive effects of ATX biochemically or histologically. CONCLUSION ATX has a potent protective effect on AP via its radical scavenging and antioxidant properties. Therefore, we believe that ATX may have therapeutic potential.
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Affiliation(s)
- Dilek Özbeyli
- Department of Medical Pathological Techniques, Marmara University, Vocational School of Health Services, İstanbul, Turkey
| | - Esra Bihter Gürler
- Department of Physiology, Atlas University School of Medicine, İstanbul, Turkey
| | - Hülya Buzcu
- Department of Physiology, Marmara University School of Medicine, İstanbul, Turkey
| | | | - Muhammet Emin Çam
- Department of Pharmacology, Marmara University School of Pharmacy, İstanbul, Turkey; University College London, Department of Mechanical Engineering,Torrington Place, London, UK
| | - Meral Yüksel
- Department of Medical Laboratory Techniques, Marmara University Vocational School of Health Services, İstanbul, Turkey
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Fusco R, Cordaro M, Siracusa R, D’Amico R, Genovese T, Gugliandolo E, Peritore AF, Crupi R, Impellizzeri D, Cuzzocrea S, Di Paola R. Biochemical Evaluation of the Antioxidant Effects of Hydroxytyrosol on Pancreatitis-Associated Gut Injury. Antioxidants (Basel) 2020; 9:antiox9090781. [PMID: 32842687 PMCID: PMC7555523 DOI: 10.3390/antiox9090781] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2020] [Revised: 08/11/2020] [Accepted: 08/21/2020] [Indexed: 12/12/2022] Open
Abstract
Acute pancreatitis is a severe abdominal pathology often associated with several complications including gut dysfunction. Oxidative stress is one of the most important pathways involved in this pathology. Hydroxytyrosol (HT), a phenolic compound obtained from olive oil, has shown anti-inflammatory and antioxidant properties. We evaluated the effects of HT administration on pancreatic and intestinal injury induced by caerulein administration. CD1 female mice were administered caerulein (50 μg/kg) for 10 h. HT treatment (5 mg/kg) was performed 30 min after the first caerulein injection and for two consecutive hours afterwards. One hour after the last caerulein injection, mice were sacrificed and serum, colon and pancreatic tissue samples were collected. HT was able to reduce the serum hallmarks of pancreatitis (amylase and lipase), histological damage score in both pancreas and colon tissue, inflammatory cells recruitment (mast cells) in both injured tissues, intrapancreatic trypsin activity and overexpression of the adhesion molecules (Intercellular Adhesion Molecule-1 (ICAM-1) and P-selectin) in colon. Additionally, HT reduced cytokine (interleukin 1 beta (IL- 1β), interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α)) levels in serum, pancreas and colon tissue and chemokine release (monocyte chemotactic protein-1 (MCP1/CCL2)) in pancreas and colon tissue. HT decreased lipid peroxidation and oxidative stress (superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione S-transferase (GST) activity) by enhancing the nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) in both injured tissues. Moreover, HT preserved intestinal barrier integrity, as shown by the diamine oxidase (DAO) serum levels and tight junction (zonula occludens (ZO) and occludin) expression in pancreas and colon. Our findings demonstrated that HT would be an important therapeutic tool against pancreatitis-induced injuries in the pancreas and gut.
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Affiliation(s)
- Roberta Fusco
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy; (R.F.); (R.S.); (R.A.); (T.G.); (E.G.); (A.F.P.); (R.D.P.)
| | - Marika Cordaro
- Department of Biomedical, Dental and Morphological and Functional Imaging University of Messina, Via Consolare Valeria, 98125 Messina, Italy;
| | - Rosalba Siracusa
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy; (R.F.); (R.S.); (R.A.); (T.G.); (E.G.); (A.F.P.); (R.D.P.)
| | - Ramona D’Amico
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy; (R.F.); (R.S.); (R.A.); (T.G.); (E.G.); (A.F.P.); (R.D.P.)
| | - Tiziana Genovese
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy; (R.F.); (R.S.); (R.A.); (T.G.); (E.G.); (A.F.P.); (R.D.P.)
| | - Enrico Gugliandolo
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy; (R.F.); (R.S.); (R.A.); (T.G.); (E.G.); (A.F.P.); (R.D.P.)
| | - Alessio Filippo Peritore
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy; (R.F.); (R.S.); (R.A.); (T.G.); (E.G.); (A.F.P.); (R.D.P.)
| | - Rosalia Crupi
- Department of Veterinary Sciences, University of Messina, 98168 Messina, Italy;
| | - Daniela Impellizzeri
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy; (R.F.); (R.S.); (R.A.); (T.G.); (E.G.); (A.F.P.); (R.D.P.)
- Correspondence: (D.I.); (S.C.); Tel.: +39-090-676-5208 (D.I. & S.C.)
| | - Salvatore Cuzzocrea
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy; (R.F.); (R.S.); (R.A.); (T.G.); (E.G.); (A.F.P.); (R.D.P.)
- Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, Saint Louis, MO 63104, USA
- Correspondence: (D.I.); (S.C.); Tel.: +39-090-676-5208 (D.I. & S.C.)
| | - Rosanna Di Paola
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy; (R.F.); (R.S.); (R.A.); (T.G.); (E.G.); (A.F.P.); (R.D.P.)
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Gao GZ, Hao YX. Progress in research of liver injury induced by acute biliary pancreatitis. Shijie Huaren Xiaohua Zazhi 2020; 28:81-85. [DOI: 10.11569/wcjd.v28.i3.81] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Acute biliary pancreatitis (ABP) not only causes acute inflammation of the pancreas, but also leads to obstruction or infection of the biliary system. Liver injury is one of the most common complications of ABP. The pathological mechanisms mainly include infection and endotoxin, cholestasis, pancreatic enzyme damage, microcirculatory disorders, and oxidative stress, and the research conclusions are mostly derived from animal experiments. On the basis of routine medical treatment of ABP, active anti-infective treatment and rapid relief of biliary obstruction can promote the recovery of ABP-related liver injury.
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Affiliation(s)
- Guang-Zhou Gao
- Department of Gastroenterology (Division II), Baoding First Central Hospital, Baoding 071300, Hebei Province, China
| | - Ying-Xia Hao
- Department of Gastroenterology (Division II), Baoding First Central Hospital, Baoding 071300, Hebei Province, China
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Sundar V, Senthil Kumar KA, Manickam V, Ramasamy T. Current trends in pharmacological approaches for treatment and management of acute pancreatitis – a review. J Pharm Pharmacol 2020; 72:761-775. [DOI: 10.1111/jphp.13229] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2019] [Accepted: 12/06/2019] [Indexed: 12/12/2022]
Abstract
Abstract
Objectives
Acute pancreatitis (AP) is an inimical disorder associated with overall mortality rates between 10-15%. It is a disorder of the exocrine pancreas which is characterized by local and systemic inflammatory responses primarily driven by oxidative stress and death of pancreatic acinar cells. The severity of AP ranges from mild pancreatic edema with complete recuperative possibilities to serious systemic inflammatory response resulting in peripancreatic/pancreatic necrosis, multiple organ failure, and death.
Key findings
We have retrieved the potential alternative approaches that are developed lately for efficacious treatment of AP from the currently available literature and recently reported experimental studies. This review summarizes the need for alternative approaches and combinatorial treatment strategies to deal with AP based on literature search using specific key words in PubMed and ScienceDirect databases.
Summary
Since AP results from perturbations of multiple signaling pathways, the so called “monotargeted smart drugs” of the past decade is highly unlikely to be effective. Also, the conventional treatment approaches were mainly involved in providing palliative care instead of curing the disease. Hence, many researchers are beginning to focus on developing alternate therapies to treat AP effectively. This review also summarizes the recent trends in the combinatorial approaches available for AP treatment.
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Affiliation(s)
- Vaishnavi Sundar
- School of Biosciences and Technology, Vellore Institute of Technology, Vellore, India
| | | | - Venkatraman Manickam
- School of Biosciences and Technology, Vellore Institute of Technology, Vellore, India
| | - Tamizhselvi Ramasamy
- School of Biosciences and Technology, Vellore Institute of Technology, Vellore, India
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Huber W, Schneider J, Schmid RM. Therapie der schweren akuten Pankreatitis. DER GASTROENTEROLOGE 2020. [DOI: 10.1007/s11377-020-00422-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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Ren YF, Wang MZ, Bi JB, Zhang J, Zhang L, Liu WM, Wei SS, Lv Y, Wu Z, Wu RQ. Irisin attenuates intestinal injury, oxidative and endoplasmic reticulum stress in mice with L-arginine-induced acute pancreatitis. World J Gastroenterol 2019; 25:6653-6667. [PMID: 31832004 PMCID: PMC6906211 DOI: 10.3748/wjg.v25.i45.6653] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2019] [Revised: 11/08/2019] [Accepted: 11/16/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Acute pancreatitis (AP) is often associated with intestinal injury, which in turn exaggerates the progression of AP. Our recent study has shown that a low level of serum irisin, a novel exercise-induced hormone, is associated with poor outcomes in patients with AP and irisin administration protects against experimental AP. However, the role of irisin in intestinal injury in AP has not been evaluated.
AIM To investigate the effect of irisin administration on intestinal injury in experimental AP.
METHODS AP was induced in male adult mice by two hourly intraperitoneal injections of L-arginine. At 2 h after the last injection of L-arginine, irisin (50 or 250 μg/kg body weight) or 1 mL normal saline (vehicle) was administered through intraperitoneal injection. The animals were sacrificed at 72 h after the induction of AP. Intestinal injury, apoptosis, oxidative and endoplasmic reticulum (ER) stress were evaluated.
RESULTS Administration of irisin significantly mitigated intestinal damage, reduced apoptosis, and attenuated oxidative and ER stress in AP mice. In addition, irisin treatment also effectively downregulated serum tumor necrosis factor-alpha and interleukin-6 levels and alleviated injury in the pancreas, liver and lung of AP mice.
CONCLUSION Irisin-mediated multiple physiological events attenuate intestinal injury following an episode of AP. Irisin has a great potential to be further developed as an effective treatment for patients with AP.
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Affiliation(s)
- Yi-Fan Ren
- National Local Joint Engineering Research Center for Precision Surgery & Regenerative Medicine, Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
| | - Meng-Zhou Wang
- National Local Joint Engineering Research Center for Precision Surgery & Regenerative Medicine, Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
| | - Jian-Bin Bi
- National Local Joint Engineering Research Center for Precision Surgery & Regenerative Medicine, Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
| | - Jia Zhang
- National Local Joint Engineering Research Center for Precision Surgery & Regenerative Medicine, Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
| | - Lin Zhang
- National Local Joint Engineering Research Center for Precision Surgery & Regenerative Medicine, Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
| | - Wu-Ming Liu
- National Local Joint Engineering Research Center for Precision Surgery & Regenerative Medicine, Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
| | - Sha-Sha Wei
- National Local Joint Engineering Research Center for Precision Surgery & Regenerative Medicine, Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
| | - Yi Lv
- National Local Joint Engineering Research Center for Precision Surgery & Regenerative Medicine, Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
| | - Zheng Wu
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
| | - Rong-Qian Wu
- National Local Joint Engineering Research Center for Precision Surgery & Regenerative Medicine, Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
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Abstract
The risks, measurements of severity, and management of severe acute pancreatitis and its complications have evolved rapidly over the past decade. Evidence suggests that initial goal directed therapy, nutritional support, and vigilance for pancreatic complications are best practice. Patients can develop pancreatic fluid collections including acute pancreatic fluid collections, pancreatic pseudocysts, acute necrotic collections, and walled-off necrosis. Several randomized controlled trials and cohort studies have recently highlighted the advantage of managing these conditions with a progressive approach, with initial draining for infection followed by less invasive techniques. Surgery is no longer an early intervention and may not be needed. Instead, interventional radiologic and endoscopic methods seem to be safer with at least as good survival outcomes. Newly developed evidence based quality indicators are available to assess and improve performance. Development and clinical testing of drugs to target the mechanisms of disease are necessary for further advancements.
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Affiliation(s)
- O Joe Hines
- Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-6904, USA
| | - Stephen J Pandol
- Department of Medicine, Cedar-Sinai Medical Center, Los Angeles, CA 90048, USA
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Abstract
PURPOSE OF REVIEW The present article will focus in pharmacologic agents that have been studied to improve acute pancreatitis outcomes, and to prevent the disease at different levels. RECENT FINDINGS Too little and too much early fluid resuscitation can be harmful. The optimal volume, rate, and duration of intravenous fluid therapy is still unknown. Nonopioid analgesics should be the first line of analgesia in patients with acute pancreatitis. A few pharmacologic agents evaluated in acute pancreatitis have resulted in positive pilot trials; however, larger randomized clinical trials (RCTs) are needed before final conclusions. Statin use is associated with lower incidence of acute pancreatitis in the general population and ongoing studies are evaluating its preventive role in acute pancreatitis recurrences. The preventive role of rectal indomethacin in post-endoscopic retrograde cholangiopancreatography pancreatitis is indisputable, with subject selection and timing of administration requiring further investigation. SUMMARY There is still no proven effective disease-specific pharmacologic therapy that changes the natural history of acute pancreatitis. New therapeutic targets and pharmacologic agents are in the horizon. Careful refinement in study design is needed when planning future RCTs. There is also a need for drug development aiming at reducing the incidence of the disease and preventing its sequelae.
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Garg PK, Singh VP. Organ Failure Due to Systemic Injury in Acute Pancreatitis. Gastroenterology 2019; 156:2008-2023. [PMID: 30768987 PMCID: PMC6486861 DOI: 10.1053/j.gastro.2018.12.041] [Citation(s) in RCA: 336] [Impact Index Per Article: 56.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2018] [Revised: 12/07/2018] [Accepted: 12/29/2018] [Indexed: 02/07/2023]
Abstract
Acute pancreatitis may be associated with both local and systemic complications. Systemic injury manifests in the form of organ failure, which is seen in approximately 20% of all cases of acute pancreatitis and defines "severe acute pancreatitis." Organ failure typically develops early in the course of acute pancreatitis, but also may develop later due to infected pancreatic necrosis-induced sepsis. Organ failure is the most important determinant of outcome in acute pancreatitis. We review here the current understanding of the risk factors, pathophysiology, timing, impact on outcome, and therapy of organ failure in acute pancreatitis. As we discuss the pathophysiology of severe systemic injury, the distinctions between markers and mediators of severity are highlighted based on evidence supporting their causality in organ failure. Emphasis is placed on clinically relevant end points of organ failure and the mechanisms underlying the pathophysiological perturbations, which offer insight into potential therapeutic targets to treat.
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Mitochondrial Targeting of Antioxidants Alters Pancreatic Acinar Cell Bioenergetics and Determines Cell Fate. Int J Mol Sci 2019; 20:ijms20071700. [PMID: 30959771 PMCID: PMC6480340 DOI: 10.3390/ijms20071700] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2019] [Revised: 03/27/2019] [Accepted: 04/03/2019] [Indexed: 12/11/2022] Open
Abstract
Mitochondrial dysfunction is a core feature of acute pancreatitis, a severe disease in which oxidative stress is elevated. Mitochondrial targeting of antioxidants is a potential therapeutic strategy for this and other diseases, although thus far mixed results have been reported. We investigated the effects of mitochondrial targeting with the antioxidant MitoQ on pancreatic acinar cell bioenergetics, adenosine triphosphate (ATP) production and cell fate, in comparison with the non-antioxidant control decyltriphenylphosphonium bromide (DecylTPP) and general antioxidant N-acetylcysteine (NAC). MitoQ (µM range) and NAC (mM range) caused sustained elevations of basal respiration and the inhibition of spare respiratory capacity, which was attributable to an antioxidant action since these effects were minimal with DecylTPP. Although MitoQ but not DecylTPP decreased cellular NADH levels, mitochondrial ATP turnover capacity and cellular ATP concentrations were markedly reduced by both MitoQ and DecylTPP, indicating a non-specific effect of mitochondrial targeting. All three compounds were associated with a compensatory elevation of glycolysis and concentration-dependent increases in acinar cell apoptosis and necrosis. These data suggest that reactive oxygen species (ROS) contribute a significant negative feedback control of basal cellular metabolism. Mitochondrial targeting using positively charged molecules that insert into the inner mitochondrial member appears to be deleterious in pancreatic acinar cells, as does an antioxidant strategy for the treatment of acute pancreatitis.
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Abstract
Acute pancreatitis (AP) has an annual incidence of 30-45 per 100,000 inhabitants. In Germany approximately one third of the cases are of biliary or alcoholic origin. The diagnosis is based on the typical epigastric pain with radiation and a threefold increase of lipase or amylase in serum. Imaging procedures only rarely need to be included for the primary diagnostics. An early risk assessment is important to be able to allocate patients with severe AP to surveillance in an intensive care unit (ICU). Elevation of blood urea nitrogen, hematocrit and blood glucose are early predictors of poor outcome.The removal of impacted gall-stones by endoscopic retrograde cholangiography (ERC) is the only causal treatment of biliary AP, which must be carried out when there are signs of cholangitis and in severe biliary AP. Pain management and early fluid substitution are the most important symptomatic approaches. In the early phase of AP 150-250 ml/h of crystalloid solution should be administered to compensate for the extravasal loss of fluid. In certain cases, the initial fluid requirement might be even higher. In the ICU setting echocardiography and advanced hemodynamic monitoring are available for guidance. Prophylactic antibiotic treatment is not recommended in mild AP and it is a matter of debate even in severe AP. Early enteral nutrition has been shown to improve the outcome. Even in cases of fluid collection and necrosis a primary surgery approach should be avoided in favor of a "step-up" procedure with radiologically guided drainage as well as endoscopic and if necessary video-assisted percutaneous retroperitoneal débridement. Surgery remains an option for complications and for infected necrosis which cannot be reached by any other means.
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Affiliation(s)
- Wolfgang Huber
- Medizinische Klinik und Poliklinik II, Universitätsklinikum rechts der Isar, Technische Universität München, Ismaninger Str. 22, 81675, München, Deutschland.
| | - Hana Algül
- Medizinische Klinik und Poliklinik II, Universitätsklinikum rechts der Isar, Technische Universität München, Ismaninger Str. 22, 81675, München, Deutschland.
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Angelino D, Godos J, Ghelfi F, Tieri M, Titta L, Lafranconi A, Marventano S, Alonzo E, Gambera A, Sciacca S, Buscemi S, Ray S, Galvano F, Del Rio D, Grosso G. Fruit and vegetable consumption and health outcomes: an umbrella review of observational studies. Int J Food Sci Nutr 2019; 70:652-667. [PMID: 30764679 DOI: 10.1080/09637486.2019.1571021] [Citation(s) in RCA: 149] [Impact Index Per Article: 24.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The aim of this study was to provide a comprehensive evaluation of current evidence on fruit and vegetable consumption and health outcomes. A systematic search for quantitative syntheses was performed. Several criteria, including study design, dose-response relationship, heterogeneity and agreement of results over time, and identification of potential confounding factors, were used to assess the level of evidence. The strongest (probable) evidence was found for cardiovascular disease protection; possible evidence for decreased risk of colon cancer, depression and pancreatic diseases was found for fruit intake; and colon and rectal cancer, hip fracture, stroke, depression and pancreatic diseases was found for vegetable intake. Suggestive and rather limited associations with other outcomes have been found. Evidence of potential confounding by sex and geographical localisation has been reported. Despite findings are consistent enough for hypothesising causation (at least for cardiovascular-related outcomes), further studies are needed to clarify the role of potential confounding factors.
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Affiliation(s)
- Donato Angelino
- a The Laboratory of Phytochemicals in Physiology, Department of Food and Drug , University of Parma , Parma , Italy
| | - Justyna Godos
- b Department of Biomedical and Biotechnological Sciences , University of Catania , Catania , Italy.,c NNEdPro Global Centre for Nutrition and Health , St John's Innovation Centre , Cambridge , United Kingdom.,d Wolfson College at the University of Cambridge , United Kingdom.,e Nutrition Innovation Centre for Food and Health at Ulster University , United Kingdom
| | - Francesca Ghelfi
- c NNEdPro Global Centre for Nutrition and Health , St John's Innovation Centre , Cambridge , United Kingdom.,d Wolfson College at the University of Cambridge , United Kingdom.,e Nutrition Innovation Centre for Food and Health at Ulster University , United Kingdom.,f SmartFood Program, Department of Experimental Oncology, IEO, European Institute of Oncology IRCCS , Milan , Italy
| | - Maria Tieri
- f SmartFood Program, Department of Experimental Oncology, IEO, European Institute of Oncology IRCCS , Milan , Italy
| | - Lucilla Titta
- f SmartFood Program, Department of Experimental Oncology, IEO, European Institute of Oncology IRCCS , Milan , Italy
| | - Alessandra Lafranconi
- g Biccoca , University of Milano , Milan , Italy.,h Care and Public Health Research Institute , Maastricht University , Maastricht , The Netherlands
| | - Stefano Marventano
- i Rimini Women's Health, Childhood and Adolescent Department , AUSL Romagna , Rimini , Italy
| | - Elena Alonzo
- j Food and Nutrition Security and Public Health Service , ASP Catania , Catania , Italy
| | - Angelo Gambera
- k Azienda Ospedaliero-Universitaria Policlinico-Vittorio Emanuele , Catania , Italy
| | - Salvatore Sciacca
- l Integrated Cancer Registry of Catania-Messina-Siracusa-Enna , Azienda Ospedaliero-Universitaria Policlinico-Vittorio Emanuele , Catania , Italy
| | - Silvio Buscemi
- m Biomedical Department of Internal and Specialist Medicine (DIBIMIS) , University of Palermo , Palermo , Italy
| | - Sumantra Ray
- c NNEdPro Global Centre for Nutrition and Health , St John's Innovation Centre , Cambridge , United Kingdom.,d Wolfson College at the University of Cambridge , United Kingdom.,e Nutrition Innovation Centre for Food and Health at Ulster University , United Kingdom.,n Medical Research Council (MRC) Human Nutrition Research Unit , Cambridge , United Kingdom
| | - Fabio Galvano
- b Department of Biomedical and Biotechnological Sciences , University of Catania , Catania , Italy
| | - Daniele Del Rio
- a The Laboratory of Phytochemicals in Physiology, Department of Food and Drug , University of Parma , Parma , Italy.,c NNEdPro Global Centre for Nutrition and Health , St John's Innovation Centre , Cambridge , United Kingdom.,d Wolfson College at the University of Cambridge , United Kingdom.,e Nutrition Innovation Centre for Food and Health at Ulster University , United Kingdom.,o The Laboratory of Phytochemicals in Physiology, Department of Veterinary Science , University of Parma , Parma , Italy
| | - Giuseppe Grosso
- b Department of Biomedical and Biotechnological Sciences , University of Catania , Catania , Italy.,c NNEdPro Global Centre for Nutrition and Health , St John's Innovation Centre , Cambridge , United Kingdom.,d Wolfson College at the University of Cambridge , United Kingdom.,e Nutrition Innovation Centre for Food and Health at Ulster University , United Kingdom
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Huber W, Algül H, Lahmer T, Mayr U, Lehmann M, Schmid RM, Faltlhauser A. Pancreatitis cytosorbents (CytoSorb) inflammatory cytokine removal: A Prospective Study (PACIFIC). Medicine (Baltimore) 2019; 98:e13044. [PMID: 30681551 PMCID: PMC6358351 DOI: 10.1097/md.0000000000013044] [Citation(s) in RCA: 11] [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] [Indexed: 01/09/2023] Open
Abstract
BACKGROUND Acute pancreatitis (AP) usually has a mild course with a mortality rate below 1%. However, around 10% of patients develop severe AP (SAP) involving extra-pancreatic tissues and other organ systems. The mortality of SAP is around 42%. The outcome of SAP is closely related to the development of systemic inflammation and consecutive organ failures. Most current therapies including fluid resuscitation, antimicrobial therapy, drainage procedures, and endoscopic management of complications are symptomatic rather than causative approaches, except sphincterotomy for gallstone pancreatitis. Regarding the high mortality of SAP and its close association with systemic inflammation, extracorporeal removal of inflammatory mediators is an appealing approach. Several recent studies have demonstrated that the CytoSorb adsorber effectively eliminates inflammatory cytokines, such as IL-1ß, IL-6, IL-8, IL-10, and TNF-alpha. Some of these trials suggested that therapy with CytoSorb might improve outcome, including a reduction in the vasopressor dosage and reversal of shock.Therefore, it is the objective of this study to evaluate the effectiveness of 2 consecutive 24 h-treatments with CytoSorb on hemodynamics in patients with early SAP. METHODS This study includes patients with early SAP (APACHE-II ≥10) and transpulmonary thermodilution hemodynamic monitoring (PiCCO; EV-1000) within a maximum of seven days from the onset of pain. Eligible patients will be treated with 2 consecutive periods of CytoSorb. A 20%-improvement in the vasopressor dependency index (VDI) - which relates is derived from mean arterial pressure (MAP) and catecholamine dosage - is the primary outcome. In addition to this clinical outcome, there are several laboratory (cytokine levels) and translational endpoints (including multiplex-ELISAs of numerous anti- and pro-inflammatory cytokines/chemokines and DNA analyses). Primary outcome analysis will compare the incidence of the primary endpoint in 30 patients from the intervention group to 60 matched controls with advanced hemodynamic monitoring recruited from recent studies in SAP within the same setting and the same centers. DISCUSSION A potential improvement in hemodynamics and/or other outcomes by CytoSorb would provide a new therapeutic option in the early treatment of SAP with a pathophysiological rationale. TRIAL REGISTRATION This study was registered on March 17, 2017 (ClinicalTrials.gov Identifier: NCT03082469). URL: https://clinicaltrials.gov/ct2/show/NCT03082469. VERSION V_PACIFIC_1.0 September 30, 2018.
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Affiliation(s)
- Wolfgang Huber
- Medizinische Klinik und Poliklinik II, Klinikum rechts der Isar; Technische Universität, München, Ismaninger Straße 22, D-81675 München
| | - Hana Algül
- Medizinische Klinik und Poliklinik II, Klinikum rechts der Isar; Technische Universität, München, Ismaninger Straße 22, D-81675 München
| | - Tobias Lahmer
- Medizinische Klinik und Poliklinik II, Klinikum rechts der Isar; Technische Universität, München, Ismaninger Straße 22, D-81675 München
| | - Ulrich Mayr
- Medizinische Klinik und Poliklinik II, Klinikum rechts der Isar; Technische Universität, München, Ismaninger Straße 22, D-81675 München
| | - Miriam Lehmann
- Medizinische Klinik und Poliklinik II, Klinikum rechts der Isar; Technische Universität, München, Ismaninger Straße 22, D-81675 München
| | - Roland M. Schmid
- Medizinische Klinik und Poliklinik II, Klinikum rechts der Isar; Technische Universität, München, Ismaninger Straße 22, D-81675 München
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Machado MCC, Souza HP. The increased severity of acute pancreatitis in the elderly is mainly related to intestinal barrier dysfunction. Hepatobiliary Pancreat Dis Int 2018; 17:575-577. [PMID: 30292687 DOI: 10.1016/j.hbpd.2018.09.018] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2018] [Accepted: 09/17/2018] [Indexed: 02/07/2023]
Affiliation(s)
| | - Heraldo Possolo Souza
- Emergency Department, Faculdade de Medicina Universidade de São Paulo, São Paulo, Brazil
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Langlois PL, Manzanares W, Adhikari NKJ, Lamontagne F, Stoppe C, Hill A, Heyland DK. Vitamin C Administration to the Critically Ill: A Systematic Review and Meta-Analysis. JPEN J Parenter Enteral Nutr 2018; 43:335-346. [PMID: 30452091 DOI: 10.1002/jpen.1471] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2018] [Accepted: 10/09/2018] [Indexed: 12/12/2022]
Abstract
Vitamin C, an enzyme cofactor and antioxidant, could hasten the resolution of inflammation, oxidative stress, and microvascular dysfunction. While observational studies have demonstrated that critical illness is associated with low levels of vitamin C, randomized controlled trials (RCTs) of vitamin C, alone or in combination with other antioxidants, have yielded contradicting results. We searched MEDLINE, EMBASE, CINAHL, and the Cochrane Central Register of Controlled Trials (inception to December 2017) for RCTs comparing vitamin C, by enteral or parenteral routes, with placebo or none, in intensive care unit (ICU) patients. Two independent reviewers assessed study eligibility without language restrictions and abstracted data. Overall mortality was the primary outcome; secondary outcomes were incident infections, ICU length of stay (LOS), hospital LOS, and duration of mechanical ventilation (MV). We prespecified 5 subgroups hypothesized to benefit more from vitamin C. Eleven randomized trials were included. When 9 RCTs (n = 1322) reporting mortality were pooled, vitamin C was not associated with reduced risk of mortality (risk ratio [RR] 0.72, 95% confidence interval [CI]: 0.43-1.20, P = .21). No effect was found on infections, ICU or hospital LOS, or duration of MV. In multiple subgroup comparison, no statistically significant subgroup effects were observed. However, we did observe a tendency towards a mortality reduction (RR 0.21; 95% CI: 0.04-1.05; P = .06) when intravenous high-dose vitamin C monotherapy was administered. Current evidence does not support supplementing critically ill patients with vitamin C. A moderately large treatment effect may exist, but further studies, particularly of monotherapy administration, are warranted.
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Affiliation(s)
- Pascal L Langlois
- Department of Anesthesiology and Reanimation, Faculty of Medicine and Health Sciences, Sherbrooke University Hospital, Sherbrooke, Québec, Canada
| | - William Manzanares
- Department of Critical Care, Intensive Care Unit, University Hospital, Faculty of Medicine, Universidad de la Republica, Montevideo, Uruguay
| | - Neill K J Adhikari
- Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Ontario, Canada
| | - François Lamontagne
- Department of Intensive Care Medicine, Faculty of Medicine and Health Sciences, Sherbrooke University Hospital, Sherbrooke, Québec, Canada
| | - Christian Stoppe
- Department of Intensive Care Medicine, University Hospital Rheinisch-Westfälische Technische Hochschule Aachen, Aachen, Germany
| | - Aileen Hill
- Department of Intensive Care Medicine, University Hospital Rheinisch-Westfälische Technische Hochschule Aachen, Aachen, Germany
| | - Daren K Heyland
- Clinical Evaluation Research Unit, Kingston General Hospital, Kingston, Ontario, Canada and Department of Critical Care, Queen's University, Kingston, Ontario, Canada
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43
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Zhang M, Jativa DF. Vitamin C supplementation in the critically ill: A systematic review and meta-analysis. SAGE Open Med 2018; 6:2050312118807615. [PMID: 30364374 PMCID: PMC6196621 DOI: 10.1177/2050312118807615] [Citation(s) in RCA: 43] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2018] [Accepted: 09/21/2018] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND Low plasma levels of vitamin C are associated with adverse outcomes, including increased mortality, in critically ill patients. Several trials have suggested that the administration of intravenous vitamin C in this setting may have beneficial effects, such as reducing the incidence of organ failure and improving survival. However, these studies have generally involved combination therapies consisting of vitamin C along with other antioxidants, confounding the effects of vitamin C alone. The primary objective of this meta-analysis is to investigate the effects of isolated intravenous supplementation of vitamin C in adults with critical illness. METHODS A database search was conducted for studies on the use of intravenous vitamin C in adult patients with critical illness. The primary outcome assessed was mortality at the longest follow-up time available. Secondary outcomes were the duration of mechanical ventilation, duration of vasopressor support, fluid requirements, and urine output in the first 24 h of intensive care unit admission. RESULTS Five studies (four randomized controlled trials and one retrospective review) enrolling a total of 142 patients were included in this meta-analysis. Compared with controls, the administration of intravenous vitamin C was associated with a decreased need for vasopressor support (standardized mean difference -0.71; 95% confidence interval (-1.16 to -0.26); p = 0.002) and decreased duration of mechanical ventilation (standardized mean difference -0.5; 95% confidence interval (-0.93 to -0.06); p = 0.03), but no difference was found in mortality (odds ratio 0.76; 95% confidence interval (0.27 to 2.16); p = 0.6). Trends were also noted toward decreased fluid requirements and increased urine output. No adverse effects were reported. CONCLUSION The administration of intravenous vitamin C may lead to vasopressor sparing effects and a reduced need for mechanical ventilation in the critically ill, without affecting overall mortality. However, these results should be interpreted in light of the limitations of the primary literature and should serve as a preview of upcoming trials in this area.
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Affiliation(s)
- Michael Zhang
- Department of Medicine, VA Medical Center, Cleveland, OH, USA
| | - David F Jativa
- Department of Medicine, Aventura Hospital & Medical Center, Aventura, FL, USA
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Padhan RK, Jain S, Agarwal S, Harikrishnan S, Vadiraja P, Behera S, Jain SK, Dhingra R, Dash NR, Sahni P, Garg PK. Primary and Secondary Organ Failures Cause Mortality Differentially in Acute Pancreatitis and Should be Distinguished. Pancreas 2018; 47:302-307. [PMID: 29401171 DOI: 10.1097/mpa.0000000000000998] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
OBJECTIVE The aim of this study was to study the development of early and late organ failure (OF) and their differential impact on mortality in patients with acute pancreatitis (AP). METHODS Consecutive patients (N = 805) with acute pancreatitis were included in an observational study. Organ failure was categorized as primary if it occurred early due to pancreatitis per se and secondary if it occurred late due to infected pancreatic necrosis (IPN). Primary outcome was a relative contribution of primary OF, secondary OF, and IPN to mortality. RESULTS Of the 614 patients (mean age, 38.8; standard deviation, 14.6 years; 430 males) in a derivation cohort, 274 (44.6%) developed OF, with 177 having primary OF and 97 secondary OF due to sepsis. Primary OF caused early mortality in 15.8% and was a risk factor for IPN in 76% of patients. Mortality in patients with primary OF and IPN was 49.5% versus 36% in those with IPN and secondary OF (P = 0.06) and 4% in those with IPN but without OF (P < 0.001). The results of the 191 patients in the validation cohort confirmed the relative contribution of primary and secondary OF to mortality. CONCLUSION Primary and secondary OF contributed to mortality independently and are distinct in their timing, window of opportunity for intervention, and prognosis.
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Pan LL, Li J, Shamoon M, Bhatia M, Sun J. Recent Advances on Nutrition in Treatment of Acute Pancreatitis. Front Immunol 2017; 8:762. [PMID: 28713382 PMCID: PMC5491641 DOI: 10.3389/fimmu.2017.00762] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2017] [Accepted: 06/16/2017] [Indexed: 12/12/2022] Open
Abstract
Acute pancreatitis (AP) is a common abdominal acute inflammatory disorder and the leading cause of hospital admission for gastrointestinal disorders in many countries. Clinical manifestations of AP vary from self-limiting local inflammation to devastating systemic pathological conditions causing significant morbidity and mortality. To date, despite extensive efforts in translating promising experimental therapeutic targets in clinical trials, disease-specific effective remedy remains obscure, and supportive care has still been the primary treatment for this disease. Emerging evidence, in light of the current state of pathophysiology of AP, has highlighted that strategic initiation of nutrition with appropriate nutrient supplementation are key to limit local inflammation and to prevent or manage AP-associated complications. The current review focuses on recent advances on nutritional interventions including enteral versus parenteral nutrition strategies, and nutritional supplements such as probiotics, glutamine, omega-3 fatty acids, and vitamins in clinical AP, hoping to advance current knowledge and practice related to nutrition and nutritional supplements in clinical management of AP.
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Affiliation(s)
- Li-Long Pan
- School of Medicine, Jiangnan University, Wuxi, China
| | - Jiahong Li
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, China
- Nutrition and Immunology Laboratory, School of Food Science and Technology, Jiangnan University, Wuxi, China
| | - Muhammad Shamoon
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, China
- Nutrition and Immunology Laboratory, School of Food Science and Technology, Jiangnan University, Wuxi, China
| | - Madhav Bhatia
- Inflammation Research Group, Department of Pathology, University of Otago, Christchurch, New Zealand
| | - Jia Sun
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, China
- Nutrition and Immunology Laboratory, School of Food Science and Technology, Jiangnan University, Wuxi, China
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Husain SZ, Srinath AI. What's unique about acute pancreatitis in children: risk factors, diagnosis and management. Nat Rev Gastroenterol Hepatol 2017; 14:366-372. [PMID: 28293024 DOI: 10.1038/nrgastro.2017.13] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Pancreatitis in children is an appreciable problem that has become increasingly prevalent. This Review covers the principles related to the definitions, epidemiology, risk factors, diagnosis and management of acute pancreatitis in children and identifies features that are unique among children. Additionally, knowledge gaps related to management principles are identified.
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Affiliation(s)
- Sohail Z Husain
- Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center, Pediatrics, 4401 Penn Avenue, Pittsburgh, Pennsylvania 15224, USA
| | - Arvind I Srinath
- Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center, Pediatrics, 4401 Penn Avenue, Pittsburgh, Pennsylvania 15224, USA
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Moggia E, Koti R, Belgaumkar AP, Fazio F, Pereira SP, Davidson BR, Gurusamy KS. Pharmacological interventions for acute pancreatitis. Cochrane Database Syst Rev 2017; 4:CD011384. [PMID: 28431202 PMCID: PMC6478067 DOI: 10.1002/14651858.cd011384.pub2] [Citation(s) in RCA: 44] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
BACKGROUND In people with acute pancreatitis, it is unclear what the role should be for medical treatment as an addition to supportive care such as fluid and electrolyte balance and organ support in people with organ failure. OBJECTIVES To assess the effects of different pharmacological interventions in people with acute pancreatitis. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL, 2016, Issue 9), MEDLINE, Embase, Science Citation Index Expanded, and trial registers to October 2016 to identify randomised controlled trials (RCTs). We also searched the references of included trials to identify further trials. SELECTION CRITERIA We considered only RCTs performed in people with acute pancreatitis, irrespective of aetiology, severity, presence of infection, language, blinding, or publication status for inclusion in the review. DATA COLLECTION AND ANALYSIS Two review authors independently identified trials and extracted data. We did not perform a network meta-analysis as planned because of the lack of information on potential effect modifiers and differences of type of participants included in the different comparisons, when information was available. We calculated the odds ratio (OR) with 95% confidence intervals (CIs) for the binary outcomes and rate ratios with 95% CIs for count outcomes using a fixed-effect model and random-effects model. MAIN RESULTS We included 84 RCTs with 8234 participants in this review. Six trials (N = 658) did not report any of the outcomes of interest for this review. The remaining 78 trials excluded 210 participants after randomisation. Thus, a total of 7366 participants in 78 trials contributed to one or more outcomes for this review. The treatments assessed in these 78 trials included antibiotics, antioxidants, aprotinin, atropine, calcitonin, cimetidine, EDTA (ethylenediaminetetraacetic acid), gabexate, glucagon, iniprol, lexipafant, NSAIDs (non-steroidal anti-inflammatory drugs), octreotide, oxyphenonium, probiotics, activated protein C, somatostatin, somatostatin plus omeprazole, somatostatin plus ulinastatin, thymosin, ulinastatin, and inactive control. Apart from the comparison of antibiotics versus control, which included a large proportion of participants with necrotising pancreatitis, the remaining comparisons had only a small proportion of patients with this condition. Most trials included either only participants with severe acute pancreatitis or included a mixture of participants with mild acute pancreatitis and severe acute pancreatitis (75 trials). Overall, the risk of bias in trials was unclear or high for all but one of the trials. SOURCE OF FUNDING seven trials were not funded or funded by agencies without vested interest in results. Pharmaceutical companies partially or fully funded 21 trials. The source of funding was not available from the remaining trials.Since we considered short-term mortality as the most important outcome, we presented only these results in detail in the abstract. Sixty-seven studies including 6638 participants reported short-term mortality. There was no evidence of any differences in short-term mortality in any of the comparisons (very low-quality evidence). With regards to other primary outcomes, serious adverse events (number) were lower than control in participants taking lexipafant (rate ratio 0.67, 95% CI 0.46 to 0.96; N = 290; 1 study; very low-quality evidence), octreotide (rate ratio 0.74, 95% CI 0.60 to 0.89; N = 770; 5 studies; very low-quality evidence), somatostatin plus omeprazole (rate ratio 0.36, 95% CI 0.19 to 0.70; N = 140; 1 study; low-quality evidence), and somatostatin plus ulinastatin (rate ratio 0.30, 95% CI 0.15 to 0.60; N = 122; 1 study; low-quality evidence). The proportion of people with organ failure was lower in octreotide than control (OR 0.51, 95% CI 0.27 to 0.97; N = 430; 3 studies; very low-quality evidence). The proportion of people with sepsis was lower in lexipafant than control (OR 0.26, 95% CI 0.08 to 0.83; N = 290; 1 study; very low-quality evidence). There was no evidence of differences in any of the remaining comparisons in these outcomes or for any of the remaining primary outcomes (the proportion of participants experiencing at least one serious adverse event and the occurrence of infected pancreatic necrosis). None of the trials reported heath-related quality of life. AUTHORS' CONCLUSIONS Very low-quality evidence suggests that none of the pharmacological treatments studied decrease short-term mortality in people with acute pancreatitis. However, the confidence intervals were wide and consistent with an increase or decrease in short-term mortality due to the interventions. We did not find consistent clinical benefits with any intervention. Because of the limitations in the prognostic scoring systems and because damage to organs may occur in acute pancreatitis before they are clinically manifest, future trials should consider including pancreatitis of all severity but power the study to measure the differences in the subgroup of people with severe acute pancreatitis. It may be difficult to power the studies based on mortality. Future trials in participants with acute pancreatitis should consider other outcomes such as complications or health-related quality of life as primary outcomes. Such trials should include health-related quality of life, costs, and return to work as outcomes and should follow patients for at least three months (preferably for at least one year).
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Affiliation(s)
- Elisabetta Moggia
- IRCCS Humanitas Research HospitalDepartment of General and Digestive SurgeryVia Manzoni 5620089 RozzanoMilanItaly20089
| | - Rahul Koti
- Royal Free Campus, UCL Medical SchoolDepartment of SurgeryRoyal Free HospitalPond StreetLondonUKNW3 2QG
| | - Ajay P Belgaumkar
- Ashford and St Peter's NHS TrustDept of Upper GI SurgerySt Peter's HospitalGuildford RoadChertseySurreyUKKT16 0PZ
| | - Federico Fazio
- Royal Free Hospital, NHS Foundation TrustHPB and Liver Transplant SurgeryLondonUK
| | - Stephen P Pereira
- Royal Free Hospital CampusUCL Institute for Liver and Digestive HealthUpper 3rd FloorLondonUKNW3 2PF
| | - Brian R Davidson
- Royal Free Campus, UCL Medical SchoolDepartment of SurgeryRoyal Free HospitalPond StreetLondonUKNW3 2QG
| | - Kurinchi Selvan Gurusamy
- Royal Free Campus, UCL Medical SchoolDepartment of SurgeryRoyal Free HospitalPond StreetLondonUKNW3 2QG
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48
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Anchi P, Khurana A, Bale S, Godugu C. The Role of Plant-derived Products in Pancreatitis: Experimental and Clinical Evidence. Phytother Res 2017; 31:591-623. [DOI: 10.1002/ptr.5792] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2016] [Revised: 02/03/2017] [Accepted: 02/06/2017] [Indexed: 12/13/2022]
Affiliation(s)
- Pratibha Anchi
- Department of Regulatory Toxicology; National Institute of Pharmaceutical Education and Research (NIPER), Balanagar; Hyderabad Telangana India
| | - Amit Khurana
- Department of Regulatory Toxicology; National Institute of Pharmaceutical Education and Research (NIPER), Balanagar; Hyderabad Telangana India
| | - Swarna Bale
- Department of Regulatory Toxicology; National Institute of Pharmaceutical Education and Research (NIPER), Balanagar; Hyderabad Telangana India
| | - Chandraiah Godugu
- Department of Regulatory Toxicology; National Institute of Pharmaceutical Education and Research (NIPER), Balanagar; Hyderabad Telangana India
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49
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Abstract
OBJECTIVES This study was conducted to assess the preventive/therapeutic effects of combined administration of resveratrol and guggulsterone on cerulein-induced acute pancreatitis in mice. METHODS Acute pancreatitis was induced by intraperitoneal injection of cerulein in mice. Serum amylase assay and histology were performed to measure the severity of pancreatitis. Western blotting and multiplex cytokine/chemokine analysis were conducted to understand the action mechanisms of the reagents. RESULTS Serum amylase assay and histology revealed that the severity of acute pancreatitis was reduced by the combinatory treatment with resveratrol and guggulsterone, but the ratio of the band intensity implied that reduced nuclear factor-κB activation is primarily responsible for the effect. The reduced amounts of keratinocyte chemoattractant (chemokine [C-X-C motif] ligand 1), interferon gamma-induced protein 10 (C-X-C motif chemokine 10) and interleukin 6 expression in the sera could be involved in attenuated immune cell migration and reduced inflammation by these reagents. CONCLUSIONS Combinatory treatment with resveratrol and guggulsterone marginally reduced cerulein-induced mild acute pancreatitis in mice.
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50
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Lodewijkx PJ, Besselink MG, Witteman BJ, Schepers NJ, Gooszen HG, van Santvoort HC, Bakker OJ. Nutrition in acute pancreatitis: a critical review. Expert Rev Gastroenterol Hepatol 2017; 10:571-80. [PMID: 26823272 DOI: 10.1586/17474124.2016.1141048] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Severe acute pancreatitis poses unique nutritional challenges. The optimal nutritional support in patients with severe acute pancreatitis has been a subject of debate for decades. This review provides a critical review of the available literature. According to current literature, enteral nutrition is superior to parenteral nutrition, although several limitations should be taken into account. The optimal route of enteral nutrition remains unclear, but normal or nasogastric tube feeding seems safe when tolerated. In patients with predicted severe acute pancreatitis an on-demand feeding strategy is advised and when patients do not tolerate an oral diet after 72 hours, enteral nutrition can be started. The use of supplements, both parenteral as enteral, are not recommended. Optimal nutritional support in severe cases often requires a tailor-made approach with day-to-day evaluation of its effectiveness.
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Affiliation(s)
- Piet J Lodewijkx
- a Department of Surgery , Jeroen Bosch hospital , s-Hertogenbosch , The Netherlands
| | - Marc G Besselink
- b Department of Surgery , Academic Medical Center , Amsterdam , The Netherlands
| | - Ben J Witteman
- c Department of Gastroenterology and Hepatology , Hospital Gelderse Vallei Ede , Ede , The Netherlands
| | - Nicolien J Schepers
- d Department of Gastroenterology and Hepatology , Erasmus MC University Medical Center , Rotterdam , The Netherlands.,e Department of Gastroenterology and Hepatology , St. Antonius Hospital , Nieuwegein , The Netherlands
| | - Hein G Gooszen
- f Department of Operating Theatres and Evidence Based Surgery , Radboud University Medical Center , Nijmegen , The Netherlands
| | | | - Olaf J Bakker
- g Department of Surgery , University Medical Center Utrecht , Utrecht , The Netherlands
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