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Mititelu A, Grama A, Colceriu MC, Benţa G, Popoviciu MS, Pop TL. Role of Interleukin 6 in Acute Pancreatitis: A Possible Marker for Disease Prognosis. Int J Mol Sci 2024; 25:8283. [PMID: 39125854 PMCID: PMC11311934 DOI: 10.3390/ijms25158283] [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: 06/23/2024] [Revised: 07/24/2024] [Accepted: 07/27/2024] [Indexed: 08/12/2024] Open
Abstract
Acute pancreatitis (AP) is a significant cause of morbidity, even in children, and is frequently associated with systemic manifestations. There are many cytokines involved in the inflammatory response characteristic of this disease. Interleukin 6 (IL-6) is one of the most important cytokines involved in AP, beginning from cellular injury and continuing to the systemic inflammatory response and distant organ involvement. IL-6 is a multifunctional cytokine that regulates acute-phase response and inflammation. It is produced by various cells and exerts its biological role on many cells through its high-affinity complex receptor. IL-6 has been investigated as a predicting maker for severe forms of AP. Many studies have validated the use of IL-6 serum levels in the first 48 h as a reliable marker for severe evolution and multisystemic involvement. Still, it has not been used in daily practice until now. This review discusses the main binding mechanisms by which IL-6 triggers cellular response and the AP pathogenetic mechanisms in which IL-6 is involved. We then emphasize the promising role of IL-6 as a prognostic marker, which could be added as a routine marker at admission in children with AP.
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Affiliation(s)
- Alexandra Mititelu
- 2nd Pediatric Discipline, Department of Mother and Child, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania; (A.M.); (M.-C.C.); (G.B.); (T.L.P.)
| | - Alina Grama
- 2nd Pediatric Discipline, Department of Mother and Child, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania; (A.M.); (M.-C.C.); (G.B.); (T.L.P.)
- 2nd Pediatric Clinic, Emergency Clinical Hospital for Children, 400177 Cluj-Napoca, Romania
| | - Marius-Cosmin Colceriu
- 2nd Pediatric Discipline, Department of Mother and Child, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania; (A.M.); (M.-C.C.); (G.B.); (T.L.P.)
| | - Gabriel Benţa
- 2nd Pediatric Discipline, Department of Mother and Child, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania; (A.M.); (M.-C.C.); (G.B.); (T.L.P.)
| | | | - Tudor Lucian Pop
- 2nd Pediatric Discipline, Department of Mother and Child, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania; (A.M.); (M.-C.C.); (G.B.); (T.L.P.)
- 2nd Pediatric Clinic, Emergency Clinical Hospital for Children, 400177 Cluj-Napoca, Romania
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Bioinformatic Analyses of Peripheral Blood Transcriptome Identify Altered Neutrophil-Related Pathway and Different Transcriptomic Profiles for Acute Pancreatitis in Patients with and without Chylomicronemia Syndrome. Biomolecules 2023; 13:biom13020284. [PMID: 36830652 PMCID: PMC9953624 DOI: 10.3390/biom13020284] [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: 11/13/2022] [Revised: 01/31/2023] [Accepted: 02/01/2023] [Indexed: 02/05/2023] Open
Abstract
Acute pancreatitis (AP) is a serious inflammatory condition of the pancreas that can be associated with chylomicronemia syndrome (CS). Currently, no study has explored the differences between non-CS-associated AP and CS-associated AP in terms of gene expression. Transcriptomic profiles of blood samples from patients with AP were retrieved from GSE194331 (non-CS-associated) and GSE149607 (CS-associated). GSE31568 was used to examine the linkage between non-CS-associated AP and the expression of micro RNAs (miRNAs). Differentially expressed genes (DEGs) were identified, a gene regulatory network was constructed, and hub genes were defined. Subsequently, single-sample gene set enrichment analysis (ssGSEA) scores of hub genes were calculated to represent their regulatory-level activity. A total of 1851 shared DEGs were identified between non-CS-associated and CS-associated AP. Neutrophils were significantly enriched in both conditions. In non-CS-associated AP, miRNAs including hsa-miR-21, hsa-miR-146a, and hsa-miR-106a demonstrated a lower expression level as compared with the healthy control. Furthermore, the expression patterns and regulatory activities were largely opposite between non-CS-associated and CS-associated AP, with significantly lower estimated neutrophils in the latter case. In summary, we found that the regulation of neutrophils was altered in AP. There was a different gene expression pattern and lower estimated neutrophil infiltration in CS-associated AP. Whether these findings are clinically significant requires further investigation.
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Sauerbrei W, Haeussler T, Balmford J, Huebner M. Structured reporting to improve transparency of analyses in prognostic marker studies. BMC Med 2022; 20:184. [PMID: 35546237 PMCID: PMC9095054 DOI: 10.1186/s12916-022-02304-5] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2021] [Accepted: 02/17/2022] [Indexed: 11/24/2022] Open
Abstract
BACKGROUND Factors contributing to the lack of understanding of research studies include poor reporting practices, such as selective reporting of statistically significant findings or insufficient methodological details. Systematic reviews have shown that prognostic factor studies continue to be poorly reported, even for important aspects, such as the effective sample size. The REMARK reporting guidelines support researchers in reporting key aspects of tumor marker prognostic studies. The REMARK profile was proposed to augment these guidelines to aid in structured reporting with an emphasis on including all aspects of analyses conducted. METHODS A systematic search of prognostic factor studies was conducted, and fifteen studies published in 2015 were selected, three from each of five oncology journals. A paper was eligible for selection if it included survival outcomes and multivariable models were used in the statistical analyses. For each study, we summarized the key information in a REMARK profile consisting of details about the patient population with available variables and follow-up data, and a list of all analyses conducted. RESULTS Structured profiles allow an easy assessment if reporting of a study only has weaknesses or if it is poor because many relevant details are missing. Studies had incomplete reporting of exclusion of patients, missing information about the number of events, or lacked details about statistical analyses, e.g., subgroup analyses in small populations without any information about the number of events. Profiles exhibit severe weaknesses in the reporting of more than 50% of the studies. The quality of analyses was not assessed, but some profiles exhibit several deficits at a glance. CONCLUSIONS A substantial part of prognostic factor studies is poorly reported and analyzed, with severe consequences for related systematic reviews and meta-analyses. We consider inadequate reporting of single studies as one of the most important reasons that the clinical relevance of most markers is still unclear after years of research and dozens of publications. We conclude that structured reporting is an important step to improve the quality of prognostic marker research and discuss its role in the context of selective reporting, meta-analysis, study registration, predefined statistical analysis plans, and improvement of marker research.
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Affiliation(s)
- Willi Sauerbrei
- Institute for Medical Biometry and Statistics, Faculty of Medicine and Medical Center - University of Freiburg, Freiburg, Germany.
| | - Tim Haeussler
- Institute for Medical Biometry and Statistics, Faculty of Medicine and Medical Center - University of Freiburg, Freiburg, Germany
| | - James Balmford
- Institute for Medical Biometry and Statistics, Faculty of Medicine and Medical Center - University of Freiburg, Freiburg, Germany
| | - Marianne Huebner
- Department of Statistics and Probability, Michigan State University, East Lansing, MI, USA
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Sternby H, Hartman H, Thorlacius H, Regnér S. The Initial Course of IL1β, IL-6, IL-8, IL-10, IL-12, IFN-γ and TNF-α with Regard to Severity Grade in Acute Pancreatitis. Biomolecules 2021; 11:biom11040591. [PMID: 33920566 PMCID: PMC8073083 DOI: 10.3390/biom11040591] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Revised: 04/10/2021] [Accepted: 04/14/2021] [Indexed: 12/12/2022] Open
Abstract
Clinical reports on early immune dysregulation in acute pancreatitis (AP) are scarce. Herein we investigate the initial temporal development of selected biomarkers. Blood samples were taken at 0–24 and 25–48 h after onsets of AP were acquired. Mean values and temporal intermediate difference (delta-values) of IL-1β, IL-6, IL-8, IL-10, IL-12, IFN-γ and TNF-α were calculated. Differences between severity groups, predictive capacity of the biomarkers and association with severe disease were analyzed. Paired comparison of samples (n = 115) taken at 0–24 and 25–48 h after onsets of AP showed a change over time for IL-1β, IL-6, IL-8 and IL-10 (p < 0.05) and a significant difference between severity groups after 24 h. In ROC-analysis an IL-6 cut-off level of 196.6 pg/mL could differentiate severe AP (sensitivity 81.9, specificity 91.3). The delta-values of IL-1β and IL-6 were significantly associated with severe outcomes (odds ratios 1.085 and 1.002, respectively). Data of this work demonstrate a distinct change in IL-1β, IL-8, IL-10 and IL-6 over the first 48 h after onset of AP. The temporal development of biomarkers can assist in the early stratification of the disease. Herein IL-1β and IL-6 were associated with severe disease, however the prognostic capacity of investigated biomarkers is low.
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Yu Y, Carey M, Pollett W, Green J, Dicks E, Parfrey P, Yilmaz YE, Savas S. The long-term survival characteristics of a cohort of colorectal cancer patients and baseline variables associated with survival outcomes with or without time-varying effects. BMC Med 2019; 17:150. [PMID: 31352904 PMCID: PMC6661748 DOI: 10.1186/s12916-019-1379-5] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2019] [Accepted: 06/27/2019] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND Colorectal cancer is the third most common cancer in the world. In this study, we assessed the long-term survival characteristics and prognostic associations and potential time-varying effects of clinico-demographic variables and two molecular markers (microsatellite instability (MSI) and BRAF Val600Glu mutation) in a population-based patient cohort followed up to ~ 19 years. METHODS The patient cohort included 738 incident cases diagnosed between 1999 and 2003. Cox models were used to analyze the association between the variables and a set of survival outcome measures (overall survival (OS), disease-specific survival (DSS), recurrence-free survival (RFS), metastasis-free survival (MFS), recurrence/metastasis-free survival (RMFS), and event-free survival (EFS)). Cox proportional hazard (PH) assumption was tested for all variables, and Cox models with time-varying effects were used if any departure from the PH assumption was detected. RESULTS During the follow-up, ~ 61% patients died from any cause, ~ 26% died from colorectal cancer, and ~ 10% and ~ 20% experienced recurrences and distant metastases, respectively. Stage IV disease and post-diagnostic recurrence or metastasis were strongly linked to risk of death from colorectal cancer. If a patient had survived the first 6 years without any disease-related event (i.e., recurrence, metastasis, or death from colorectal cancer), their risks became very minimal after this time period. Distinct sets of markers were associated with different outcome measures. In some cases, the effects by variables were constant throughout the follow-up. For example, MSI-high tumor phenotype and older age at diagnosis predicted longer MFS times consistently over the follow-up. However, in some other cases, the effects of the variables varied with time. For example, adjuvant radiotherapy treatment was associated with increased risk of metastasis in patients who received this treatment after 5.5 years post-diagnosis, but not before that. CONCLUSIONS This study describes the long-term survival characteristics of a prospective cohort of colorectal cancer patients, relationships between baseline variables and a detailed set of patient outcomes over a long time, and time-varying effects of a group of variables. The results presented advance our understanding of the long-term prognostic characteristics in colorectal cancer and are expected to inspire future studies and clinical care strategies.
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Affiliation(s)
- Yajun Yu
- Discipline of Genetics, Faculty of Medicine, Memorial University, 300 Prince Philip Drive, New Medical Education Building, St. John's, NL, A1B 3V6, Canada
| | - Megan Carey
- Discipline of Genetics, Faculty of Medicine, Memorial University, 300 Prince Philip Drive, New Medical Education Building, St. John's, NL, A1B 3V6, Canada
| | - William Pollett
- Discipline of Surgery, Faculty of Medicine, Memorial University, St. John's, NL, Canada
| | - Jane Green
- Discipline of Genetics, Faculty of Medicine, Memorial University, 300 Prince Philip Drive, New Medical Education Building, St. John's, NL, A1B 3V6, Canada
| | - Elizabeth Dicks
- Discipline of Medicine, Faculty of Medicine, Memorial University, St. John's, NL, Canada
| | - Patrick Parfrey
- Discipline of Medicine, Faculty of Medicine, Memorial University, St. John's, NL, Canada
| | - Yildiz E Yilmaz
- Discipline of Genetics, Faculty of Medicine, Memorial University, 300 Prince Philip Drive, New Medical Education Building, St. John's, NL, A1B 3V6, Canada.,Discipline of Medicine, Faculty of Medicine, Memorial University, St. John's, NL, Canada.,Department of Mathematics and Statistics, Faculty of Science, Memorial University, St. John's, NL, Canada
| | - Sevtap Savas
- Discipline of Genetics, Faculty of Medicine, Memorial University, 300 Prince Philip Drive, New Medical Education Building, St. John's, NL, A1B 3V6, Canada. .,Discipline of Oncology, Faculty of Medicine, Memorial University, St. John's, NL, Canada.
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Sauerbrei W, Taube SE, McShane LM, Cavenagh MM, Altman DG. Reporting Recommendations for Tumor Marker Prognostic Studies (REMARK): An Abridged Explanation and Elaboration. J Natl Cancer Inst 2018; 110:803-811. [PMID: 29873743 PMCID: PMC6093349 DOI: 10.1093/jnci/djy088] [Citation(s) in RCA: 330] [Impact Index Per Article: 47.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2017] [Revised: 03/16/2018] [Accepted: 04/17/2018] [Indexed: 12/15/2022] Open
Abstract
The Reporting Recommendations for Tumor Marker Prognostic Studies (REMARK) were developed to address widespread deficiencies in the reporting of such studies. The REMARK checklist consists of 20 items to report for published tumor marker prognostic studies. A detailed paper was published explaining the rationale behind checklist items, providing positive examples and giving empirical evidence of the quality of reporting. REMARK provides a comprehensive overview to educate on good reporting and provide a valuable reference for the many issues to consider when designing, conducting, and analyzing tumor marker studies and prognostic studies in medicine in general. Despite support for REMARK from major cancer journals, prognostic factor research studies remain poorly reported. To encourage dissemination and uptake of REMARK, we have produced this considerably abridged version of the detailed explanatory manuscript, which may also serve as a brief guide to key issues for investigators planning tumor marker prognostic studies. To summarize the current situation, more recent papers investigating the quality of reporting and related reporting guidelines are cited, but otherwise the literature is not updated. Another important impetus for this paper is that it serves as a basis for literal translations into other languages. Translations will help to bring key information to a larger audience world-wide. Many more details can be found in the original paper.
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Affiliation(s)
- Willi Sauerbrei
- Institute for Medical Biometry and Statistics, Faculty of Medicine and
Medical Center, University of Freiburg, Freiburg, Germany
| | - Sheila E Taube
- Cancer Diagnosis Program and Biometric Research Program, Division of
Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD
| | - Lisa M McShane
- Cancer Diagnosis Program and Biometric Research Program, Division of
Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD
| | - Margaret M Cavenagh
- Cancer Diagnosis Program and Biometric Research Program, Division of
Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD
| | - Douglas G Altman
- Centre for Statistics in Medicine, Nuffield Department of Orthopaedics,
Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK
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Sternby H, Hartman H, Johansen D, Thorlacius H, Regnér S. IL-6 and CRP are superior in early differentiation between mild and non-mild acute pancreatitis. Pancreatology 2017; 17:550-554. [PMID: 28610827 DOI: 10.1016/j.pan.2017.05.392] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2017] [Revised: 05/03/2017] [Accepted: 05/29/2017] [Indexed: 02/06/2023]
Abstract
BACKGROUND The revised Atlanta classification on acute pancreatitis (AP) presents distinct criteria for severity categorization. Due to the lack of reliable prognostic markers, a majority of patients with AP are currently hospitalized and initially managed identically. As incidence and financial costs are rising the need for early severity differentiation will increase. This study aimed to investigate the capacity of biomarkers to stratify AP patients during the initial course of the disease. METHODS Patients with AP were prospectively enrolled and dichotomized into mild or non-mild (moderately severe and severe AP) according to the revised Atlanta classification. Serum samples taken within 13-36 h after onset of disease were analyzed for 20 biomarkers. Through receiver operating curves cut-off levels were set for 5 biomarkers whose stratifying ability was further analyzed. Additionally, the patients were classified according to the harmless acute pancreatitis score (HAPS). RESULTS Among the 175 patients, 70.9% had mild and 29.1% non-mild AP. CRP and IL-6 combined, with cut-off levels 57.0 and 23.6 respectively, demonstrated superior discriminative capacity with an area under the curve of 0.803, sensitivity 98%, specificity 54% and a positive and negative likelihood ratio of 2.1 and 0.06 for the non-mild group. Regarding the mild group likelihood ratios were positive 26.5 and negative 0.48. The identification potential of the HAPS was generally inferior when compared to CRP plus IL-6. CONCLUSIONS In this study CRP and IL-6 demonstrate a clinically relevant capacity to differentiate mild from non-mild AP early in the course of AP.
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Affiliation(s)
- Hanna Sternby
- Department of Surgery, Institution of Clinical Sciences, Malmö, Skåne University Hospital, Lund University, Sweden
| | - Hannes Hartman
- Department of Gastroenterology, Institution of Clinical Sciences, Malmö, Skåne University Hospital, Lund University, Sweden
| | - Dorthe Johansen
- Department of Surgery, Institution of Clinical Sciences, Malmö, Skåne University Hospital, Lund University, Sweden
| | - Henrik Thorlacius
- Department of Surgery, Institution of Clinical Sciences, Malmö, Skåne University Hospital, Lund University, Sweden
| | - Sara Regnér
- Department of Surgery, Institution of Clinical Sciences, Malmö, Skåne University Hospital, Lund University, Sweden.
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Ioannidis JPA, Bossuyt PMM. Waste, Leaks, and Failures in the Biomarker Pipeline. Clin Chem 2017; 63:963-972. [DOI: 10.1373/clinchem.2016.254649] [Citation(s) in RCA: 90] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2016] [Accepted: 11/30/2016] [Indexed: 01/05/2023]
Abstract
Abstract
BACKGROUND
The large, expanding literature on biomarkers is characterized by almost ubiquitous significant results, with claims about the potential importance, but few of these discovered biomarkers are used in routine clinical care.
CONTENT
The pipeline of biomarker development includes several specific stages: discovery, validation, clinical translation, evaluation, implementation (and, in the case of nonutility, deimplementation). Each of these stages can be plagued by problems that cause failures of the overall pipeline. Some problems are nonspecific challenges for all biomedical investigation, while others are specific to the peculiarities of biomarker research. Discovery suffers from poor methods and incomplete and selective reporting. External independent validation is limited. Selection for clinical translation is often shaped by nonrational choices. Evaluation is sparse and the clinical utility of many biomarkers remains unknown. The regulatory environment for biomarkers remains weak and guidelines can reach biased or divergent recommendations. Removing inefficient or even harmful biomarkers that have been entrenched in clinical care can meet with major resistance.
SUMMARY
The current biomarker pipeline is too prone to failures. Consideration of clinical needs should become a starting point for the development of biomarkers. Improvements can include the use of more stringent methodology, better reporting, larger collaborative studies, careful external independent validation, preregistration, rigorous systematic reviews and umbrella reviews, pivotal randomized trials, and implementation and deimplementation studies. Incentives should be aligned toward delivering useful biomarkers.
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Affiliation(s)
- John P A Ioannidis
- Departments of Medicine, Health Research and Policy, and Statistics, and the Meta-Research Innovation Center at Stanford (METRICS), Stanford University, Stanford, CA
| | - Patrick M M Bossuyt
- Department of Clinical Epidemiology, Biostatistics & Bioinformatics, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
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Zhang XX, Deng LH, Chen WW, Shi N, Jin T, Lin ZQ, Ma Y, Jiang K, Yang XN, Xia Q. Circulating microRNA 216 as a Marker for the Early Identification of Severe Acute Pancreatitis. Am J Med Sci 2016; 353:178-186. [PMID: 28183420 DOI: 10.1016/j.amjms.2016.12.007] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2016] [Revised: 12/04/2016] [Accepted: 12/08/2016] [Indexed: 02/05/2023]
Abstract
BACKGROUND To study the value of circulating microRNA 216 (miR-216) as a marker for the severity of acute pancreatitis (AP) in both murine models and patients. MATERIALS AND METHODS Mice with AP were induced by intraperitoneal injection of 50μg/kg/hour cerulean either 7 times, sacrificed at 8, 9, 10, 11 or 12 hours after the first injection, or 12 times, sacrificed at 24 hours after the first injection. Plasma samples and data from patients with AP were obtained from a prospective cohort. Quantitative reverse transcription polymerase chain reaction was used to determine the miR-216a and miR-216b level. RESULTS The upregulation of miR-216a and miR-216b in the serum of mice was induced by cerulean injection in both the 7- and 12-injection groups (P < 0.05). The downregulation of miR-216a in pancreatic tissues of mice with AP was detected (P < 0.05), but no difference was observed in pancreatic miR-216b levels among any of the groups (all P > 0.05). The serum miR-216a level was positively correlated with pancreatic histopathology severity scores, and was negatively correlated with pancreatic miR-216a (r = -0.483, P = 0.009). The plasma miR-216a level was significantly upregulated in patients with severe AP (SAP) compared with patients with mild AP (MAP) or moderate severe AP (MSAP) (SAP versus MAP, P = 0.04; SAP versus MSAP, P = 0.00), but no difference was seen between patients with MAP and those with MSAP (P = 0.73). CONCLUSIONS Circulating miR-216a might be a potential biomarker for the early identification of SAP.
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Affiliation(s)
- Xiao-Xin Zhang
- Department of Integrated Traditional Chinese and Western Medicine, West China Hospital of Sichuan University, Chengdu, China
| | - Li-Hui Deng
- Department of Integrated Traditional Chinese and Western Medicine, West China Hospital of Sichuan University, Chengdu, China.
| | - Wei-Wei Chen
- Department of Integrated Traditional Chinese and Western Medicine, West China Hospital of Sichuan University, Chengdu, China
| | - Na Shi
- Department of Integrated Traditional Chinese and Western Medicine, West China Hospital of Sichuan University, Chengdu, China
| | - Tao Jin
- Department of Integrated Traditional Chinese and Western Medicine, West China Hospital of Sichuan University, Chengdu, China
| | - Zi-Qi Lin
- Department of Integrated Traditional Chinese and Western Medicine, West China Hospital of Sichuan University, Chengdu, China
| | - Yun Ma
- Department of Integrated Traditional Chinese and Western Medicine, West China Hospital of Sichuan University, Chengdu, China
| | - Kun Jiang
- Department of Integrated Traditional Chinese and Western Medicine, West China Hospital of Sichuan University, Chengdu, China
| | - Xiao-Nan Yang
- Department of Integrated Traditional Chinese and Western Medicine, West China Hospital of Sichuan University, Chengdu, China
| | - Qing Xia
- Department of Integrated Traditional Chinese and Western Medicine, West China Hospital of Sichuan University, Chengdu, China.
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Sternby H, Hartman H, Johansen D, Thorlacius H, Regnér S. Predictive Capacity of Biomarkers for Severe Acute Pancreatitis. Eur Surg Res 2016; 56:154-63. [DOI: 10.1159/000444141] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2015] [Accepted: 01/19/2016] [Indexed: 11/19/2022]
Abstract
Background: Early prediction of severe acute pancreatitis (SAP) substantially improves treatment of patients. A large amount of biomarkers have been studied with this objective. The aim of this work was to study predictive biomarkers using preset cut-off levels in an unselected population of patients with acute pancreatitis (AP). Methods: 232 patients (52.2% males, median age 66 years) with AP admitted to Skåne University Hospital, Malmö, were consecutively enrolled. Blood samples were collected upon admission and clinical data were gathered both prospectively at inclusion and through review of medical notes. Cut-off levels were defined based on the reports of prior studies, and through their results eight biomarkers (IL-1β, IL-6, IL-8, IL-10, TNF-α, MCP-1, procalcitonin and D-dimer) were selected for analysis. Results: Of the patients, 83.2% had mild AP and 16.8% had SAP. Levels of IL-1β, IL-6 and IL-10 were significantly (p < 0.05) higher upon admission in the group with SAP. When applying the preset cut-off levels on our material, sensitivity and specificity for prediction of severity were low. Receiver operating characteristic curves showed that selected cut-off levels were acceptable, but areas under the curves were inferior compared to other studies. The results did not improve when using the revised Atlanta 2012 classification. Conclusions: Previous studies on severity prediction of AP are difficult to compare due to large variations in setups and outcomes. Calculated cut-offs in our cohort were in acceptable range from preset levels, however areas under the curves were low, indicating suboptimal biomarkers for the unselected population investigated. For comparable results and possible clinical implementations, future studies need large consecutive series with a reasonable percentage of severe cases. Additionally, novel biomarkers need to be explored.
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Role of Biomarkers in Diagnosis and Prognostic Evaluation of Acute Pancreatitis. J Biomark 2015; 2015:519534. [PMID: 26345247 PMCID: PMC4541003 DOI: 10.1155/2015/519534] [Citation(s) in RCA: 60] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2015] [Revised: 07/14/2015] [Accepted: 07/15/2015] [Indexed: 02/07/2023] Open
Abstract
Acute pancreatitis is a potentially life threatening disease. The spectrum of severity of the illness ranges from mild self-limiting disease to a highly fatal severe necrotizing pancreatitis. Despite intensive research and improved patient care, overall mortality still remains high, reaching up to 30–40% in cases with infected pancreatic necrosis. Although little is known about the exact pathogenesis, it has been widely accepted that premature activation of digestive enzymes within the pancreatic acinar cell is the trigger that leads to autodigestion of pancreatic tissue which is followed by infiltration and activation of leukocytes. Extensive research has been done over the past few decades regarding their role in diagnosis and prognostic evaluation of severe acute pancreatitis. Although many standalone biochemical markers have been studied for early assessment of severity, C-reactive protein still remains the most frequently used along with Interleukin-6. In this review we have discussed briefly the pathogenesis and the role of different biochemical markers in the diagnosis and severity evaluation in acute pancreatitis.
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Schanaider A, de Carvalho TP, de Oliveira Coelho S, Renteria JM, Eleuthério ECA, Castelo-Branco MTL, Madi K, Baetas-da-Cruz W, de Souza HSP. Ischemia-reperfusion rat model of acute pancreatitis: protein carbonyl as a putative early biomarker of pancreatic injury. Clin Exp Med 2015; 15:311-320. [PMID: 24934325 DOI: 10.1007/s10238-014-0289-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2014] [Accepted: 04/14/2014] [Indexed: 02/08/2023]
Abstract
Acute pancreatitis (AP) is an inflammatory disorder that can affect adjacent and/or remote organs. Some evidence indicates that the production of reactive oxygen species is able to induce AP. Protein carbonyl (PC) derivatives, which can also be generated through oxidative cleavage mechanisms, have been implicated in several diseases, but there is little or no information on this biomarker in AP. We investigated the association between some inflammatory mediators and PC, with the severity of ischemia-reperfusion AP. Wistar rats (n = 56) were randomly assigned in the following groups : control; sham, 15- or 180-min clamping of splenic artery, with 24 or 72 h of follow-up. The relationships between serum level of PC and thiobarbituric acid reactive species (TBARS) to myeloperoxidase (MPO) activity in tissue homogenates and to cytokines in culture supernatants of pancreatic samples were analyzed. MPO activity was related to the histology scores and increased in all clamping groups. Tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-1β), and interleukin-6 were higher in the 180-min groups. Significant correlations were found between MPO activity and the concentrations of TNF-α and IL-1β. PC levels increased in the 15-min to 24-h group. TBARS levels were not altered substantially. MPO activity and TNF-α and IL-1β concentrations in pancreatic tissue are correlated with AP severity. Serum levels of PC appear to begin to rise early in the course of the ischemia-reperfusion AP and are no longer detected at later stages in the absence of severe pancreatitis. These data suggest that PC can be an efficient tool for the diagnosis of early stages of AP.
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Affiliation(s)
- Alberto Schanaider
- Postgraduate Program in Surgical Science, Center of Experimental Surgery, Department of Surgery, School of Medicine, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
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High phosphate serum levels correlate with the severity of experimental severe acute pancreatitis: insight into the purinergic system. Pancreas 2015; 44:619-25. [PMID: 25815645 DOI: 10.1097/mpa.0000000000000303] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
OBJECTIVES Extracellular purines are a component of the systemic inflammatory response, and their levels are modulated by ectonucleotidases. In addition, nucleotide hydrolysis releases phosphate. We studied serum phosphate levels as a predictor of severity in acute pancreatitis (AP) and their correlation with extracellular purinergic metabolism. METHODS Acute pancreatitis was induced by the retrograde injection of sodium taurocholate. The AP group was compared with animals submitted to a model of sepsis by cecal ligation and puncture. The sham group was submitted to laparotomy and closure. We measured the phosphate and purine levels in serum and the expression of 5'-nucleotidase (CD73) and the adenosine A2a receptor in pancreatic tissue by quantitative real-time polymerase chain reaction. RESULTS Serum phosphate levels were higher in severe AP and correlated with severity. Severe AP led to increased serum levels of adenosine diphosphate, adenosine monophosphate, and adenosine. In addition, adenosine monophosphate conversion to adenosine in serum was accelerated in the AP groups. We found a positive correlation between serum adenosine and phosphate in the AP groups. The expression levels of CD73 and the adenosine A2a receptor in the pancreas were not altered. CONCLUSIONS Our study suggests that serum phosphate correlates with severity in AP and implicates extracellular purines in the systemic response to severe AP.
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Sauerbrei W, Abrahamowicz M, Altman DG, le Cessie S, Carpenter J. STRengthening analytical thinking for observational studies: the STRATOS initiative. Stat Med 2014; 33:5413-32. [PMID: 25074480 PMCID: PMC4320765 DOI: 10.1002/sim.6265] [Citation(s) in RCA: 81] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2013] [Revised: 05/28/2014] [Accepted: 06/20/2014] [Indexed: 12/18/2022]
Abstract
The validity and practical utility of observational medical research depends critically on good study design, excellent data quality, appropriate statistical methods and accurate interpretation of results. Statistical methodology has seen substantial development in recent times. Unfortunately, many of these methodological developments are ignored in practice. Consequently, design and analysis of observational studies often exhibit serious weaknesses. The lack of guidance on vital practical issues discourages many applied researchers from using more sophisticated and possibly more appropriate methods when analyzing observational studies. Furthermore, many analyses are conducted by researchers with a relatively weak statistical background and limited experience in using statistical methodology and software. Consequently, even 'standard' analyses reported in the medical literature are often flawed, casting doubt on their results and conclusions. An efficient way to help researchers to keep up with recent methodological developments is to develop guidance documents that are spread to the research community at large. These observations led to the initiation of the strengthening analytical thinking for observational studies (STRATOS) initiative, a large collaboration of experts in many different areas of biostatistical research. The objective of STRATOS is to provide accessible and accurate guidance in the design and analysis of observational studies. The guidance is intended for applied statisticians and other data analysts with varying levels of statistical education, experience and interests. In this article, we introduce the STRATOS initiative and its main aims, present the need for guidance documents and outline the planned approach and progress so far. We encourage other biostatisticians to become involved.
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Affiliation(s)
- Willi Sauerbrei
- Center for Medical Biometry and Medical Informatics, Medical Center – University of Freiburg
| | - Michal Abrahamowicz
- Department of Epidemiology and Biostatistics, McGill UniversityMontréal, QC H3A 0G4, Canada
| | - Douglas G Altman
- Centre for Statistics in Medicine, University of OxfordOxford OX3 7LD [Correction added on 15 August 2014, after first online publication: Postcode OX1 2JD has been corrected to OX3 7LD], U.K.
| | - Saskia le Cessie
- Department of Clinical Epidemiology and Department for Medical Statistics and Bioinformatics, Leiden University Medical Centre2333 ZA Leiden, The Netherlands
| | - James Carpenter
- Medical Statistics Unit, London School of Hygiene and Tropical Medicine, and MRC Clinical Trials UnitKingsway, London, U.K.
| | - on behalf of the STRATOS initiative
- Center for Medical Biometry and Medical Informatics, Medical Center – University of Freiburg
- Department of Epidemiology and Biostatistics, McGill UniversityMontréal, QC H3A 0G4, Canada
- Centre for Statistics in Medicine, University of OxfordOxford OX3 7LD [Correction added on 15 August 2014, after first online publication: Postcode OX1 2JD has been corrected to OX3 7LD], U.K.
- Department of Clinical Epidemiology and Department for Medical Statistics and Bioinformatics, Leiden University Medical Centre2333 ZA Leiden, The Netherlands
- Medical Statistics Unit, London School of Hygiene and Tropical Medicine, and MRC Clinical Trials UnitKingsway, London, U.K.
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Weitz G, Woitalla J, Wellhöner P, Schmidt K, Büning J, Fellermann K. Detrimental effect of high volume fluid administration in acute pancreatitis - a retrospective analysis of 391 patients. Pancreatology 2014; 14:478-83. [PMID: 25451185 DOI: 10.1016/j.pan.2014.07.016] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2014] [Revised: 06/23/2014] [Accepted: 07/09/2014] [Indexed: 12/11/2022]
Abstract
BACKGROUND Early fluid resuscitation is recommended for the therapy of acute pancreatitis in order to prevent complications. There are, however, no convincing data supporting this approach. METHODS We reviewed 391 consecutive cases of confirmed acute pancreatitis. Admitting physicians had been advised to administer an aggressive fluid resuscitation in the early phase of disease, if possible. We tested whether disease severity according to the revised Atlanta Classification, local complications, and maximum C-reactive protein levels were predictable by the initial volume therapy in logistic and linear regression models, respectively. We also determined which parameters on admission encouraged a more aggressive fluid resuscitation. RESULTS The recorded fluid administered within the first 24 h was 5300 [3760; 7100] ml (median [1st; 3rd quartile]). More aggressive volume therapy was associated with disease severity and a higher rate of local complications. There was a linear relationship between administered volume and the maximum C-reactive protein. The amount of administered fluid was significantly attributed to age, hematocrit, and white blood cell count on admission. When adjusted for these parameters the impact of administered volume on outcome was still present but attenuated. CONCLUSIONS We found detrimental effects of fluid therapy on major outcome parameters throughout the whole range of administered volume. More volume was administered in younger patients and in patients with evidence of hemoconcentration and inflammation. The adverse effects of volume therapy persisted after elimination of these parameters. Caution should therefore be advised with regards to volume therapy in patients with acute pancreatitis.
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Affiliation(s)
- Gunther Weitz
- Medical Department I, Gastroenterology, University Hospital of Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany.
| | - Julia Woitalla
- Medical Department I, Gastroenterology, University Hospital of Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany
| | - Peter Wellhöner
- Medical Department I, Gastroenterology, University Hospital of Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany
| | - Klaus Schmidt
- Medical Department I, Gastroenterology, University Hospital of Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany
| | - Jürgen Büning
- Medical Department I, Gastroenterology, University Hospital of Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany
| | - Klaus Fellermann
- Medical Department I, Gastroenterology, University Hospital of Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany
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Sigounas DE, Christodoulou DK, Karamoutsios A, Tatsioni A, Dova L, Vartholomatos G, Kolaitis N, Katsanos KH, Zervou E, Ioannidis JPA, Tsianos EV. Changes of serum adhesion molecules and cytokines in post-ERCP pancreatitis: adhesion molecules and cytokines in acute pancreatitis. Clin Biochem 2014; 47:1245-9. [PMID: 24845714 DOI: 10.1016/j.clinbiochem.2014.05.007] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2014] [Revised: 04/23/2014] [Accepted: 05/11/2014] [Indexed: 01/18/2023]
Abstract
OBJECTIVES To assess the early changes of soluble IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, TNF-α, TNF-β, IL-17A, IL-22, soluble (s) P-Selectin, sE-Selectin and sICAM-1 in post-ERCP pancreatitis (PEP). METHODS Single center, prospective study of 318 ERCP procedures. Serum samples were acquired from all patients prior to ERCP, 6 hours and 24 hours after the procedure. For every PEP case, another patient was chosen as a control, matched for gender, age and time period in which ERCP took place. RESULTS Totally, 28 cases and 28 controls were studied. Except for significantly higher IL-1b levels in cases at baseline, no significant differences were observed between cases and controls after Bonferroni corrections. An increase in IL-6 was noted between baseline and 6 h in cases alone (p=0.016). There was a significant fall in sP-selectin levels at 6 and 24 hours compared to baseline in all patients (corrected p=0.008 and 0.016 for cases and 0.016 and 0.048 for controls respectively). An increase of sE-selectin in cases was observed between 6 and 24 hours post-ERCP (corrected p=0.03). CONCLUSIONS Soluble forms of cytokines and adhesion molecules studied seem not to play a major role in PEP.
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Affiliation(s)
- Dimitrios E Sigounas
- 1(st) Division of Internal Medicine and Division of Gastroenterology, Medical School, University of Ioannina, Ioannina, Greece
| | - Dimitrios K Christodoulou
- 1(st) Division of Internal Medicine and Division of Gastroenterology, Medical School, University of Ioannina, Ioannina, Greece
| | | | - Athina Tatsioni
- Department of Internal Medicine, University of Ioannina School of Medicine, Ioannina, Greece; Department of Medicine, Tufts University School of Medicine and Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Boston, MA, USA
| | - Lefkothea Dova
- Hematology Laboratory, University Hospital of Ioannina, Ioannina, Greece
| | | | - Nikolaos Kolaitis
- Hematology Laboratory, University Hospital of Ioannina, Ioannina, Greece
| | - Konstantinos H Katsanos
- 1(st) Division of Internal Medicine and Division of Gastroenterology, Medical School, University of Ioannina, Ioannina, Greece
| | | | - John P A Ioannidis
- Stanford Prevention Research Center, Department of Medicine and Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA, USA
| | - Epameinondas V Tsianos
- 1(st) Division of Internal Medicine and Division of Gastroenterology, Medical School, University of Ioannina, Ioannina, Greece.
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Maraví-Poma E, Patchen Dellinger E, Forsmark CE, Layer P, Lévy P, Shimosegawa T, Siriwardena AK, Uomo G, Whitcomb DC, Windsor JA, Petrov MS. [International multidisciplinary classification of acute pancreatitis severity: the 2013 Spanish edition]. Med Intensiva 2014; 38:211-217. [PMID: 23747189 DOI: 10.1016/j.medin.2013.03.013] [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: 02/13/2013] [Revised: 03/13/2013] [Accepted: 03/15/2013] [Indexed: 11/25/2022]
Abstract
OBJECTIVE To develop a new classification of acute pancreatitis severity on the basis of a sound conceptual framework, comprehensive review of the published evidence, and worldwide consultation. BACKGROUNDS The Atlanta definitions of acute pancreatitis severity are ingrained in the lexicon of specialist in pancreatic diseases, but are suboptimal because these definitions are based on the empiric description of events not associated with severity. METHODS A personal invitation to contribute to the development of a new classification of acute pancreatitis severity was sent to all surgeons, gastroenterologists, internists, intensivists and radiologists currently active in the field of clinical acute pancreatitis. The invitation was not limited to members of certain associations or residents of certain countries. A global web-based survey was conducted, and a dedicated international symposium was organized to bring contributors from different disciplines together and discuss the concept and definitions. RESULTS The new classification of severity is based on the actual local and systemic determinants of severity, rather than on the description of events that are non-causally associated with severity. The local determinant relates to whether there is (peri) pancreatic necrosis or not, and if present, whether it is sterile or infected. The systemic determinant relates to whether there is organ failure or not, and if present, whether it is transient or persistent. The presence of one determinant can modify the effect of another, whereby the presence of both infected (peri) pancreatic necrosis and persistent organ failure has a greater impact upon severity than either determinant alone. The derivation of a classification based on the above principles results in four categories of severity: mild, moderate, severe, and critical. CONCLUSIONS This classification is the result of a consultative process among specialists in pancreatic diseases from 49 countries spanning North America, South America, Europe, Asia, Oceania and Africa. It provides a set of concise up to date definitions of all the main entities pertinent to classifying the severity of acute pancreatitis in clinical practice and research. This ensures that the determinant-based classification can be used in a uniform manner throughout the world.
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Affiliation(s)
- E Maraví-Poma
- UCI-B, Complejo Hospitalario de Navarra (antiguo Hospital Virgen del Camino), Pamplona, España.
| | - E Patchen Dellinger
- Department of Surgery, University of Washington School of Medicine, Seattle, Estados Unidos
| | - C E Forsmark
- Division of Gastroenterology, Hepatology, and Nutrition, University of Florida College of Medicine, Gainesville, Estados Unidos
| | - P Layer
- Department of Internal Medicine, Israelitic Hospital, Hamburgo, Alemania
| | - P Lévy
- Pôle des Maladies de l'Appareil Digestif, Service de Gastroenterologie-Pancreatologie, Hopital Beaujon, Clichy, Francia
| | - T Shimosegawa
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japón
| | - A K Siriwardena
- Department of Surgery, Manchester Royal Infirmary, University of Manchester, Manchester, Reino Unido
| | - G Uomo
- Department of Internal Medicine, Cardarelli Hospital, Nápoles, Italia
| | - D C Whitcomb
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, Department of Cell Biology and Molecular Physiology, Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA, Estados Unidos
| | - J A Windsor
- Department of Surgery, University of Auckland, Miembro International Association of Pancreatology, Auckland, Nueva Zelanda
| | - M S Petrov
- Department of Surgery, University of Auckland, Miembro International Association of Pancreatology, Auckland, Nueva Zelanda
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Nutrition, inflammation, and acute pancreatitis. ISRN INFLAMMATION 2013; 2013:341410. [PMID: 24490104 PMCID: PMC3893749 DOI: 10.1155/2013/341410] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/10/2013] [Accepted: 10/30/2013] [Indexed: 12/14/2022]
Abstract
Acute pancreatitis is acute inflammatory disease of the pancreas. Nutrition has a number of anti-inflammatory effects that could affect outcomes of patients with pancreatitis. Further, it is the most promising nonspecific treatment modality in acute pancreatitis to date. This paper summarizes the best available evidence regarding the use of nutrition with a view of optimising clinical management of patients with acute pancreatitis.
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19
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Dellinger EP, Forsmark CE, Layer P, Lévy P, Maraví-Poma E, Petrov MS, Shimosegawa T, Siriwardena AK, Uomo G, Whitcomb DC, Windsor JA. Determinant-based classification of acute pancreatitis severity: an international multidisciplinary consultation. Ann Surg 2012; 256:875-880. [PMID: 22735715 DOI: 10.1097/sla.0b013e318256f778] [Citation(s) in RCA: 335] [Impact Index Per Article: 25.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECTIVE To develop a new international classification of acute pancreatitis severity on the basis of a sound conceptual framework, comprehensive review of published evidence, and worldwide consultation. BACKGROUND The Atlanta definitions of acute pancreatitis severity are ingrained in the lexicon of pancreatologists but suboptimal because these definitions are based on empiric description of occurrences that are merely associated with severity. METHODS A personal invitation to contribute to the development of a new international classification of acute pancreatitis severity was sent to all surgeons, gastroenterologists, internists, intensivists, and radiologists who are currently active in clinical research on acute pancreatitis. The invitation was not limited to members of certain associations or residents of certain countries. A global Web-based survey was conducted and a dedicated international symposium was organized to bring contributors from different disciplines together and discuss the concept and definitions. RESULT The new international classification is based on the actual local and systemic determinants of severity, rather than description of events that are correlated with severity. The local determinant relates to whether there is (peri)pancreatic necrosis or not, and if present, whether it is sterile or infected. The systemic determinant relates to whether there is organ failure or not, and if present, whether it is transient or persistent. The presence of one determinant can modify the effect of another such that the presence of both infected (peri)pancreatic necrosis and persistent organ failure have a greater effect on severity than either determinant alone. The derivation of a classification based on the above principles results in 4 categories of severity-mild, moderate, severe, and critical. CONCLUSIONS This classification is the result of a consultative process amongst pancreatologists from 49 countries spanning North America, South America, Europe, Asia, Oceania, and Africa. It provides a set of concise up-to-date definitions of all the main entities pertinent to classifying the severity of acute pancreatitis in clinical practice and research. This ensures that the determinant-based classification can be used in a uniform manner throughout the world.
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Affiliation(s)
- E Patchen Dellinger
- Department of Surgery, University of Washington School of Medicine, Seattle, WA, USA
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20
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Lippi G, Valentino M, Cervellin G. Laboratory diagnosis of acute pancreatitis: in search of the Holy Grail. Crit Rev Clin Lab Sci 2012; 49:18-31. [PMID: 22339380 DOI: 10.3109/10408363.2012.658354] [Citation(s) in RCA: 72] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Acute pancreatitis is an acute inflammatory condition of the pancreas, which might extend to local and distant extrapancreatic tissues. The global incidence varies between 17.5 and 73.4 cases per 100,000 and the pathogenesis recognizes alcohol exposure and biliary tract disease as the leading causes, ahead of post-endoscopic retrograde cholangiopancreatography, drugs and abdominal trauma. The diagnosis of acute pancreatitis is substantially based on a combination of clinical signs and symptoms, imaging techniques and laboratory investigations. Contrast-enhanced computed tomography is the reference standard for the diagnosis, as well as for establishing disease severity. The assessment of pancreatic enzymes, early released from necrotic tissue, is the cornerstone of laboratory diagnosis in this clinical setting. Although there is no single test that shows optimal diagnostic accuracy, most current guidelines and recommendations indicate that lipase should be preferred over total and pancreatic amylase. Although a definitive diagnostic threshold cannot be identified, cut-offs comprised between ≥ 2 and ≥ 4 times the upper limit of the reference interval are preferable. The combination of amylase and lipase has been discouraged as although it marginally improves the diagnostic efficiency of either marker alone, it increases the cost of investigation. Some interesting biomarkers have been also suggested (e.g., serum and urinary trypsinogen-1, -2 and -3, phospholipase A2, pancreatic elastase, procalcitonin, trypsinogen activated protein, activation peptide of carboxypeptidase B, trypsin-2-alpha1 antitrypsin complex and circulating DNA), but none of them has found widespread application for a variety of reasons, including the inferior diagnostic accuracy when compared with the traditional enzymes, the use of cumbersome techniques, or their recent discovery. The promising results of recent proteomics studies showed that this innovative technique might allow the identification of changes characterizing pancreatic tissue injury, thus highlighting new potential biomarkers of acute pancreatitis.
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Affiliation(s)
- Giuseppe Lippi
- Diagnostica Ematochimica, Azienda Ospedaliero-Universitaria di Parma, Italy. ,
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Altman DG, McShane LM, Sauerbrei W, Taube SE. Reporting recommendations for tumor marker prognostic studies (REMARK): explanation and elaboration. BMC Med 2012; 10:51. [PMID: 22642691 PMCID: PMC3362748 DOI: 10.1186/1741-7015-10-51] [Citation(s) in RCA: 281] [Impact Index Per Article: 21.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2011] [Accepted: 05/29/2012] [Indexed: 12/26/2022] Open
Abstract
BACKGROUND The Reporting Recommendations for Tumor Marker Prognostic Studies (REMARK) checklist consists of 20 items to report for published tumor marker prognostic studies. It was developed to address widespread deficiencies in the reporting of such studies. In this paper we expand on the REMARK checklist to enhance its use and effectiveness through better understanding of the intent of each item and why the information is important to report. METHODS REMARK recommends including a transparent and full description of research goals and hypotheses, subject selection, specimen and assay considerations, marker measurement methods, statistical design and analysis, and study results. Each checklist item is explained and accompanied by published examples of good reporting, and relevant empirical evidence of the quality of reporting. We give prominence to discussion of the 'REMARK profile', a suggested tabular format for summarizing key study details. SUMMARY The paper provides a comprehensive overview to educate on good reporting and provide a valuable reference for the many issues to consider when designing, conducting, and analyzing tumor marker studies and prognostic studies in medicine in general. To encourage dissemination of the Reporting Recommendations for Tumor Marker Prognostic Studies (REMARK): Explanation and Elaboration, this article has also been published in PLoS Medicine.
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Gallo V, Egger M, McCormack V, Farmer PB, Ioannidis JPA, Kirsch-Volders M, Matullo G, Phillips DH, Schoket B, Stromberg U, Vermeulen R, Wild C, Porta M, Vineis P. STrengthening the Reporting of OBservational studies in Epidemiology - Molecular Epidemiology (STROBE-ME): An extension of the STROBE statement. Mutagenesis 2012; 27:17-29. [DOI: 10.1093/mutage/ger039] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/30/2023] Open
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Gallo V, Egger M, McCormack V, Farmer PB, Ioannidis JPA, Kirsch-Volders M, Matullo G, Phillips DH, Schoket B, Stromberg U, Vermeulen R, Wild C, Porta M, Vineis P. STrengthening the Reporting of OBservational studies in Epidemiology - Molecular Epidemiology (STROBE-ME): an extension of the STROBE statement. Eur J Clin Invest 2012; 42:1-16. [PMID: 22023344 DOI: 10.1111/j.1365-2362.2011.02561.x] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Advances in laboratory techniques have led to a rapidly increasing use of biomarkers in epidemiological studies. Biomarkers of internal dose, early biological change, susceptibility and clinical outcomes are used as proxies for investigating interactions between external and/or endogenous agents and body components or processes. The need for improved reporting of scientific research led to influential statements of recommendations such as the STrengthening Reporting of OBservational studies in Epidemiology (STROBE) statement. The STROBE initiative established in 2004 aimed to provide guidance on how to report observational research. Its guidelines provide a user-friendly checklist of 22 items to be reported in epidemiological studies, with items specific to the three main study designs: cohort studies, case-control studies and cross-sectional studies. The present STrengthening the Reporting of OBservational studies in Epidemiology -Molecular Epidemiology (STROBE-ME) initiative builds on the STROBE statement implementing nine existing items of STROBE and providing 17 additional items to the 22 items of STROBE checklist. The additions relate to the use of biomarkers in epidemiological studies, concerning collection, handling and storage of biological samples; laboratory methods, validity and reliability of biomarkers; specificities of study design; and ethical considerations. The STROBE-ME recommendations are intended to complement the STROBE recommendations.
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Affiliation(s)
- Valentina Gallo
- Department of Epidemiology and Biostatistics, Imperial College London, London, UK.
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Abstract
The REMARK (Reporting Recommendations for Tumor Marker Prognostic Studies) guideline includes a checklist which aims to improve the reporting of these types of studies. Here, we expand on the REMARK checklist to enhance its use and effectiveness through better understanding of the intent of each item and why the information is important to report. Each checklist item of the REMARK guideline is explained in detail and accompanied by published examples of good reporting. The paper provides a comprehensive overview to educate on good reporting and provide a valuable reference of issues to consider when designing, conducting, and analyzing tumor marker studies and prognostic studies in medicine in general.
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25
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Gallo V, Egger M, McCormack V, Farmer PB, Ioannidis JPA, Kirsch-Volders M, Matullo G, Phillips DH, Schoket B, Stromberg U, Vermeulen R, Wild C, Porta M, Vineis P. STrengthening the Reporting of OBservational studies in Epidemiology--Molecular Epidemiology STROBE-ME: an extension of the STROBE statement. J Clin Epidemiol 2011; 64:1350-63. [PMID: 22030070 DOI: 10.1016/j.jclinepi.2011.07.010] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2010] [Revised: 05/17/2011] [Accepted: 05/24/2011] [Indexed: 11/30/2022]
Abstract
Advances in laboratory techniques have led to a rapidly increasing use of biomarkers in epidemiological studies. Biomarkers of internal dose, early biological change susceptibility and clinical outcomes are used as proxies for investigating the interactions between external and/or endogenous agents and body components or processes. The need for improved reporting of scientific research led to influential statements of recommendations such as the STrengthening Reporting of OBservational studies in Epidemiology (STROBE) statement. The STROBE initiative established in 2004 aimed to provide guidance on how to report observational research. Its guidelines provide a user-friendly checklist of 22 items to be reported in epidemiological studies, with items specific to the three main study designs: cohort studies, case-control studies and cross-sectional studies. The present STrengthening the Reporting of OBservational studies in Epidemiology -Molecular Epidemiology (STROBE-ME) initiative builds on the STROBE statement implementing 9 existing items of STROBE and providing 17 additional items to the 22 items of STROBE checklist. The additions relate to the use of biomarkers in epidemiological studies, concerning collection, handling and storage of biological samples; laboratory methods, validity and reliability of biomarkers; specificities of study design; and ethical considerations. The STROBE-ME recommendations are intended to complement the STROBE recommendations.
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Affiliation(s)
- Valentina Gallo
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
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STrengthening the Reporting of OBservational studies in Epidemiology - Molecular Epidemiology (STROBE-ME): an extension of the STROBE statement. Prev Med 2011; 53:377-87. [PMID: 22029945 DOI: 10.1016/j.ypmed.2011.08.007] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2011] [Revised: 07/14/2011] [Accepted: 08/07/2011] [Indexed: 11/21/2022]
Abstract
Advances in laboratory techniques have led to a rapidly increasing use of biomarkers in epidemiological studies. Biomarkers of internal dose, early biological change, susceptibility and clinical outcomes are used as proxies for investigating the interactions between external and/or endogenous agents and the body components or processes. The need for improved reporting of scientific research led to influential statements of recommendations such as the STrenghtening Reporting of Observational studies in Epidemiology (STROBE) statement. The STROBE initiative established in 2004 aimed to provide guidance on how to report observational research. Its guidelines provide a user-friendly checklist of 22 items to be reported in epidemiological studies, with items specific to the three main study designs: cohort studies, case-control studies and cross-sectional studies. The present STrengthening the Reporting of OBservational studies in Epidemiology - Molecular Epidemiology (STROBE-ME) initiative builds on the STROBE Statement implementing 9 existing items of STROBE and providing 17 additional items to the 22 items of STROBE checklist. The additions relate to the use of biomarkers in epidemiological studies, concerning collection, handling and storage of biological samples; laboratory methods, validity and reliability of biomarkers; specificities of study design; and ethical considerations. The STROBE-ME recommendations are intended to complement the STROBE recommendations.
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Gallo V, Egger M, McCormack V, Farmer PB, Ioannidis JPA, Kirsch-Volders M, Matullo G, Phillips DH, Schoket B, Stromberg U, Vermeulen R, Wild C, Porta M, Vineis P. STrengthening the reporting of OBservational studies in Epidemiology-Molecular Epidemiology (STROBE-ME): an extension of the STROBE statement. Eur J Epidemiol 2011; 26:797-810. [PMID: 22037796 DOI: 10.1007/s10654-011-9622-1] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2010] [Accepted: 09/30/2011] [Indexed: 11/26/2022]
Abstract
Advances in laboratory techniques have led to a rapidly increasing use of biomarkers in epidemiological studies. Biomarkers of internal dose, early biological change, susceptibility, and clinical outcomes are used as proxies for investigating the interactions between external and/or endogenous agents and the body components or processes. The need for improved reporting of scientific research led to influential statements of recommendations such as STrengthening Reporting of Observational studies in Epidemiology (STROBE) statement. The STROBE initiative established in 2004 aimed to provide guidance on how to report observational research. Its guidelines provide a user-friendly checklist of 22 items to be reported in epidemiological studies, with items specific to the three main study designs: cohort studies, case-control studies and cross-sectional studies. The present STrengthening the Reporting of OBservational studies in Epidemiology-Molecular Epidemiology (STROBE-ME) initiative builds on the STROBE Statement implementing 9 existing items of STROBE and providing 17 additional items to the 22 items of STROBE checklist. The additions relate to the use of biomarkers in epidemiological studies, concerning collection, handling and storage of biological samples; laboratory methods, validity and reliability of biomarkers; specificities of study design; and ethical considerations. The STROBE-ME recommendations are intended to complement the STROBE recommendations.
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Affiliation(s)
- Valentina Gallo
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, St Mary's Campus Norfolk Place, W2 1PG London, UK.
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Gallo V, Egger M, McCormack V, Farmer PB, Ioannidis JPA, Kirsch-Volders M, Matullo G, Phillips DH, Schoket B, Stromberg U, Vermeulen R, Wild C, Porta M, Vineis P. STrengthening the Reporting of OBservational studies in Epidemiology--Molecular Epidemiology (STROBE-ME): an extension of the STROBE Statement. PLoS Med 2011; 8:e1001117. [PMID: 22039356 PMCID: PMC3201942 DOI: 10.1371/journal.pmed.1001117] [Citation(s) in RCA: 102] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
Abstract
Valentina Gallo and colleagues provide detailed guidance to authors to help more accurately report the findings of epidemiological studies involving biomarkers. Their guidance covers issues regarding collection, handling and storage of biological samples; laboratory methods, validity and reliability of biomarkers; specificities of study design; and ethical considerations.
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Affiliation(s)
- Valentina Gallo
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom
- Social and Environmental Health Research, London School of Hygiene and Tropical Medicine, London, United Kingdom
| | - Matthias Egger
- Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland
| | | | - Peter B. Farmer
- Department of Cancer Studies and Molecular Medicine, University of Leicester, Leicester, United Kingdom
| | - John P. A. Ioannidis
- Stanford Prevention Research Centre, Stanford University School of Medicine, Stanford, California, United States of America
- Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece
| | | | - Giuseppe Matullo
- HuGeF Human Genetics Foundation, Turin, Italy
- Department of Genetics, Biology and Biochemistry, University of Turin, Turin, Italy
| | | | | | - Ulf Stromberg
- Division of Occupational and Environmental Medicine, Lund University, Lund, Sweden
| | - Roel Vermeulen
- Institute for Risk Assessment Sciences (IRAS), Division Environmental Epidemiology, Utrecht University, Utrecht, the Netherlands
| | | | - Miquel Porta
- Institut Municipal d'Investigacio Medica (IMIM), Universitat Autonoma de Barcelona, Barcelona, Spain
| | - Paolo Vineis
- HuGeF Human Genetics Foundation, Turin, Italy
- MRC-HPA Centre for Environment and Health, School of Public Health, Imperial College London, London, United Kingdom
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