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      Role of biomarkers in early infectious complications after lung transplantation

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          Abstract

          Background

          Infections and primary graft dysfunction are devastating complications in the immediate postoperative period following lung transplantation. Nowadays, reliable diagnostic tools are not available. Biomarkers could improve early infection diagnosis.

          Methods

          Multicentre prospective observational study that included all centres authorized to perform lung transplantation in Spain. Lung infection and/or primary graft dysfunction presentation during study period (first postoperative week) was determined. Biomarkers were measured on ICU admission and daily till ICU discharge or for the following 6 consecutive postoperative days.

          Results

          We included 233 patients. Median PCT levels were significantly lower in patients with no infection than in patients with Infection on all follow up days. PCT levels were similar for PGD grades 1 and 2 and increased significantly in grade 3. CRP levels were similar in all groups, and no significant differences were observed at any study time point. In the absence of PGD grade 3, PCT levels above median (0.50 ng/ml on admission or 1.17 ng/ml on day 1) were significantly associated with more than two- and three-fold increase in the risk of infection (adjusted Odds Ratio 2.37, 95% confidence interval 1.06 to 5.30 and 3.44, 95% confidence interval 1.52 to 7.78, respectively).

          Conclusions

          In the absence of severe primary graft dysfunction, procalcitonin can be useful in detecting infections during the first postoperative week. PGD grade 3 significantly increases PCT levels and interferes with the capacity of PCT as a marker of infection. PCT was superior to CRP in the diagnosis of infection during the study period.

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          Most cited references33

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          Procalcitonin as a diagnostic test for sepsis in critically ill adults and after surgery or trauma: a systematic review and meta-analysis.

          To quantify the accuracy of serum procalcitonin as a diagnostic test for sepsis, severe sepsis, or septic shock in adults in intensive care units or after surgery or trauma, alone and compared with C-reactive protein. To draw and compare the summary receiver operating characteristics curves for procalcitonin and C-reactive protein from the literature. MEDLINE (keywords: procalcitonin, intensive care, sepsis, postoperative sepsis, trauma); screening of the literature. Meta-analysis of all 49 published studies in medical, surgical, or polyvalent intensive care units or postoperative wards. Children, medical patients, and immunocompromised patients were excluded. Thirty-three studies fulfilled inclusion criteria (3,943 patients, 1,828 males, 922 females; mean age: 56.1 yrs; 1,825 patients with sepsis, severe sepsis, or septic shock; 1,545 with only systemic inflammatory response syndrome); eight studies could not be analyzed statistically. Global mortality rate was 29.3%. Global odds ratios for diagnosis of infection complicated by systemic inflammation were 15.7 for the 25 studies (2,966 patients) using procalcitonin (95% confidence interval, 9.1-27.1) and 5.4 for the 15 studies (1,322 patients) using C-reactive protein (95% confidence interval, 3.2-9.2). The summary receiver operating characteristics curve for procalcitonin was better than for C-reactive protein. In the 15 studies using both markers, the Q* value (intersection of summary receiver operating characteristics curve with the diagonal line where sensitivity equals specificity) was significantly higher for procalcitonin than for C-reactive protein (0.78 vs. 0.71, p = .02), the former test showing better accuracy. Procalcitonin represents a good biological diagnostic marker for sepsis, severe sepsis, or septic shock, difficult diagnoses in critically ill patients. Procalcitonin is superior to C-reactive protein. Procalcitonin should be included in diagnostic guidelines for sepsis and in clinical practice in intensive care units.
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            Procalcitonin for diagnosis of infection and guide to antibiotic decisions: past, present and future

            There are a number of limitations to using conventional diagnostic markers for patients with clinical suspicion of infection. As a consequence, unnecessary and prolonged exposure to antimicrobial agents adversely affect patient outcomes, while inappropriate antibiotic therapy increases antibiotic resistance. A growing body of evidence supports the use of procalcitonin (PCT) to improve diagnosis of bacterial infections and to guide antibiotic therapy. For patients with upper and lower respiratory tract infection, post-operative infections and for severe sepsis patients in the intensive care unit, randomized-controlled trials have shown a benefit of using PCT algorithms to guide decisions about initiation and/or discontinuation of antibiotic therapy. For some other types of infections, observational studies have shown promising first results, but further intervention studies are needed before use of PCT in clinical routine can be recommended. The aim of this review is to summarize the current evidence for PCT in different infections and clinical settings, and discuss the reliability of this marker when used with validated diagnostic algorithms.
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              Report of the ISHLT Working Group on Primary Lung Graft Dysfunction part II: definition. A consensus statement of the International Society for Heart and Lung Transplantation.

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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                13 July 2017
                2017
                : 12
                : 7
                : e0180202
                Affiliations
                [1 ] Critical Care Department, Hospital Universitario Marqués de Valdecilla – IDIVAL, Santander, Spain
                [2 ] Department of Anesthesiology, Complexo Hospitalario Universitario A Coruna, A Coruna, Spain
                [3 ] Critical Care Department, Hospital Vall d'Hebron, Barcelona, Spain
                [4 ] Department of Anesthesiology, Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain
                [5 ] Department of Anesthesiology, Hospital Universitario 12 de Octubre, Madrid, Spain
                [6 ] Transplant Coordination Unit, Hospital Universitario Reina Sofia, Cordoba, Spain
                [7 ] Department of Anesthesiology, Hospital Universitario y Politécnico de La Fe, Valencia, Spain
                [8 ] Critical Care Department - Transplant Coordination Unit, Hospital Universitario Marques de Valdecilla – IDIVAL, Santander, Spain
                [9 ] Nurse School, Universidad de Cantabria – IDIVAL, Santander, Spain
                University of Toledo, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                • Conceptualization: BS EM MS.

                • Data curation: BS LR JR RI AGC JCR RV EM MS.

                • Formal analysis: BS MS.

                • Funding acquisition: BS EM MS.

                • Investigation: BS EM MS.

                • Methodology: BS MS.

                • Writing – original draft: BS MS.

                • Writing – review & editing: BS LR JR RI AGC JCR RV EM MS.

                Author information
                http://orcid.org/0000-0001-7047-3661
                Article
                PONE-D-17-03628
                10.1371/journal.pone.0180202
                5509107
                28704503
                9459acd8-98dd-466b-985b-6424fc86e02d
                © 2017 Suberviola et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 28 January 2017
                : 12 June 2017
                Page count
                Figures: 2, Tables: 4, Pages: 13
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/100008061, Fundación Mutua Madrileña;
                Award ID: FMM 14/01
                Award Recipient :
                This study has been supported by a grant from the Mutua Madrileña Foundation (Code: FMM 14/01).
                Categories
                Research Article
                Medicine and Health Sciences
                Surgical and Invasive Medical Procedures
                Transplantation
                Organ Transplantation
                Lung Transplantation
                Medicine and Health Sciences
                Surgical and Invasive Medical Procedures
                Respiratory System Procedures
                Lung Transplantation
                Medicine and Health Sciences
                Diagnostic Medicine
                Medicine and Health Sciences
                Pulmonology
                Respiratory Infections
                Medicine and Health Sciences
                Surgical and Invasive Medical Procedures
                Cardiovascular Procedures
                Heart-Lung Transplantation
                Medicine and Health Sciences
                Surgical and Invasive Medical Procedures
                Transplantation
                Organ Transplantation
                Heart-Lung Transplantation
                Medicine and Health Sciences
                Surgical and Invasive Medical Procedures
                Respiratory System Procedures
                Heart-Lung Transplantation
                Biology and Life Sciences
                Biochemistry
                Biomarkers
                Medicine and Health Sciences
                Surgical and Invasive Medical Procedures
                Cardiovascular Procedures
                Cardiac Transplantation
                Medicine and Health Sciences
                Surgical and Invasive Medical Procedures
                Transplantation
                Organ Transplantation
                Cardiac Transplantation
                Biology and Life Sciences
                Physiology
                Physiological Processes
                Secretion
                Medicine and Health Sciences
                Physiology
                Physiological Processes
                Secretion
                Medicine and Health Sciences
                Surgical and Invasive Medical Procedures
                Digestive System Procedures
                Liver Transplantation
                Medicine and Health Sciences
                Surgical and Invasive Medical Procedures
                Transplantation
                Organ Transplantation
                Liver Transplantation
                Custom metadata
                Data cannot be made publicly available in order to protect patient privacy. The data are available on request from the University of Cantabria Archive ( http://repositorio.unican.es/) for researchers who meet the criteria for access to confidential data. Requests may be sent to the Ethics Committee or Dr. Borja Suberviola ( bsuberviola@ 123456yahoo.es ). The contact for the ethics committee is as follows: Comité Ético de Investigación Clínica de Cantabria, Dirección: Edificio IFIMAV, 3ª Planta, Avda. Cardenal Herrera Oria s/n, 39011 Santander, email: ceicc@ 123456idival.org .

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