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      An elevated glycemic gap predicts adverse outcomes in diabetic patients with necrotizing fasciitis

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          Abstract

          Background

          Diabetes is the most common comorbidity of necrotizing fasciitis (NF), but the effect of stress-induced hyperglycemia (SIH) on diabetic patients with NF has never been investigated. The aim of this study was to assess whether SIH, as determined by the glycemic gap between admission glucose levels and A 1C-derived average glucose levels, predicts adverse outcomes in diabetic patients hospitalized with NF.

          Methods

          We retrospectively reviewed the glycemic gap and clinical outcomes in 252 diabetic patients hospitalized due to NF from 2011 to 2018 in a single medical center in Taiwan. A receiver operating characteristic (ROC) curve was used to analyze the optimal cutoff values for predicting adverse outcomes. Univariate and multivariate logistic regression analyses were employed to identify significant predictors of adverse outcomes.

          Results

          In total, 194 diabetic NF patients were enrolled. Compared with patients without adverse outcomes, patients with adverse outcomes had significantly higher glycemic gaps, Acute Physiology and Chronic Health Evaluation (APACHE) II scores and C-reactive protein (CRP) levels; lower albumin and hemoglobin levels; greater incidence of limb loss; and longer hospital and intensive care unit stays. The glycemic gap positively correlates with the laboratory risk indicator for NF scores, APACHE II scores and CRP levels. A glycemic gap of 146 mg/dL was the optimal cutoff value for predicting adverse outcomes using the ROC curve. Compared with patients with glycemic gaps ≤146 mg/dL, those with glycemic gaps >146 mg/dL had higher APACHE II scores and incidence rates of adverse outcomes, especially bacteremia and acute kidney injury. Multivariate analysis revealed that a glycemic gap >146 mg/dL and APACHE II score >15 were independent predictors of adverse outcomes, while the presence of hyperglycemia at admission was not.

          Conclusions

          An elevated glycemic gap was significantly independently associated with adverse outcomes in diabetic NF patients. Further prospective studies are warranted to validate the role of the glycemic gap in NF patients with diabetes.

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          Most cited references33

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          Necrotizing fasciitis: clinical presentation, microbiology, and determinants of mortality.

          Necrotizing fasciitis is a life-threatening soft-tissue infection primarily involving the superficial fascia. The present report describes the clinical presentation and microbiological characteristics of this condition as well as the determinants of mortality associated with this uncommon surgical emergency. The medical records of eighty-nine consecutive patients who had been admitted to our institution for necrotizing fasciitis from January 1997 to August 2002 were reviewed retrospectively. The paucity of cutaneous findings early in the course of the disease makes the diagnosis difficult, and only thirteen of the eighty-nine patients had a diagnosis of necrotizing fasciitis at the time of admission. Preadmission treatment with antibiotics modified the initial clinical picture and often masked the severity of the underlying infection. Polymicrobial synergistic infection was the most common cause (forty-eight patients; 53.9%), with streptococci and enterobacteriaceae being the most common isolates. Group-A streptococcus was the most common cause of monomicrobial necrotizing fasciitis. The most common associated comorbidity was diabetes mellitus (sixty-three patients; 70.8%). Advanced age, two or more associated comorbidities, and a delay in surgery of more than twenty-four hours adversely affected the outcome. Multivariate analysis showed that only a delay in surgery of more than twenty-four hours was correlated with increased mortality (p < 0.05; relative risk = 9.4). Early operative débridement was demonstrated to reduce mortality among patients with this condition. A high index of suspicion is important in view of the paucity of specific cutaneous findings early in the course of the disease.
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            Early diagnosis of necrotizing fasciitis.

            Necrotizing fasciitis is a rapidly progressing skin infection characterized by necrosis of the fascia and subcutaneous tissue, accompanied by severe systemic toxicity. The objective of this systematic review was to identify clinical features and investigations that will aid early diagnosis. A systematic literature search of PubMed was undertaken using the keywords 'necrotising fasciitis', 'necrotising skin infection', 'diagnosis' and 'outcome'. Case series of 50 or more subjects with information on symptoms and signs at initial presentation, investigations and clinical outcome were included. Nine case series were selected, with a total of 1463 patients. Diabetes mellitus was a co-morbidity in 44.5 per cent of patients. Contact with marine life or ingestion of seafood in patients with liver disease were risk factors in some parts of Asia. The top three early presenting clinical features were: swelling (80.8 per cent), pain (79.0 per cent) and erythema (70.7 per cent). These being non-specific features, initial misdiagnosis was common and occurred in almost three-quarters of patients. Clinical features that helped early diagnosis were: pain out of proportion to the physical findings; failure to improve despite broad-spectrum antibiotics; presence of bullae in the skin; and gas in the soft tissue on plain X-ray (although this occurred in only 24.8 per cent of patients). A high index of suspicion of necrotizing fasciitis is needed in a patient presenting with cutaneous infection causing swelling, pain and erythema, with co-morbidity of diabetes or liver disease. The presence of bullae, or gas on plain X-ray can be diagnostic. Early surgical exploration is the best approach in the uncertain case. © 2013 BJS Society Ltd. Published by John Wiley & Sons Ltd.
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              Type 2 diabetes and pneumonia outcomes: a population-based cohort study.

              We sought to examine whether type 2 diabetes increases risk of death and complications following pneumonia and to assess the prognostic value of admission hyperglycemia. This was a population-based cohort study of adults with a first-time hospitalization for pneumonia between 1997 and 2004 (n = 29,900) in northern Denmark. Information on diabetes, comorbidity, laboratory findings, pulmonary complications, and bacteremia was obtained from medical databases. We used regression to compute adjusted relative risks of pulmonary complications, bacteremia, and mortality rate ratios (MRRs) within 90 days following hospitalization among patients with and without type 2 diabetes. The prognostic impact of admission hyperglycemia was studied in a subcohort (n = 13,574). In total, 2,931 (9.8%) pneumonia patients had type 2 diabetes. Mortality among diabetic patients was greater than that among other patients: 19.9 vs. 15.1% after 30 days and 27.0 vs. 21.6% after 90 days, respectively, corresponding to adjusted 30- and 90-day MRRs of 1.16 (95% CI 1.07-1.27) and 1.10 (1.02-1.18). Presence of type 2 diabetes did not predict pulmonary complications or bacteremia. Adjustment for hyperglycemia attenuated the association between type 2 diabetes and mortality. High glucose level on admission was a predictor of death among patients with diabetes and more so among those without diagnosed diabetes: adjusted 30-day MRRs for glucose level >or=14 mmol/l were 1.46 (1.01-2.12) and 1.91 (1.40-2.61), respectively. Type 2 diabetes and admission hyperglycemia predict increased pneumonia-related mortality.
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                Author and article information

                Contributors
                Role: Data curationRole: Funding acquisitionRole: Writing – original draft
                Role: ConceptualizationRole: MethodologyRole: Writing – review & editing
                Role: Data curation
                Role: Conceptualization
                Role: Methodology
                Role: Formal analysis
                Role: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: Funding acquisitionRole: MethodologyRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                3 October 2019
                2019
                : 14
                : 10
                : e0223126
                Affiliations
                [1 ] Department of Emergency Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
                [2 ] Department of Physiology and Biophysics, Graduate Institute of Physiology, National Defense Medical Center, Taipei, Taiwan
                [3 ] Division of Plastic and Reconstructive Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
                [4 ] Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
                [5 ] School of Public Health, National Defense Medical Center, Taipei, Taiwan
                [6 ] Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
                Wayne State University, UNITED STATES
                Author notes

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

                Author information
                http://orcid.org/0000-0003-0864-177X
                Article
                PONE-D-19-10642
                10.1371/journal.pone.0223126
                6776331
                31581199
                137b3845-47be-4a29-9285-526c2f1215cf
                © 2019 Chen 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
                : 13 April 2019
                : 13 September 2019
                Page count
                Figures: 2, Tables: 6, Pages: 15
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100010425, Tri-Service General Hospital;
                Award ID: TSGH-C107-044
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100010425, Tri-Service General Hospital;
                Award ID: TSGH-C108-065
                Award Recipient :
                Funded by: Ministry of Science and Technology
                Award ID: MOST 107-2314-B-016-043
                Award Recipient :
                Funded by: Ministry of Science and Technology (TW)
                Award ID: MOST 107-2314-B-016-071
                Award Recipient :
                Funded by: National Defense Medical Center
                Award ID: MAB-106-066
                Award Recipient :
                Funded by: National Defense Medical Center
                Award ID: MAB-107-012
                Award Recipient :
                This study was supported by a grant from Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan (TSGH-C107-044, TSGH-C108-065); the National Defense Medical Center, Taipei, Taiwan (MAB-106-066, MAB-107-012); and the Ministry of Science and Technology, Taiwan (MOST 107-2314-B-016-043, MOST 107-2314-B-016-071). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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