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Wang N, Zheng Y, Tao S, Chen L. Risk factors and prognosis of pulmonary infection in hepatitis B-related acute-on-chronic liver failure: a retrospective cohort study. BMC Pulm Med 2025; 25:178. [PMID: 40229810 PMCID: PMC11995551 DOI: 10.1186/s12890-025-03628-7] [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: 08/16/2024] [Accepted: 03/25/2025] [Indexed: 04/16/2025] Open
Abstract
OBJECTIVE To identify risk factors for pulmonary infection in patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF), assess its impact on prognosis, and develop a prognostic prediction model. METHODS We retrospectively analyzed the clinical data of 393 patients with HBV-ACLF. Logistic regression was used to analyze the risk factors for lung infection in ACLF patients, as well as the factors affecting the prognosis of those who were infected. Additionally, a prognostic prediction model was established using the Nomogram method. RESULTS The incidence of pulmonary infections in patients with ACLF was 38.7%, and patients with ACLF combined with pulmonary infections had a higher short-term mortality rate than those without infections (65.71% vs. 35.02%). Multivariate logistic regression analysis indicated that independent risk factors for pulmonary infection included TBIL, CRP, invasive procedures, peritoneal effusion, and hepatic encephalopathy. Additionally, creatinine, INR, comorbid diabetes mellitus, neutrophil counts, and lymphocyte counts were identified as independent risk factors affecting 30-day mortality in patients with pulmonary infection. Incorporating these risk factors, a new predictive model was established, with an area under the receiver operating characteristic curve of 0.832 (95% CI, 0.765-0.900). This model demonstrated higher discriminatory performance compared to traditional prognostic models such as CTP, MELD, and MELD-Na, with statistically significant differences (P < 0.05). CONCLUSION HBV-ACLF patients are susceptible to pulmonary infection, with fungal infection posing a significant threat. Pulmonary infection is associated with worse prognosis in HBV-ACLF patients. Early identification of risk factors and prognostic assessment can facilitate timely intervention and improve prognosis.
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Affiliation(s)
- Neng Wang
- Department of Liver Disease, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Yu Zheng
- Center of Infectious Disease, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, P.R. China
| | - Shuai Tao
- Department of Liver Disease, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Liang Chen
- Department of Liver Disease, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
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Hashem HE, Ahmed WO, Hassan SH. The Role of Neutrophil CD11b Compared to Neutrophil CD64 as an Early Diagnostic, Monitoring, and Prognostic Sepsis Marker in Neonatal ICUs: Case-Control-Methodological Study. BIOMED RESEARCH INTERNATIONAL 2025; 2025:7206112. [PMID: 40224545 PMCID: PMC11991832 DOI: 10.1155/bmri/7206112] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Revised: 12/26/2024] [Accepted: 02/06/2025] [Indexed: 04/15/2025]
Abstract
Background: Early diagnosis and treatment of neonatal sepsis are crucial to cut off its major medical consequences: lifelong morbidities, neurodevelopmental disabilities, and a high number of neonatal mortalities. Aim of the Work: This study is aimed at determining the diagnostic and prognostic performance of CD11b as a sepsis biomarker for detecting neonatal sepsis at early stages compared to nCD64 and the other conventional sepsis parameters. Methods: Two hundred eleven neonates were enrolled from three Egyptian neonatal ICUs (NICUs), and they were classified into two main groups: the control group (n = 101) and the sepsis group (n = 110). Enrolled neonates were subjected to full sepsis screening, including complete blood count (CBC), C-reactive protein (CRP), blood cultures, and flow cytometry analysis for both CD64 and CD11b on the neutrophil surface (results represented as a percentage (percent) and mean fluorescent intensity (MFI) units for either biomarker). Results: nCD64% (median = 44.15%) was significantly enhanced in the sepsis group compared to the controls (median = 25%), achieving 90.8% specificity, 92.8% sensitivity, and AUC = 0.894, respectively. CD64 MFI and CD11b MFI could differentiate between sepsis and control groups but with low undesirable diagnostic performance (sensitivity: 72.5% and 59.1%; specificity: 54.4% and 69.4%; AUC: 0.634 and 0.144, respectively). CD11b% could not discriminate between sepsis and control neonates (sensitivity and specificity of 31.8% and 73.6%, respectively) with an AUC of 0.405. hs-CRP had moderate diagnostic performance, achieving sensitivity and specificity of 69% and 78.15%, respectively, and AUC = 0.586. ROC analysis showed that combined hs-CRP and CD64% results had the highest sensitivity and specificity in the current study, being 93.9% and 97.2%, with AUC = 0.938, respectively. Conclusion: CD64%, CD64 MFI, CD11b MFI, and hs-CRP are increased in neonates with sepsis comparable to the controls. CD64% has a superior diagnostic performance comparable to nCD11b and hs-CRP. Combined nCD64 with hs-CRP measurement can provide rapid and accurate diagnostic modality for sepsis diagnosis in correlation with the patient's clinical condition and context with the results of other hematological indices; neutrophil CD64 can be routinely applicable in NICUs for better sepsis management. It is statistically evident that nCD11b is less ideal compared to nCD64 as a diagnostic, prognostic, or monitoring sepsis marker.
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Affiliation(s)
- Heba E. Hashem
- Clinical Pathology Department, Ain Shams University Hospitals, Cairo, Egypt
| | - Wafaa O. Ahmed
- Clinical Pathology Department, Ain Shams University Hospitals, Cairo, Egypt
| | - Safeya H. Hassan
- Clinical Pathology Department, Ain Shams University Hospitals, Cairo, Egypt
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Campagner A, Agnello L, Carobene A, Padoan A, Del Ben F, Locatelli M, Plebani M, Ognibene A, Lorubbio M, De Vecchi E, Cortegiani A, Piva E, Poz D, Curcio F, Cabitza F, Ciaccio M. Complete Blood Count and Monocyte Distribution Width-Based Machine Learning Algorithms for Sepsis Detection: Multicentric Development and External Validation Study. J Med Internet Res 2025; 27:e55492. [PMID: 40009841 PMCID: PMC11904381 DOI: 10.2196/55492] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2023] [Revised: 05/04/2024] [Accepted: 09/09/2024] [Indexed: 02/28/2025] Open
Abstract
BACKGROUND Sepsis is an organ dysfunction caused by a dysregulated host response to infection. Early detection is fundamental to improving the patient outcome. Laboratory medicine can play a crucial role by providing biomarkers whose alteration can be detected before the onset of clinical signs and symptoms. In particular, the relevance of monocyte distribution width (MDW) as a sepsis biomarker has emerged in the previous decade. However, despite encouraging results, MDW has poor sensitivity and positive predictive value when compared to other biomarkers. OBJECTIVE This study aims to investigate the use of machine learning (ML) to overcome the limitations mentioned earlier by combining different parameters and therefore improving sepsis detection. However, making ML models function in clinical practice may be problematic, as their performance may suffer when deployed in contexts other than the research environment. In fact, even widely used commercially available models have been demonstrated to generalize poorly in out-of-distribution scenarios. METHODS In this multicentric study, we developed ML models whose intended use is the early detection of sepsis on the basis of MDW and complete blood count parameters. In total, data from 6 patient cohorts (encompassing 5344 patients) collected at 5 different Italian hospitals were used to train and externally validate ML models. The models were trained on a patient cohort encompassing patients enrolled at the emergency department, and it was externally validated on 5 different cohorts encompassing patients enrolled at both the emergency department and the intensive care unit. The cohorts were selected to exhibit a variety of data distribution shifts compared to the training set, including label, covariate, and missing data shifts, enabling a conservative validation of the developed models. To improve generalizability and robustness to different types of distribution shifts, the developed ML models combine traditional methodologies with advanced techniques inspired by controllable artificial intelligence (AI), namely cautious classification, which gives the ML models the ability to abstain from making predictions, and explainable AI, which provides health operators with useful information about the models' functioning. RESULTS The developed models achieved good performance on the internal validation (area under the receiver operating characteristic curve between 0.91 and 0.98), as well as consistent generalization performance across the external validation datasets (area under the receiver operating characteristic curve between 0.75 and 0.95), outperforming baseline biomarkers and state-of-the-art ML models for sepsis detection. Controllable AI techniques were further able to improve performance and were used to derive an interpretable set of diagnostic rules. CONCLUSIONS Our findings demonstrate how controllable AI approaches based on complete blood count and MDW may be used for the early detection of sepsis while also demonstrating how the proposed methodology can be used to develop ML models that are more resistant to different types of data distribution shifts.
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Affiliation(s)
| | | | - Anna Carobene
- IRCCS San Raffaele Scientific Institute, Milano, Italy
| | - Andrea Padoan
- Department of Medicine, University of Padova, Padova, Italy
- Laboratory Medicine Unit, University-Hospital of Padova, Padova, Italy
| | - Fabio Del Ben
- IRCCS Centro Di Riferimento Oncologico Aviano, Aviano, Italy
| | | | - Mario Plebani
- Department of Medicine, University of Padova, Padova, Italy
- Laboratory Medicine Unit, University-Hospital of Padova, Padova, Italy
| | | | | | | | - Andrea Cortegiani
- University of Palermo, Palermo, Italy
- University Hospital Policlinico Paolo Giaccone, Palermo, Italy
| | - Elisa Piva
- Azienda Socio Sanitaria Territoriale di Mantova, Mantova, Italy
| | | | | | - Federico Cabitza
- IRCCS Ospedale Galeazzi Sant'Ambrogio, Milan, Italy
- Department of Computer Science, Systems and Communication, University of Milano-Bicocca, Milano, Italy
| | - Marcello Ciaccio
- University of Palermo, Palermo, Italy
- University Hospital Policlinico Paolo Giaccone, Palermo, Italy
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Sun Q, Lin Q, Lv Y, Tian Z, Yan Q, Yu Y, Fu X, Yao H, Sun F, Xia Y, Zhu G, Feng S. Predictive value of serum procalcitonin level for the diagnosis of bloodstream infections in hematological patients. BMC Infect Dis 2025; 25:162. [PMID: 39901114 PMCID: PMC11792228 DOI: 10.1186/s12879-024-10415-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2024] [Accepted: 12/26/2024] [Indexed: 02/05/2025] Open
Abstract
OBJECTIVES Procalcitonin (PCT) is a critical diagnostic biomarker for bacterial infections in patients. Numerous studies have shown that PCT have high sensitivity and specificity for diagnosing bloodstream infection. However, the cut-off value of PCT for the diagnosis of bloodstream infections in patients with hematolgic diseases is still unclear and unreliable. METHODS We conducted a retrospective study involving 2299 cases with hematological diseases and who had been performed blood culture and PCT test within 24 h. RESULTS For patients with hematological diseases, the serum PCT was slightly elevated in the BSI group. We found that most hematological patients with bloodstream infection were in the stage of severe neutropenia. The main infected strains were Escherichia coli (n = 84, 21%), Klebsiella pneumoniae (n = 61, 15.25%) and Pseudomonas aeruginosa (n = 65, 16.25%), and the increasing trend of PCT level was more obvious in patients infected with Gram-negative bacteria. ROC analysis results showed that the area under the receiver operating characteristic curve for distinguishing bacterial infection from non-bacterial infection was 0.554 (95%CI: 0.522-0.585) with the diagnostic threshold of BSI (PCT > 0.5ng/mL). CONCLUSIONS In our study, low PCT levels were found in patients with hematological diseases, and a better cut-off value may be necessary to determine infection in hematology patients.
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Affiliation(s)
- Qi Sun
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, China
- Tianjin Institutes of Health Science, Tianjin, 301600, China
| | - Qingsong Lin
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, China
- Tianjin Institutes of Health Science, Tianjin, 301600, China
| | - Yanxia Lv
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, China
- Tianjin Institutes of Health Science, Tianjin, 301600, China
| | - Zhiying Tian
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, China
- Tianjin Institutes of Health Science, Tianjin, 301600, China
| | - Qiushuang Yan
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, China
- Tianjin Institutes of Health Science, Tianjin, 301600, China
| | - Yaqing Yu
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, China
- Tianjin Institutes of Health Science, Tianjin, 301600, China
| | - Xue Fu
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, China
- Tianjin Institutes of Health Science, Tianjin, 301600, China
| | - Hongjing Yao
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, China
- Tianjin Institutes of Health Science, Tianjin, 301600, China
| | - Fujun Sun
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, China
- Tianjin Institutes of Health Science, Tianjin, 301600, China
| | - Yonghui Xia
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, China
- Tianjin Institutes of Health Science, Tianjin, 301600, China
| | - Guoqing Zhu
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, China.
- Tianjin Institutes of Health Science, Tianjin, 301600, China.
| | - Sizhou Feng
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, China.
- Tianjin Institutes of Health Science, Tianjin, 301600, China.
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Shih PC, Wang YH, Chen SY, Tseng M, Hsu CA, Yang MY, Wang HY, Lee JA. Delta Immature Platelet Fraction Is Associated With Mortality in Bacteremia Patients. Int J Lab Hematol 2025; 47:51-60. [PMID: 39222719 DOI: 10.1111/ijlh.14365] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2024] [Revised: 08/05/2024] [Accepted: 08/17/2024] [Indexed: 09/04/2024]
Abstract
OBJECTIVES Immature platelet fraction (IPF) for differentiating bacteremia has been explored, whereas its prognostic correlation remains uncertain. This study aims to confirm the predictive capability of IPF for bacteremia and investigate its association with prognosis. METHODS Patients with complete blood count (CBC) on the blood culture day (D1) and the preceding day (D0) were retrospectively recruited and categorized into bacteremia and nonbacteremia groups. Immature platelet (IP) analysis, alongside CBC, was conducted. Delta IPF, defined by the absolute values of D1 minus D0 results was calculated. The ability to distinguish bacteremia from nonbacteremia patients, and the correlation with mortality were analyzed. RESULTS From February to December 2020, a total of 150 patients were enrolled, with 75 having bacteremia. The specificity for delta IPF ≥3.4% to predict bacteremia was 97.3% (95% confidence interval [CI]: 90.7-99.7). When delta IPF ≥3.4% combined with procalcitonin ≥0.5 (ng/mL), the sensitivity was 90.5% (95% CI: 69.6%-98.8%). Within the bacteremia group, delta IPF and the proportion of patients with delta IPF ≥1.5% were significantly higher in nonsurvival, while delta platelet levels did not. Furthermore, delta IPF ≥1.5% was independently associated with 30-day mortality (adjusted odds ratio: 3.88, 95% CI: 1.2%-11.4%; p = 0.020). The 30-day survival curve demonstrated a significant difference between patients with delta IPF ≥1.5% and those without (p < 0.001). CONCLUSIONS Delta IPF correlates with mortality in bacteremia patients. Our findings suggest IPF not only helps detect bacteremia but also predicts prognosis in the early stage.
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Affiliation(s)
- Pei-Chun Shih
- Department of Laboratory Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Yi-Hua Wang
- Department of Laboratory Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Shey-Ying Chen
- Center for Quality Management, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Min Tseng
- Department of Laboratory Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Cheng-An Hsu
- Department of Laboratory Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Ming-Yan Yang
- Department of Medical Education, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Hsin-Yao Wang
- Department of Laboratory Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan City, Taiwan
- School of Medicine, National Tsing Hua University, Hsinchu, Taiwan
| | - Jia-Arng Lee
- Department of Laboratory Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
- Graduate Institute of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University, Taipei, Taiwan
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Christopher O, Yanmei W, Yeko ME, Nanyunja DM, Kabbali KJ. Impact of estimated glomerular filtration rate (eGFR) on in-hospital mortality: an age- and HIV status-specific retrospective cohort study in Uganda. BMC Nephrol 2025; 26:43. [PMID: 39875843 PMCID: PMC11776265 DOI: 10.1186/s12882-025-03976-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2024] [Accepted: 01/21/2025] [Indexed: 01/30/2025] Open
Abstract
BACKGROUND Limited studies have explored the relationship between estimated Glomerular Filtration Rate(eGFR) and in-hospital mortality(IHM) in low-income sub-Saharan African countries. This study aimed to explores this association, offering insights into its impact in resource-limited settings. METHODS AND RESULTS We retrospectively included 226 patients(age 45.35 ± 18.85yrs, 54.4% women) admitted to Naguru-referral hospital between January 1st and June 30th, 2024. Baseline demographics and clinical variables, including eGFR, were recorded at admission. Patients were followed from date of admission to discharge and primary outcome was IHM. Multivariable Hazard regression analysis assessed the association between eGFR and IHM, respectively. During follow-up, 45(19.9%) of patients died. Per-standard deviation(SD) increase in eGFR(48.60 mL/min/1.73m2) was associated with Hazard Ratio(HR) of 0.46[95%CI: 0.282-0.759, p = 0.002, β = -0.77] for IHM in fully adjusted models. When stratified by eGFR quartiles, using highest quartile(≥ 120 mL/min/1.73m2) as reference, HR was 1.08[95%CI: 0.276-4.226, p = 0.912, β = + 0.08] for 99.0-120 mL/min/1.73m2; 4.08[95%CI: 1.284-12.954, p = 0.017, β = + 1.41] for 66.8-99.0 mL/min/1.73m2, and 4.08[95%CI: 1.284-12.954, p = 0.037, β = + 1.25] for < 66.8 mL/min/1.73m2. Among age stratification-subgroups: age < 40yrs: 0.93[95%CI: 0.89-0.97, p < 0.001, β = -0.07]; 40-60yrs: 0.98[95%CI: 0.966-0.999, p = 0.039, β = -0.02]; ≥ 60yrs, p < 0.005 with p-value-interaction for age = 0.046; and HIV-positive: 0.94[95%CI: 0.905-0.974, p < 0.001, β = -0.06] with p-value-interaction = 0.021. Significant Pearsons-correlation(r) was observed only in: [< 40yrs, HIV(-)] with p = 0.016, r = -0.275; [40-60yrs, HIV( +)] with p = 0.020, r = -0.397; and [≥ 60yrs,HIV( +)] with p = 0.003, r = -0.997. CONCLUSIONS We report that eGFR was associated with in-hospital mortality, with a stronger association observed in HIV-negative patients(< 40yrs) and HIV-positive patients (aged ≥ 60yrs yrs). Further research is warranted to validate these findings.
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Affiliation(s)
- Odong Christopher
- Department of Internal Medicine, Naguru Referral Hospital, Kampala, Uganda.
| | - Wang Yanmei
- Department of Internal Medicine, Naguru Referral Hospital, Kampala, Uganda
- Department of Tuberculosis, Yunnan Provincial Infectious Disease Hospital, Kunming, Yunnan Province, China
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Alsewy FZ, Megallaa MH, Imbaby SA, Zidan HM, Kassab HS, Badrah MH. Prognostic Value of Hyperglycemia and Insulin Resistance Among Patients with Confirmed COVID-19 Infections at Admission to the Alexandria Fever Hospital, Egypt. Metab Syndr Relat Disord 2024; 22:551-557. [PMID: 38683638 DOI: 10.1089/met.2024.0066] [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] [Indexed: 05/01/2024] Open
Abstract
Background: The interaction between COVID-19 infection, hyperglycemia, and insulin resistance (IR) may lead to poor outcome. Methods: This prospective study included 100 adult participants without diabetes attending Alexandria Fever Hospital with confirmed COVID-19 infections. They were classified into four groups according to disease severity using World Health Organization (WHO) criteria. Demographic and clinical parameters were collected. Laboratory investigations were obtained. Another follow-up fasting plasma glucose (FPG) value was measured after 3 months in cured patients. Results: Admission FPG, follow-up FPG, lipid profile, markers of IR, and inflammation were significantly higher in severe and critical cases than in mild and moderate cases with increasing values with increased severity. Furthermore, these parameters were significantly higher in died cases compared with cured cases. Admission FPG, TyG index, and homeostatic model assessment (HOMA)-IR showed significant positive correlations with follow-up FPG. Admission FPG was the only independent mortality predictor in multivariate analysis (P = 0.027) with 1.7-folds increased mortality risk with each 10 mg/dL increments. Values exceeding 117 mg/dL, 2.2, and 6.33 for admission FPG, HOMA-IR, and Fasting Insulin Resistance Index, respectively, were able to predict mortality in the studied sample. Conclusions: These results will help in identifying patients at high risk of severe infection and death at admission and take early actions to improve outcome.
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Affiliation(s)
- Fathy Z Alsewy
- Department of Internal Medicine (Diabetes and Metabolism Unit), Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Magdy H Megallaa
- Department of Internal Medicine (Diabetes and Metabolism Unit), Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Salma A Imbaby
- Department of Clinical and Chemical Pathology, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Huda M Zidan
- Department of Internal Medicine (Diabetes and Metabolism Unit), Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Heba S Kassab
- Department of Internal Medicine (Diabetes and Metabolism Unit), Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Mai H Badrah
- Department of Internal Medicine (Diabetes and Metabolism Unit), Faculty of Medicine, Alexandria University, Alexandria, Egypt
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Zhang N, Liu Y, Yang C, Li X. Review of the Predictive Value of Biomarkers in Sepsis Mortality. Emerg Med Int 2024; 2024:2715606. [PMID: 38938850 PMCID: PMC11208822 DOI: 10.1155/2024/2715606] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2023] [Revised: 01/26/2024] [Accepted: 05/11/2024] [Indexed: 06/29/2024] Open
Abstract
Sepsis is a leading cause of mortality among severely ill individuals, primarily due to its potential to induce fatal organ dysfunction. For clinicians, it is vital to have appropriate indicators, including the physiological status and personal experiences of patients with sepsis, to monitor the condition and assess prognosis. This approach aids in preventing the worsening of the illness and reduces mortality. Recent guidelines for sepsis focus on improving patient outcomes through early detection and timely treatment. Nonetheless, identifying severe cases and predicting their prognoses remain challenging. In recent years, there has been considerable interest in utilising the C-reactive protein (CRP)/albumin ratio (CAR) to evaluate the condition and forecast the prognosis of patients with sepsis. This research concentrates on the significance of CAR in the pathological process of sepsis, its association with prognosis, and the latest developments in employing procalcitonin, lactic acid, CRP, and other potential biomarkers. The CAR, with its predictive value for sepsis prognosis and mortality, is increasingly used as a clinical biochemical marker in diagnosing and monitoring patients with sepsis.
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Affiliation(s)
- Nai Zhang
- Department of Emergency, Jiangxi Province Hospital of Integrated Chinese and Western Medicine, Nanchang 330003, China
| | - Yujuan Liu
- Department of Emergency, Jiangxi Province Hospital of Integrated Chinese and Western Medicine, Nanchang 330003, China
| | - Chuang Yang
- Department of Emergency, Jiangxi Province Hospital of Integrated Chinese and Western Medicine, Nanchang 330003, China
| | - Xinai Li
- Department of Respiratory Medicine, Jiangxi Province Hospital of Integrated Chinese and Western Medicine, Nanchang 330003, China
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9
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Trebuian CI, Brici OM, Sutoi D, Popa DI, Chioibas DR, Mederle OA. Lactate Levels and Clearance: Key Predictors of Prognosis for COVID-19 and Non-COVID-19 Septic Shock Patients in the Emergency Department. Clin Pract 2024; 14:834-845. [PMID: 38804397 PMCID: PMC11130935 DOI: 10.3390/clinpract14030065] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Revised: 04/30/2024] [Accepted: 05/08/2024] [Indexed: 05/29/2024] Open
Abstract
BACKGROUND This investigation assesses the prognostic value of lactate levels and their clearance in septic shock patients, particularly emphasizing the comparative analysis between COVID-19 and non-COVID-19 patients in the emergency department. This study aims to elucidate the unique prognostic implications of lactate dynamics in these distinct patient groups, thereby enhancing the management of septic shock. METHODS An observational prospective study was conducted, enrolling 114 septic shock patients from the Emergency County Hospital Resita, Romania, categorizing them into COVID-19 and non-COVID-19 groups to examine their initial lactate levels, clearance rates, and their correlation with patient outcomes. RESULTS This study identified significant differences in the initial lactate levels and clearance rates between the two groups, indicating higher initial lactate levels and slower clearance rates in COVID-19 patients. Survivors demonstrated significantly lower initial lactate levels (1.5 ± 0.4 mmol/L) and higher lactate clearance rates (33 ± 15%) compared to non-survivors (2.5 ± 0.5 mmol/L and 24 ± 9%, respectively; lactate levels p = 0.001, clearance rates p = 0.002). CONCLUSIONS Lactate monitoring, particularly clearance rates, is crucial in the prognostic assessment of septic shock patients. These findings highlight the need for targeted interventions in COVID-19 patients to improve outcomes, underscoring lactate dynamics as a vital component of septic shock management in differing patient populations.
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Affiliation(s)
- Cosmin Iosif Trebuian
- Department of Surgery I, “Victor Babes” University of Medicine and Pharmacy, E. Murgu Square No. 2, 300041 Timisoara, Romania; (C.I.T.); (D.S.); (D.R.C.); (O.A.M.)
| | - Octavia Maria Brici
- Department of Doctoral Studies, “Victor Babes” University of Medicine and Pharmacy, E. Murgu Square No. 2, 300041 Timisoara, Romania;
| | - Dumitru Sutoi
- Department of Surgery I, “Victor Babes” University of Medicine and Pharmacy, E. Murgu Square No. 2, 300041 Timisoara, Romania; (C.I.T.); (D.S.); (D.R.C.); (O.A.M.)
| | - Daian Ionel Popa
- Department of Doctoral Studies, “Victor Babes” University of Medicine and Pharmacy, E. Murgu Square No. 2, 300041 Timisoara, Romania;
| | - Daniel Raul Chioibas
- Department of Surgery I, “Victor Babes” University of Medicine and Pharmacy, E. Murgu Square No. 2, 300041 Timisoara, Romania; (C.I.T.); (D.S.); (D.R.C.); (O.A.M.)
| | - Ovidiu Alexandru Mederle
- Department of Surgery I, “Victor Babes” University of Medicine and Pharmacy, E. Murgu Square No. 2, 300041 Timisoara, Romania; (C.I.T.); (D.S.); (D.R.C.); (O.A.M.)
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10
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Nishida Y, Yamamoto R, Ono S, Sasaki J. Association between preoperative lactate level and early complications after surgery for isolated extremity fracture. BMC Musculoskelet Disord 2024; 25:314. [PMID: 38654188 PMCID: PMC11036590 DOI: 10.1186/s12891-024-07409-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2023] [Accepted: 04/02/2024] [Indexed: 04/25/2024] Open
Abstract
BACKGROUND The role of lactate level in selecting the timing of definitive surgery for isolated extremity fracture remains unclear. Therefore, we aimed to elucidate the use of preoperative lactate level for predicting early postoperative complications. METHODS This was a single-center retrospective observational study of patients with isolated extremity fracture who underwent orthopedic surgery. Patients who underwent lactate level assessment within 24 h prior to surgery were included. The incidence of early postoperative complications was compared between patients with a preoperative lactate level of ≥ 2 and < 2 mmol/L. Moreover, subgroup analyses were performed based on the time from hospital arrival to surgery and fracture type. RESULTS In total, 187 patients were included in the study. The incidence of postoperative complications was significantly higher in patients with a preoperative lactate level of ≥ 2 mmol/L than those with a preoperative lactate level of < 2 mmol/L. This result did not change after adjusting for age and severity. Further, a high preoperative lactate level was associated with a greater incidence of postoperative complications in patients who underwent definitive surgery within 6 h after arrival. CONCLUSION A preoperative lactate level of ≥ 2 mmol/L was associated with a greater incidence of early postoperative complications in isolated extremity fractures. Nevertheless, this correlation was only observed among patients who underwent definitive fixation within 6 h after hospital arrival.
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Affiliation(s)
- Yusho Nishida
- Department of Emergency and Critical Care Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo, 160-8582, Japan.
| | - Ryo Yamamoto
- Department of Emergency and Critical Care Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo, 160-8582, Japan
| | - Soichiro Ono
- Department of Emergency and Critical Care Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo, 160-8582, Japan
| | - Junichi Sasaki
- Department of Emergency and Critical Care Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo, 160-8582, Japan
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11
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Wang Q, Sun J, Liu X, Ping Y, Feng C, Liu F, Feng X. Comparison of risk prediction models for the progression of pelvic inflammatory disease patients to sepsis: Cox regression model and machine learning model. Heliyon 2024; 10:e23148. [PMID: 38163183 PMCID: PMC10754857 DOI: 10.1016/j.heliyon.2023.e23148] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2023] [Revised: 11/27/2023] [Accepted: 11/27/2023] [Indexed: 01/03/2024] Open
Abstract
Introduction The present study presents the development and validation of a clinical prediction model using random survival forest (RSF) and stepwise Cox regression, aiming to predict the probability of pelvic inflammatory disease (PID) progressing to sepsis. Methods A retrospective cohort study was conducted, gathering clinical data of patients diagnosed with PID between 2008 and 2019 from the Medical Information Mart for Intensive Care (MIMIC)-IV database. Patients who met the Sepsis 3.0 diagnostic criteria were selected, with sepsis as the outcome. Univariate Cox regression and stepwise Cox regression were used to screen variables for constructing a nomogram. Moreover, an RSF model was created using machine learning algorithms. To verify the model's performance, a calibration curve, decision curve analysis (DCA), and receiver operating characteristic (ROC) curve were utilized. Furthermore, the capabilities of the two models for estimating the incidence of sepsis in PID patients within 3 and 7 days were compared. Results A total of 1064 PID patients were included, of whom 54 had progressed to sepsis. The established nomogram highlighted dialysis, reduced platelet (PLT) counts, history of pneumonia, medication of glucocorticoids, and increased leukocyte counts as significant predictive factors. The areas under the curve (AUCs) of the nomogram for prediction of PID progression to sepsis at 3-day and 7-day (3-/7-day) in the training set and the validation set were 0.886/0.863 and 0.824/0.726, respectively, and the C-index of the model was 0.8905. The RSF displayed excellent performance, with AUCs of 0.939/0.919 and 0.712/0.571 for 3-/7-day risk prediction in the training set and validation set, respectively. Conclusion The nomogram accurately predicted the incidence of sepsis in PID patients, and relevant risk factors were identified. While the RSF model outperformed the Cox regression models in predicting sepsis incidence, its performance exhibited some instability. On the other hand, the Cox regression-based nomogram displayed stable performance and improved interpretability, thereby supporting clinical decision-making in PID treatment.
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Affiliation(s)
- Qingyi Wang
- Department of First Clinical Medical College, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Jianing Sun
- Department of First Clinical Medical College, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Xiaofang Liu
- Department of First Clinical Medical College, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Yunlu Ping
- Department of First Clinical Medical College, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Chuwen Feng
- Department of First Clinical Medical College, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Fanglei Liu
- Department of First Clinical Medical College, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Xiaoling Feng
- Department of Gynecology, The First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, China
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12
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Han H, Kim DS, Kim M, Heo S, Chang H, Lee GT, Lee SU, Kim T, Yoon H, Hwang SY, Cha WC, Sim MS, Jo IJ, Park JE, Shin TG. A Simple Bacteremia Score for Predicting Bacteremia in Patients with Suspected Infection in the Emergency Department: A Cohort Study. J Pers Med 2023; 14:57. [PMID: 38248758 PMCID: PMC10817606 DOI: 10.3390/jpm14010057] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2023] [Revised: 12/23/2023] [Accepted: 12/24/2023] [Indexed: 01/23/2024] Open
Abstract
Bacteremia is a life-threatening condition that has increased in prevalence over the past two decades. Prompt recognition of bacteremia is important; however, identification of bacteremia requires 1 to 2 days. This retrospective cohort study, conducted from 10 November 2014 to November 2019, among patients with suspected infection who visited the emergency department (ED), aimed to develop and validate a simple tool for predicting bacteremia. The study population was randomly divided into derivation and development cohorts. Predictors of bacteremia based on the literature and logistic regression were assessed. A weighted value was assigned to predictors to develop a prediction model for bacteremia using the derivation cohort; discrimination was then assessed using the area under the receiver operating characteristic curve (AUC). Among the 22,519 patients enrolled, 18,015 were assigned to the derivation group and 4504 to the validation group. Sixteen candidate variables were selected, and all sixteen were used as significant predictors of bacteremia (model 1). Among the sixteen variables, the top five with higher odds ratio, including procalcitonin, neutrophil-lymphocyte ratio (NLR), lactate level, platelet count, and body temperature, were used for the simple bacteremia score (model 2). The proportion of bacteremia increased according to the simple bacteremia score in both cohorts. The AUC for model 1 was 0.805 (95% confidence interval [CI] 0.785-0.824) and model 2 was 0.791 (95% CI 0.772-0.810). The simple bacteremia prediction score using only five variables demonstrated a comparable performance with the model including sixteen variables using all laboratory results and vital signs. This simple score is useful for predicting bacteremia-assisted clinical decisions.
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Affiliation(s)
- Hyelin Han
- Department of Emergency Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06355, Republic of Korea (W.C.C.); (M.S.S.); (I.J.J.)
| | - Da Seul Kim
- Department of Emergency Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06355, Republic of Korea (W.C.C.); (M.S.S.); (I.J.J.)
- Department of Digital Health, Samsung Advanced Institute for Health Sciences & Technology (SAIHST), Sunkyunkwan University, Seoul 06351, Republic of Korea
| | - Minha Kim
- Department of Emergency Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06355, Republic of Korea (W.C.C.); (M.S.S.); (I.J.J.)
| | - Sejin Heo
- Department of Emergency Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06355, Republic of Korea (W.C.C.); (M.S.S.); (I.J.J.)
| | - Hansol Chang
- Department of Emergency Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06355, Republic of Korea (W.C.C.); (M.S.S.); (I.J.J.)
| | - Gun Tak Lee
- Department of Emergency Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06355, Republic of Korea (W.C.C.); (M.S.S.); (I.J.J.)
| | - Se Uk Lee
- Department of Emergency Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06355, Republic of Korea (W.C.C.); (M.S.S.); (I.J.J.)
| | - Taerim Kim
- Department of Emergency Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06355, Republic of Korea (W.C.C.); (M.S.S.); (I.J.J.)
| | - Hee Yoon
- Department of Emergency Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06355, Republic of Korea (W.C.C.); (M.S.S.); (I.J.J.)
| | - Sung Yeon Hwang
- Department of Emergency Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06355, Republic of Korea (W.C.C.); (M.S.S.); (I.J.J.)
| | - Won Chul Cha
- Department of Emergency Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06355, Republic of Korea (W.C.C.); (M.S.S.); (I.J.J.)
- Department of Digital Health, Samsung Advanced Institute for Health Sciences & Technology (SAIHST), Sunkyunkwan University, Seoul 06351, Republic of Korea
- Digital Innovation, Samsung Medical Center, Seoul 06351, Republic of Korea
| | - Min Sub Sim
- Department of Emergency Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06355, Republic of Korea (W.C.C.); (M.S.S.); (I.J.J.)
| | - Ik Joon Jo
- Department of Emergency Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06355, Republic of Korea (W.C.C.); (M.S.S.); (I.J.J.)
| | - Jong Eun Park
- Department of Emergency Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06355, Republic of Korea (W.C.C.); (M.S.S.); (I.J.J.)
- Department of Emergency Medicine, College of Medicine, Kangwon National University, Kangwon 20341, Republic of Korea
| | - Tae Gun Shin
- Department of Emergency Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06355, Republic of Korea (W.C.C.); (M.S.S.); (I.J.J.)
- Department of Digital Health, Samsung Advanced Institute for Health Sciences & Technology (SAIHST), Sunkyunkwan University, Seoul 06351, Republic of Korea
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13
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Elek Z, Losoncz E, Fülep Z, Kovács-Nagy R, Bánlaki Z, Szlobodnyik G, Keszler G, Rónai Z. Persistent sepsis-induced transcriptomic signatures in signaling pathways of peripheral blood leukocytes: A pilot study. Hum Immunol 2023; 84:600-608. [PMID: 37673769 DOI: 10.1016/j.humimm.2023.08.146] [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: 03/10/2023] [Revised: 08/09/2023] [Accepted: 08/28/2023] [Indexed: 09/08/2023]
Abstract
Sepsis is a dysregulated immune response to infections that frequently precipitates multiple organ dysfunction and death despite intensive supportive therapy. The aim of the present study was to identify sepsis-induced alterations in the signaling transcriptome of peripheral blood leukocytes that might shed light on the elusive transition from proinflammatory to anti-inflammatory responses and underlie long-term post-sepsis immunosuppression. Peripheral blood leukocytes were collected from subjects (i) with systemic inflammation, (ii) with sepsis in the acute phase and (iii) 6 months after recovery from sepsis, corresponding to progressive stages of the disease. Transcriptomic analysis was performed with the QuantStudio 12K Flex OpenArray Human Signal Transduction Panel analyzing transcripts of 573 genes playing a significant role in signaling. Of them, 145 genes exhibited differential expression in sepsis as compared to systemic inflammation. Pathway analysis revealed enhanced expression levels of genes involved in primary immune responses (proinflammatory cytokines, neutrophil and macrophage activation markers) and signatures characteristic of immunosuppression (increased expression of anti-inflammatory cytokines and proapoptotic genes; diminished expression of T and B cell receptor dependent activating and survival pathways). Importantly, sepsis-induced expression patterns of 39 genes were not normalized by the end of the 6-month follow-up period, indicating expression aberrations persisting long after clinical recovery. Functional analysis of these transcripts revealed downregulation of the antiapoptotic Wnt and mTOR signaling pathways that might explain the post-sepsis immunosuppression commonly seen in sepsis survivors.
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Affiliation(s)
- Zsuzsanna Elek
- Institute of Biochemistry and Molecular Biology, Department of Molecular Biology, Semmelweis University, Budapest, Hungary
| | - Eszter Losoncz
- Department of Anesthesiology and Intensive Therapy, Bács-Kiskun County Teaching Hospital, Kecskemét, Hungary; Doctoral School, Semmelweis University, Budapest, Hungary
| | - Zoltán Fülep
- Department of Anesthesiology and Intensive Therapy, Bács-Kiskun County Teaching Hospital, Kecskemét, Hungary
| | - Réka Kovács-Nagy
- Institute of Biochemistry and Molecular Biology, Department of Molecular Biology, Semmelweis University, Budapest, Hungary
| | - Zsófia Bánlaki
- Institute of Biochemistry and Molecular Biology, Department of Molecular Biology, Semmelweis University, Budapest, Hungary
| | - Gergely Szlobodnyik
- Faculty of Information Technology and Bionics, Pázmány Péter Catholic University, Budapest, Hungary
| | - Gergely Keszler
- Institute of Biochemistry and Molecular Biology, Department of Molecular Biology, Semmelweis University, Budapest, Hungary.
| | - Zsolt Rónai
- Institute of Biochemistry and Molecular Biology, Department of Molecular Biology, Semmelweis University, Budapest, Hungary
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14
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Barbarewicz F, Henkel KO, Dudde F. Diagnosis and management of postoperative wound infections in the head and neck region. Oncoscience 2023; 10:56-58. [PMID: 37799961 PMCID: PMC10549770 DOI: 10.18632/oncoscience.589] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2023] [Accepted: 09/28/2023] [Indexed: 10/07/2023] Open
Affiliation(s)
- Filip Barbarewicz
- Department of Oral and Maxillofacial Surgery, Army Hospital Hamburg, Hamburg 22049, Germany
| | - Kai-Olaf Henkel
- Department of Oral and Maxillofacial Surgery, Army Hospital Hamburg, Hamburg 22049, Germany
| | - Florian Dudde
- Department of Oral and Maxillofacial Surgery, Army Hospital Hamburg, Hamburg 22049, Germany
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15
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Mubaraki MA, Faqihi A, AlQhtani F, Hafiz TA, Alalhareth A, Thagfan FA, Elshanat S, Abdel-Gaber RA, Dkhil MA. Blood Biomarkers of Neonatal Sepsis with Special Emphasis on the Monocyte Distribution Width Value as an Early Sepsis Index. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:1425. [PMID: 37629715 PMCID: PMC10456917 DOI: 10.3390/medicina59081425] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/18/2023] [Revised: 07/22/2023] [Accepted: 08/01/2023] [Indexed: 08/27/2023]
Abstract
Background and Objectives: Early detection of neonatal sepsis is critical because it is potentially fatal. Therefore, sepsis biomarkers of sufficient sensitivity and specificity are needed. This study aimed to evaluate the utility of peripheral blood parameters as neonatal sepsis biomarkers and the diagnostic performance of the monocyte distribution width (MDW) in sepsis in a neonatal intensive care unit. Materials and Methods: A cross-sectional study was conducted from September 2019 to August 2020 at the King Saud University Medical City in Riyadh, Saudi Arabia. Samples were collected and organised as follows: 77 study cases were subdivided into two subgroups (other health complication (49) and sepsis (28)), and there were 70 controls. The causative microorganisms of neonatal sepsis were isolated. Peripheral blood samples were collected from each neonate in an ethylenediaminetetraacetic acid tube for a complete blood count and a leukocyte differential count. Moreover, the receiver operating characteristic (ROC) curve analysis was used to measure the diagnostic performance of the MDW. Results: The haematological parameters and neonatal sepsis cases had a considerable correlation. The MDW was the most significant haematological parameter. The ROC analysis of the MDW demonstrated that the area under the curve was 0.89 (95% confidence interval: 0.867 to 0.998) with a sensitivity of 89.3%, a specificity of 88.2%, and a negative predictive value of 97.2% at the cut-off point of 23. Conclusions: The use of haematological parameters is feasible and can be performed rapidly. Neonatal sepsis showed a strong correlation with leukopenia, anaemia, thrombocytopenia, and an elevated MDW value. Moreover, the ROC curve analysis confirmed the high diagnostic ability of the MDW in neonatal sepsis prediction.
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Affiliation(s)
- Murad A. Mubaraki
- Clinical Laboratory Sciences Department, College of Applied Medical Sciences, King Saud University, Riyadh 12372, Saudi Arabia; (M.A.M.)
| | - Ayman Faqihi
- Pathology Department, King Saud University Medical City (KSUMC), Riyadh 12372, Saudi Arabia
| | - Fatmah AlQhtani
- Pathology Department, King Saud University Medical City (KSUMC), Riyadh 12372, Saudi Arabia
| | - Taghreed A. Hafiz
- Clinical Laboratory Sciences Department, College of Applied Medical Sciences, King Saud University, Riyadh 12372, Saudi Arabia; (M.A.M.)
| | | | - Felwa A. Thagfan
- Department of Biology, College of Science, Princess Nourah Bint Abdulrahman University, Riyadh 11671, Saudi Arabia
| | - Sherif Elshanat
- Department of Parasitology, Faculty of Veterinary Medicine, Alexandria University, Alexandria 22758, Egypt
| | | | - Mohamed A. Dkhil
- Department of Zoology and Entomology, Faculty of Sciences, Helwan University, Cairo 11795, Egypt
- Applied Science Research Center, Applied Science Private University, Amman 11931, Jordan
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16
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Zhou T, Ren Z, Ma Y, He L, Liu J, Tang J, Zhang H. Early identification of bloodstream infection in hemodialysis patients by machine learning. Heliyon 2023; 9:e18263. [PMID: 37519767 PMCID: PMC10375788 DOI: 10.1016/j.heliyon.2023.e18263] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2022] [Revised: 07/08/2023] [Accepted: 07/12/2023] [Indexed: 08/01/2023] Open
Abstract
Background Bloodstream infection (BSI) is a prevalent cause of admission in hemodialysis (HD) patients and is associated with increased morbidity and mortality. This study aimed to establish a diagnostic, predictive model for the early identification of BSI in HD patients. Methods HD patients who underwent blood culture testing between August 2018 and March 2022 were enrolled in this study. Machine learning algorithms, including stepwise logistic regression (SLR), Lasso logistic regression (LLR), support vector machine (SVM), decision tree, random forest (RF), and gradient boosting machine (XGboost), were used to predict the risk of developing BSI from the patient's clinical data. The accuracy (ACC) and area under the subject working curve (AUC) were used to evaluate the performance of such models. The Shapley Additive Explanation (SHAP) values were used to explain each feature's predictive value on the models' output. Finally, a simplified nomogram for predicting BSI was devised. Results A total of 391 HD patients were enrolled in this study, of whom 74 (18.9%) were diagnosed with BSI. The XGboost model achieved the highest AUC (0.914, 95% confidence interval [CI]: 0.861-0.964) and ACC (86.3%) for BSI prediction. The four most significant co-variables in both the significance matrix plot of the XGboost model variables and the SHAP summary plot were body temperature, dialysis access via a non-arteriovenous fistula (non-AVF), the procalcitonin levels (PCT), and neutrophil-lymphocyte ratio (NLR). Conclusions This study created an effective machine-learning model for predicting BSI in HD patients. The model could be used to detect BSI at an early stage and hence guide antibiotic treatment in HD patients.
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Affiliation(s)
- Tong Zhou
- Department of Nephrology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
| | - Zhouting Ren
- Department of Nephrology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
| | - Yimei Ma
- Department of Nephrology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
| | - Linqian He
- Department of Nephrology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
| | - Jiali Liu
- Department of Clinical Medicine, North Sichuan Medical College, Nanchong, China
| | - Jincheng Tang
- Department of Nephrology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
| | - Heping Zhang
- Department of Nephrology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
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17
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Valera E, Kindratenko V, Jankelow AM, Heredia J, Kim AY, Cowell TW, Chen CL, White K, Han HS, Bashir R. Electrochemical point-of-care devices for the diagnosis of sepsis. CURRENT OPINION IN ELECTROCHEMISTRY 2023; 39:101300. [PMID: 37483649 PMCID: PMC10357885 DOI: 10.1016/j.coelec.2023.101300] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/25/2023]
Abstract
Sepsis is a life-threatening dysfunction of organ systems caused by a dysregulated immune system because of an infectious process. It remains one of the leading causes of hospital mortality and of hospital readmissions in the United States. Mortality from sepsis increases with each hour of delayed treatment, therefore, diagnostic devices that can reduce the time from the onset of a patient's infection to the delivery of appropriate therapy are urgently needed. Likewise, tools that are capable of high-frequency testing of clinically relevant biomarkers are required to study disease progression. Electrochemical biosensors offer important advantages such as high sensitivity, fast response, miniaturization, and low cost that can be adapted to clinical needs. In this review paper, we discuss the current state, limitations, and future directions of electrochemical-based point-of-care detection platforms that contribute to the diagnosis and monitoring of sepsis.
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Affiliation(s)
- Enrique Valera
- Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
- Nick Holonyak Jr. Micro and Nanotechnology Laboratory, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
| | - Victoria Kindratenko
- Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
- Nick Holonyak Jr. Micro and Nanotechnology Laboratory, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
| | - Aaron M. Jankelow
- Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
- Nick Holonyak Jr. Micro and Nanotechnology Laboratory, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
| | - John Heredia
- Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
- Nick Holonyak Jr. Micro and Nanotechnology Laboratory, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
| | - Alicia Y. Kim
- Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
- Nick Holonyak Jr. Micro and Nanotechnology Laboratory, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
| | - Thomas W. Cowell
- Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
| | - Chih-Lin Chen
- Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
| | - Karen White
- Department of Biomedical and Translation Science, Carle Illinois College of Medicine, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
- Carle Foundation Hospital, Urbana, Illinois 61801, United States
| | - Hee-Sun Han
- Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
- Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
| | - Rashid Bashir
- Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
- Nick Holonyak Jr. Micro and Nanotechnology Laboratory, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
- Department of Biomedical and Translation Science, Carle Illinois College of Medicine, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
- Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
- Department of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
- Department of Mechanical Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
- Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
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18
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Kraemer M, Bellion M, Kissmann AK, Herberger T, Synatschke CV, Bozdogan A, Andersson J, Rodriguez A, Ständker L, Wiese S, Stenger S, Spellerberg B, Gottschalk KE, Cetinkaya A, Pietrasik J, Weil T, Rosenau F. Aptamers as Novel Binding Molecules on an Antimicrobial Peptide-Armored Composite Hydrogel Wound Dressing for Specific Removal and Efficient Eradication of Pseudomonas aeruginosa. Int J Mol Sci 2023; 24:ijms24054800. [PMID: 36902270 PMCID: PMC10002764 DOI: 10.3390/ijms24054800] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2023] [Revised: 02/15/2023] [Accepted: 02/23/2023] [Indexed: 03/06/2023] Open
Abstract
Here we present for the first time a potential wound dressing material implementing aptamers as binding entities to remove pathogenic cells from newly contaminated surfaces of wound matrix-mimicking collagen gels. The model pathogen in this study was the Gram-negative opportunistic bacterium Pseudomonas aeruginosa, which represents a considerable health threat in hospital environments as a cause of severe infections of burn or post-surgery wounds. A two-layered hydrogel composite material was constructed based on an established eight-membered focused anti-P. aeruginosa polyclonal aptamer library, which was chemically crosslinked to the material surface to form a trapping zone for efficient binding of the pathogen. A drug-loaded zone of the composite released the C14R antimicrobial peptide to deliver it directly to the bound pathogenic cells. We demonstrate that this material combining aptamer-mediated affinity and peptide-dependent pathogen eradication can quantitatively remove bacterial cells from the "wound" surface, and we show that the surface-trapped bacteria are completely killed. The drug delivery function of the composite thus represents an extra safeguarding property and thus probably one of the most important additional advances of a next-generation or smart wound dressing ensuring the complete removal and/or eradication of the pathogen of a freshly infected wound.
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Affiliation(s)
- Markus Kraemer
- Institute of Pharmaceutical Biotechnology, Ulm University, Albert-Einstein-Allee 11, 89081 Ulm, Germany
| | - Magali Bellion
- Institute of Pharmaceutical Biotechnology, Ulm University, Albert-Einstein-Allee 11, 89081 Ulm, Germany
| | - Ann-Kathrin Kissmann
- Institute of Pharmaceutical Biotechnology, Ulm University, Albert-Einstein-Allee 11, 89081 Ulm, Germany
- Max-Planck-Institute for Polymer Research Mainz, Ackermannweg 10, 55128 Mainz, Germany
- Correspondence: (A.-K.K.); (F.R.)
| | - Tilmann Herberger
- Max-Planck-Institute for Polymer Research Mainz, Ackermannweg 10, 55128 Mainz, Germany
| | | | - Anil Bozdogan
- Center for Electrochemical Surface Technology (CEST), Austrian Institute of Technology, 3420 Tulln, Austria
- Austrian Institute of Technology, Giefinggasse 4, 1210 Vienna, Austria
| | - Jakob Andersson
- Austrian Institute of Technology, Giefinggasse 4, 1210 Vienna, Austria
| | - Armando Rodriguez
- Core Facility for Functional Peptidomics, Ulm Peptide Pharmaceuticals (U-PEP), Faculty of Medicine, Ulm University, 89081 Ulm, Germany
- Core Unit of Mass Spectrometry and Proteomics, Faculty of Medicine, Ulm University, 89081 Ulm, Germany
| | - Ludger Ständker
- Core Unit of Mass Spectrometry and Proteomics, Faculty of Medicine, Ulm University, 89081 Ulm, Germany
| | - Sebastien Wiese
- Core Unit of Mass Spectrometry and Proteomics, Faculty of Medicine, Ulm University, 89081 Ulm, Germany
| | - Steffen Stenger
- Institute for Medical Microbiology and Hygiene, University Hospital Ulm, 89081 Ulm, Germany
| | - Barbara Spellerberg
- Institute for Medical Microbiology and Hygiene, University Hospital Ulm, 89081 Ulm, Germany
| | - Kay-Eberhard Gottschalk
- Institute of Experimental Physics, Ulm University, Albert-Einstein-Allee 11, 89081 Ulm, Germany
| | - Ahmet Cetinkaya
- Institute of Polymer and Dye Technology, Lodz University of Technology, Stefanowskiego 16, 90-537 Lodz, Poland
| | - Joanna Pietrasik
- Institute of Polymer and Dye Technology, Lodz University of Technology, Stefanowskiego 16, 90-537 Lodz, Poland
| | - Tanja Weil
- Max-Planck-Institute for Polymer Research Mainz, Ackermannweg 10, 55128 Mainz, Germany
| | - Frank Rosenau
- Institute of Pharmaceutical Biotechnology, Ulm University, Albert-Einstein-Allee 11, 89081 Ulm, Germany
- Max-Planck-Institute for Polymer Research Mainz, Ackermannweg 10, 55128 Mainz, Germany
- Correspondence: (A.-K.K.); (F.R.)
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19
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Hou W, Han T, Qu G, Sun Y, Yang D, Lin Y. Is early time to positivity of blood culture associated with clinical prognosis in patients with Klebsiella pneumoniae bloodstream infection? Epidemiol Infect 2023; 151:e43. [PMID: 36805070 PMCID: PMC10028975 DOI: 10.1017/s0950268823000262] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/23/2023] Open
Abstract
The association between time to positivity (TTP) of blood culture and the clinical prognosis of patients with Klebsiella pneumoniae bloodstream infection (BSI) remains unclear. A retrospective study of 148 inpatients with BSI caused by K. pneumoniae was performed at Shanghai Tongji Hospital, China, from October 2016-2020. The total in-hospital fatality rate was 32%. The median TTP was 11.0 (7.7-16.1) h and the optimal cutoff for prediction of in-hospital mortality was 9.4 h according to the ROC curve. Early TTP (<9.4 h) was a risk factor for in-hospital mortality by univariate analysis (OR = 2.5, 95% CI 1.2-5.0, P = 0.01), but not by multivariate analysis (OR = 2.7, 95% CI 1.0-7.4, P = 0.06). Old age, serum creatinine, white blood cells, and C-reactive protein values were risk factors for in-hospital mortality by multivariate analysis. Early TTP was not a risk factor for septic shock (OR = 1.8, 95% CI 0.6-5.1, P = 0.27) or ICU admission (OR = 1.0, 95% CI 1.0-1.0, P = 0.32). In conclusion, the in-hospital fatality rate of patients with K. pneumoniae BSI was relatively high and associated with an early TTP of blood cultures. However, no increased risk of mortality, septic shock or ICU admission was evident in early TTP patients.
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Affiliation(s)
- Weiwei Hou
- Department of Laboratory Medicine, Tongji Hospital, School of Medicine, Tongji University, Shanghai 200065, China
| | - Tiantian Han
- Department of Hospital Infection Control, Tongji Hospital, School of Medicine, Tongji University, Shanghai 200065, China
| | - Guangbo Qu
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, 230032, Anhui Province, China
| | - Yehuan Sun
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, 230032, Anhui Province, China
| | - Dianyu Yang
- Department of Laboratory Medicine, Tongji Hospital, School of Medicine, Tongji University, Shanghai 200065, China
| | - Yan Lin
- Department of Hospital Infection Control, Tongji Hospital, School of Medicine, Tongji University, Shanghai 200065, China
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Bajić D, Matijašević J, Andrijević L, Zarić B, Lalić-Popović M, Andrijević I, Todorović N, Mihajlović A, Tapavički B, Ostojić J. Prognostic Role of Monocyte Distribution Width, CRP, Procalcitonin and Lactate as Sepsis Biomarkers in Critically Ill COVID-19 Patients. J Clin Med 2023; 12:jcm12031197. [PMID: 36769843 PMCID: PMC9917557 DOI: 10.3390/jcm12031197] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2022] [Revised: 01/26/2023] [Accepted: 01/31/2023] [Indexed: 02/05/2023] Open
Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a global pandemic and one group of patients has developed a severe form of COVID-19 pneumonia with an urgent need for hospitalization and intensive care unit (ICU) admission. The aim of our study was to evaluate the prognostic role of MDW, CRP, procalcitonin (PCT), and lactate in critically ill COVID-19 patients. The primary outcome of interest is the 28 day mortality of ICU patients with confirmed SARS-CoV-2 infection and sepsis (according to Sepsis 3 criteria with acute change in SOFA score ≥ 2 points). Patients were divided into two groups according to survival on the 28th day after admission to the ICU. Every group was divided into two subgroups (women and men). Nonparametric tests (Mann-Whitney) for variables age, PCT, lactate, and MDW were lower than alpha p < 0.05, so there was a significant difference between survived and deceased patients. The Chi-square test confirmed statistically significant higher values of MDW and lactate in the non-survivor group. We found a significant association between MDW, lactate, procalcitonin, and fatal outcome, higher values were reported in the deceased group.
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Affiliation(s)
- Dejana Bajić
- Department of Biochemistry, Faculty of Medicine, University of Novi Sad, Street Hajduk Veljkova 3, 21137 Novi Sad, Serbia
- Correspondence: ; Tel.: +381-60-6-330-550
| | - Jovan Matijašević
- Institute for Pulmonary Diseases of Vojvodina, Put Dr Goldmana Street 4, 21204 Sremska Kamenica, Serbia
- Faculty of Medicine, University of Novi Sad, Street Hajduk Veljkova 3, 21137 Novi Sad, Serbia
| | - Ljiljana Andrijević
- Department of Biochemistry, Faculty of Medicine, University of Novi Sad, Street Hajduk Veljkova 3, 21137 Novi Sad, Serbia
| | - Bojan Zarić
- Institute for Pulmonary Diseases of Vojvodina, Put Dr Goldmana Street 4, 21204 Sremska Kamenica, Serbia
- Faculty of Medicine, University of Novi Sad, Street Hajduk Veljkova 3, 21137 Novi Sad, Serbia
| | - Mladena Lalić-Popović
- Department of Pharmacy, Faculty of Medicine, University of Novi Sad, Street Hajduk Veljkova 3, 21137 Novi Sad, Serbia
| | - Ilija Andrijević
- Institute for Pulmonary Diseases of Vojvodina, Put Dr Goldmana Street 4, 21204 Sremska Kamenica, Serbia
- Faculty of Medicine, University of Novi Sad, Street Hajduk Veljkova 3, 21137 Novi Sad, Serbia
| | - Nemanja Todorović
- Department of Pharmacy, Faculty of Medicine, University of Novi Sad, Street Hajduk Veljkova 3, 21137 Novi Sad, Serbia
| | - Andrea Mihajlović
- Department of Physiology, Faculty of Medicine, University of Novi Sad, Street Hajduk Veljkova 3, 21137 Novi Sad, Serbia
| | - Borislav Tapavički
- Department of Physiology, Faculty of Medicine, University of Novi Sad, Street Hajduk Veljkova 3, 21137 Novi Sad, Serbia
| | - Jelena Ostojić
- Faculty of Medicine, University of Novi Sad, Street Hajduk Veljkova 3, 21137 Novi Sad, Serbia
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21
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Velasque MJSG, Branchini G, Catarina AV, Bettoni L, Fernandes RS, Da Silva AF, Dorneles GP, da Silva IM, Santos MA, Sumienski J, Peres A, Roehe AV, Kohek MBDF, Porawski M, Nunes FB. Fish Oil - Omega-3 Exerts Protective Effect in Oxidative Stress and Liver Dysfunctions Resulting from Experimental Sepsis. J Clin Exp Hepatol 2023; 13:64-74. [PMID: 36647406 PMCID: PMC9840085 DOI: 10.1016/j.jceh.2022.07.001] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2022] [Revised: 06/24/2022] [Accepted: 07/03/2022] [Indexed: 01/19/2023] Open
Abstract
Background Sepsis is a severe global health problem, with high morbidity and mortality. In sepsis, one of the main affected organs is the liver. Hepatic alterations characterize a negative prognostic. Omega-3 fatty acids (ω3), eicosapentaenoic acid, and docosahexaenoic acid, are part of the main families of polyunsaturated fatty acids. ω3 has been used in studies as sepsis treatment and as a treatment for non-alcoholic liver disease. Aim We aimed to evaluate the effects of treatment with fish oil (FO) rich in ω3 on liver changes and damage resulting from experimental sepsis. Methodology A model of severe sepsis in Wistar rats was used. Oxidative stress in the liver tissue was evaluated by means of tests of thiobarbituric acid reactive substances, 2,7-dihydrodichlorofluorescein diacetate , catalase, and glutathione peroxidase, in the serum TBARS, DCF, thiols and, to assess liver dysfunction, alanine aminotransferase and aspartate aminotransferase. Hepatic tissue damage was evaluated using H&E histology. Results In assessments of oxidative stress in liver tissue, a protective effect was observed in the tests of TBARS, DCF, CAT, and GPx, when compared the sepsis versus sepsis+ω3 groups. Regarding the oxidative stress in serum, a protective effect of treatment with ω3 was observed in the TBARS, DCF, and thiols assays, in the comparison between the sepsis and sepsis+ω3 groups. ω3 had also a beneficial effect on biochemical parameters in serum in the analysis of ALT, creatinine, urea, and lactate, observed in the comparison between the sepsis and sepsis+ω3 groups. Conclusion The results suggest ω3 as a liver protector during sepsis with an antioxidant effect, alleviating injuries and dysfunctions.
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Key Words
- ALT, alanine aminotransferase
- AST, aspartate aminotransferase
- CAT, catalase
- DCF, 2,7-dihydrodichlorofluorescein diacetate
- DHA, docosahexaenoic acid
- EPA, eicosapentaenoic acid
- FO, fish oil
- GPx, glutathione peroxidase
- GTO, oxaloacetic transaminase
- GTP, pyruvic transaminase
- HE, Hematoxylin and Eosin
- ICON, Intensive Care Over Nations
- ICU, intensive care unit
- IFN- γ, interferon gamma
- Liver injury
- RNS, reactive nitrogen species
- ROS, reactive oxygen species
- TBARS, Thiobarbituric Acid Reactive Substances
- TGF-β, transforming growth factor beta
- TNF-α, tumor necrosis factor alpha
- antioxidant
- inflammation
- omega-3
- oxidative stress
- sepsis
- ω3, omega-3
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Affiliation(s)
- Mary J. Soares Gonçalves Velasque
- Graduate Program in Pathology – Laboratory of Computational, Molecular, and Cellular Biophysics, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Brazil
| | - Gisele Branchini
- Graduate Program in Pathology – Laboratory of Computational, Molecular, and Cellular Biophysics, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Brazil
| | - Anderson V. Catarina
- Graduate Program in Pathology – Laboratory of Computational, Molecular, and Cellular Biophysics, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Brazil
| | - Lais Bettoni
- Graduate Program in Pathology – Laboratory of Computational, Molecular, and Cellular Biophysics, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Brazil
| | - Renata S. Fernandes
- Graduate Program in Health Sciences – Laboratory of Translational Physiology – Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Brazil
| | | | - Gilson P. Dorneles
- Laboratory of Cellular and Molecular Immunology – Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Brazil
| | - Igor Martins da Silva
- Laboratory of Cellular and Molecular Immunology – Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Brazil
| | - Maeli A. Santos
- Laboratory of Cellular and Molecular Immunology – Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Brazil
| | - Juliana Sumienski
- Laboratory of Immunology and Microbiology - Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Brazil
| | - Alessandra Peres
- Laboratory of Cellular and Molecular Immunology – Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Brazil
| | - Adriana V. Roehe
- Graduate Program in Pathology – Laboratory of Pathology – Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Brazil
| | - Maria B. da Fonte Kohek
- Laboratory of Cellular and Molecular Immunology – Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Brazil
| | - Marilene Porawski
- Laboratory of Behavioral and Metabolic Physiology – Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Brazil
| | - Fernanda B. Nunes
- Graduate Program in Pathology – Laboratory of Computational, Molecular, and Cellular Biophysics, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Brazil
- Laboratory of Inflammation and Cellular Biophysics - Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Brazil
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22
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Li Q, Yan W, Liu S, Li H. Study on the correlation and clinical significance of T-lymphocyte Subsets, IL-6 and PCT in the severity of patients with sepsis. Pak J Med Sci 2023; 39:227-231. [PMID: 36694784 PMCID: PMC9843026 DOI: 10.12669/pjms.39.1.5711] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2021] [Revised: 10/13/2022] [Accepted: 10/18/2022] [Indexed: 11/17/2022] Open
Abstract
Objective To evaluate the correlation and clinical significance of T lymphocyte subsets, IL-6 and PCT in the severity of patients with sepsis. Methods One-hundred and twenty patients with sepsis admitted to Baoding No.1 Central Hospital from March 05, 2021 to March 05, 2022 were selected and divided into three groups according to the severity of the disease: the sepsis group, the severe sepsis group and the septic shock group, with 40 cases in each group. The venous blood of all patients was drawn with a sterile vacuum blood collection tube after admission to detect the levels of T lymphocyte subsets CD3+, CD4+, CD8+, CD4+/CD8+, and the venous blood was collected to detect the levels of interleukin-6 (IL-6) and procalcitonin (PCT). The three groups of patients were compared to analyze whether there were differences, and whether there was a correlation between the level of each indicator and the prognosis of patients after treatment. Results The levels of CD3+, CD4+ and CD4+/CD8+ in the three groups decreased with the aggravation of the disease, with a significant difference (p=0.00). The levels of IL-6 and PCT increased with the aggravation of the disease among the three groups, with statistically significant differences (IL-6, p=0.00; PCT, p=0.01). The better the patients recovered after treatment, the higher the levels of CD4+ and CD4+/CD8+, and the two were positively correlated; While the lower the levels of IL-6 and PCT, the two were negatively correlated. Conclusion Peripheral blood T lymphocyte subsets and serum IL-6, PCT are abnormally expressed in patients with sepsis, and have a close bearing on the severity of the disease, which has a certain predictive value for patients after recovery. In view of this, the above indicators are of high clinical significance.
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Affiliation(s)
- Qian Li
- Qian Li, Department of Critical Care Medicine, Baoding No.1 Central Hospital, Baoding 071000, Hebei, P.R. China
| | - Wenwen Yan
- Wenwen Yan, Department of Critical Care Medicine, Baoding No.1 Central Hospital, Baoding 071000, Hebei, P.R. China
| | - Sha Liu
- Sha Liu, Department of Critical Care Medicine, Baoding No.1 Central Hospital, Baoding 071000, Hebei, P.R. China
| | - Hui Li
- Hui Li, Department of Critical Care Medicine, Baoding No.1 Central Hospital, Baoding 071000, Hebei, P.R. China
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23
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Pérez-Hernández EG, De la Puente-Díaz de León V, Luna-Reyes I, Delgado-Coello B, Sifuentes-Osornio J, Mas-Oliva J. The cholesteryl-ester transfer protein isoform (CETPI) and derived peptides: new targets in the study of Gram-negative sepsis. Mol Med 2022; 28:157. [PMID: 36536294 PMCID: PMC9764724 DOI: 10.1186/s10020-022-00585-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Accepted: 12/04/2022] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Sepsis is a syndrome where the dysregulated host response to infection threatens the life of the patient. The isoform of the cholesteryl-ester transfer protein (CETPI) is synthesized in the small intestine, and it is present in human plasma. CETPI and peptides derived from its C-terminal sequence present the ability to bind and deactivate bacterial lipopolysaccharides (LPS). The present study establishes the relationship between the plasma levels of CETPI and disease severity of sepsis due to Gram-negative bacteria. METHODS Plasma samples from healthy subjects and patients with positive blood culture for Gram-negative bacteria were collected at the Intensive Care Unit (ICU) of INCMNSZ (Mexico City). 47 healthy subjects, 50 patients with infection, and 55 patients with sepsis and septic shock, were enrolled in this study. CETPI plasma levels were measured by an enzyme-linked immunosorbent assay and its expression confirmed by Western Blot analysis. Plasma cytokines (IL-1β, TNFα, IL-6, IL-8, IL-12p70, IFNγ, and IL-10) were measured in both, healthy subjects, and patients, and directly correlated with their CETPI plasma levels and severity of clinical parameters. Sequential Organ Failure Assessment (SOFA) scores were evaluated at ICU admission and within 24 h of admission. Plasma LPS and CETPI levels were also measured and studied in patients with liver dysfunction. RESULTS The level of CETPI in plasma was found to be higher in patients with positive blood culture for Gram-negative bacteria that in control subjects, showing a direct correlation with their SOFA values. Accordingly, septic shock patients showing a high CETPI plasma concentration, presented a negative correlation with cytokines IL-8, IL-1β, and IL-10. Also, in patients with liver dysfunction, since higher CETPI levels correlated with a high plasma LPS concentration, LPS neutralization carried out by CETPI might be considered a physiological response that will have to be studied in detail. CONCLUSIONS Elevated levels of plasma CETPI were associated with disease severity and organ failure in patients with Gram-negative bacteraemia, defining CETPI as a protein implicated in the systemic response to LPS.
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Affiliation(s)
- Eréndira G. Pérez-Hernández
- grid.9486.30000 0001 2159 0001Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, 04510 Ciudad de Mexico, Mexico
| | - Víctor De la Puente-Díaz de León
- grid.416850.e0000 0001 0698 4037Departamento de Medicina Interna, Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán”, 14080 Ciudad de Mexico, Mexico
| | - Ismael Luna-Reyes
- grid.9486.30000 0001 2159 0001Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, 04510 Ciudad de Mexico, Mexico
| | - Blanca Delgado-Coello
- grid.9486.30000 0001 2159 0001Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, 04510 Ciudad de Mexico, Mexico
| | - José Sifuentes-Osornio
- grid.416850.e0000 0001 0698 4037Dirección de Medicina, Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán”, 14080 Ciudad de Mexico, Mexico
| | - Jaime Mas-Oliva
- grid.9486.30000 0001 2159 0001Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, 04510 Ciudad de Mexico, Mexico
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24
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Walsh TJ, Bright RA, Ahuja A, McCarthy MW, Marfuggi RA, Simpson SQ. Meeting the Challenges of Sepsis in Severe Coronavirus Disease 2019: A Call to Arms. Open Forum Infect Dis 2022; 10:ofac645. [PMID: 36686626 PMCID: PMC9850274 DOI: 10.1093/ofid/ofac645] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2022] [Accepted: 11/29/2022] [Indexed: 12/03/2022] Open
Abstract
Sepsis is a life-threatening organ dysfunction that is caused by a dysregulated host response to infection. Sepsis may be caused by bacterial, fungal, or viral pathogens. The clinical manifestations exhibited by patients with severe coronavirus disease 2019 (COVID-19)-related sepsis overlap with those exhibited by patients with sepsis from secondary bacterial or fungal infections and can include an altered mental status, dyspnea, reduced urine output, tachycardia, and hypotension. Critically ill patients hospitalized with severe acute respiratory syndrome coronavirus 2 infections have increased risk for secondary bacterial and fungal infections. The same risk factors that may predispose to sepsis and poor outcome from bloodstream infections (BSIs) converge in patients with severe COVID-19. Current diagnostic standards for distinguishing between (1) patients who are critically ill, septic, and have COVID-19 and (2) patients with sepsis from other causes leave healthcare providers with 2 suboptimal choices. The first choice is to empirically administer broad-spectrum, antimicrobial therapy for what may or may not be sepsis. Such treatment may not only be ineffective and inappropriate, but it also has the potential to cause harm. The development of better methods to identify and characterize antimicrobial susceptibility will guide more accurate therapeutic interventions and reduce the evolution of new antibiotic-resistant strains. The ideal diagnostic test should (1) be rapid and reliable, (2) have a lower limit of detection than blood culture, and (3) be able to detect a specific organism and drug sensitivity directly from a clinical specimen. Rapid direct detection of antimicrobial-resistant pathogens would allow targeted therapy and result in improved outcomes in patients with severe COVID-19 and sepsis.
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Affiliation(s)
- Thomas J Walsh
- Correspondence: Thomas J. Walsh MD, PhD, Center for Innovative Therapeutics and Diagnostics, 6641 West Broad Street, Room 100, Richmond, Virginia 23220 ()
| | - Rick A Bright
- The Rockefeller Foundation, Pandemic Prevention Institute, New York, New York, USA
| | | | - Matthew W McCarthy
- Weill Cornell Medicine and New York Presbyterian Hospital, New York, New York, USA
| | - Richard A Marfuggi
- American Medical Association Foundation, Chicago, Illinois, USA,WBB Research Institute, Cranford, New Jersey, USA
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25
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Zhao XF, Yang MF, Wu YQ, Zhao PN, Zhu SY, Xiong F, Fan M, Li YF. Association between Interleukin-6 rs1800795 Polymorphism and Serum Interleukin-6 Levels and Full-Term Neonatal Sepsis. J PEDIAT INF DIS-GER 2022. [DOI: 10.1055/s-0042-1757882] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Abstract
Objective Cytokines are involved in the pathogenesis of sepsis. Association between IL-6 rs1800795 G/C polymorphism and the risks of sepsis is controversial. The aim of this study was to investigate the association of IL-6 rs1800795 G/C gene polymorphism with full-term neonatal sepsis and to determine its effect on the serum IL6 levels in these infants by a prospective study.
Methods The study included 200 full-term neonates from January 2019 to December 2020: 100 with sepsis (sepsis group), 47 with culture proven sepsis, and 53 with clinical sepsis, and 100 without infection (control group). The concentrations of IL-6 in serum were determined using enzyme-linked immunosorbent assay (ELISA). The polymorphisms of IL-6 rs1800795 G/C were analyzed to compare the genotypic and allelic frequencies in the groups by using the first-generation sequencing (Sanger sequencing). The association was studied between IL-6 rs1800795 G/C polymorphisms and serum IL-6 levels, and neonatal sepsis. The relationships between IL-6 rs1800795G/C polymorphisms and sepsis and serum IL-6 levels were separately analyzed by logistic regression and analysis of variance.
Results There were no significant differences in genotypic frequencies and allelic frequencies of IL-6 rs1800795(G/C) in the groups (p >0.05). There were no relations between IL-6 rs1800795G/C polymorphisms and sepsis and serum IL-6 levels by statistical analysis (p >0.05).
Conclusion IL-6rs1800795G/C may not be genetic risk factors for full-term neonates; There was no association between serum IL-6 levels and IL-6 rs1800795G/C polymorphisms.
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Affiliation(s)
- Xiao-Fen Zhao
- Department of Neonatology, Kunming Children's Hospital, Yunnan, China
| | - Mi-feng Yang
- Department of Neonatology, Kunming Children's Hospital, Yunnan, China
| | - Yu-qin Wu
- Department of Neonatology, Kunming Children's Hospital, Yunnan, China
| | - Peng-na Zhao
- Department of Neonatology, Kunming Children's Hospital, Yunnan, China
| | - Shuang-Yan Zhu
- Department of Neonatology, Kunming Children's Hospital, Yunnan, China
| | - Fei Xiong
- Department of Neonatology, Kunming Children's Hospital, Yunnan, China
| | - Mao Fan
- Department of Neonatology, Kunming Children's Hospital, Yunnan, China
| | - Yang-Fang Li
- Department of Neonatology, Kunming Children's Hospital, Yunnan, China
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26
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Pociute A, Kottilingal Farook MF, Dagys A, Kevalas R, Laucaityte G, Jankauskaite L. Platelet-Derived Biomarkers: Potential Role in Early Pediatric Serious Bacterial Infection and Sepsis Diagnostics. J Clin Med 2022; 11:jcm11216475. [PMID: 36362702 PMCID: PMC9658833 DOI: 10.3390/jcm11216475] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Revised: 10/27/2022] [Accepted: 10/28/2022] [Indexed: 11/06/2022] Open
Abstract
Fever is the most common complaint of children who are attending a pediatric emergency department (PED). Most of the fever cases are of viral origin; however, the most common markers, such as leucocyte, neutrophil count, or C-reactive protein, are not sensitive or specific enough to distinguish the etiology of fever, especially if children present at the early phase of infection. Currently, platelets have been attributed a role as important sentinels in viral and bacterial infection pathogenesis. Thus, our aim was to analyze different platelet indices, such as PNLR (platelet-to-neutrophil/lymphocyte ratio), PNR (platelet-to-neutrophil ratio) as well as specific secreted proteins, such as sP-selectin, CXCL4, CXCL7, and serotonin. We included 68 children who were referred to PED with the early onset of fever (<12 h). All children with comorbidities, older than five years, and psychiatric diseases, who refused to participate were excluded. All the participants were divided into viral, bacterial, or serious bacterial infection (SBI) groups. All the children underwent blood sampling, and an additional sample was collected for protein analysis. Our analysis revealed statistically significant differences between leucocyte, neutrophil, and CRP levels between SBI and other groups. However, leucocyte and neutrophil counts were within the age norms. A higher PNLR value was observed in a bacterial group, PNR-in viral. As we tested CXCL7 and sP-selectin, alone and together those markers were statistically significant to discriminate SBI and sepsis from other causes of infection. Together with tachypnoe and SpO2 < 94%, it improved the prediction value of sepsis as well as SBI. CXCL4 and serotonin did not differ between the groups. Concluding, CXCL7 and sP-selectin showed promising results in early SBI and sepsis diagnosis.
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Affiliation(s)
- Aiste Pociute
- Faculty of Medicine, Lithuanian University of Health Sciences, 44307 Kaunas, Lithuania
| | | | - Algirdas Dagys
- Department of Pediatrics, Faculty of Medicine, Lithuanian University of Health Sciences, 44307 Kaunas, Lithuania
| | - Rimantas Kevalas
- Department of Pediatrics, Faculty of Medicine, Lithuanian University of Health Sciences, 44307 Kaunas, Lithuania
| | - Goda Laucaityte
- Department of Pediatrics, Faculty of Medicine, Lithuanian University of Health Sciences, 44307 Kaunas, Lithuania
| | - Lina Jankauskaite
- Department of Pediatrics, Faculty of Medicine, Lithuanian University of Health Sciences, 44307 Kaunas, Lithuania
- Institute of Physiology and Pharmacology, Faculty of Medicine, Lithuanian University of Health Sciences, 44307 Kaunas, Lithuania
- Correspondence:
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Routine laboratory biomarkers used to predict Gram-positive or Gram-negative bacteria involved in bloodstream infections. Sci Rep 2022; 12:15466. [PMID: 36104449 PMCID: PMC9474441 DOI: 10.1038/s41598-022-19643-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2022] [Accepted: 08/31/2022] [Indexed: 11/08/2022] Open
Abstract
AbstractThis study evaluated routine laboratory biomarkers (RLB) to predict the infectious bacterial group, Gram-positive (GP) or Gram-negative (GN) associated with bloodstream infection (BSI) before the result of blood culture (BC). A total of 13,574 BC of 6787 patients (217 BSI-GP and 238 BSI-GN) and 68 different RLB from these were analyzed. The logistic regression model was built considering BSI-GP or BSI-GN as response variable and RLB as covariates. After four filters applied total of 320 patients and 16 RLB remained in the Complete-Model-CM, and 4 RLB in the Reduced-Model-RM (RLB p > 0.05 excluded). In the RM, only platelets, creatinine, mean corpuscular hemoglobin and erythrocytes were used. The reproductivity of both models were applied to a test bank of 2019. The new model presented values to predict BSI-GN of the area under the curve (AUC) of 0.72 and 0.69 for CM and RM, respectively; with sensitivity of 0.62 and 0.61 (CM and RM) and specificity of 0.67 for both. These data confirm the discriminatory capacity of the new models for BSI-GN (p = 0.64). AUC of 0.69 using only 4 RLB, associated with the patient's clinical data could be useful for better targeted antimicrobial therapy in BSI.
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“Omic” Approaches to Bacteria and Antibiotic Resistance Identification. Int J Mol Sci 2022; 23:ijms23179601. [PMID: 36077000 PMCID: PMC9455953 DOI: 10.3390/ijms23179601] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2022] [Revised: 08/19/2022] [Accepted: 08/21/2022] [Indexed: 11/28/2022] Open
Abstract
The quick and accurate identification of microorganisms and the study of resistance to antibiotics is crucial in the economic and industrial fields along with medicine. One of the fastest-growing identification methods is the spectrometric approach consisting in the matrix-assisted laser ionization/desorption using a time-of-flight analyzer (MALDI-TOF MS), which has many advantages over conventional methods for the determination of microorganisms presented. Thanks to the use of a multiomic approach in the MALDI-TOF MS analysis, it is possible to obtain a broad spectrum of data allowing the identification of microorganisms, understanding their interactions and the analysis of antibiotic resistance mechanisms. In addition, the literature data indicate the possibility of a significant reduction in the time of the sample preparation and analysis time, which will enable a faster initiation of the treatment of patients. However, it is still necessary to improve the process of identifying and supplementing the existing databases along with creating new ones. This review summarizes the use of “-omics” approaches in the MALDI TOF MS analysis, including in bacterial identification and antibiotic resistance mechanisms analysis.
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Nour Z, El-Hamamsy K, Ehsan I, Fawaz L, Shaker O, Mossallam D, ElGindy H. MicroRNAs as Potential Diagnostic New Biomarkers in Diagnosis of Sepsis in Pediatric Patients. Rep Biochem Mol Biol 2022; 11:327-335. [PMID: 36164637 PMCID: PMC9455182 DOI: 10.52547/rbmb.11.2.327] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2022] [Accepted: 03/08/2022] [Indexed: 06/16/2023]
Abstract
BACKGROUND Sepsis is one of the most common causes of multiorgan failure. Sepsis requires the presence of infection with a resultant systemic inflammatory state. Organ dysfunction occurs from the combination of the two processes. Sepsis is the main cause of mortality at intensive care units, with 30-50% mortality rate for all septic episodes. MicroRNA (miRNA) profile data could be beneficial as a specific diagnostic biomarker for sepsis and systemic inflammatory response syndrome (SIRS). METHODS Expression of miRNAs -122, -181b, -223 and -146a levels were assayed by quantitative real time polymerase chain reaction (qRT-PCR) in a prospective case control study, where forty septic cases were compared to 40 healthy controls of matched age and gender. RESULTS miRNAs -122 and -181b were significantly upregulated during early septic conditions, indicating that they could be sensitive and specific biomarkers for diagnosing sepsis. miRNA-223 and miRNA-146a could also represent highly specific and sensitive diagnostic biomarkers, as they were found to be significantly down-regulated. Serum levels of miRNA-223 could be used to predict poor prognosis with 70% sensitivity and 75% specificity, whereas the other three miRNAs could not predict prognosis. CONCLUSION Our study shows that all tested miRNAs can be used for early detection of sepsis, with miRNA-223 being predictive of mortality, hence preventing multi-organ failure and reducing mortality, and predicting poor outcomes, thereby assisting in early categorization of ICU patients for rapid appropriate treatment and medico legal aspects.
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Affiliation(s)
- Zeinab Nour
- Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Cairo University, Cairo, Egypt.
| | | | - Iman Ehsan
- Department of Pediatrics, Faculty of Medicine Cairo University, Egypt.
| | - Lobna Fawaz
- Department of Pediatrics, Faculty of Medicine Cairo University, Egypt.
| | - Olfat Shaker
- Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Cairo University, Cairo, Egypt.
| | - Dalia Mossallam
- Department of Pediatrics, Faculty of Medicine Cairo University, Egypt.
| | - Hala ElGindy
- Department of Pediatrics, Faculty of Medicine Cairo University, Egypt.
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Mehta Y, Paul R, Rabbani R, Acharya SP, Withanaarachchi UK. Sepsis Management in Southeast Asia: A Review and Clinical Experience. J Clin Med 2022; 11:3635. [PMID: 35806919 PMCID: PMC9267826 DOI: 10.3390/jcm11133635] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2022] [Revised: 06/17/2022] [Accepted: 06/20/2022] [Indexed: 02/06/2023] Open
Abstract
Sepsis is a life-threatening condition that causes a global health burden associated with high mortality and morbidity. Often life-threatening, sepsis can be caused by bacteria, viruses, parasites or fungi. Sepsis management primarily focuses on source control and early broad-spectrum antibiotics, plus organ function support. Comprehensive changes in the way we manage sepsis patients include early identification, infective focus identification and immediate treatment with antimicrobial therapy, appropriate supportive care and hemodynamic optimization. Despite all efforts of clinical and experimental research over thirty years, the capacity to positively influence the outcome of the disease remains limited. This can be due to limited studies available on sepsis in developing countries, especially in Southeast Asia. This review summarizes the progress made in the diagnosis and time associated with sepsis, colistin resistance and chloramphenicol boon, antibiotic abuse, resource constraints and association of sepsis with COVID-19 in Southeast Asia. A personalized approach and innovative therapeutic alternatives such as CytoSorb® are highlighted as potential options for the treatment of patients with sepsis in Southeast Asia.
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Affiliation(s)
- Yatin Mehta
- Institute of Critical Care and Anesthesiology, Medanta the Medicity, Sector-38, Gurugram 22001, India
| | - Rajib Paul
- Internal Medicine, Apollo Hospitals, Road Number 72, Jubilee Hills, Hyderabad 500033, India;
| | - Raihan Rabbani
- Critical Care & Internal Medicine, Square Hospitals Ltd., 18 Bir Uttam Qazi NuruzzamanSarak West, Panthapath, Dhaka 1205, Bangladesh;
| | - Subhash Prasad Acharya
- Critical Care Medicine, Institute of Medicine, Tribhuvan University, Maharajgunj, Kathmandu 44618, Nepal;
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Li S, Jiang H, Xing W, Wang S, Zhang Y, Li Y, Mao C, Zeng D, Lan P, Tang D, Zhan J, Li L, Xu X, Fei J. A Clinical Diagnostic Study: Fibulin-2 is a Novel Promising Biomarker for Predicting Infection. Infect Dis Ther 2022; 11:1057-1073. [PMID: 35303288 PMCID: PMC8931586 DOI: 10.1007/s40121-022-00622-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2022] [Accepted: 03/07/2022] [Indexed: 12/14/2022] Open
Abstract
INTRODUCTION Infection remains a major cause of morbidity and mortality in hospital. As uncontrolled early infection may develop into systemic infection and eventually progress to sepsis, it is important to address infection at an early stage. Furthermore, early detection and prompt diagnosis of infection are the basis of clinical intervention. However, as a result of the interference of complex aetiologies, including fever and trauma, problems regarding the sensitivity and specificity of current diagnostic indices remain, such as for C-reactive protein (CRP), procalcitonin (PCT), white blood cells (WBC), neutrophil ratio (NEU%), interleukin-6 (IL-6) and D-dimer. As a result, there is an urgent need to develop new biomarkers to diagnose infection. METHODS From January to October 2021, consecutive patients in the emergency department (ED) were recruited to investigate the feasibility of fibulin-2 as a diagnostic indicator of early infection. Fibulin-2 concentrations in plasma were determined with enzyme-linked immunosorbent assay (ELISA). The performance of fibulin-2 for predicting infection was analysed by receiver operating characteristic (ROC) curves. RESULTS We found that the plasma fibulin-2 level was elevated in patients with infection compared with those without infection. ROC curve analysis showed that the area under the curve (AUC) for fibulin-2 was 0.712. For all patients included, the diagnostic ability of fibulin-2 (AUC 0.712) performed as well as CRP (AUC 0.667) and PCT (AUC 0.632), and better than WBC (AUC 0.620), NEU% (AUC 0.619), IL-6 (AUC 0.561) and D-dimer (AUC 0.630). In patients with fever, fibulin-2 performed as well as PCT and better than the other biomarkers in infection diagnosis. In particular, fibulin-2 performed better than all these biomarkers in patients with trauma. CONCLUSION Fibulin-2 is a novel promising diagnostic biomarker for predicting infection.
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Affiliation(s)
- Shidan Li
- Department of Orthopaedics, State Key Laboratory of Trauma, Burn and Combined Injury, Daping Hospital, Army Medical University, Chongqing, 400042, People's Republic of China
| | - Hao Jiang
- Department of Orthopaedics, Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People's Republic of China
| | - Wei Xing
- Department of Stem Cell and Regenerative Medicine, State Key Laboratory of Trauma, Burn and Combined Injury, Daping Hospital, Army Medical University, Chongqing, 400042, People's Republic of China
| | - Shaochuan Wang
- Department of Orthopaedics, State Key Laboratory of Trauma, Burn and Combined Injury, Daping Hospital, Army Medical University, Chongqing, 400042, People's Republic of China
| | - Yao Zhang
- Department of Epidemiology, Army Medical University, Chongqing, 400042, People's Republic of China
| | - Youbin Li
- Department of Orthopaedics, State Key Laboratory of Trauma, Burn and Combined Injury, Daping Hospital, Army Medical University, Chongqing, 400042, People's Republic of China
| | - Chengyi Mao
- Department of Pathology, Daping Hospital, Army Medical University, Chongqing, 400042, People's Republic of China
| | - Delian Zeng
- Department of Emergency, State Key Laboratory of Trauma, Burn and Combined Injury, Daping Hospital, Army Medical University, Chongqing, 400042, People's Republic of China
| | - Ping Lan
- Department of Anesthesiology, Daping Hospital, Army Medical University, Chongqing, 400042, People's Republic of China
| | - Dongqin Tang
- Department of Emergency, State Key Laboratory of Trauma, Burn and Combined Injury, Daping Hospital, Army Medical University, Chongqing, 400042, People's Republic of China
| | - Jijie Zhan
- Department of Emergency, State Key Laboratory of Trauma, Burn and Combined Injury, Daping Hospital, Army Medical University, Chongqing, 400042, People's Republic of China
| | - Lei Li
- Department of Stem Cell and Regenerative Medicine, State Key Laboratory of Trauma, Burn and Combined Injury, Daping Hospital, Army Medical University, Chongqing, 400042, People's Republic of China
| | - Xiang Xu
- Department of Stem Cell and Regenerative Medicine, State Key Laboratory of Trauma, Burn and Combined Injury, Daping Hospital, Army Medical University, Chongqing, 400042, People's Republic of China.
| | - Jun Fei
- Department of Emergency, State Key Laboratory of Trauma, Burn and Combined Injury, Daping Hospital, Army Medical University, Chongqing, 400042, People's Republic of China.
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Firouzi M, Sherkatolabbasieh H, Garmsiri M. A cross-sectional study on the correlation between blood phosphorus level with sepsis and associated prognostic factors in neonates. Ann Med Surg (Lond) 2022; 77:103582. [PMID: 35638028 PMCID: PMC9142385 DOI: 10.1016/j.amsu.2022.103582] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2022] [Revised: 03/30/2022] [Accepted: 03/31/2022] [Indexed: 11/30/2022] Open
Abstract
Objective Neonatal sepsis is one of the most critical causes of infant mortality. Alteration in phosphorous levels is known to be associated with sepsis. The aim of this study is to evaluate the level of blood phosphorus in neonates admitted to ICU and its relation with different factors and prognosis of patients. Methods In this cross-sectional study, all neonates admitted to the intensive care unit diagnosed with neonatal sepsis were included. Serum phosphorus levels were evaluated along with c-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and urine and blood culture. Demographic data along with clinical findings were collected in a research questionnaire for all the patients. Results Of 211 neonates, 98 (46.4%) were female and 113 (53.6%) were male, and the mean age of the patients was 10.51 days. The mean phosphorus level was 4.39 ± 0.67 mg/dL. The mean phosphorus levels among girls and boys was significantly different, p = 0.001 (4.23 ± 0.62 vs 4.53 ± 0.69 mg/dL). The mean phosphorus among positive and negative blood culture patients was also significant, p < 0.001 (4.74 ± 0.67 vs 4.29 ± 0.64 mg/dL). However, type of feeding, ESR, urine culture and CRP status was not associated with phosphorus levels, p > 0.05. Conclusion The alterations in phosphorous levels among neonatal sepsis patient is likely to be correlated with gender and blood culture status. Other prognostic markers might not have an effect on phosphorous levels in these patients.
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Affiliation(s)
- Majid Firouzi
- Department of Pediatrics, Faculty of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran
| | | | - Mahshid Garmsiri
- Student of Research Committee, Lorestan University of Medical Sciences, Khorramabad, Iran
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Effendi B, Pitoyo CW, Sinto R, Suwarto S. Procalcitonin prognostic value in predicting mortality among adult patients with sepsis due to Gram-negative bacteria. MEDICAL JOURNAL OF INDONESIA 2022. [DOI: 10.13181/mji.oa.225864] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022] Open
Abstract
BACKGROUND Sepsis is a leading cause of mortality and morbidity globally. Gram-negative bacteremia was reported to have a high risk of septic shock and poor prognosis. This study aimed to evaluate the role of procalcitonin in predicting mortality in patients with sepsis due to Gram-negative bacteria.
METHODS This was a retrospective cohort study performed based on medical records and sepsis registry of Tropical and Infectious Disease Division, Department of Internal Medicine, Cipto Mangunkusumo Hospital. The inclusion criteria were patients aged ≥18 years diagnosed with sepsis due to Gram-negative bacteria based on blood culture on admission and hospitalized between March 2017 and October 2020. Data taken from medical records included subjects’ characteristics, laboratory parameters, and 28-day mortality outcomes during hospitalization. Receiver operating characteristic was used to determine the area under the curve (AUC) of procalcitonin and its accuracy.
RESULTS A total of 128 patients were eligible. The cumulative survival of patients with Gram-negative bacteremia was 48.4% (standard error 0.96%). The AUC of procalcitonin to predict mortality was 0.45 (95% confidence interval 0.36–0.54). Escherichia coli was the predominant microorganism in blood culture (n = 38, 29.7%).
CONCLUSIONS Procalcitonin has a poor performance in predicting mortality of patients with sepsis due to Gram-negative bacteria.
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Zhao L, Yang J, Zhou C, Wang Y, Liu T. A novel prognostic model for predicting the mortality risk of patients with sepsis-related acute respiratory failure: a cohort study using the MIMIC-IV database. Curr Med Res Opin 2022; 38:629-636. [PMID: 35125039 DOI: 10.1080/03007995.2022.2038490] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
OBJECTIVES Acute respiratory failure increases short-term mortality in sepsis patients. Hence, in this study, we aimed to develop a novel model for predicting the risk of hospital mortality in sepsis patients with acute respiratory failure. METHODS From the Medical Information Mart for Intensive Care (MIMIC)-IV database, we developed a matched cohort of adult sepsis patients with acute respiratory failure. After applying a multivariate COX regression analysis, we developed a nomogram based on the identified risk factors of mortality. Further, we evaluated the ability of the nomogram in predicting individual hospital death by the area under a receiver operating characteristic (ROC) curve. RESULTS A total of 663 sepsis patients with acute respiratory failure were included in this study. Systolic blood pressure, neutrophil percentage, white blood cells count, mechanical ventilation, partial pressure of oxygen < 60 mmHg, abdominal cavity infection, Klebsiella pneumoniae and Acinetobacter baumannii infection, and immunosuppressive diseases were the independent risk factors of mortality in sepsis patients with acute respiratory failure. The area under the ROC curve of the nomogram was 0.880 (95% CI: 0.851-0.908), which provided significantly higher discrimination compared to that of the simplified acute physiology score II [0.656 (95% CI: 0.612-0.701)]. CONCLUSION The model shows a good performance in predicting the mortality risk of patients with sepsis-related acute respiratory failure. Hence, this model can be used to evaluate the short-term prognosis of critically ill patients with sepsis and acute respiratory failure.
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Affiliation(s)
- Lina Zhao
- Emergency Department, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
- Department of critical care medicine, Chifeng Municipal Hospital, Chifeng Clinical Medical College of Inner Mongolia Medical University, Chifeng, China
| | - Jing Yang
- Emergency Department, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Cong Zhou
- Department of critical care medicine, Peking university shenzhen hospital, Shenzhen, China
| | - Yunying Wang
- Department of critical care medicine, Chifeng Municipal Hospital, Chifeng Clinical Medical College of Inner Mongolia Medical University, Chifeng, China
| | - Tao Liu
- Respiratory Department, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
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D'Onofrio V, Heylen D, Pusparum M, Grondman I, Vanwalleghem J, Meersman A, Cartuyvels R, Messiaen P, Joosten LAB, Netea MG, Valkenborg D, Ertaylan G, Gyssens IC. A prospective observational cohort study to identify inflammatory biomarkers for the diagnosis and prognosis of patients with sepsis. J Intensive Care 2022; 10:13. [PMID: 35264246 PMCID: PMC8905560 DOI: 10.1186/s40560-022-00602-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2021] [Accepted: 02/21/2022] [Indexed: 11/24/2022] Open
Abstract
BACKGROUND Sepsis is a life-threatening organ dysfunction. A fast diagnosis is crucial for patient management. Proteins that are synthesized during the inflammatory response can be used as biomarkers, helping in a rapid clinical assessment or an early diagnosis of infection. The aim of this study was to identify biomarkers of inflammation for the diagnosis and prognosis of infection in patients with suspected sepsis. METHODS In total 406 episodes were included in a prospective cohort study. Plasma was collected from all patients with suspected sepsis, for whom blood cultures were drawn, in the emergency department (ED), the department of infectious diseases, or the haemodialysis unit on the first day of a new episode. Samples were analysed using a 92-plex proteomic panel based on a proximity extension assay with oligonucleotide-labelled antibody probe pairs (OLink, Uppsala, Sweden). Supervised and unsupervised differential expression analyses and pathway enrichment analyses were performed to search for inflammatory proteins that were different between patients with viral or bacterial sepsis and between patients with worse or less severe outcome. RESULTS Supervised differential expression analysis revealed 21 proteins that were significantly lower in circulation of patients with viral infections compared to patients with bacterial infections. More strongly, higher expression levels were observed for 38 proteins in patients with high SOFA scores (> 4), and for 21 proteins in patients with worse outcome. These proteins are mostly involved in pathways known to be activated early in the inflammatory response. Unsupervised, hierarchical clustering confirmed that inflammatory response was more strongly related to disease severity than to aetiology. CONCLUSION Several differentially expressed inflammatory proteins were identified that could be used as biomarkers for sepsis. These proteins are mostly related to disease severity. Within the setting of an emergency department, they could be used for outcome prediction, patient monitoring, and directing diagnostics. TRAIL REGISTRATION NUMBER clinicaltrial.gov identifier NCT03841162.
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Affiliation(s)
- Valentino D'Onofrio
- Faculty of Medicine and Life Sciences, Hasselt University, Martelarenlaan 42, 3500, Hasselt, Belgium.
- Department of Infectious Diseases and Immunity, Jessa Hospital, Hasselt, Belgium.
- Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525 GA, Nijmegen, The Netherlands.
| | - Dries Heylen
- Unit Health, Flemish Institute for Technological Research (VITO), Mol, Belgium
- Data Science Institute, Hasselt University, Hasselt, Belgium
| | - Murih Pusparum
- Unit Health, Flemish Institute for Technological Research (VITO), Mol, Belgium
- Data Science Institute, Hasselt University, Hasselt, Belgium
| | - Inge Grondman
- Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525 GA, Nijmegen, The Netherlands
| | | | | | | | - Peter Messiaen
- Faculty of Medicine and Life Sciences, Hasselt University, Martelarenlaan 42, 3500, Hasselt, Belgium
- Department of Infectious Diseases and Immunity, Jessa Hospital, Hasselt, Belgium
| | - Leo A B Joosten
- Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525 GA, Nijmegen, The Netherlands
| | - Mihai G Netea
- Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525 GA, Nijmegen, The Netherlands
- Human Genomics Laboratory, Craiova University of Medicine and Pharmacy, Craiova, Romania
| | - Dirk Valkenborg
- Data Science Institute, Hasselt University, Hasselt, Belgium
| | - Gökhan Ertaylan
- Unit Health, Flemish Institute for Technological Research (VITO), Mol, Belgium
| | - Inge C Gyssens
- Faculty of Medicine and Life Sciences, Hasselt University, Martelarenlaan 42, 3500, Hasselt, Belgium.
- Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525 GA, Nijmegen, The Netherlands.
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Lemkus L, Lawrie D, Vaughan J. The utility of extended differential parameters as a biomarker of bacteremia at a tertiary academic hospital in persons with and without HIV infection in South Africa. PLoS One 2022; 17:e0262938. [PMID: 35176042 PMCID: PMC8853519 DOI: 10.1371/journal.pone.0262938] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2021] [Accepted: 01/07/2022] [Indexed: 12/29/2022] Open
Abstract
INTRODUCTION Extended differential parameters (EDPs) are generated with the automated differential count by Sysmex XN-series automated hematology analysers, and include the immature granulocyte count (IG%), the neutrophil fluorescent light intensity (NE-SFL) and the neutrophil fluorescent light distribution width (NE-WY). These have been proposed as early biomarkers of bacteremia. This study aimed to evaluate the NE-SFL, NE-WY and IG% in comparison to neutrophil CD64 (nCD64) expression (as a high quality sepsis biomarker) among patients with suspected bacterial sepsis at the Chris Hani Baragwanath Academic Hospital in Johannesburg, South Africa. METHODS A daily search of the laboratory information system identified samples submitted for a blood culture (BC) and a concurrent full blood count (FBC). Automated differential counts using a Sysmex XN-9000 haematology analyser and neutrophil CD64 expression by flow cytometry were assessed on the residual FBC samples. RESULTS A total of 151 samples were collected, of which 83 were excluded due to equivocal results with regards to the presence of bacterial infection. The remaining 68 samples included 23 with bacteremia, 28 with evidence of non-bacteremic bacterial infection, 13 with no evidence of bacterial infection and 4 with Tuberculosis. HIV status was documented in 90 of the patients, with a seropositivity rate of 57.8%. The EDPs were all significantly higher among patients with bacteremia as compared to those without bacterial infection, but on ROC curve analyses, only the NE-SFL showed good performance (AUC>0.8) for discriminating cases with bacteremia from those without bacterial infection at a cut-off value of 49.75. In comparison to the nCD64, the NE-SFL showed moderate agreement (kappa = 0.5). On stratification of the ROC analysis by HIV status, the NE-SFL showed superior performance among persons with HIV infection (AUC = 1), while the automated IG% showed better performance among the patients without HIV infection (AUC = 0.9). CONCLUSION In this study, EDPs showed differential performance as biomarkers for bacteremia according to HIV-status in the South African setting, with the most promising results seen with the NE-SFL and IG% parameters among people with and without HIV infection, respectively. Further assessment of these parameters without pre-selection of patients likely to have infection is required to further determine their clinical utility, particularly among patients with underlying inflammatory conditions or malignancy.
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Affiliation(s)
- Lauren Lemkus
- Department of Molecular Medicine and Haematology, University of the Witwatersrand, Johannesburg, South Africa
- National Health Laboratory Services, Johannesburg, South Africa
| | - Denise Lawrie
- Department of Molecular Medicine and Haematology, University of the Witwatersrand, Johannesburg, South Africa
- National Health Laboratory Services, Johannesburg, South Africa
| | - Jenifer Vaughan
- Department of Molecular Medicine and Haematology, University of the Witwatersrand, Johannesburg, South Africa
- National Health Laboratory Services, Johannesburg, South Africa
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A diagnostic platform for rapid, simultaneous quantification of procalcitonin and C-reactive protein in human serum. EBioMedicine 2022; 76:103867. [PMID: 35149284 PMCID: PMC8841998 DOI: 10.1016/j.ebiom.2022.103867] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2021] [Revised: 01/12/2022] [Accepted: 01/19/2022] [Indexed: 01/08/2023] Open
Abstract
Background Early and accurate determination of bacterial infections as a potential cause for a patient's systemic inflammatory response is required for timely administration of appropriate treatment and antibiotic stewardship. Procalcitonin (PCT) and C-reactive protein (CRP) have both been used as biomarkers to infer bacterial infections, particularly in the context of sepsis. There is an urgent need to develop a platform for simultaneous quantification of PCT and CRP, to enable the potential use of these biomarkers at the point-of-care. Methods A multiplexed lateral flow assay (LFA) and a fluorescence optical reader were developed. Assay performance was validated by testing spiked antigens in the buffer, followed by a validation study comparing results with conventional assays (Roche Cobas e411 Elecsys PCT and Siemens ADVIA XPT CRP) in 25 archived remnant human serum samples. Findings A linear regression correlation of 0·97 (P < 0·01) was observed for PCT, and a correlation of 0·95 (P < 0·01) was observed for CRP using direct patient samples. We also validated our platform's ability to accurately quantify high-dose CRP in the hook effect range where excess unlabeled analytes occupy binding sites at test lines. Interpretation A fluorescence reader-based duplex LFA for simultaneous quantification of PCT and CRP was developed and successfully validated with clinical samples. The rapid, portable, and low-cost nature of the platform offers potential for differentiation of bacterial and viral infections in emergency and low-resource settings at the point-of-care. Funding NIH/NIBIB Award 1R01EB021331, and Academic Venture Fund from the Atkinson Center for a Sustainable Future at Cornell University.
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Yang X, Ru J, Li Z, Jiang X, Fan C. Lower vitamin D levels and VDR FokI variants are associated with susceptibility to sepsis: a hospital-based case-control study. Biomarkers 2022; 27:188-195. [PMID: 35001797 DOI: 10.1080/1354750x.2021.2024598] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Background: Vitamin D deficiency has been associated with increased sepsis incidence and mortality in various populations. Vitamin D exerts its effect through vitamin receptor (VDR), and various single nucleotide polymorphisms have been reported to affects the expression and structure of the VDR. In the present study, we investigated the possible role of vitamin D deficiency and VDR polymorphisms in susceptibility to sepsis.Methods: 576 sepsis patients and 421 healthy controls were enrolled in the present study. Plasma vitamin D levels in patients and healthy controls were quantified by ELISA. Genetic variants in the VDR (FokI, TaqI, BsmI, and ApaI) were genotyped by TaqMan assay.Results: Reduced serum Vitamin D level was observed in subjects with sepsis compared to healthy controls (p ≤ 0.0001). Further, subjects with septic shock had diminished 25(OH) vitamin D compared to severe sepsis cases (p ≤ 0.0001). FokI variants and minor alleles were more prevalent in sepsis patients compared to healthy controls (Ff: p ≤ 0.0001, χ2 =17.39; ff: p=0.001, χ2 =10.79; f: p ≤ 0.0001, χ2 =23.51). Furthermore, combined plasma levels of 25(OH) vitamin D and FokI polymorphism revealed a significant role in a predisposition to sepsis and septic shock. However, the prevalence of other VDR polymorphisms (TaqI, BsmI and ApaI) were comparable among different clinical categories.Conclusions: Low 25(OH) vitamin D levels and FokI mutants are associated with an increased risk of sepsis and septic shock in a Chinese cohort.Clinical significanceLower levels of 25-OH vitamin D are highly prevalent in Sepsis patients.Subjects harbouring VDR FokI variants are predisposed to susceptibility to sepsis in the studied cohort.
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Affiliation(s)
- Xinyue Yang
- Department of Critical Care Medicine, The First People's Hospital of Yunnan Province, Yunnan, China
| | - Jin Ru
- Department of Critical Care Medicine, The First People's Hospital of Yunnan Province, Yunnan, China
| | - Zhengchao Li
- Department of Critical Care Medicine, The First People's Hospital of Yunnan Province, Yunnan, China
| | - Xingpeng Jiang
- Department of Critical Care Medicine, The First People's Hospital of Yunnan Province, Yunnan, China
| | - Chuming Fan
- Department of Critical Care Medicine, The First People's Hospital of Yunnan Province, Yunnan, China
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OUP accepted manuscript. J Appl Lab Med 2022; 7:1088-1097. [DOI: 10.1093/jalm/jfac031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2022] [Accepted: 03/29/2022] [Indexed: 11/13/2022]
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Kijpaisalratana N, Sanglertsinlapachai D, Techaratsami S, Musikatavorn K, Saoraya J. Machine learning algorithms for early sepsis detection in the emergency department: a retrospective study. Int J Med Inform 2022; 160:104689. [DOI: 10.1016/j.ijmedinf.2022.104689] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2021] [Revised: 12/14/2021] [Accepted: 01/11/2022] [Indexed: 10/19/2022]
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Ebrahimpour A, Okhovatpour MA, Tabrizi A, Bakhshmandi M. Value of D-Dimer as a Diagnostic Marker of Infection Associated with Orthopedic Implants. Adv Biomed Res 2021; 10:28. [PMID: 34760810 PMCID: PMC8531734 DOI: 10.4103/abr.abr_277_20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2020] [Revised: 04/11/2021] [Accepted: 04/26/2021] [Indexed: 11/06/2022] Open
Abstract
Background: Recently, the D-dimer biomarker has gained the researchers' attention for predicting infections. We aimed to determine the relationship between this marker and other inflammatory markers involved in orthopedic implant-associated infections. Materials and Methods: In this study, all patients diagnosed with an orthopedic implant-associated infection were investigated in 3 years. The serum level of D-dimer, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) was measured. Infection was diagnosed based on the clinical and culture results of biopsy samples. Results: The cultured microorganisms, detected in 26 patients with infections, included Staphylococcus aureus (n = 13, 50%), Staphylococcus epidermidis (n = 2, 7.7%), Klebsiella aerogenes (n = 8, 30.8%), and Pseudomonas aeruginosa (n = 3, 11. 5%). Based on laboratory findings, there was a significant difference in the CRP level and ESR (P = 0.001). Although the level of D-dimer was higher in infected patients, compared to the controls (992.6 ± 667.2 vs. 690.1 ± 250.2 ng/mL), the difference was not statistically significant. There was no significant correlation between the elevated D-dimer level and CRP level, whereas ESR had a positive correlation with the elevated D-dimer level (r = 0.6, P = 0.03). The sensitivity, specificity, and positive predictive value (PPV) of D-dimer in the prediction of infection were 65%, 57%, and 45%, respectively. Furthermore, the sensitivity, specificity, and PPV of CRP were 100%, 92.3%, and 95%, respectively, whereas the corresponding values for ESR were 85%, 69.2%, and 62%, respectively. Conclusion: Measurement of the serum D-dimer level is not efficient for the diagnosis of orthopedic implant-associated infections due to its low predictive value. Furthermore, there was no significant correlation between the serum D-dimer level and CRP.
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Affiliation(s)
- Adel Ebrahimpour
- Department of Orthopedic Surgery, Shohadaye Tajrish Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Ali Okhovatpour
- Department of Orthopedic Surgery, Shohadaye Tajrish Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ali Tabrizi
- Department of Hand and Microsurgery, Panzdahe Khordad Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mahsa Bakhshmandi
- Department of Orthopedics, Urmia University of Medical Sciences, Urmia, Iran
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Brandes F, Borrmann M, Buschmann D, Meidert AS, Reithmair M, Langkamp M, Pridzun L, Kirchner B, Billaud JN, Amin NM, Pearson JC, Klein M, Hauer D, Gevargez Zoubalan C, Lindemann A, Choukér A, Felbinger TW, Steinlein OK, Pfaffl MW, Kaufmann I, Schelling G. Progranulin signaling in sepsis, community-acquired bacterial pneumonia and COVID-19: a comparative, observational study. Intensive Care Med Exp 2021; 9:43. [PMID: 34476621 PMCID: PMC8412980 DOI: 10.1186/s40635-021-00406-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2021] [Accepted: 07/22/2021] [Indexed: 03/28/2023] Open
Abstract
Background Progranulin is a widely expressed pleiotropic growth factor with a central regulatory effect during the early immune response in sepsis. Progranulin signaling has not been systematically studied and compared between sepsis, community-acquired pneumonia (CAP), COVID-19 pneumonia and a sterile systemic inflammatory response (SIRS). We delineated molecular networks of progranulin signaling by next-generation sequencing (NGS), determined progranulin plasma concentrations and quantified the diagnostic performance of progranulin to differentiate between the above-mentioned disorders using the established biomarkers procalcitonin (PCT), interleukin-6 (IL-6) and C-reactive protein (CRP) for comparison. Methods The diagnostic performance of progranulin was operationalized by calculating AUC and ROC statistics for progranulin and established biomarkers in 241 patients with sepsis, 182 patients with SIRS, 53 patients with CAP, 22 patients with COVID-19 pneumonia and 53 healthy volunteers. miRNAs and mRNAs in blood cells from sepsis patients (n = 7) were characterized by NGS and validated by RT-qPCR in an independent cohort (n = 39) to identify canonical gene networks associated with upregulated progranulin at sepsis onset. Results Plasma concentrations of progranulin (ELISA) in patients with sepsis were 57.5 (42.8–84.9, Q25–Q75) ng/ml and significantly higher than in CAP (38.0, 33.5–41.0 ng/ml, p < 0.001), SIRS (29.0, 25.0–35.0 ng/ml, p < 0.001) and the healthy state (28.7, 25.5–31.7 ng/ml, p < 0.001). Patients with COVID-19 had significantly higher progranulin concentrations than patients with CAP (67.6, 56.6–96.0 vs. 38.0, 33.5–41.0 ng/ml, p < 0.001). The diagnostic performance of progranulin for the differentiation between sepsis vs. SIRS (n = 423) was comparable to that of procalcitonin. AUC was 0.90 (95% CI = 0.87–0.93) for progranulin and 0.92 (CI = 0.88–0.96, p = 0.323) for procalcitonin. Progranulin showed high discriminative power to differentiate bacterial CAP from COVID-19 (sensitivity 0.91, specificity 0.94, AUC 0.91 (CI = 0.8–1.0) and performed significantly better than PCT, IL-6 and CRP. NGS and partial RT-qPCR confirmation revealed a transcriptomic network of immune cells with upregulated progranulin and sortilin transcripts as well as toll-like-receptor 4 and tumor-protein 53, regulated by miR-16 and others. Conclusions Progranulin signaling is elevated during the early antimicrobial response in sepsis and differs significantly between sepsis, CAP, COVID-19 and SIRS. This suggests that progranulin may serve as a novel indicator for the differentiation between these disorders. Trial registration: Clinicaltrials.gov registration number NCT03280576 Registered November 19, 2015. Supplementary Information The online version contains supplementary material available at 10.1186/s40635-021-00406-7.
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Affiliation(s)
- Florian Brandes
- Department of Anaesthesiology, University Hospital, Ludwig-Maximilians-University of Munich, Munich, Germany. .,Institute of Human Genetics, University Hospital, Ludwig-Maximilians-University, Munich, Germany.
| | - Melanie Borrmann
- Department of Anaesthesiology, University Hospital, Ludwig-Maximilians-University of Munich, Munich, Germany
| | - Dominik Buschmann
- Department of Anaesthesiology, University Hospital, Ludwig-Maximilians-University of Munich, Munich, Germany.,Division of Animal Physiology and Immunology, TUM School of Life Sciences Weihenstephan, Technical University of Munich, Munich, Germany
| | - Agnes S Meidert
- Department of Anaesthesiology, University Hospital, Ludwig-Maximilians-University of Munich, Munich, Germany
| | - Marlene Reithmair
- Institute of Human Genetics, University Hospital, Ludwig-Maximilians-University, Munich, Germany
| | - Markus Langkamp
- MEDIAGNOST Company, Aspenhausstr. 25, 72770, Reutlingen, Germany
| | - Lutz Pridzun
- MEDIAGNOST Company, Aspenhausstr. 25, 72770, Reutlingen, Germany
| | - Benedikt Kirchner
- Division of Animal Physiology and Immunology, TUM School of Life Sciences Weihenstephan, Technical University of Munich, Munich, Germany
| | | | | | | | - Matthias Klein
- Department of Neurology, University Hospital, Ludwig-Maximilians-University of Munich, Munich, Germany
| | - Daniela Hauer
- Department of Anaesthesiology, University Hospital, Ludwig-Maximilians-University of Munich, Munich, Germany
| | - Clarissa Gevargez Zoubalan
- Department of Anaesthesiology, University Hospital, Ludwig-Maximilians-University of Munich, Munich, Germany
| | - Anja Lindemann
- Institute of Human Genetics, University Hospital, Ludwig-Maximilians-University, Munich, Germany
| | - Alexander Choukér
- Department of Anaesthesiology, University Hospital, Ludwig-Maximilians-University of Munich, Munich, Germany
| | - Thomas W Felbinger
- Department of Anaesthesiology, Neuperlach Hospital, City Hospitals of Munich, Munich, Germany
| | - Ortrud K Steinlein
- Institute of Human Genetics, University Hospital, Ludwig-Maximilians-University, Munich, Germany
| | - Michael W Pfaffl
- Division of Animal Physiology and Immunology, TUM School of Life Sciences Weihenstephan, Technical University of Munich, Munich, Germany
| | - Ines Kaufmann
- Department of Anaesthesiology, Neuperlach Hospital, City Hospitals of Munich, Munich, Germany
| | - Gustav Schelling
- Department of Anaesthesiology, University Hospital, Ludwig-Maximilians-University of Munich, Munich, Germany
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Tian S, Deng J, Huang W, Liu L, Chen Y, Jiang Y, Liu G. FAM89A and IFI44L for distinguishing between viral and bacterial infections in children with febrile illness. Pediatr Investig 2021; 5:195-202. [PMID: 34589675 PMCID: PMC8458721 DOI: 10.1002/ped4.12295] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Accepted: 08/06/2021] [Indexed: 11/11/2022] Open
Abstract
IMPORTANCE The current lack of reliable rapid tests for distinguishing between bacterial and viral infections has contributed to antibiotic misuse. OBJECTIVE This study aimed to develop a novel biomarker assay that integrates FAM89A and IFI44L measurements to assist in differentiating between bacterial and viral infections. METHODS This prospective study recruited children with febrile illness from two hospitals between July 1, 2018, and June 30, 2019. A panel of three experienced pediatricians performed reference standard diagnoses of all patients (i.e., bacterial or viral infection) using available clinical and laboratory data, including a 28-day follow-up assessment. Assay operators were blinded to the reference standard diagnoses. The expression levels of FAM89A and IFI44L were determined by quantitative real-time polymerase chain reaction assessment. RESULTS Of 133 potentially eligible patients with suspected bacterial or viral infection, 35 were excluded after the application of exclusion criteria. The resulting cohort included 98 patients: 59 with viral diagnoses and 39 with bacterial diagnoses. The areas under the curve (AUCs) of diagnoses using FAM89A and IFI44L were 0.694 [95% confidence interval (CI): 0.583-0.804] and 0.751 (95% CI: 0.651-0.851), respectively. The disease risk score (DRS) [log2(FAM89A expression) - log2(IFI44L expression)] signature achieved an improved area under the receiver operating characteristic curve (AUC, 0.825; 95% CI: 0.735-0.915), compared with the AUC generated from individual host RNA. A combination of the DRS and the C-reactive protein (CRP) level achieved an AUC of 0.896 (95% CI: 0.825-0.966). Optimal cutoffs for the DRS and CRP level were -3.18 and 19.80 mg/L, respectively. INTERPRETATION The DRS was significantly more accurate than the CRP level in distinguishing between bacterial and viral infections; the combination of these two parameters exhibited greater sensitivity and specificity. This study provides information that could be useful for the clinical application of FAM89A and IFI44L in terms of distinguishing between viral and bacterial infections.
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Affiliation(s)
- Shufeng Tian
- Key Laboratory of Major Diseases in ChildrenMinistry of EducationResearch Unit of Critical Infection in ChildrenChinese Academy of Medical Sciences2019RU016Department of Infectious DiseasesBeijing Children’s HospitalCapital Medical UniversityNational Center for Children’s HealthBeijingChina
- Department of Infectious DiseasesShenzhen Children’s HospitalShenzhenGuangdongChina
| | - Jikui Deng
- Department of Infectious DiseasesShenzhen Children’s HospitalShenzhenGuangdongChina
| | - Wenhua Huang
- State Key Laboratory of Pathogens and BiosecurityInstitute of Microbiology and EpidemiologyBeijingChina
| | - Linlin Liu
- Key Laboratory of Major Diseases in ChildrenMinistry of EducationResearch Unit of Critical Infection in ChildrenChinese Academy of Medical Sciences2019RU016Department of Infectious DiseasesBeijing Children’s HospitalCapital Medical UniversityNational Center for Children’s HealthBeijingChina
| | - Yunsheng Chen
- Department of Clinical LaboratoryShenzhen Children’s HospitalShenzhenGuangdongChina
| | - Yongqiang Jiang
- State Key Laboratory of Pathogens and BiosecurityInstitute of Microbiology and EpidemiologyBeijingChina
| | - Gang Liu
- Key Laboratory of Major Diseases in ChildrenMinistry of EducationResearch Unit of Critical Infection in ChildrenChinese Academy of Medical Sciences2019RU016Department of Infectious DiseasesBeijing Children’s HospitalCapital Medical UniversityNational Center for Children’s HealthBeijingChina
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Li F, Yin KN, Hu Q, Zhang QX, Chen Q, Yang LL, Chen X, Sun YJ. [Application of metagenomic next-generation sequencing technology in pathogen detection in patients with burns and patients with acute or chronic wounds]. ZHONGHUA SHAO SHANG ZA ZHI = ZHONGHUA SHAOSHANG ZAZHI = CHINESE JOURNAL OF BURNS 2021; 37:764-769. [PMID: 34404164 PMCID: PMC11917314 DOI: 10.3760/cma.j.cn501120-20200623-00322] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
Objective: To explore the value of using metagenomic next-generation sequencing (mNGS) technology to detect pathogens in patients with burns and patients with acute or chronic wounds. Methods: A retrospective observational study was conducted. From March 2019 to June 2020, 11 patients with burns and patients with acute or chronic wounds (including 10 males and 1 female, aged 23 to 85 years) in the Fourth Medical Center of PLA General Hospital met the inclusion criteria and were recruited. A total of 23 specimens were collected, including 6 whole blood specimens, 1 skin tissue specimen, 1 drained pus specimen, and 15 wound secretion swab specimens. Each specimen was divided into two parts, which were subjected for pathogen detection using microbial culture method and mNGS method, respectively. The number and types of pathogens detected by the 2 methods and the relative abundance detected by the mNGS method were recorded, and the consistency of the two methods were compared. Data were statistically analyzed with paired Wilcoxon rank sum test. Results: With the microbial culture method, no pathogen was detected in 5 of the 23 specimens, while 35 pathogens were detected in the remaining 18 specimens, belonging to 9 species of bacteria and 2 species of fungi. Five specimens had one pathogen while 9 specimens had 2 pathogens and 4 specimens had 3 pathogens detected in each specimen. With the mNGS method, no pathogen was detected in one of the 23 specimens, while 75 pathogens were detected in the remaining 22 specimens, belonging to 28 species of bacteria, 3 species of fungi, and 3 species of viruses. Eight specimens had one pathogen, 5 specimens had 2 pathogens, 2 specimens had 3 pathogens, 3 specimens had 4 pathogens, 2 specimens had 6 pathogens, and 1 specimen had 7 pathogens, and 1 specimen had 20 pathogens detected in each specimen. The number of pathogens detected in each specimen by microbial culture method was 2 (1, 2) types, which was significantly less than 2 (1, 4) types by mNGS method (Z=3.359, P<0.01). In 5 specimens, no bacteria were detected by microbial culture method but mNGS method detected bacteria in 2 specimens and virus in 2 different specimens. The mNGS method detected two or more types of bacteria in 13 specimens, the relative abundance of bacteria with the 1st relative abundance ranking ranged from 28.8% to 95.9% in each specimen. Of the 23 specimens detected by two detection methods, 7 specimens (30.4%) showed identical detection results, 5 specimens (21.7%) showed totally different detection results, and 11 specimens (47.8%) had partially consistent detection results. Conclusions: Compared with the traditional microbial culture method, the mNGS method has higher detection sensitivity and stronger capacity to detect pathogens, and can determine the relative abundance of pathogens in mixed infections. As a supplement to the culture method, the mNGS method is expected to play an important role in the diagnosis of infectious pathogens in burns and acute or chronic wounds.
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Affiliation(s)
- F Li
- Burns and Plastic Department, the Fourth Medical Center of PLA General Hospital, Beijing 100048, China
| | - K N Yin
- Burns and Plastic Department, the Fourth Medical Center of PLA General Hospital, Beijing 100048, China
| | - Q Hu
- Burns and Plastic Department, the Fourth Medical Center of PLA General Hospital, Beijing 100048, China
| | - Q X Zhang
- Burns and Plastic Department, the Fourth Medical Center of PLA General Hospital, Beijing 100048, China
| | - Q Chen
- Burns and Plastic Department, the Fourth Medical Center of PLA General Hospital, Beijing 100048, China
| | - L L Yang
- Burns and Plastic Department, the Fourth Medical Center of PLA General Hospital, Beijing 100048, China
| | - X Chen
- Burns and Plastic Department, the Fourth Medical Center of PLA General Hospital, Beijing 100048, China
| | - Y J Sun
- Burns and Plastic Department, the Fourth Medical Center of PLA General Hospital, Beijing 100048, China
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Dixon RV, Skaria E, Lau WM, Manning P, Birch-Machin MA, Moghimi SM, Ng KW. Microneedle-based devices for point-of-care infectious disease diagnostics. Acta Pharm Sin B 2021; 11:2344-2361. [PMID: 34150486 PMCID: PMC8206489 DOI: 10.1016/j.apsb.2021.02.010] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2020] [Revised: 11/25/2020] [Accepted: 01/28/2021] [Indexed: 02/08/2023] Open
Abstract
Recent infectious disease outbreaks, such as COVID-19 and Ebola, have highlighted the need for rapid and accurate diagnosis to initiate treatment and curb transmission. Successful diagnostic strategies critically depend on the efficiency of biological sampling and timely analysis. However, current diagnostic techniques are invasive/intrusive and present a severe bottleneck by requiring specialist equipment and trained personnel. Moreover, centralised test facilities are poorly accessible and the requirement to travel may increase disease transmission. Self-administrable, point-of-care (PoC) microneedle diagnostic devices could provide a viable solution to these problems. These miniature needle arrays can detect biomarkers in/from the skin in a minimally invasive manner to provide (near-) real-time diagnosis. Few microneedle devices have been developed specifically for infectious disease diagnosis, though similar technologies are well established in other fields and generally adaptable for infectious disease diagnosis. These include microneedles for biofluid extraction, microneedle sensors and analyte-capturing microneedles, or combinations thereof. Analyte sampling/detection from both blood and dermal interstitial fluid is possible. These technologies are in their early stages of development for infectious disease diagnostics, and there is a vast scope for further development. In this review, we discuss the utility and future outlook of these microneedle technologies in infectious disease diagnosis.
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Key Words
- AC, alternating current
- APCs, antigen-presenting cells
- ASSURED, affordable, sensitive, specific, user-friendly, rapid and robust, equipment-free and deliverable to end-users
- Biomarker detection
- Biosensor
- CMOS, complementary metal-oxide semiconductor
- COVID, coronavirus disease
- COVID-19
- CSF, cerebrospinal fluid
- CT, computerised tomography
- CV, cyclic voltammetry
- DC, direct current
- DNA, deoxyribonucleic acid
- DPV, differential pulse voltammetry
- EBV, Epstein–Barr virus
- EDC/NHS, 1-ethyl-3-(3-dimethylaminoproply) carbodiimide/N-hydroxysuccinimide
- ELISA, enzyme-linked immunosorbent assay
- GOx, glucose oxidase
- HIV, human immunodeficiency virus
- HPLC, high performance liquid chromatography
- HRP, horseradish peroxidase
- IP, iontophoresis
- ISF, interstitial fluid
- IgG, immunoglobulin G
- Infectious disease
- JEV, Japanese encephalitis virus
- MN, microneedle
- Microneedle
- NA, nucleic acid
- OBMT, one-touch-activated blood multidiagnostic tool
- OPD, o-phenylenediamine
- PCB, printed circuit board
- PCR, polymerase chain reaction
- PDMS, polydimethylsiloxane
- PEDOT, poly(3,4-ethylenedioxythiophene)
- PNA, peptide nucleic acid
- PP, polyphenol
- PPD, poly(o-phenylenediamine)
- PoC, point-of-care
- Point-of-care diagnostics (PoC)
- SALT, skin-associated lymphoid tissue
- SAM, self-assembled monolayer
- SEM, scanning electron microscope
- SERS, surface-enhanced Raman spectroscopy
- SWV, square wave voltammetry
- Skin
- TB, tuberculosis
- UV, ultraviolet
- VEGF, vascular endothelial growth factor
- WHO, World Health Organisation
- cfDNA, cell-free deoxyribonucleic acid
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Affiliation(s)
- Rachael V. Dixon
- School of Pharmacy, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne NE1 7RU, UK
- Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne NE2 4HH, UK
| | - Eldhose Skaria
- Wellcome Trust Centre for Cell-Matrix Research, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PT, UK
| | - Wing Man Lau
- School of Pharmacy, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne NE1 7RU, UK
- Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne NE2 4HH, UK
| | - Philip Manning
- Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne NE2 4HH, UK
| | - Mark A. Birch-Machin
- Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne NE2 4HH, UK
| | - S. Moein Moghimi
- School of Pharmacy, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne NE1 7RU, UK
- Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne NE2 4HH, UK
| | - Keng Wooi Ng
- School of Pharmacy, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne NE1 7RU, UK
- Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne NE2 4HH, UK
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Lu HY, Wang GY, Zhao JW, Jiang HT. Knockdown of lncRNA MALAT1 ameliorates acute kidney injury by mediating the miR-204/APOL1 pathway. J Clin Lab Anal 2021; 35:e23881. [PMID: 34240756 PMCID: PMC8373329 DOI: 10.1002/jcla.23881] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Revised: 05/09/2021] [Accepted: 05/28/2021] [Indexed: 12/11/2022] Open
Abstract
Background Acute kidney injury (AKI) was characterized by loss of renal function, associated with chronic kidney disease, end‐stage renal disease, and length of hospital stay. Long non‐coding RNAs (lncRNAs) participated in AKI development and progression. Here, we aimed to investigate the roles and mechanisms of lncRNA MALAT1 in AKI. Methods AKI serum samples were obtained from 129 AKI patients. ROC analysis was conducted to confirm the diagnostic value of MALAT1 in differentiating AKI from healthy volunteers. After hypoxic treatment on HK‐2 cells, the expressions of inflammatory cytokines, MALAT1, miR‐204, APOL1, p65, and p‐p65, were measured by RT‐qPCR and Western blot assays. The targeted relationship between miR‐204 and MALAT1 or miR‐204 and APOL1 was determined by luciferase reporter assay and RNA pull‐down analysis. After transfection, CCK‐8, flow cytometry, and TUNEL staining assays were performed to evaluate the effects of MALAT1 and miR‐204 on AKI progression. Results From the results, lncRNA MALAT1 was strongly elevated in serum samples from AKI patients, with the high sensitivity and specificity concerning differentiating AKI patients from healthy controls. In vitro, we established the AKI cell model after hypoxic treatment. After experiencing hypoxia, we found significantly increased MALAT1, IL‐1β, IL‐6, and TNF‐α expressions along with decreased miR‐204 level. Moreover, the targeted relationship between MALAT1 and miR‐204 was confirmed. Silencing of MALAT1 could reverse hypoxia‐triggered promotion of HK‐2 cell apoptosis. Meanwhile, the increase of IL‐1β, IL‐6, and TNF‐α after hypoxia treatment could be repressed by MALAT1 knockdown as well. After co‐transfection with MALAT1 silencing and miR‐204 inhibition, we found that miR‐204 could counteract the effects of MALAT1 on HK‐2 cell progression and inflammation after under hypoxic conditions. Finally, NF‐κB signaling was inactivated while APOL1 expression was increased in HK‐2 cells after hypoxia treatment, and lncRNA MALAT1 inhibition reactivated NF‐κB signaling while suppressed APOL1 expression by sponging miR‐204. Conclusions Collectively, these results illustrated that knockdown of lncRNA MALAT1 could ameliorate AKI progression and inflammation by targeting miR‐204 through APOL1/NF‐κB signaling.
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Affiliation(s)
- Hai-Yuan Lu
- Department of Nephrology, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huai'an, China
| | - Guo-Yi Wang
- Department of Nephrology, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huai'an, China
| | - Jin-Wen Zhao
- Department of Nephrology, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huai'an, China
| | - Hai-Tao Jiang
- Department of Orthopedics, Huai'an First People's Hospital, Huai'an, China
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de’Angelis N, Catena F, Memeo R, Coccolini F, Martínez-Pérez A, Romeo OM, De Simone B, Di Saverio S, Brustia R, Rhaiem R, Piardi T, Conticchio M, Marchegiani F, Beghdadi N, Abu-Zidan FM, Alikhanov R, Allard MA, Allievi N, Amaddeo G, Ansaloni L, Andersson R, Andolfi E, Azfar M, Bala M, Benkabbou A, Ben-Ishay O, Bianchi G, Biffl WL, Brunetti F, Carra MC, Casanova D, Celentano V, Ceresoli M, Chiara O, Cimbanassi S, Bini R, Coimbra R, Luigi de’Angelis G, Decembrino F, De Palma A, de Reuver PR, Domingo C, Cotsoglou C, Ferrero A, Fraga GP, Gaiani F, Gheza F, Gurrado A, Harrison E, Henriquez A, Hofmeyr S, Iadarola R, Kashuk JL, Kianmanesh R, Kirkpatrick AW, Kluger Y, Landi F, Langella S, Lapointe R, Le Roy B, Luciani A, Machado F, Maggi U, Maier RV, Mefire AC, Hiramatsu K, Ordoñez C, Patrizi F, Planells M, Peitzman AB, Pekolj J, Perdigao F, Pereira BM, Pessaux P, Pisano M, Puyana JC, Rizoli S, Portigliotti L, Romito R, Sakakushev B, Sanei B, Scatton O, Serradilla-Martin M, Schneck AS, Sissoko ML, Sobhani I, ten Broek RP, Testini M, Valinas R, Veloudis G, Vitali GC, Weber D, Zorcolo L, Giuliante F, Gavriilidis P, Fuks D, Sommacale D. 2020 WSES guidelines for the detection and management of bile duct injury during cholecystectomy. World J Emerg Surg 2021; 16:30. [PMID: 34112197 PMCID: PMC8190978 DOI: 10.1186/s13017-021-00369-w] [Citation(s) in RCA: 96] [Impact Index Per Article: 24.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Accepted: 05/18/2021] [Indexed: 12/16/2022] Open
Abstract
Bile duct injury (BDI) is a dangerous complication of cholecystectomy, with significant postoperative sequelae for the patient in terms of morbidity, mortality, and long-term quality of life. BDIs have an estimated incidence of 0.4-1.5%, but considering the number of cholecystectomies performed worldwide, mostly by laparoscopy, surgeons must be prepared to manage this surgical challenge. Most BDIs are recognized either during the procedure or in the immediate postoperative period. However, some BDIs may be discovered later during the postoperative period, and this may translate to delayed or inappropriate treatments. Providing a specific diagnosis and a precise description of the BDI will expedite the decision-making process and increase the chance of treatment success. Subsequently, the choice and timing of the appropriate reconstructive strategy have a critical role in long-term prognosis. Currently, a wide spectrum of multidisciplinary interventions with different degrees of invasiveness is indicated for BDI management. These World Society of Emergency Surgery (WSES) guidelines have been produced following an exhaustive review of the current literature and an international expert panel discussion with the aim of providing evidence-based recommendations to facilitate and standardize the detection and management of BDIs during cholecystectomy. In particular, the 2020 WSES guidelines cover the following key aspects: (1) strategies to minimize the risk of BDI during cholecystectomy; (2) BDI rates in general surgery units and review of surgical practice; (3) how to classify, stage, and report BDI once detected; (4) how to manage an intraoperatively detected BDI; (5) indications for antibiotic treatment; (6) indications for clinical, biochemical, and imaging investigations for suspected BDI; and (7) how to manage a postoperatively detected BDI.
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Affiliation(s)
- Nicola de’Angelis
- Unit of Minimally Invasive and Robotic Digestive Surgery, General Regional Hospital “F. Miulli”, Strada Prov. 127 Acquaviva – Santeramo Km. 4, 70021 Acquaviva delle Fonti BA, Bari, Italy
- Unit of Digestive, Hepatobiliary and Pancreatic Surgery, CARE Department, Henri Mondor University Hospital (AP-HP), and Faculty of Medicine, University of Paris Est, UPEC, Creteil, France
| | - Fausto Catena
- Department of Emergency and Trauma Surgery of the University Hospital of Parma, Parma, Italy
| | - Riccardo Memeo
- Department of Hepato-Pancreatic-Biliary Surgery, General Regional Hospital “F. Miulli”, Acquaviva delle Fonti, Bari, Italy
| | - Federico Coccolini
- General, Emergency and Trauma Department, Pisa University Hospital, Pisa, Italy
| | - Aleix Martínez-Pérez
- Department of General and Digestive Surgery, Hospital Universitario Doctor Peset, Valencia, Spain
| | - Oreste M. Romeo
- Trauma, Burn, and Surgical Care Program, Bronson Methodist Hospital, Kalamazoo, Michigan USA
| | - Belinda De Simone
- Service de Chirurgie Générale, Digestive, et Métabolique, Centre hospitalier de Poissy/Saint Germain en Laye, Saint Germain en Laye, France
| | - Salomone Di Saverio
- Department of Surgery, Cambridge University Hospital, NHS Foundation Trust, Cambridge, UK
| | - Raffaele Brustia
- Unit of Digestive, Hepatobiliary and Pancreatic Surgery, CARE Department, Henri Mondor University Hospital (AP-HP), and Faculty of Medicine, University of Paris Est, UPEC, Creteil, France
| | - Rami Rhaiem
- Department of HBP and Digestive Oncologic Surgery, Robert Debré University Hospital, Reims, France
| | - Tullio Piardi
- Department of HBP and Digestive Oncologic Surgery, Robert Debré University Hospital, Reims, France
- Department of Surgery, HPB Unit, Troyes Hospital, Troyes, France
| | - Maria Conticchio
- Department of Hepato-Pancreatic-Biliary Surgery, General Regional Hospital “F. Miulli”, Acquaviva delle Fonti, Bari, Italy
| | - Francesco Marchegiani
- Department of Surgical, Oncological and Gastroenterological Sciences, University of Padua, Padua, Italy
| | - Nassiba Beghdadi
- Unit of Digestive, Hepatobiliary and Pancreatic Surgery, CARE Department, Henri Mondor University Hospital (AP-HP), and Faculty of Medicine, University of Paris Est, UPEC, Creteil, France
| | - Fikri M. Abu-Zidan
- Department of Surgery, College of Medicine and Health Sciences, UAE University, Al-Ain, United Arab Emirates
| | - Ruslan Alikhanov
- Department of Hepato-Pancreato-Biliary Surgery, Moscow Clinical Scientific Center, Shosse Enthusiastov, 86, 111123 Moscow, Russia
| | | | - Niccolò Allievi
- 1st Surgical Unit, Department of Emergency, Papa Giovanni Hospital XXIII, Bergamo, Italy
| | - Giuliana Amaddeo
- Service d’Hepatologie, APHP, Henri Mondor University Hospital, Creteil, and Faculty of Medicine, University of Paris Est, UPEC, Creteil, France
| | - Luca Ansaloni
- General Surgery, San Matteo University Hospital, Pavia, Italy
| | | | - Enrico Andolfi
- Department of Surgery, Division of General Surgery, San Donato Hospital, 52100 Arezzo, Italy
| | - Mohammad Azfar
- Department of Surgery, Al Rahba Hospital, Abu Dhabi, UAE
| | - Miklosh Bala
- Trauma and Acute Care Surgery Unit, Hadassah Hebrew University Medical Center, Jerusalem, Israel
| | - Amine Benkabbou
- Surgical Oncology Department, National Institute of Oncology, Mohammed V University in Rabat, Rabat, Morocco
| | - Offir Ben-Ishay
- Department of General Surgery, Rambam Healthcare Campus, Haifa, Israel
| | - Giorgio Bianchi
- Unit of Minimally Invasive and Robotic Digestive Surgery, General Regional Hospital “F. Miulli”, Strada Prov. 127 Acquaviva – Santeramo Km. 4, 70021 Acquaviva delle Fonti BA, Bari, Italy
| | - Walter L. Biffl
- Division of Trauma and Acute Care Surgery, Scripps Memorial Hospital La Jolla, La Jolla, California USA
| | - Francesco Brunetti
- Unit of Digestive, Hepatobiliary and Pancreatic Surgery, CARE Department, Henri Mondor University Hospital (AP-HP), and Faculty of Medicine, University of Paris Est, UPEC, Creteil, France
| | | | - Daniel Casanova
- Hospital Universitario Marqués de Valdecilla, University of Cantabria, Santander, Spain
| | - Valerio Celentano
- Colorectal Unit, Chelsea and Westminster Hospital, NHS Foundation Trust, London, UK
| | - Marco Ceresoli
- Emergency and General Surgery Department, University of Milan Bicocca, Milan, Italy
| | - Osvaldo Chiara
- General Surgery and Trauma Team, ASST Niguarda Milano, University of Milano, Milan, Italy
| | - Stefania Cimbanassi
- General Surgery and Trauma Team, ASST Niguarda Milano, University of Milano, Milan, Italy
| | - Roberto Bini
- General Surgery and Trauma Team, ASST Niguarda Milano, University of Milano, Milan, Italy
| | - Raul Coimbra
- Riverside University Health System Medical Center, Comparative Effectiveness and Clinical Outcomes Research Center – CECORC and Loma Linda University School of Medicine, Loma Linda, USA
| | - Gian Luigi de’Angelis
- Gastroenterology and Endoscopy Unit, Department of Medicine and Surgery, University of Parma, Parma, Italy
| | - Francesco Decembrino
- Gastroenterology and Endoscopy Unit, General Regional Hospital “F. Miulli”, Acquaviva delle Fonti, Bari, Italy
| | - Andrea De Palma
- General, Emergency and Trauma Department, Pisa University Hospital, Pisa, Italy
| | - Philip R. de Reuver
- Department of Surgery, Radboud University Medical Centre Nijmegen, Nijmegen, The Netherlands
| | - Carlos Domingo
- Department of General and Digestive Surgery, Hospital Universitario Doctor Peset, Valencia, Spain
| | | | - Alessandro Ferrero
- Department of General and Oncological Surgery, Azienda Ospedaliera Ordine Mauriziano “Umberto I”, Turin, Italy
| | - Gustavo P. Fraga
- Division of Trauma Surgery, Department of Surgery, School of Medical Sciences, University of Campinas (Unicamp), Campinas, SP Brazil
| | - Federica Gaiani
- Gastroenterology and Endoscopy Unit, Department of Medicine and Surgery, University of Parma, Parma, Italy
| | - Federico Gheza
- Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
| | - Angela Gurrado
- Unit of General Surgery “V. Bonomo”, Department of Biomedical Sciences and Human Oncology, University of Bari “Aldo Moro”, Bari, Italy
| | - Ewen Harrison
- Department of Clinical Surgery and Centre for Medical Informatics, Usher Institute, University of Edinburgh, Little France Crescent, Edinburgh, UK
| | | | - Stefan Hofmeyr
- Division of Surgery, Surgical Gastroenterology Unit, Tygerberg Academic Hospital, University of Stellenbosch Faculty of Medicine and Health Sciences, Stellenbosch, South Africa
| | - Roberta Iadarola
- Department of Emergency and Trauma Surgery of the University Hospital of Parma, Parma, Italy
| | - Jeffry L. Kashuk
- Department of Surgery, Tel Aviv University, Sackler School of Medicine, Tel Aviv, Israel
| | - Reza Kianmanesh
- Department of HBP and Digestive Oncologic Surgery, Robert Debré University Hospital, Reims, France
| | - Andrew W. Kirkpatrick
- Department of Surgery, Critical Care Medicine and the Regional Trauma Service, Foothills Medical Center, Calgari, Alberta Canada
| | - Yoram Kluger
- Department of General Surgery, Rambam Healthcare Campus, Haifa, Israel
| | - Filippo Landi
- Department of HPB and Transplant Surgery, Hospital Clínic, Universidad de Barcelona, Barcelona, Spain
| | - Serena Langella
- Department of General and Oncological Surgery, Azienda Ospedaliera Ordine Mauriziano “Umberto I”, Turin, Italy
| | - Real Lapointe
- Department of HBP Surgery and Liver Transplantation, Department of Surgery, Centre Hospitalier de l’Université de Montreal, Montreal, QC Canada
| | - Bertrand Le Roy
- Department of Digestive Surgery, University Hospital of Saint-Etienne, Saint-Priest-en-Jarez, France
| | - Alain Luciani
- Unit of Radiology, Henri Mondor University Hospital (AP-HP), Creteil, and Faculty of Medicine, University of Paris Est, UPEC, Creteil, France
| | - Fernando Machado
- Department of Emergency Surgery, Hospital de Clínicas, School of Medicine UDELAR, Montevideo, Uruguay
| | - Umberto Maggi
- General Surgery and Liver Transplantation Unit, Fondazione IRCCS Ca’Granda, Ospedale Maggiore Policlinico di Milano, Milan, Italy
| | - Ronald V. Maier
- Department of Surgery, University of Washington, Seattle, WA USA
| | - Alain Chichom Mefire
- Department of Surgery and Obstetrics/Gynecologic, Regional Hospital, Limbe, Cameroon
| | - Kazuhiro Hiramatsu
- Department of General Surgery, Toyohashi Municipal Hospital, Toyohashi, Aichi Japan
| | - Carlos Ordoñez
- Division of Trauma and Acute Care Surgery, Department of Surgery, Fundacion Valle del Lili, Universidad del Valle Cali, Cali, Colombia
| | - Franca Patrizi
- Unit of Gastroenterology and Endoscopy, Maggiore Hospital, Bologna, Italy
| | - Manuel Planells
- Department of General and Digestive Surgery, Hospital Universitario Doctor Peset, Valencia, Spain
| | - Andrew B. Peitzman
- Department of Surgery, UPMC, University of Pittsburg, School of Medicine, Pittsburg, USA
| | - Juan Pekolj
- General Surgery, Liver Transplant Unit, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
| | - Fabiano Perdigao
- Liver Transplant Unit, APHP, Unité de Chirurgie Hépatobiliaire et Transplantation hépatique, Hôpital Pitié Salpêtrière, Paris, France
| | - Bruno M. Pereira
- Division of Trauma Surgery, Department of Surgery, School of Medical Sciences, University of Campinas (Unicamp), Campinas, SP Brazil
| | - Patrick Pessaux
- Hepatobiliary and Pancreatic Surgical Unit, Visceral and Digestive Surgery, IHU mix-surg, Institute for Minimally Invasive Image-Guided Surgery, University of Strasbourg, Strasbourg, France
| | - Michele Pisano
- 1st Surgical Unit, Department of Emergency, Papa Giovanni Hospital XXIII, Bergamo, Italy
| | - Juan Carlos Puyana
- Trauma & Acute Care Surgery – Global Health, University of Pittsburgh, Pittsburgh, USA
| | - Sandro Rizoli
- Trauma and Acute Care Service, St Michael’s Hospital, Toronto, ON Canada
| | - Luca Portigliotti
- Chirurgia Epato-Gastro-Pancreatica, Azienda Ospedaliera-Universitaria Maggiore della Carità, Novara, Italy
| | - Raffaele Romito
- Chirurgia Epato-Gastro-Pancreatica, Azienda Ospedaliera-Universitaria Maggiore della Carità, Novara, Italy
| | - Boris Sakakushev
- General Surgery Department, Medical University, University Hospital St George, Plovdiv, Bulgaria
| | - Behnam Sanei
- Department of Surgery, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Olivier Scatton
- Liver Transplant Unit, APHP, Unité de Chirurgie Hépatobiliaire et Transplantation hépatique, Hôpital Pitié Salpêtrière, Paris, France
| | - Mario Serradilla-Martin
- Instituto de Investigación Sanitaria Aragón, Department of Surgery, Hospital Universitario Miguel Servet, Zaragoza, Spain
| | - Anne-Sophie Schneck
- Digestive Surgery Unit, Centre Hospitalier Universitaire de Guadeloupe, Pointe-À-Pitre, Les Avymes, Guadeloupe France
| | - Mohammed Lamine Sissoko
- Service de Chirurgie, Hôpital National Blaise Compaoré de Ouagadougou, Ouagadougou, Burkina Faso
| | - Iradj Sobhani
- Department of Gastroenterology and Digestive Endoscopy, Henri Mondor Hospital, AP-HP, Creteil, and Faculty of Medicine, University of Paris Est, UPEC, Creteil, France
| | - Richard P. ten Broek
- Department of Surgery, Radboud University Medical Centre Nijmegen, Nijmegen, The Netherlands
| | - Mario Testini
- Unit of General Surgery “V. Bonomo”, Department of Biomedical Sciences and Human Oncology, University of Bari “Aldo Moro”, Bari, Italy
| | - Roberto Valinas
- Department of Surgery “F”, Faculty of Medicine, Clinic Hospital “Dr. Manuel Quintela”, Montevideo, Uruguay
| | | | - Giulio Cesare Vitali
- Division of Transplantation, Department of Surgery, Geneva University Hospitals, Geneva, Switzerland
| | - Dieter Weber
- Department of Trauma Surgery, Royal Perth Hospital, Perth, Australia
| | - Luigi Zorcolo
- Department of Surgery, Colorectal Surgery Unit, University of Cagliari, Cagliari, Italy
| | - Felice Giuliante
- Hepatobiliary Surgery Unit, Foundation “Policlinico Universitario A. Gemelli”, IRCCS, Rome, Italy
| | - Paschalis Gavriilidis
- Division of Gastrointestinal and HBP Surgery, Imperial College HealthCare, NHS Trust, Hammersmith Hospital, London, UK
| | - David Fuks
- Institut Mutualiste Montsouris, Paris, France
| | - Daniele Sommacale
- Unit of Digestive, Hepatobiliary and Pancreatic Surgery, CARE Department, Henri Mondor University Hospital (AP-HP), and Faculty of Medicine, University of Paris Est, UPEC, Creteil, France
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van Wijk XMR, Yun C, Lynch KL. Evaluation of Biomarkers in Sepsis: High Dimethylarginine (ADMA and SDMA) Concentrations Are Associated with Mortality. J Appl Lab Med 2021; 6:592-605. [PMID: 33382901 DOI: 10.1093/jalm/jfaa156] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2020] [Accepted: 08/14/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND As modulators of nitric oxide generation, asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) may play important roles in sepsis. Current data on dimethylarginines are conflicting, and direct comparison data with other biomarkers are limited. METHODS Fifty-five patients were included in the final analysis and were divided into 4 groups: infection without sepsis, sepsis, severe sepsis, and septic shock. The first available samples on hospital admission were analyzed for ADMA, SDMA, procalcitonin (PCT), C-reactive protein, heparin binding protein (HBP), zonulin, soluble CD25 (sCD25), and soluble CD163 (sCD163). White blood cell (WBC) counts and lactate results were obtained from the medical record. RESULTS There were no statistically significant differences in ADMA and SDMA concentrations among the 4 groups; however, PCT, WBC, HBP, and sCD25 showed statistically significant differences. Lactate only trended toward statistical significance, likely because of limited availability in the medical record. Differences between survivors of sepsis and nonsurvivors at 30 days were highly statistically significant for ADMA and SDMA. Areas under the curve (AUCs) for ROC analysis were 0.88 and 0.95, respectively. There was also a statistically significant difference between survivors of sepsis and nonsurvivors for HBP, lactate, sCD25, and sCD163; however, AUCs for ROC curves were not statistically significantly different from 0.5. CONCLUSIONS Analysis of biomarkers other than dimethylarginines were in general agreement with expectations from the literature. ADMA and SDMA may not be specific markers for diagnosis of sepsis; however, they may be useful in short-term mortality risk assessment.
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Affiliation(s)
- Xander M R van Wijk
- Laboratory Medicine, University of California, San Francisco and Zuckerberg San Francisco General, Chicago, IL
| | - Cassandra Yun
- Laboratory Medicine, University of California, San Francisco and Zuckerberg San Francisco General, Chicago, IL
| | - Kara L Lynch
- Laboratory Medicine, University of California, San Francisco and Zuckerberg San Francisco General, Chicago, IL
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De Ritis Ratio as a Significant Prognostic Factor in Patients with Sepsis: A Retrospective Analysis. J Surg Res 2021; 264:375-385. [PMID: 33848836 DOI: 10.1016/j.jss.2021.03.018] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2020] [Revised: 01/20/2021] [Accepted: 03/03/2021] [Indexed: 12/29/2022]
Abstract
PURPOSE This study was performed to investigate the relationship between the aspartate transaminase and/or alanine transaminase ratio (DRR) and long-term mortality of patients diagnosed with sepsis or septic shock. MATERIALS AND METHODS We conducted a retrospective study among adult septic patients who were admitted to the surgical intensive care unit (ICU) of the Chinese People's Liberation Army (PLA) General Hospital from January 2014 to December 2018. Baseline characteristics were compared between survivors and non survivors. We performed univariate and multivariate Cox regression analyses to evaluate the relation of DRR with 180-day mortality. The potential prognostic value of DRR in predicting mortality rate was assessed by receiver operating characteristic (ROC) curve analysis. In addition, we conducted subgroup analysis by the optimal DRR cutoff value. RESULTS We included a total of 183 patients in the current study, and 44 (24%) patients died within 180 days of hospitalization. Univariate and multivariate Cox analyses revealed that DRR was an independent predictor of 180-day mortality (hazard ratio [HR] 1.421, 95% confidence interval [CI] 1.073-1.883, P = 0.014). The predictive accuracy of DRR for 180-day mortality was presented as an ROC curve, which had an area under the curve (AUC) of 0.708 (95% CI 0.629-0.786, P < 0.001). After we stratified all enrolled patients into two groups by using the optimal cutoff value of 1.29, we observed a significantly higher mortality in patients with a relatively high DRR. CONCLUSIONS An elevated DRR was associated with higher 180-day mortality among septic patients, and DRR might be an optimal marker for predicting the long-term mortality of sepsis. More prospective and randomized trials are needed to confirm the prognostic value of DRR.
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Piva E, Zuin J, Pelloso M, Tosato F, Fogar P, Plebani M. Monocyte distribution width (MDW) parameter as a sepsis indicator in intensive care units. Clin Chem Lab Med 2021; 59:1307-1314. [PMID: 33675202 DOI: 10.1515/cclm-2021-0192] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2021] [Accepted: 02/22/2021] [Indexed: 02/06/2023]
Abstract
OBJECTIVES Patients in Intensive Care Units (ICU) are a high-risk population for sepsis, recognized as a major cause of admission and death. The aim of the current study was to evaluate the diagnostic accuracy and prognostication of monocyte distribution width (MDW) in sepsis for patients admitted to ICU. METHODS Between January and June 2020, we conducted a prospective observational study during the hospitalization of 506 adult patients admitted to the ICU. MDW was evaluated in 2,367 consecutive samples received for routine complete blood counts (CBC) performed once a day and every day during the study. Sepsis was diagnosed according to Sepsis-3 criteria and patients enrolled were classified in the following groups: no sepsis, sepsis and septic shock. RESULTS MDW values were significantly higher in patients with sepsis or septic shock in comparison to those within the no sepsis group [median 26.23 (IQR: 23.48-29.83); 28.97 (IQR: 21.27-37.21); 21.99 (IQR: 19.86-24.36) respectively]. ROC analysis demonstrated that AUC is 0.785 with a sensitivity of 66.88% and specificity of 77.79% at a cut-off point of 24.63. In patients that developed an ICU-acquired sepsis MDW showed an increase from 21.33 [median (IQR: 19.47-21.72)] to 29.19 [median (IQR: 27.46-31.47)]. MDW increase is not affected by the aetiology of sepsis, even in patients with COVID-19. In sepsis survivors a decrease of MDW values were found from the first time to the end of their stay [median from 29.14 (IQR: 26.22-32.52) to 25.67 (IQR: 22.93-30.28)]. CONCLUSIONS In ICU, MDW enhances the sepsis detection and is related to disease severity.
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Affiliation(s)
- Elisa Piva
- Department of Laboratory Medicine, University-Hospital of Padova, Padova, Italy
| | - Jenny Zuin
- Department of Medicine-DIMED, University of Padova, Padova, Italy
| | - Michela Pelloso
- Department of Laboratory Medicine, University-Hospital of Padova, Padova, Italy
| | - Francesca Tosato
- Department of Laboratory Medicine, University-Hospital of Padova, Padova, Italy
| | - Paola Fogar
- Department of Laboratory Medicine, University-Hospital of Padova, Padova, Italy
| | - Mario Plebani
- Department of Laboratory Medicine, University-Hospital of Padova, Padova, Italy.,Department of Medicine-DIMED, University of Padova, Padova, Italy
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