Area Under The Curve For C-reactive Protein Research Articles

The infected diabetic foot: Modulation of traditional biomarkers for osteomyelitis diagnosis in the setting of diabetic foot infection and renal impairment.

The objective of this paper was to investigate erythrocyte sedimentation rate (ESR) and c-reactive protein (CRP) in diagnosing pedal osteomyelitis (OM) in patients with and without diabetes, and with and without severe renal impairment (SRI). This was a retrospective cohort study of patients with moderate and severe foot infections. We evaluated three groups: Subjects without diabetes (NDM), subjects with diabetes and without severe renal insufficiency (DM-NSRI), and patients with diabetes and SRI (DM-SRI). SRI was defined as eGFR <30. We evaluated area under the curve (AUC), cutoff point, sensitivity and specificity to characterize the accuracy of ESR and CRP to diagnose OM. A total of 408 patients were included in the analysis. ROC analysis in the NDM group revealed the AUC for ESR was 0.62, with a cutoff value of 46 mm/h (sensitivity, 49.0%; specificity, 76.0%). DM-NSRI subjects showed the AUC for ESR was 0.70 with the cutoff value of 61 mm/h (sensitivity, 68.9%; specificity 61.8%). In DM-SRI, the AUC for ESR was 0.67, with a cutoff value of 119 mm/h (sensitivity, 46.4%; specificity, 82.40%). In the NDM group, the AUC for CRP was 0.55, with a cutoff value of 6.4 mg/dL (sensitivity, 31.3%; specificity, 84.0%). For DM-NSRI, the AUC for CRP was 0.70, with a cutoff value of 8 mg/dL (sensitivity, 49.2%; specificity, 80.6%). In DM-SRI, the AUC for CRP was 0.62, with a cutoff value of 7 mg/dL (sensitivity, 57.1%; specificity, 67.7%). While CRP demonstrated relatively consistent utility, ESR's diagnostic cutoff points diverged significantly. These results highlight the necessity of considering patient-specific factors when interpreting ESR results in the context of OM diagnosis.

Diabetes mellitus and response to IL-1 blockade with Anakinra after ST-elevation myocardial infarction: a pooled analysis of the VCU-ART studies

Abstract Background ST segment elevation myocardial infarction (STEMI) elicits an intense inflammatory response which is thought to contribute to subsequent maladaptive myocardial healing and remodeling, ultimately leading to heart failure (HF). The interleukin-1 (IL-1) blocker anakinra administered during the first 14 days after STEMI patients has been shown to effectively dampen the inflammatory response and reduce the incidence of HF events in pilot randomized controlled trials. Diabetes mellitus is a condition of enhanced systemic inflammation. Purpose To assess the role of diabetes mellitus as a modulating factor in respect to the efficacy of anakinra treatment during the first 14 days after STEMI. Methods We conducted a pooled analysis of three previous proof of principle trials on anakinra in STEMI. Diabetes mellitus was defined based on clinical history, use of glucose-lowering medications, or elevated hemoglobin A1c &amp;gt;6.5% at time of enrollment and further characterized as type I or type II based on the available clinical assessment. The area-under-the-curve for C reactive protein (AUC-CRP) at 14 days was used as a measure of the systemic inflammatory response during STEMI. The clinical endpoint was composite of death, hospitalizations for HF and urgent HF visits. Results The study population included 139 patients, of whom 39 (28%) had a diagnosis of diabetes mellitus at time of enrolment, all with type II. Median age was 56 [49-63] and 56 [49-63] years in patients with and without diabetes, respectively (p=0.652). There were 29 (21%) female and 52 (37%) Black-African American patients among those with diabetes compared to 29 (21%) female and 52 (37%) Black-African American patients in those without diabetes (p=0.69 and p=0.16, respectively). Treatment with anakinra (N=84) significantly dampened acute inflammation associated with STEMI in patients with diabetes (AUC-CRP 223 [117-399] vs 76 [42-148] mg•day/L, p&amp;lt;0.001) and in those without diabetes (AUC-CRP 223 [117-399] vs 76 [42-148] mg•day/L, p&amp;lt;0.001 – Figure 1). No statistically significant interaction between diabetes status and treatment with anakinra on outcomes was detected (pint=0.92): treatment with anakinra was associated with a hazard ratio [HR] 0.28 [0.09-0.84](p=0.02) in non-diabetic patients and HR 0.26 [0.11-1.32](p=0.10) in diabetic patients – Figure 2. Conclusion In this pooled analysis of the VCU-ART trials, the presence of type II diabetes mellitus showed no interaction with the efficacy of the treatment with anakinra early after STEMI in reducing the systemic inflammatory response or preventing new onset heart failure, hospitalization for HF or death.Figure 1.Figure 2

Serum procalcitonin has no significance in the diagnosis of periprosthesis joint infection before total hip and knee replacement.

Currently, there is no "gold standard" for early diagnosing PJI. The diagnosis of periprosthetic joint infection (PJI) is a challenging problem in the clinic. As we know, many serum markers have been used in the early diagnosis of PJI. The aim of this study was to validate the value of PCT in the diagnosis of PJI. A retrospective review of 77 patients with revision arthroplasties from January 2013 to July 2020 was conducted. PJI was defined using the modified Musculoskeletal Infection Society (MSIS) criteria combined with follow-up results. Besides medical history, clinical and laboratory data was gathered. Preoperative blood was taken for serum PCT and other biomarkers measurement. Receiver operating characteristic (ROC) curves were generated to evaluate the biomarkers' diagnostic performance and optimal cut-off value. Forty-one patients were identified as the PJI group (27 hips and 14 knees), while thirty-six patients were identified as the aseptic loosening (AL) group (33 hips and 3 knees). The AUCs for C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), Platelets (PLT), Fibrinogen (FIB), and Procalcitonin (PCT) were 0.845 (95% CI 0.755-0.936, p < 0.001), 0.817 (95% CI 0.718-0.916, p < 0.001), 0.728 (95% CI 0.613-0.843, p < 0.001), 0.810 (95% CI 0.710-0.910, p < 0.001) and 0.504 (95% CI 0.373-0.635, p = 0.950), respectively. Higher Area under the Curve (AUC) values were obtained for the combinations of PCT and CRP (AUC = 0.870) (95% CI, 0.774-0.936), PCT and ESR (AUC = 0.817) (95% CI, 0.712-0.896), PCT and PLT (AUC = 0.731) (95% CI, 0.617-0.825), PCT and FIB (AUC = 0.815) (95% CI, 0.710-0.894). The serum PCT indicated a sensitivity of 19.51% and a specificity of 83.33% for diagnosing PJI. When the optimal cut-off value for PCT was set as 0.05 ng/ml, its positive and negative likelihood ratios were 57.1% and 47.6%, respectively. In conclusion, serum PCT appeared to be no reliable biomarker in differentiating PJI from aseptic loosening before revision arthroplasties. However, PCT combined with other biomarkers further increases the diagnostic accuracy.

Clinical and Pharmacological Implications of Time to Treatment with Interleukin-1 Blockade in ST-Segment Elevation Myocardial Infarction.

Interleukin-1 (IL-1) blockade with anakinra given within 12 hours from reperfusion has been shown to reduce the inflammatory response as well as prevent heart failure (HF) events in patients with STEMI.We sought to determine whether time-to-treatment influences the efficacy of anakinra on systemic inflammation and incidence of HF events in patients with STEMI. We divided the cohort in two groups based on the median time from percutaneous coronary intervention (PCI) to investigational drug, and analyzed the effects of anakinra on the area-under-the-curve for C reactive protein (AUC-CRP) and on incidence of the composite endpoint of death or new onset HF. We analyzed data from 139 patients: 84 (60%) treated with anakinra and 55 (40%) with placebo. The median time from PCI to investigational treatment was 271(182-391) minutes. The AUC-CRP was significantly higher in patients receiving placebo versus anakinra both in those with time from PCI to treatment <271 min (222.6[103.9-325.2] vs 78.4[44.3-131.2], p<0.001) and those with time from PCI to treatment {greater than or equal to}271 min (235.2[131.4-603.4] vs 75.5[38.9-171.9], p<0.001) (p>0.05 for interaction). Anakinra significantly reduced the combined endpoint of death or new onset HF in patients with time from PCI to treatment <271 min (5[11%] vs 9[36%], log-rank Chi-square 5.985, p=0.014) as well as in patients with time from PCI to drug {greater than or equal to}271 min (2[5%] vs 7[23%], log-rank Chi-square 3.995, p=0.046) (p>0.05 for interaction). IL-1 blockade with anakinra blunts the acute systemic inflammatory response and prevents HF events independent of time-to-treatment. Significance Statement In patients with ST segment elevation presenting within 12 hours of pain onset and treated within 12 hours of reperfusion, IL-1 blockade with anakinra blunts the acute systemic inflammatory response, a surrogate of IL-1 activity, and prevents HF events independent of time-to-treatment.

Changes in C-reactive protein, erythrocyte sedimentation rate, human leukocyte antigen-B27, and immunoglobulins A, G, M in patients with ankylosing spondylitis

Abstract Background To explore the changes in C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), human leukocyte antigen-B27 (HLA-B27), and immunoglobulin (Ig) (IgA, IgG, and IgM) in patients suffering from ankylosing spondylitis (AS). Methods A total of 232 patients with axial spondyloarthritis admitted from January 2020 to December 2021 were selected, among whom 132 were AS patients (AS group) and 100 were non-AS cases (non-AS group). Meanwhile, 100 healthy subjects undergoing physical examination were included as a control group. Peripheral blood was collected to detect the levels of CRP, ESR, HLA-B27, IgA, IgG, and IgM. Results The positive rates and levels of CRP, ESR, HLA-B27, IgG, and IgM in non-AS and AS groups were significantly higher, and the IgA level of the AS group was higher than those of the control group (P&lt;0.05). The AS group had significantly higher positive rates and levels of CRP, ESR, HLA-B27, and IgA than those of the non-AS group (P&lt;0.05). The levels of HLA-B27, ESR and CRP had positive correlations with those of IgA, IgG and IgM (P&lt;0.05). The area under the curve (AUC) of HLA-B27 with a cut-off value of 53.18 U/mL for the diagnosis of AS was 0.879. AUC of ESR with a cut-off value of 23.83 mm/h for the diagnosis of AS was 0.811. AUC of CRP with a cut-off value of 14.35 mg/L for the diagnosis of AS was 0.745. With the cut-off values of 2.75 g/L, respectively, AUC of IgA for the diagnosis of AS were 0.668. AUC of the combined diagnosis was 0.929 (P&lt;0.05). Conclusions AS patients have abnormally elevated levels of HLA-B27, ESR, CRP, and IgA, and the combined detection has a higher diagnostic value. The abnormal increase in IgA, IgG, and IgM is positively correlated with rheumatic inflammation marker HLA-B27, CRP, and ESR.

Abstract 13994: Time to Treatment and Efficacy of IL-1 Blockade With Anakinra in ST-Segment Elevation Myocardial Infarction

Introduction: Interleukin-1 (IL-1) blockade with anakinra given within 12 hours from reperfusion has recently showed to reduce the inflammatory response as well as prevent heart failure (HF) events in patients with STEMI. Hypothesis: The aim of this study was to determine whether time to anakinra treatment influences the efficacy on systemic inflammation and HF events in patients with STEMI. Methods: This is a secondary analysis of the data from the three VCUART clinical trials, including adult patients with STEMI presenting within 12 hours of pain onset, enrolled within 12 hours of reperfusion and randomly assigned to anakinra or placebo for 14 days. We divided the cohort in two groups based on the median time from percutaneous coronary intervention (PCI) to investigational drug, and analyzed the effects of anakinra on the area-under-the-curve for C reactive protein (AUC-CRP) and on incidence of the composite endpoint of death or new onset HF. Results: We analyzed data from 139 patients: 84 (60%) treated with anakinra and 55 (40%) with placebo. The median time from PCI to investigational treatment was 271 [182-391] minutes. The AUC-CRP was significantly higher in patients receiving placebo versus anakinra both in those with from PCI to treatment &lt;271 min (222.6 [103.9-325.2] vs 78.4 [44.3-131.2], p&lt;0.001) and those with time from PCI to drug ≥271 min (235.2 [131.4-603.4] vs 75.5 [38.9-171.9, p&lt;0.001]. Anakinra significantly reduced the combined endpoint of death or new onset HF in patients with time from PCI to treatment &lt;271 min (5 [11%] vs 9 [36%], log-rank p value=0.014) as well as in patients with time from PCI to drug ≥271 min (2 [5%] vs 7 [23%], log-rank p value= 0.046). Conclusions: In patients with STEMI treated with anakinra within 12 hours of reperfusion, the therapeutic window of IL-1 blockade on the systemic inflammatory response and on HF events in reperfused STEMI appears to be stable for several hours.

The Diagnostic Value of Various Inflammatory Biomarkers for Diagnosing Periprosthetic Joint Infection is Gender-Specific.

ObjectivePrevious studies have suggested that the diagnostic biomarkers of periprosthetic joint infection (PJI) are largely influenced by gender. In the present study, we aimed to evaluate the diagnostic value of traditional inflammatory biomarkers, fibrinolytic biomarkers (fibrinogen and D-dimer), and C-reactive protein (CRP)/albumin for PJI in different genders.MethodsA single-center retrospective analysis was performed on revision total hip or knee arthroplasty between June 2013 to June 2021, and the study included 80 patients in the PJI group and 136 patients in the non-PJI group. PJI was diagnosed based on the International Consensus Meeting (ICM) in 2018. The levels of CRP, fibrinogen, erythrocyte sedimentation rate (ESR), D-dimer, and albumin count were determined. Receiver operating characteristic (ROC) curves and Youden’s index were used to evaluate the diagnostic ability of various biomarkers.ResultsThe levels of CRP, fibrinogen, D-dimer, ESR, and CRP/albumin were significantly higher in the PJI group (P < 0.001). In PJI of females, the predictive value of CRP was the highest among the five biomarkers, with the area under the curve (AUC) of 0.98. The optimal predictive cut-off for CRP was 8.86 mg/L, with a sensitivity and specificity of 90.2% and 95.7%, respectively. When combined with the other four biomarkers, the AUC of CRP was 0.98, 0.99, 0.98, and 0.99, respectively. In PJI of males, the predictive value of ESR was the highest among the five biomarkers, with an AUC of 0.92. The optimal predictive cut-off for ESR was 14.50 mm/h, with a sensitivity and specificity of 84.6% and 86.6%, respectively. When combined with the other four biomarkers, the AUC of ESR was 0.95, 0.94, 0.93, and 0.97, respectively.ConclusionCRP and ESR were excellent biomarkers for diagnosing PJI in female and male patients, respectively, and their combined use with CPR/albumin could provide higher diagnostic value in different genders.

Clinical utility of inflammatory biomarkers in COVID-19 in direct comparison to other respiratory infections-A prospective cohort study.

Inflammatory biomarkers are associated with severity of coronavirus disease 2019 (COVID-19). However, direct comparisons of their utility in COVID-19 versus other respiratory infections are largely missing. We aimed to investigate the prognostic utility of various inflammatory biomarkers in COVID-19 compared to patients with other respiratory infections. Patients presenting to the emergency department with symptoms suggestive of COVID-19 were prospectively enrolled. Levels of Interleukin-6 (IL-6), c-reactive protein (CRP), procalcitonin, ferritin, and leukocytes were compared between COVID-19, other viral respiratory infections, and bacterial pneumonia. Primary outcome was the need for hospitalisation, secondary outcome was the composite of intensive care unit (ICU) admission or death at 30 days. Among 514 patients with confirmed respiratory infections, 191 (37%) were diagnosed with COVID-19, 227 (44%) with another viral respiratory infection (viral controls), and 96 (19%) with bacterial pneumonia (bacterial controls). All inflammatory biomarkers differed significantly between diagnoses and were numerically higher in hospitalized patients, regardless of diagnoses. Discriminative accuracy for hospitalisation was highest for IL-6 and CRP in all three diagnoses (in COVID-19, area under the curve (AUC) for IL-6 0.899 [95%CI 0.850-0.948]; AUC for CRP 0.922 [95%CI 0.879-0.964]). Similarly, IL-6 and CRP ranged among the strongest predictors for ICU admission or death at 30 days in COVID-19 (AUC for IL-6 0.794 [95%CI 0.694-0.894]; AUC for CRP 0.807 [95%CI 0.721-0.893]) and both controls. Predictive values of inflammatory biomarkers were generally higher in COVID-19 than in controls. In patients with COVID-19 and other respiratory infections, inflammatory biomarkers harbour strong prognostic information, particularly IL-6 and CRP. Their routine use may support early management decisions.

Prediction of intrauterine inflammation in patients with preterm premature rupture of membranes at 28 to 34 weeks of gestation

Background: To analyze the influence of white blood cells (WBC), serum C-reactive protein (CRP), procalcitonin (PCT), and other risk factors on the prognosis of patients with preterm premature rupture of membranes (PPROM) from 28 to 34 weeks of gestation. Methods: We performed a retrospective study of 425 patients with PPROM from 28 to 34 weeks of gestation who delivered infants at Shandong Provincial Hospitals between January 1, 2013 and December 31, 2019. Risk factors for puerperal infection were analyzed using a logistic regression model. A receiver operating characteristic (ROC) curve was constructed, and the area under the curve (AUC) was estimated. Results: Of the 425 patients (mean ± SD age, 34.69 ± 5.55 years), 104 (24.47%) had chorioamnionitis. The CRP level (odds ratio [OR], 1.009; 95% Confidence Interval (CI), 1.003–1.014; P = 0.002), WBC count (OR, 1.170; 95% CI, 1.092–1.254; P &lt; 0.001) and gestational age (OR, 0.772; 95% CI, 0.648–0.921; P = 0.004) were risk factors of chorioamnionitis. Patients who did not undergo previous cesarean section had twice the risk of developing chorionic inflammation (P = 0.022). The cut-off value of CRP level for prediction of chorioamnionitis was 19.69 mg/L with a sensitivity of 65.4%, a specificity of 75.7%, a positive predictive value (PPV) of 46.58%, and a negative predictive value (NPV) of 90.24%. The cut-off value of WBC count was 12.99 × 109/L with a sensitivity of 62.4%, a specificity of 65.8%, a PPV of 36.65%, and an NPV of 84.61%. The cut-off value of PCT level was 0.054 ng/mL with a sensitivity of 81.0%, a specificity of 75.7%, a PPV of 32.08%, and an NPV of 90.67%. The AUC for CRP was 0.731. Conclusions: Study results suggested that CRP level (&lt;19.69 mg/L), WBC count (&lt;12.99 × 109/L) and PCT level (&lt;0.054 ng/mL) had good NPVs for chorioamnionitis, whereas their PPVs were low. The CRP level was found to have the most accurate prediction of chorioamnionitis among patients with PPROM from 28 to 34 weeks of gestation.

Diagnostic value of C-reactive protein and procalcitonin for postoperative pancreatic fistula following pancreatoduodenectomy: a systematic review and meta-analysis.

C-reactive protein (CRP) and procalcitonin (PCT) have recently been used to diagnose and screen for postoperative pancreatic fistula (POPF) following pancreatoduodenectomy (PD), but their reliability is still unclear. Our study aims to assess the efficacy of CRP and PCT in the diagnosis of POPF after PD. Electronic databases such as PubMed, Excerpta Medica (EMBASE), the Web of Science (WOS) and the China National Knowledge Infrastructure (CNKI) were used to search for studies and full-text articles that assessed the diagnostic efficacy of CRP and PCT for POPF. Review Manager 5.4 and STATA 14.0 were used to estimate the pooled diagnostic value of CRP and PCT. Sensitivity analyses and Deeks' funnel plot tests were conducted on the selected studies. Twenty studies that satisfied the established selection criteria were chosen. Both CRP and PCT were shown to be highly effective in diagnosing POPF, each with a high area under the curve (AUC). The AUC of CRP on postoperative day (POD) 4 had a value of 0.86, with a sensitivity and specificity of 0.85 and 0.69, respectively. The AUC of PCT on POD 5 had a value of 0.87, with a sensitivity and specificity of 0.84 and 0.74, respectively. Our research supports the hypothesis that CRP and PCT are valuable diagnostic tools for predicting POPF, especially given the CRP levels on POD 4 and PCT levels on POD 5. Limited by the small number of the studies analyzed herein, we recommend that more randomized controlled trials be performed to verify our conclusions.

Diagnostic value of platelet associated biomarkers in chronic periprosthetic joint infection

Objective: To evaluate the diagnostic value of platelet count(PC),PC to mean platelet volume(MPV) ratio(PC/MPV) and plateletcrit(PCT) in chronic periprosthetic joint infection(PJI). Method: The medical records of 159 patients who underwent hip or knee revisions at Department of Joint Surgery,Affiliated Hospital of Qingdao University from August 2013 to June 2019 were retrospectively reviewed. There were 51 patients(26 knees and 25 hips) in the PJI group,which included 28 males and 23 females,aged (68.0±11.8)years (range:32 to 84 years)with a body mass index(BMI)of (26.1±3.6) kg/m².There were 116 patients(19 knees and 97 hips) in the aseptic loosening(AL) group,including 67 males and 49 females,aged (70.3±8.9)years(range:49 to 89 years)with a BMI of (25.0±3.6)kg/m².The plasma C-reactive protein(CRP),erythrocyte sedimentation rate(ESR),PC,MPV,PC/MPV and PCT levels of the two groups were recorded and analyzed. Receiver operating characteristic curve was used to calculate the sensitivity and specificity of each biomarker,expect for MPV,and the diagnostic value of each biomarker was compared according to the area under the curve(AUC).Independent-sample t test or Mann-Whitney U test were used for comparison between groups. Result: Compared with AL group,AJI group had significantly higher levels of CRP,ESR,PC,PC/MPV and PCT(all P<0.05),but lower level of MPV (P<0.05).The AUCs for CRP,ESR,PC,PC/MPV and PCT were 0.820, 0.829, 0.689, 0.668 and 0.676,respectively. Based on the Youden index,the optimal predictive cutoff for CRP was 11.12 mg/L,with a sensitivity of 74.4% and a specificity of 87.1%.The optimal predictive cutoff for ESR was 17.60 mm/1 h,with a sensitivity of 81.4% and a specificity of 75.3%.The optimal predictive cutoff for PC was 243.00×109/L,with a sensitivity of 60.6% and a specificity of 71.8%.The optimal predictive cutoff for PC/MPV was 24.95,the sensitivity was 58.1% and the specificity was 74.1%.And the optimal predictive cutoff for PCT was 0.24%,with a sensitivity of 69.8% and a specificity of 63.5%. Conclusion: PC,PC to MPV ratio and PCT were of limited value to diagnose PJI.

Blood-based host biomarker diagnostics in active case finding for pulmonary tuberculosis: A diagnostic case-control study.

BackgroundThere is a need to identify scalable tuberculosis screening strategies among high burden populations. The WHO has identified a non-sputum-based triage test as a development priority.MethodsWe performed a diagnostic case-control study of point-of-care C-reactive protein (CRP) and Prototype-Xpert-MTB-Host-Response (Xpert-MTB-HR) assays in the context of a mass screening program for tuberculosis in two prisons in Brazil. All incarcerated individuals irrespective of symptoms were screened by sputum Xpert MTB/RIF and sputum culture. Among consecutive, Xpert MTB/RIF or culture-confirmed cases and Xpert MTB/RIF and culture-negative controls, CRP was quantified in serum by a point-of-care assay (iChroma-II) and a 3-gene expression score was quantified from whole blood using the Xpert-MTB-HR cartridge. We evaluated receiver operating characteristic area under the curve (AUC) and assessed specificity at 90% sensitivity and sensitivity at 70% specificity, consistent with WHO target product profile (TPP) benchmarks.FindingsTwo hundred controls (no TB) and 100 culture- or Xpert MTB/RIF-positive tuberculosis cases were included. Half of tuberculosis cases and 11% of controls reported any tuberculosis symptoms. AUC for CRP was 0·79 (95% CI: 0·73–0·84) and for Xpert-MTB-HR was 0·84 (95% CI: 0·79–0·89). At 90% sensitivity, Xpert-MTB-HR had significantly higher specificity (53·0%, 95% CI: 45·0–69·0%) than CRP (28·1%, 95% CI: 20·2–41·8%) (p = 0·003), both well below the TPP benchmark of 70%. Among individuals with medium or high sputum Xpert MTB/RIF semi-quantitative load, sensitivity (at 70% specificity) of CRP (90·3%, 95% CI: 74·2–98·0) and Xpert-MTB-HR (96·8%, 95% CI: 83·3–99·9%) was higher.InterpretationFor active case finding in this high tuberculosis-burden setting, CRP and Xpert-MTB-HR did not meet TPP benchmarks for a triage test. However, Xpert-MTB-HR was highly sensitive in detecting individuals with medium or high sputum bacillary burden.FundingNational Institutes of Health (R01 AI130058 and R01 AI149620) and Brazilian National Council for Scientific and Technological Development (CNPq-404182/2019-4).

Combined score of C-reactive protein level and neutrophil-to-lymphocyte ratio: A novel marker in distinguishing children with exacerbated asthma.

BackgroundBoth C-reactive protein (CRP) level and neutrophil-to-lymphocyte ratio (NLR) are commonly elevated in patients with asthma. It is necessary to develop a novel marker, the combined score of CRP level and NLR (C-NLR score) based on cutoff points of CRP and NLR, and apply it in asthma diagnosis. The aim of this study was to explore whether C-NLR could distinguish children with exacerbated asthma.MethodsChildren suffering from exacerbated asthma were regarded as the asthmatic group (n = 86), which was divided into three groups: mild (n = 54), moderate (n = 17), and severe (n = 15). The control group consisted of children without any allergic disease and infection (n = 38). To compare CRP level and NLR between the asthmatic group and control group, a receiver-operating characteristic curve was constructed to determine area under the curve (AUC) and optimal cutoff point. Thereafter, the C-NLR score was classified as follows: C-NLR score of 2 with an elevated CRP level and high NLR, a C-NLR score of 1 with one of these abnormalities, and a C-NLR score of 0 with a normal CRP level and low NLR. The C-NLR score was then compared among different asthma groups.ResultsIn the control group, the CRP level and NLR were 1.9 (0.5–2.6) mg/L and 1.01 (0.69–1.31), respectively. In the asthmatic group, the CRP level and NLR were 7.3 (3.2–14.2) mg/L and 3.08 (1.73–5.34), respectively, which were higher than those in the control group (p < 0.001 for CRP and p < 0.001 for NLR). The AUC of CRP was 0.86, and the optimal cutoff point was 3.6 mg/L. The AUC of NLR was 0.86, and the optimal cutoff point was 1.72. The AUC of the C-NLR score was 0.94, and the optimal cutoff point was 1.ConclusionsC-NLR, a novel inflammatory marker, was applied here for the exacerbated asthma for the first time. Our study has shown C-NLR is a promising marker to distinguish children with exacerbated asthma from healthy children.

Laparoscopic sleeve gastrectomy: A role of inflammatory markers in the early detection of gastric leak.

Setting:Laparoscopic sleeve gastrectomy (LSG) is gaining popularity as a bariatric option. Gastric leak (GL) is the most dreaded septic complication of LSG. Early detection and treatment of this complication may improve outcomes.Objectives:This study investigates biomarkers that might be useful to predict GL before its clinical presentation in patients who underwent LSG.Patients and Methods:This study, prospective observational, was carried out in 151 patients, who underwent LSG for morbid obesity between February 2014 and October 2019. Blood samples were collected before the operation and on post-operative days one, three and five to dose serum C-reactive protein (CRP), pro-calcitonin (PCT), fibrinogen, white blood cells (WBCs) count and neutrophil-to-lymphocyte ratio (NLR).Results:GL occurred in 6 patients (3.97%). According to the receiver operating characteristics curve, NLR detected leak with remarkably higher sensitivity (100%) and specificity (100%) than CRP, fibrinogen, WBC on all the days and higher than PCT in post-operative days 3 and 5. Moreover, the area under the curve (AUC) of NLR (AUC = 1) was higher than the AUC of CRP, fibrinogen, WBC on all the days and higher than PCT in post-operative days 3 and 5, suggesting important statistical significance.Conclusions:Because NLR and PCT detected GL with remarkably higher sensitivity and specificity than CRP, fibrinogen and WBC, these two markers seem to be more accurate for the early detection of this complication.

Clinical predictive efficacy of C-reactive protein for diagnosing infectious complications after gastric surgery.

Background:With the popularization of Enhanced Recovery After Surgery (ERAS), identifying patients with complications before discharging becomes important. This study aimed to explore the efficacy of C-reactive protein (CRP) in predicting infectious complications after gastrectomy.Methods:Patients with gastric cancer who underwent gastrectomy at Beijing Cancer Hospital from March 2017 to April 2018 were enrolled in the training set. Complications were prospectively registered. Receiver operating characteristic analysis was performed to assess the diagnostic accuracy of CRP via evaluating the area under the curve (AUC). Patients who had CRP tested on postoperative day (POD) 5 and accepted gastrectomy from April to December 2018 were included in the validation set to validate the cut-off value of CRP obtained from the training set.Results:A total of 350 patients were included (263 patients in the training set and 87 patients in the validation set). Out of these, 24 patients were diagnosed with infectious complications and 17 patients had anastomotic leakage in the training set. The CRP level on POD5 had superior diagnostic accuracy for infectious complications with an AUC of 0.81. The cut-off value of CRP on POD5 at 166.65 mg/L yielded 93% specificity and 97.2% negative predict value (NPV); For anastomotic leakage, the AUC of CRP on POD5 was 0.81. Using the cut-off value of CRP at 166.65 mg/L on POD5 achieved 92% specificity and 98.6% NPV. The optimal cut-off value (CRP 166.65 mg/L on POD5) was validated in the validation set. It achieved 97.5% specificity and 94.0% NPV for infectious complications, and 97.6% specificity and 96.4% NPV for anastomotic leakage.Conclusion:CRP is a reliable predictive marker for the diagnosis of inflammatory complications following gastric surgery. However, this study was based on preliminary data. The validity of this data needs confirmation by a larger number of cases.

Long‐Term Self‐Reported Cognitive Problems After Delirium in the Intensive Care Unit and the Effect of Systemic Inflammation

To describe the association between intensive care unit (ICU) delirium and self-reported cognitive problems in 1-year ICU survivors, and investigate whether this association was altered by exposure to systemic inflammation during ICU stay. Prospective cohort study. Dutch medical-surgical ICU. One-year ICU survivors, admitted to the ICU ≥48 hours. Self-reported cognitive problems were measured with the Cognitive Failures Questionnaire (CFQ). Cumulative exposure to systemic inflammation was based on all daily C-reactive protein (CRP) measurements during ICU stay, expressed as the area under the curve (AUC). Multivariable linear regression was conducted to evaluate the association between delirium and the CFQ. The effect of inflammation on the association between delirium and CFQ was assessed, comparing the effect estimate (B) of delirium and CFQ between models with and without inclusion of the AUC of CRP. Among 567 1-year ICU survivors, the CFQ was completed by 363 subjects. Subjects with multiple days of delirium during ICU stay reported more self-reported cognitive problems (Badj = 5.10, 95% CI 1.01-9.20), whereas a single day delirium was not associated with higher CFQ scores (Badj = -0.72, 95% CI -5.75 to 4.31). Including the AUC of CRP did not change the association between delirium and the CFQ (ratio for a single and multiple days were respectively: 1.00, 95%CI 0.59-1.44 and 0.86, 95% CI 0.47-1.16). Multiple days of delirium was associated with long-term self-reported cognitive problems. The cumulative exposure to systemic inflammation did not alter this association, suggesting that delirium in the context of little inflammation is also detrimental.

The Diagnostic Accuracy of Serum Procalcitonin for Bacteremia in Critically Ill Children.

Bacterial sepsis is frequently encountered in children admitted to the Pediatric Intensive Care Unit (PICU) and requires early recognition and treatment. Procalcitonin (PCT) is a serum biomarker with a high sensitivity to predict bacteremia in critically-ill adults. This study sought to evaluate the diagnostic accuracy of PCT for bacteremia in febrile children in the PICU. This retrospective observational study used data from children admitted to the PICU from October 2010 to October 2012. Patients up to 21 years of age were included if they had an abnormal temperature, serum PCT and blood culture assayed, and were not receiving empiric antibiotics at the time. There were 202 PCT values that met inclusion criteria. The prevalence of positive blood cultures was 13.2% (27 total positive blood cultures). The area under the curve (AUC) for PCT was 0.79 (95% CI, 0.70-0.89), the AUC for lactate was 0.76 (95% CI, 0.65-0.87), and the AUC for C-reactive protein was 0.68 (95% CI, 0.57-0.80). The optimal threshold of PCT for accuracy was determined to be 2 ng/mL (sensitivity = 69.2%, specificity = 74.4%, positive predictive value = 28.6%, negative predictive value = 94.2%). The combination of an abnormal lactate (> 2.0mmol/L) increased the specificity of PCT for diagnosing bacteremia. PCT has a good diagnostic accuracy to rule-out bacteremia in critically-ill, febrile children. The combination of PCT and an abnormal lactate value increases the specificity and may improve the ability to diagnose bacteremia.

Usefulness of several biomarkers in the management of septic patients: C-reactive protein, procalcitonin, presepsin and mid-regional pro-adrenomedullin.

Our objective is to analyze whether the combination of C-reactive protein (CRP), procalcitonin (PCT), presepsin or SCD14-ST and mid-regional pro-adrenomedullin (MR-proADM) measured in the first 24 h from ICU admission allowing a better management of septic patients (diagnostic and prognostic) both in severe sepsis (SS) and septic shock (SSh). Cohort study of 388 patients admitted in the ICU during 12 months of whom 142 were controls. Biomarkers were measured through immunoluminometric assays in samples of serum or plasma within the first 24 h after admission. Data were evaluated with non-parametric statistics bivariant, ROC curve analysis for diagnostic evaluation and multivariate analyses for survival analysis. In the analyzed cohort, 61.8% of patients were males, mean age: 63 years range (18-90) and 67.8% in controls mean age: 63 years, range (39-91). PCT showed the highest area under the curve (AUC) (0.989) as compared with the rest of biomarkers (p<0.01). PCT also enabled the difference between Gram-positive or Gram-negative bacteria to be determined. The AUCs for CRP (0.922) and presepsin (0.948) showed a similar diagnostic value. In cases of SSh, the AUC of presepsin experienced a noticeable increase (p<0.0001). MR-proADM showed a better prognostic value (p=0.00022) particularly in cases of SSh (p=0.00001) increasing along with the APACHE-II score. PCT, MR-proADM and presepsin are complementary markers that could be of great help in the management of septic patients when they are measured in the first 24 h after ICU admission.

Disease Factors in Early Rheumatoid Arthritis Are Associated with Differential Risks for Cardiovascular Events and Mortality Depending on Age at Onset: A 10-year Observational Cohort Study

To investigate, within the first 2 years of diagnosis with rheumatoid arthritis (RA), associations between disease-related measures and cardiovascular disease (CVD) and mortality in patients with RA onset before and after 65 years of age. The study population (n = 741; 67.5% women) was derived from the Better Anti-Rheumatic Pharmaco Therapy (BARFOT) early RA cohort, recruited 1993-1999. The mean age was 55 years (SD 14.7). The outcomes were incident CVD events and all-cause mortality until 2010. Area under the curve (AUC) for disease measures at inclusion, 1 and 2 years, and decrease in measures after 1 year were calculated. In all, 177 CVD events and 151 deaths occurred over 10 years of observation. In adjusted Cox regression analyses, seropositivity for rheumatoid factor (RF) or anticitrullinated protein antibodies (ACPA); white blood (cell) count at diagnosis; and AUC of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and visual analog scale (VAS)-pain were associated with higher CVD risk among patients with disease onset before 65 years of age. Among patients with disease onset after 65 years, larger decreases in CRP, ESR, health assessment questionnaire (HAQ), and use of methotrexate decreased CVD risk, whereas use of glucocorticoids heightened CVD risk. AUC of CRP, ESR, HAQ, and HAQ after 2 years was related to risk of death in both age groups. Seropositivity and AUC for VAS-pain in the younger group and use of glucocorticoids in the elderly were associated with poorer survival. Early treatment of RA may improve longterm outcomes. Presence of RF or ACPA associates with CVD and mortality among RA patients with disease onset before 65 years. Age stratification may improve evaluation of risk for CVD and mortality in early RA.

Procalcitonin and Conventional Markers of Inflammation in Peritoneal Dialysis Patients and Peritonitis

To determine the significance of a newly described marker of inflammation procalcitonin (PCT), and to investigate its relationship to conventional markers of inflammation, such as C-reactive protein (CRP), fibrinogen, and erythrocyte sedimentation rate (ESR), in patients on peritoneal dialysis (PD) and with peritonitis. A prospective, observational clinical study. The Nephrology Division of a University-affiliated teaching hospital. 51 consecutive patients on PD were included in the study. Of this number, 16 developed peritonitis during the observational period. Baseline PCT, CRP, and fibrinogen concentrations and ESR of 51 PD patients were determined at a time point (TB) prior to any evidence of infection. These results were compared with laboratory values from 74 hemodialysis patients and 34 nonuremic control subjects. All PD patients then were followed prospectively for evidence of peritonitis. In addition to routine blood tests, including hemoglobin and leukocyte count, and routine biochemical tests, blood samples were taken to measure PCT, CRP, and fibrinogen concentrations and ESR at the time (T0) when patients first were diagnosed with PD peritonitis and also on the 4th (T4) and the 14th (T14) days after treatment for peritonitis was initiated. PCT was assayed by immunoluminometry. No significant difference was observed between baseline median serum PCT concentrations in PD and hemodialysis patients; however, in both groups, baseline median PCT concentrations were significantly higher than those of nonuremic controls (p < 0.05). The 16 patients on PD who developed peritonitis had 21 PD peritonitis episodes during the study period. The increased PCT concentration observed at T0 in PD peritonitis episodes decreased with therapy, and this change was statistically significant (p < 0.05). In a receiver operating characteristic curve analysis for peritonitis, the area under the curve (AUC) for PCT was 0.80, which was significantly lower than the AUC for CRP and greater than the AUCs for fibrinogen and ESR. The sensitivity of PCT for peritonitis was lower than the sensitivity of conventional markers of inflammation; however, the specificity of PCT was higher. Median serum PCT concentration in PD patients was significantly higher than in nonuremic controls but not hemodialysis patients. Serum PCT concentrations may serve as a useful adjunct to traditional markers of inflammation in detecting and monitoring inflammation and peritonitis in PD patients.