Blood C-reactive Protein Concentrations Research Articles

A cohort study of the multipollutant effects of PM2.5, NO2, and O3 on C-reactive protein levels during pregnancy.

PM2.5, NO2, and O3 contribute to the development of adverse pregnancy complications. While studies have investigated the independent effects of these exposures, literature on their combined effects is limited. Our objective was to study the multipollutant effects of PM2.5, NO2, and O3 on maternal systemic C-reactive protein (CRP) levels. We used data from 1170 pregnant women enrolled in the Maternal-Infant Research on Environmental Chemicals Study (MIREC) study in Canada. Air pollution exposures were assigned to each participant based on residential location. CRP was measured in third-trimester blood samples. We fit multipollutant linear regression models and evaluated the effects of air pollutant mixtures (14-day averages) using repeated-holdout Weighted Quantile Sum (WQS) regression and by calculating the Air Quality Health Index (AQHI). In multipollutant models adjusting for NO2, O3, and green space, each interquartile range (IQR) increase in 14-day average PM2.5 (IQR: 6.9 µg/m3) was associated with 27.1% (95% confidence interval [CI] = 6.2, 50.7) higher CRP. In air pollution mixture models adjusting for green space, each IQR increase in AQHI was associated with 37.7% (95% CI = 13.9, 66.5) higher CRP; and an IQR increase in the WQS index was associated with 78.6% (95% CI = 29.7, 146.0) higher CRP. PM2.5 has the strongest relationship of the individual pollutants examined with maternal blood CRP concentrations. Mixtures incorporating all three pollutants, assessed using the AQHI and WQS index, showed stronger relationships with CRP compared with individual pollutants and illustrate the importance of conducting multipollutant analyses.

C-reactive protein concentration has limited value in the diagnosis of meningoencephalitis of unknown origin in dogs.

To evaluate blood and cerebrospinal fluid (CSF) concentrations of C-reactive protein (CRP) in dogs with meningoencephalitis of unknown origin (MUO); to evaluate whether blood CRP concentration is associated with epidemiological, clinicopathologic, and MRI findings; and to investigate blood CRP predictive power in survival. 30 client-owned dogs with MUO, 15 client-owned dogs with steroid-responsive meningitis arteritis (SRMA; positive control group), and 15 healthy dogs (negative control group). Blood CRP concentration was measured in each group, while it was performed in CSF only in the MUO and SRMA groups. The analysis of epidemiological data included breed, age, sex, duration of clinical signs, and history of seizures. Blinded analysis of MRI was performed based on a classification grid, and traditional CSF analysis parameters were assessed. The predictive power of blood CRP concentration regarding survival at 6 months was investigated. Of the 30 dogs with MUO, 9 (30%) had an increased CRP concentration in blood, and 3 (10%) showed a measurable CRP in CSF. Median blood CRP concentration in dogs with MUO was 0.1 mg/L (range, 0.1 to 102 mg/L), which was not statistically different from the healthy dog group but significantly lower than the SRMA control group. Only the duration of clinical signs was positively associated with an increased blood CRP level. Blood CRP concentration was not associated with survival at 6 months. Blood CRP concentration is of limited value for the diagnosis and prognosis of dogs with MUO. Chronicity of the disease may be associated with an increased concentration of blood CRP.

Predictors of an unfavorable course of COVID-19

The aim of the study was to identify the features of the unfavorable clinical course of a new coronavirus infection.Material and methods. The analysis of clinical data, laboratory results and comorbidity of 168 patients with a confirmed diagnosis of a new coronavirus infection aged 65,0 [57,0; 74,0] years was carried out. Two groups of patients were distinguished – 126 persons with a moderate course and with clinical recovery in the outcome of the disease and 42 persons with a severe course and a fatal outcome of the disease. Transnosological polymorbidity was assessed by the average number of nosologies corresponding to the three-digit ICD-10 rubricification, transsystemic – by the number of affected systems. Hemogram parameters, blood content of C-reactive protein, creatinine, urea, glucose, prothrombin index, international normalized ratio, activated partial thromboplastin time, platelet count, D-dimer concentration were estimated.Results. In the group of patients with fatal outcomes, compared to patients with recovery, there were statistically significantly higher indices of transnosological and transsystemic polymorbidity (1.5 and 2 times, respectively), they were more likely to have ischaemic heart disease, myocardial infarction, transient ischemic attack in anamnesis, atrial fibrillation, chronic heart failure; blood concentration of C-reactive protein, fasting glucose, urea, D-dimer in the blood serum was higher, the number of thrombocytes was less.Conclusions. A high degree of transnosological and transsystemic polymorbidity, a history of myocardial infarction and transient ischemic attack, comorbid chronic heart failure, atrial fibrillation, an increase in D-dimer, CRP content, and a decrease in platelet number are predictors of severe course and the lethal outcome of COVID-19.

Some immunological biomarkers of the severity of neonatal sepsis in newborns depending on different inflammatory response

Background. Objective: to study the diagnostic value and indicators of clinical and epidemiological risk of some immunological biomarkers as indicators of the severity of the clinical course of neonatal sepsis in order to improve treatment outcomes in newborns with neonatal sepsis with an alternative serum content of C-reactive protein. Materials and methods. A comprehensive clinical and paraclinical examination of 56 children with neonatal sepsis was conducted. The severity of neonatal sepsis was determined using the constellation-diagnostic scales of multiple organ dysfunction such as SNAPII, SNAPРЕII, PELOD, SOFA, nSOFA, PEMOD, SCRIB, NEOMOD. The comprehensive immunological examination with evaluation of immunoglobulin A, G, M, C-reactive protein, presepsin, procalcitonin, interleukins (IL) 6, 8, 10 content in blood serum was conducted in all newborns. Two clinical groups were formed. The clinical group I included 25 infants with neonatal sepsis with a serum level of C-reactive protein < 20 mg/l (boys — 52.0 %, city residents — 80.0 %, the average content of C-reactive protein — 8.80 ± 0.41 mg/l). The clinical group II was formed by 31 children with neonatal sepsis and C-reactive protein blood concentration > 20 mg/l (with 62.8 % of boys, p > 0.05; 57.1 % of city residents, p > 0.05; the average content of C-reactive protein — 29.70 ± 1.89 mg/l, р < 0.05). According to the main clinical characteristics, the observation groups were comparable. Results. The conducted studies showed that the severity of the clinical course of neonatal sepsis, determined using the constellation-diagnostic scales of multiple organ dysfunction (SNAPII, SNAPРЕII, PELOD, SOFA, nSOFA, PEMOD, SCRIB, NEOMOD), did not reveal any significant differences in the comparison groups. It was found that in newborns with a C-reactive protein content < 20 mg/l, compared to representatives of the clinical group II, the concentration of IL-6, IL-8 and IL-10 was lower by 1.7, 1.5 and 1.8 times, respectively. Thus, patients of the group II had the risk of increasing serum content of IL-6 > 31.4 pg/ml (relative risk (RR) 1.7 (95% confidence interval (CI): 1.3–2.2) with an odds ratio (OR) 2.8 (95% CI: 1.6–5.1)), IL-10 > 18 pg/ml (RR 1.7 (95% CI: 1.1–2.4) with an OR 2.9 (95% CI: 1.6–5.3)), and IL-8 > 24.0 pg/ml (RR 1.9 (95% CI: 1.2–3.1) with an OR 4.7 (95% CI: 2.5–8.8)). Among the studied immunological biomarkers, the concentration of presepsin > 1,000 ng/ml was accompanied by the best indicators of the clinical and epidemiological risk of severe sepsis according to the constellation-diagnostic scales of multiple organ dysfunction (odds ratio 4.3–6.0, relative risk 2.3–2.5, attributable risk 32.0–42.0 %). Conclusions. Elevated content of some markers of neonatal sepsis (presepsin, procalcitonin) and interleukins (IL-6, IL-8) can be considered a biomarker of a severe course of neonatal sepsis with probable development of multiple organ dysfunction.

C- REACTIVE PROTEIN LEVELS AMONG COVID-19 POSITIVE CASES PRESENTING IN GULAB DEVI HOSPITAL LAHORE: A DESCRIPTIVE CROSS-SECTIONAL STUDY

Background & Objectives: Severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) is a highly infectious virus associated with the development of COVID 19. Lack of valid biomarkers makes it difficult to predict disease severity. C-reactive protein (CRP) is an acute phase inflammatory marker that which may predict COVID-19 infection and its severity. The aim of this study was to describe the CRP levels in COVID- 19 positive cases presenting in Gulab Devi hospital Lahore.
 Methods: In this cross sectional study conducted in Gulab Devi Hospital Lahore for six month, 100 COVID- 19 positive cases were selected using convenient sampling technique. About 3 ml of venous blood was drawn for qualitative and semi-quantitative titration analyses to determine CRP concentration in blood. Descriptive analysis was performed using SPSS version-26 to describe the levels of CRP in relation to clinical features and disease severity.
 Results: CRP levels were elevated above normal range in 93% COVID-19 positive cases. Patients with severe infection had high levels of CRP (>6mg/L, range: 12-96 mg/L), mildly infected patients had moderate values of CRP and recovering patients of COVID-19 showed lowest value of CRP (<3mg/L ).
 Conclusion: The serum CRP level was substantially higher in COVID-19 positive cases in this study. CRP is an inexpensive, rapid test available to physicians for early detection of COVID-19 severity. Determining CRP levels can also help physicians to identify patients at higher risk of mortality and complications.

A prognostic baseline blood biomarker and tumor growth kinetics integrated model in paclitaxel/platinum treated advanced non-small cell lung cancer patients.

Paclitaxel/platinum chemotherapy, the backbone of standard first-line treatment of advanced non-small cell lung cancer (NSCLC), exhibits high interpatient variability in treatment response and high toxicity burden. Baseline blood biomarker concentrations and tumor size (sum of diameters) at week 8 relative to baseline (RS8) are widely investigated prognostic factors. However, joint analysis of data on demographic/clinical characteristics, blood biomarker levels, and chemotherapy exposure-driven early tumor response for improved prediction of overall survival (OS) is clinically not established. We developed a Weibull time-to-event model to predict OS, leveraging data from 365 patients receiving paclitaxel/platinum combination chemotherapyonceeverythreeweeks for ≤six cycles. A developed tumor growth inhibition model, combining linear tumor growth and first-order paclitaxel area under the concentration-time curve-induced tumor decay, was used to derive individual RS8. The median model-derived RS8 in all patients was a 20.0% tumor size reduction (rangefrom -78% to +15%). Whereas baseline carcinoembryonic antigen, cytokeratin fragments, and thyroid stimulating hormone levels were not significantly associated with OS in a subset of 221 patients, and lactate dehydrogenase, interleukin-6 and neutrophil-to-lymphocyte ratio levels were significant only in univariate analyses (p value < 0.05); C-reactive protein (CRP) in combination with RS8 most significantly affected OS (p value < 0.01). Compared to the median population OS of 11.3months, OS was 128% longer at the 5th percentile levels of both covariates and 60% shorter at their 95th percentiles levels. The combined paclitaxel exposure-driven RS8 and baseline blood CRP concentrations enables early individual prognostic predictions for different paclitaxel dosing regimens, forming the basis for treatment decision and optimizing paclitaxel/platinum-based advanced NSCLC chemotherapy.

Eu-Chelate Polystyrene Microsphere-Based Lateral Flow Immunoassay Platform for hs-CRP Detection.

Inflammation caused by viral or bacterial infection is a major threat to human health globally. Blood C-reactive protein (CRP) has been proven to be a sensitive indicator for the occurrence and development of inflammation. Furthermore, a tiny change of blood CRP concentration may portend chronic diseases; therefore, high-sensitivity CRP (hs-CRP) detection in a quantitative, rapid, user-friendly, and low-cost manner is highly demanded. In this paper, we developed a europium-chelate polystyrene microsphere (EuPSM)-based lateral flow immunoassay (LFIA) integrating with a benchtop fluorescence analyzer for hs-CRP detection. The optimization of the EuPSM-based LFIA was implemented through adjusting the antibody density on EuPSM from 100% to 60% of the saturated density. Finally, the limit of detection of 0.76 pg/mL and detection range of 0.025-250 ng/mL were obtained. Moreover, the clinical application capability of the proposed platform was validated through detecting CRP in clinical serum samples, showing high consistency with the results obtained from the clinical standard method. Hence, the proposed EuPSM-based LFIA has been verified to be well suitable for hs-CRP detection, while also showing great applicability for sensitively and rapidly detecting other biomarkers.

Sustainability of C-Reactive Protein Apheresis in Acute Myocardial Infarction-Results from a Supplementary Data Analysis of the Exploratory C-Reactive Protein in Acute Myocardial Infarction-1 Study.

In the multicenter, non-randomized, exploratory C-reactive protein (CRP) Apheresis in Myocardial Infarction (CAMI-1) study, CRP apheresis after ST-Elevation Myocardial Infarction (STEMI) significantly decreased blood CRP concentrations in humans. Cardiac damage was assessed by Cardiac Magnetic Resonance (CMR1) 3-9 d after onset of STEMI symptoms and quantified by myocardial infarct size (IS; %), left ventricular ejection fraction (LVEF; %), circumferential strain (CS) and longitudinal strain (LS). Compared with the control group (n = 34), cardiac damage was significantly lower in the apheresis group (n = 32). These findings suggested improved wound healing due to CRP apheresis already within few days after the STEMI event. In the current supplementary data analysis of CAMI-1, we have tested by a follow-up CMR (CMR2) after an average of 88 (65-177) d whether the effect of CRP apheresis is clinically maintained. After this time period, wound healing in STEMI is considered complete. Whereas patients with low CRP production and a CRP gradient cut off of &lt;0.6 mg/L/h in the hours after STEMI (9 of 32 patients in the CRP apheresis group) did not significantly benefit from CRP apheresis in CMR2, patients with high CRP production and a CRP gradient cut off of &gt;0.6 mg/L/h (23 of 32 patients in the CRP apheresis group) showed significant treatment benefit. In the latter patients, CMR2 revealed a lower IS (-5.4%; p = 0.05), a better LVEF (+6.4%; p = 0.03), and an improved CS (-6.1%; p = 0.005). No significant improvement, however, was observed for LS (-2.9%; p = 0.1). These data suggest a sustained positive effect of CRP apheresis on heart physiology in STEMI patients with high CRP production well beyond the period of its application. The data demonstrate the sustainability of the CRP removal from plasma which is associated with less scar tissue.

Reduction of blood C-reactive protein concentration complements the resolution of sputum bacillary load in patients on anti-tuberculosis therapy.

BackgroundTuberculosis (TB) is a difficult-to-treat disease requiring the combination of four antibiotics for a minimum of 6 months. Rapid and quantitative biomarkers to monitor treatment response are urgently needed for individual patient management and clinical trials. C-reactive protein (CRP) is often used clinically as a rapid marker of inflammation caused by infection. We assessed the relationship of TB bacillary load and CRP as biomarkers of treatment response.MethodsXpert MTB/RIF-confirmed pulmonary TB cases were enrolled for treatment response assessment in Mozambique. Treatment response was measured using the Tuberculosis Molecular Bacterial Load Assay (TB-MBLA) in comparison with standard-of-care Mycobacterium Growth Indicator Tube (MGIT) culture at baseline and at weeks 1, 2, 4, 8, 12, 17, and 26 of treatment. Blood CRP concentration was measured at baseline, week 8, and week 26. Treatment response was defined as increase in MGIT culture time to positivity (TTP), and reduction in TB-MBLA-measured bacillary load and blood CRP concentration.ResultsOut of the 81 screened presumptive TB cases, 69 were enrolled for 6-month treatment follow-up resulting in 94% treatment completion rate. Four participants did not complete TB treatment and 22 participants had missing CRP or TB-MBLA results and were excluded from TB-MBLA-CRP analysis. The remaining 43 participants—median age, 31 years old [interquartile range (IQR): 18–56]; 70% (30/43) male; and 70% (30/43) infected with HIV—were considered for analysis. Culture TTP and bacillary load were inversely correlated, Spearman’s r = −0.67, p < 0.0001. Resolution of sputum bacillary load concurred with reduction of blood CRP, r = 0.70, p < 0.0001. At baseline, bacillary load had a median (IQR) of 6.4 (5.5–7.2), which reduced to 2.4 (0.0–2.9) and 0.0 (0.0–0.0) log10 CFU/ml at months 2 and 6 of treatment, respectively. Correspondingly, blood CRP reduced from 1.9 (1.6–2.1) at baseline to 1.3 (0.9–1.7) and 0.4 (0.1–0.8) log10 mg/dl at months 2 and 6 of treatment, respectively. CRP reduction trialed bacteriological resolution at a rate of −0.06 log10 mg/dl compared to a bacillary load of 0.23 log10 CFU/ml per week. Consequently, 14 (33%) and 37 (88%) patients had reduced CRP to normal concentration and bacillary load to zero by the end of treatment, respectively. Pre-treatment CRP concentration and bacillary load, and resolution during treatment were slightly lower in HIV co-infected patients but not significantly different from HIV-uninfected TB patients.ConclusionTB-MBLA-measured bacillary load and blood CRP complement each other in response to anti-TB therapy. Slow CRP reduction probably reflects residual TB bacilli in the lung not expectorated in sputum. Combining both measures can improve the accuracy of these biomarkers for monitoring TB treatment response and shorten turnaround time since the results of both assays could be available in 24 h.

Community-acquired bacterial meningitis in patients of 80 years and older.

BackgroundAdvanced age is a risk factor for unfavorable outcome in community‐acquired bacterial meningitis, but clinical characteristics and outcome in meningitis patients of 80 years or older have not been defined.MethodsWe compared clinical characteristics and outcome of community‐acquired bacterial meningitis patients aged 80 years or older and adults under 80 years old within a prospective nationwide cohort study.ResultsOut of 2140 episodes identified between March 2006 and July 2018, 149 occurred in patients aged 80 years or older (7%). Common predisposing factors other than age were diabetes mellitus (25 of 148 [17%]), otitis or sinusitis (30 of 136 [22%]), and pneumonia (23 of 141 [16%]). The triad of fever, neck stiffness and altered consciousness was present in 60 of 139 (43%). The most common causative pathogen was Streptococcus pneumoniae (99 of 149 [66%]). Atypical causative pathogens, such as Listeria monocytogenes, Staphylococcus aureus, and Escherichia coli, occurred more often compared to younger patients (49 of 149 [33%] vs 362 of 1991 [18%]; p < 0.001). Patients of 80 years and older had high case fatality rate (75 of 149 [50%]), but 45 of 149 (30%) had a favorable outcome. Characteristics associated with an unfavorable outcome were absence of otitis or sinusitis, presence of aphasia, mono‐ or hemiparesis, a lower score on the Glasgow Coma Scale, a higher heart rate, a higher blood C‐reactive protein concentration and CSF leukocytes <100 per mm3.ConclusionsBacterial meningitis in patients of 80 years of older is associated with high rates of unfavorable outcome and death. Atypical causative pathogens such as L. monocytogenes, S. aureus, and E. coli occur commonly and should be considered when starting empirical antimicrobial therapy in this age group.

Contribution of inflammation to heart failure development in human immunodeficiency virus-infected patients

Aim. To determine the peculiarities of heart failure (HF) development in human immunodeficiency virus (HIV)-infected patients, depending on the blood concentration of C-reactive protein (CRP).Material and methods. This cross-sectional screening clinical trial included 100 patients hospitalized with HIV infection and a history of HF for 28 months. The patients were divided into 2 groups depending on blood CRP concentration. The cut-off point was CRP of 15 mg/l. The first group included 37 HIV-infected patients with HF and blood CRP &lt;15 mg/l, while the second group — 63 HIV-infected patients with HF and CRP concentration ≥15 mg/l. The inclusion criteria were HIV infection and prior HF, stable medical state, taking into account the underlying disease that required hospitalization. The study did not include patients with acute cardiovascular diseases within prior 3 months, acute decompensated and acute heart failure, cancer, infectious diseases, conditions that required surgical intervention. N-terminal pro-brain natriuretic peptide (NT-proBNP) was determined in all patients.Results. Correlation analysis revealed a strong inverse relationship between the blood concentrations of NT-proBNP and CRP (r=-0,639; p&lt;0,005). A ROC curve revealed the most optimal cut-off threshold of 9,8 mg/l (AUC=0,796, p&lt;0,05), which ensures sensitivity of 92,9% (p&lt;0,05) and specificity of 57,6% (p&lt;0,05). The odds ratio (OR) of an increase in NT-proBNP &gt;450 pg/ml, and hence the risk of acute decompensated HF in the presence of a CRP concentration of 1-9,8 mg/l in HIV-infected patients with HF was 44,73 (95% CI=8,62;311,10), while relative risk (RR) — 18,73 (95% CI=4,94;112,94). In the presence of in hospital inflammatory diseases and CRP ≥15 mg/l in HIV-infected patients and prior HF, the RR of acute decompensated HF is reduced by 88% (RR=0,12, 95% CI=0,03-0,33).Conclusion. CRP values from 1 to 9,8 mg/l in HIV-infected patients with HF are predictors of its severity, characterized by a higher incidence of HF with reduced ejection fraction, diastolic dysfunction and left ventricular hypertrophy without significant differences with patients who have CRP &gt;9,8 mg/l. CRP concentration &gt;9,8 mg/l in HIV-infected patients and prior HF indicates the development of an inflammatory process, and not a worsening of the HF course.

Association Between Genetic Predictors for C-Reactive Protein and Venous Thromboembolism With Severe Adverse Coronavirus Disease 2019 Outcomes.

Retrospective cohort study. U.K. Biobank. U.K. Biobank participants with European ancestry who were recorded to have a positive polymerase chain reaction test result for severe acute respiratory syndrome coronavirus 2 between March 16, 2020, and August 14, 2020. Not applicable. We constructed separate genetic risk scores for C-reactive protein and venous thromboembolism consisting of 56 and 37 genetic variants that have been significantly associated with venous thromboembolism and C-reactive protein, respectively. Among 1,126 individuals who were diagnosed with coronavirus disease 2019, 48% had a coronavirus disease 2019-related hospitalization, 16% received critical care support, 10% had critical respiratory support, and 21% died from coronavirus disease 2019. Genetic predisposition to high C-reactive protein concentrations was marginally associated with a lower risk of death from coronavirus disease 2019 (odds ratio, 0.85; 95% CI, 0.73-1.00; p = 0.05). No other associations were significant. Our results do not support associations between polygenic risk for elevated blood C-reactive protein concentrations or venous thromboembolism and severe coronavirus disease 2019 health outcomes. Thus, considering genetic predisposition associated with C-reactive protein concentrations or venous thromboembolism risk is not meaningful for predicting severe coronavirus disease 2019 health outcomes.

Effects of resistant starch supplementation on oxidative stress and inflammation biomarkers: A systematic review and meta-analysis of randomized controlled trials.

Animal experiments showed that resistant starch (RS) had an antioxidant and antiinflammatory effect. However, clinical studies showed both insignificant and significant effects of RS on inflammation and oxidative stress. The purpose of this work is to conduct a systematic review and meta-analysis of previous randomized controlled trials (RCTs) to investigate these effects. A systematic literature search was conducted on Web of Science, Scopus, PubMed and Cochrane electronic databases, which included studies from the earliest date of the database to September 2021. Key inclusion criteria were: RCTs; reporting at least one inflammatory or oxidative stress biomarker as endpoint; more than seven day intervention. Key exclusion criteria were: using a mixture of RS and other functional food ingredients as intervention substance; inappropriate controls. A total of 16 RCTs including 706 subjects were included. RS supplementation significantly improved total antioxidant capacity [standard mean difference (SMD) (95% CI): 2.64 (0.34, 4.94), p=0.03], and significantly reduced blood malondialdehyde concentration [SMD (95% CI): -0.55 (- 0.94, -0.17), p=0.01]. RS supplementation significantly reduced blood C-reactive protein concentration in type 2 diabetes mellitus (T2DM) patients [SMD (95% CI): -0.35 (-0.65, -0.05), p=0.02]. RS consumption significantly reduced blood interlukin-6 and tumor necrosis factor- concentration if removing one distinct trial. RS supplementation may significantly reduce a few oxidative-stress and inflammation biomarkers such as malondialdehyde and C-reactive protein, particularly in T2DM patients. Future work should investigate the optimal dosage of RS supplementation for modulating oxidative stress and inflammation biomarkers related to T2DM.

Does C-reactive protein predict time to recovery and benefit from oseltamivir treatment in primary care patients with influenza-like illness? A randomized controlled trial secondary analysis

Objective Recovery time and treatment effect of oseltamivir in influenza-like illness (ILI) differs between patient groups. A point-of-care test to better predict ILI duration and identify patients who are most likely to benefit from oseltamivir treatment would aid prescribing decisions in primary care. This study aimed to investigate whether a C-reactive protein (CRP) concentration of ≥30 mg/L can predict (1) ILI disease duration, and (2) which patients are most likely to benefit from oseltamivir treatment. Design Secondary analysis of randomized controlled trial data. Setting Primary care in Lithuania, Sweden and Norway during three consecutive influenza seasons 2016–2018. Subjects A total of 277 ILI patients aged one year or older and symptom duration of ≤72 h. Main outcome measures Capillary blood CRP concentration at baseline, and ILI recovery time defined as having ‘returned to usual daily activity’ with residual symptoms minimally interfering. Results At baseline, 20% (55/277) had CRP concentrations ≥30mg/L (range 0–210). CRP concentration ≥30 mg/L was not associated with recovery time (adjusted hazards ratio (HR) 0.80: 95% CI 0.50–1.3; p = 0.33). Interaction analysis of CRP concentration ≥30 mg/L and oseltamivir treatment did not identify which patients benefit more from oseltamivir treatment (adjusted HR 0.69: 95% CI 0.37–1.3; p = 0.23). Conclusion There was no association between CRP concentration of ≥30 mg/L and recovery time from ILI. Furthermore, CRP could not predict which ILI patients benefit more from oseltamivir treatment. Hence, we do not recommend CRP testing for predicting ILI recovery time or identifying patients who will receive particular benefit from oseltamivir treatment. Key Points Predicting disease course of influenza-like illness (ILI), and identifying which patients benefit from oseltamivir treatment is a challenge for physicians. • There was no association between CRP concentration at baseline and recovery time in patients consulting with ILI in primary care. • There was no association between CRP concentration at baseline and benefit from oseltamivir treatment. • We, therefore, do not recommend CRP testing for predicting recovery time or in decision-making concerning oseltamivir prescribing in ILI patients.

Effect of Canakinumab vs Placebo on Survival Without Invasive Mechanical Ventilation in Patients Hospitalized With Severe COVID-19

Effective treatments for patients with severe COVID-19 are needed. To evaluate the efficacy of canakinumab, an anti-interleukin-1β antibody, in patients hospitalized with severe COVID-19. This randomized, double-blind, placebo-controlled phase 3 trial was conducted at 39 hospitals in Europe and the United States. A total of 454 hospitalized patients with COVID-19 pneumonia, hypoxia (not requiring invasive mechanical ventilation [IMV]), and systemic hyperinflammation defined by increased blood concentrations of C-reactive protein or ferritin were enrolled between April 30 and August 17, 2020, with the last assessment of the primary end point on September 22, 2020. Patients were randomly assigned 1:1 to receive a single intravenous infusion of canakinumab (450 mg for body weight of 40-<60 kg, 600 mg for 60-80 kg, and 750 mg for >80 kg; n = 227) or placebo (n = 227). The primary outcome was survival without IMV from day 3 to day 29. Secondary outcomes were COVID-19-related mortality, measurements of biomarkers of systemic hyperinflammation, and safety evaluations. Among 454 patients who were randomized (median age, 59 years; 187 women [41.2%]), 417 (91.9%) completed day 29 of the trial. Between days 3 and 29, 198 of 223 patients (88.8%) survived without requiring IMV in the canakinumab group and 191 of 223 (85.7%) in the placebo group, with a rate difference of 3.1% (95% CI, -3.1% to 9.3%) and an odds ratio of 1.39 (95% CI, 0.76 to 2.54; P = .29). COVID-19-related mortality occurred in 11 of 223 patients (4.9%) in the canakinumab group vs 16 of 222 (7.2%) in the placebo group, with a rate difference of -2.3% (95% CI, -6.7% to 2.2%) and an odds ratio of 0.67 (95% CI, 0.30 to 1.50). Serious adverse events were observed in 36 of 225 patients (16%) treated with canakinumab vs 46 of 223 (20.6%) who received placebo. Among patients hospitalized with severe COVID-19, treatment with canakinumab, compared with placebo, did not significantly increase the likelihood of survival without IMV at day 29. ClinicalTrials.gov Identifier: NCT04362813.

Lack of Associations Between C-Reactive Protein and Mood and Anxiety Symptoms in Adolescents.

Introduction: Increased peripheral inflammation has been consistently documented in both adult and pediatric depression. However, elevated levels of C-reactive protein (CRP), a nonspecific biomarker for inflammation, have been primarily reported in adults; whether CRP plays a similar role in adolescent depression has not been conclusively established. In our prior work, we identified relationships between CRP and reward neurocircuitry in adolescents with psychiatric symptoms (N = 64) but not with depressive symptoms. Extending this work, we sought to examine CRP across the full range of mood and anxiety symptom severity in a larger, clinically diverse cohort of psychotropic medication-free adolescents and healthy controls (HCs). Methods: Subjects were adolescents (N = 127, age: 15.17 ± 2.19 years, 78 female) with psychiatric symptoms (n = 96, including previous cohort of 64) and HC (n = 31). All completed a semi-structured psychiatric evaluation and dimensional assessments for depression, anxiety, anhedonia, and suicidality. Group-comparison and correlation analyses utilized nonparametric statistics controlled for body mass index, sex, and age at pFWE < 0.05. Results: No group differences were identified in CRP levels between the clinical cohort and HCs. In addition, correlations between CRP and clinical symptomatology were not significant in either the whole sample or the psychiatric group. Conclusions: We found that, unlike in adults, CRP was not associated with depressive symptoms. This suggests that inflammation in pediatric depression is more narrowly delimited at the onset of psychiatric symptoms and may only become systemic with chronicity.

Biomarkers of inflammation, parameters characterizing obesity and cardiac remodeling in patients with atrial fibrillation and metabolic syndrome

Aim. To determine the blood level of inflammatory markers, parameters characterizing obesity and cardiac remodeling in patients with atrial fibrillation (AF) in combination with metabolic syndrome (MS).Material and methods. This single-stage case-control study included 677 subjects aged 35 to 65 years: patients with MS (n=407), of which 128 patients with AF; comparison group — patients with AF without MS (n=75); control group — practically healthy subjects without cardiovascular diseases and metabolic disorders (n=195).Results. It was found that the blood concentration of circulating pro-inflammatory biomarkers in patients with AF and MS is higher than in patients with AF without MS: C-reactive protein (CRP) (4,43 (2,68-4,98) and 2,33 (1,08-4,7) mg/L, p&lt;0,0001), interleukin-6 (IL-6) (2,5 (1,28-5,13) and 1,27 (0,68-2,7) pg/ml, p&lt;0,0001) and tumor necrosis factor-α (TNF-α) (5,18 (2,63-7,32) and 3,42 (2,115,48) pg/ml, p&lt;0,0001). The serum CRP concentration positively correlates with left (ρ=0,451, p&lt;0,0001) and right atrial (ρ=0,412, p&lt;0,000) volumes, as well as with the waist circumference (ρ=0,503, p&lt;0,001) and epicardial fat thickness (ρ=0,550, p&lt;0,001). Plasma IL-6 and serum TNF-α levels correlated to a lesser extent with parameters characterizing atrial remodeling, but had a strong positive relationship with epicardial fat thickness. According to multivariate analysis, it was found that an increase in the epicardial fat thickness had a greater effect on an increase in blood concentration of CRP, IL-6 and TNF-α, in contrast to other parameters characterizing obesity, such as body mass index and waist circumference.Conclusion. An increase in the blood concentration of proinflammatory biomarkers CRP, IL-6, and TNF-α is associated with cardiac remodeling and epicardial fat thickness in patients with MS and probably has a pathogenetic role in increasing the AF risk in this cohort of patients.

A Modest Increase in 11C-PK11195-Positron Emission Tomography TSPO Binding in Depression Is Not Associated With Serum C-Reactive Protein or Body Mass Index

BackgroundImmune mechanisms have been implicated in the pathogenesis of depression. Translocator protein (TSPO)–targeted positron emission tomography (PET) has been used to assess neuroinflammation in major depressive disorder. We aimed to 1) test the hypothesis of significant case-control differences in TSPO binding in the anterior cingulate cortex, prefrontal cortex, and insula regions; and 2) explore the relationship between cerebral TSPO binding and peripheral blood C-reactive protein (CRP) concentration. MethodsA total of 51 depressed subjects with Hamilton Depression Rating Scale score >13 (median 17; interquartile range, 16–22) and 25 healthy control subjects underwent dynamic brain 11C-PK11195 PET and peripheral blood immune marker characterization. Depressed subjects were divided into high CRP (>3 mg/L; n = 20) and low CRP (<3 mg/L; n = 31). ResultsAcross the three regions, TSPO binding was significantly increased in depressed versus control subjects (η2p = .09; F1,71 = 6.97, p = .01), which was not influenced by body mass index. The case-control difference was greatest in the anterior cingulate cortex (d = 0.49; t74 = 2.00, p = .03) and not significant in the prefrontal cortex or insula (d = 0.27 and d = 0.36, respectively). Following CRP stratification, significantly higher TSPO binding was observed in low-CRP depression compared with controls (d = 0.53; t54 = 1.96, p = .03). These effect sizes are comparable to prior major depressive disorder case-control TSPO PET data. No significant correlations were observed between TSPO and CRP measures. ConclusionsConsistent with previous findings, there is a modest increase in TSPO binding in depressed patients compared with healthy control subjects. The lack of a significant correlation between brain TSPO binding and blood CRP concentration or body mass index poses questions about the interactions between central and peripheral immune responses in the pathogenesis of depression.

Thermovaccination – thermoheliox as a stimulator of the immune response. Kinetics of the synthesis of antibodies and C-reactive protein in coronavirus infection

Clinical trials of thermoheliox application (inhalation with a high-temperature mixture of oxygen and helium, 90 °C) in the treatment of the acute phase of coronavirus infection were conducted. Dynamics of disease development in infected patients (PCR test for the virus) and, dynamics of changes in blood concentration of C-reactive protein, immunoglobulin M, specific immunoglobulin G were studied. High efficiency of thermoheliox in releasing the organism from the virus and stimulating the immune response (thermovaccination effect) was shown. The kinetic model of the process is proposed and analyzed.

Increased C-reactive protein concentrations were associated with suicidal behavior in patients with depressive disorders: a meta-analysis

Suicide is devastating with a high incidence in patients with depressive disorder (PDDs). Although some studies have explored underlying associations between C-reactive protein (CRP) levels and suicidal behavior in PDDs, consistent results have not been reached. Therefore, the aim of this meta-analysis was to explore the differences of peripheral blood CRP concentrations between suicidal and non-suicidal PDDs, and between suicidal PDDs and healthy controls (HCs). To this end, PubMed, Embase, and Web of science were searched for eligible studies, and pooled effect sizes from eligible studies were calculated by random-effect models. Furthermore, sensitivity and meta-regression analyses were performed to explain the causes of heterogeneity. Eventually, 7 studies with 2,108 participants were included. Our statistical results suggested that the concentrations of peripheral CRP may be significantly increased for suicidal PDDs, both compared with non-suicidal PDDs and HCs, respectively. The differences of detection methods may be linked with the sources of heterogeneity. In short, our findings showed both compared with non-suicidal PDDs and HCs, peripheral blood CRP levels may be significantly increased in suicidal PDDs, while more studies with large sample sizes are needed to validate our findings.