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The current literature provides a body of evidence on C-Reactive Protein (CRP) and its potential role in inflammation. However, most pieces of evidence are sparse and controversial. This critical state-of-the-art monography provides all the crucial data on the potential biochemical properties of the protein, along with further evidence on its potential pathobiology, both for its pentameric and monomeric forms, including information for its ligands as well as the possible function of autoantibodies against the protein. Furthermore, the current evidence on its potential utility as a biomarker of various diseases is presented, of all cardiovascular, respiratory, hepatobiliary, gastrointestinal, pancreatic, renal, gynecological, andrological, dental, oral, otorhinolaryngological, ophthalmological, dermatological, musculoskeletal, neurological, mental, splenic, thyroid conditions, as well as infections, autoimmune-supposed conditions and neoplasms, including other possible factors that have been linked with elevated concentrations of that protein. Moreover, data on molecular diagnostics on CRP are discussed, and possible etiologies of false test results are highlighted. Additionally, this review evaluates all current pieces of evidence on CRP and systemic inflammation, and highlights future goals. Finally, a novel diagnostic algorithm to carefully assess the CRP level for a precise diagnosis of a medical condition is illustrated.

High sensitivity C-reactive protein (hsCRP) is a marker of systemic inflammation that has been associated with persistent depressive symptoms. Depression and anxiety are frequently associated with a chronic inflammatory state, yet the nature of this relationship has not been rigorously examined in diverse Hispanic/Latino populations. We aimed to study the association of anxiety and depressive symptoms as well as comorbid presentations, with circulating high sensitivity C-reactive protein (hsCRP) levels in a large Latino cohort of diverse heritages. We hypothesized a significant positive associations of both anxiety and depressive symptoms and hsCRP levels and potential variations among the heritage groups. Depressive symptoms and anxiety were measured by the Center for Epidemiological Studies Depression Scale (CES-D) and State-Trait Anxiety Inventory (STAI), respectively. Serum hsCRP (hsCRP) levels of 15,448 participants (age 18 to 75 years; 52.3% women) from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) were measured and categorized based on the established cardiovascular disease (CVD) risk reference values (< 1mg/L, low; 1-<3 mg/L, intermediate; [greater than or equal to] 3mg/L, high). Mean CES-D, STAI scores, and hsCRP levels were 7.0 (SD = 5.9), 17.0 (SD = 5.7), and 3.84 (SD = 7.85), respectively. Generalized linear modeling, adjusted for sociodemographic characteristics revealed significant associations between depression (exp([beta]) = 1.12; p<0.01) and anxiety symptoms (exp([beta]) = 1.10; p<0.05) with continuous hsCRP levels. For categorical values of hsCRP, one SD increase in CES-D and STAI scores was associated with a 10% and 8% increase in the RRRs of high vs. low hsCRP, respectively. However, these relationships between CES-D or STAI and hsCRP were no longer statistically significant after adjustment for CVD risk factors and medications. We found modest associations between anxiety and depressive symptoms and systemic inflammation measured by hsCRP among diverse Hispanics/Latinos that did not appreciably differ between heritage groups.

High sensitivity C-reactive protein (hsCRP) is a marker of systemic inflammation that has been associated with persistent depressive symptoms. Depression and anxiety are frequently associated with a chronic inflammatory state, yet the nature of this relationship has not been rigorously examined in diverse Hispanic/Latino populations. We aimed to study the association of anxiety and depressive symptoms as well as comorbid presentations, with circulating high sensitivity C-reactive protein (hsCRP) levels in a large Latino cohort of diverse heritages. We hypothesized a significant positive associations of both anxiety and depressive symptoms and hsCRP levels and potential variations among the heritage groups. Depressive symptoms and anxiety were measured by the Center for Epidemiological Studies Depression Scale (CES-D) and State-Trait Anxiety Inventory (STAI), respectively. Serum hsCRP (hsCRP) levels of 15,448 participants (age 18 to 75 years; 52.3% women) from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) were measured and categorized based on the established cardiovascular disease (CVD) risk reference values (< 1mg/L, low; 1-<3 mg/L, intermediate; [greater than or equal to] 3mg/L, high). Mean CES-D, STAI scores, and hsCRP levels were 7.0 (SD = 5.9), 17.0 (SD = 5.7), and 3.84 (SD = 7.85), respectively. Generalized linear modeling, adjusted for sociodemographic characteristics revealed significant associations between depression (exp([beta]) = 1.12; p<0.01) and anxiety symptoms (exp([beta]) = 1.10; p<0.05) with continuous hsCRP levels. For categorical values of hsCRP, one SD increase in CES-D and STAI scores was associated with a 10% and 8% increase in the RRRs of high vs. low hsCRP, respectively. However, these relationships between CES-D or STAI and hsCRP were no longer statistically significant after adjustment for CVD risk factors and medications. We found modest associations between anxiety and depressive symptoms and systemic inflammation measured by hsCRP among diverse Hispanics/Latinos that did not appreciably differ between heritage groups.

Objective High-sensitivity C-reactive protein to HDL-C ratio (HCHR) and high-sensitivity C-reactive protein to lymphocyte count ratio (HCLR) are two novel inflammatory indicators, and heart failure (HF) is linked to chronic inflammation. This study sought to evaluate the link between HCHR, HCLR, and HF. Methods We carried out a cross-sectional investigation using the National Health and Nutrition Examination Survey (NHANES, 2015–2018). We used multivariate logistic regression to determine the association between HCHR, HCLR, and HF, followed by smoothed curve fitting and threshold effect analysis, as well as subgroup analyses of the underlying demographic variables to investigate potential impacts. The receiver operating characteristic curves were employed to examine the correlation between each index and HF. Results This study included 8751 subjects, and multivariate logistic regression after Ln conversion for HCHR and HCLR showed that subjects in the highest tertile of Ln(HCHR) had a significantly higher risk of 45% than those in the lowest tertile in the fully adjusted model 3 (OR = 1.45, 95% CI 1.02–2.07; P for trend = 0.0269), whereas subjects in the highest tertile of Ln(HCLR) had a significantly higher risk of 52% (OR = 1.52, 95% CI 1.07–2.17; P for trend = 0.0184) than those in the lowest tertile. Ln(HCHR) and HF exhibited a nonlinear relationship, with an inflection point of -2.71 and a log-likelihood ratio of 0.024. Subgroup analyses revealed no significant interactions between Ln(HCHR), Ln(HCLR), and specific subgroups (all P for interactions > 0.05). The ROC curve indicated that Ln(HCLR) had the greatest diagnostic efficacy for HF (AUC: 0.638, 95% CI 0.607–0.669), succeeded by Ln(HCHR) (AUC: 0.620, 95% CI 0.589–0.652). Conclusion Our findings indicate that Ln(HCHR) and Ln(HCLR) are positively linked with the prevalence of HF among US adults. Specifically, Ln(HCHR) levels demonstrated a nonlinear correlation with HF, featuring an inflection point at -2.71.

C-reactive protein (CRP) point-of-care testing (POCT) is increasingly being promoted to reduce diagnostic uncertainty and enhance antibiotic stewardship. In primary care, respiratory tract infections (RTIs) are the most common reason for inappropriate antibiotic prescribing, which is a major driver for antibiotic resistance. We systematically reviewed the available evidence on the impact of CRP-POCT on antibiotic prescribing for RTIs in primary care. Thirteen moderate to high-quality studies comprising 9844 participants met our inclusion criteria. Meta-analyses showed that CRP-POCT significantly reduced immediate antibiotic prescribing at the index consultation compared with usual care (RR 0.79, 95%CI 0.70 to 0.90, p = 0.0003, I2 = 76%) but not during 28-day (n = 7) follow-up. The immediate effect was sustained at 12 months (n = 1). In children, CRP-POCT reduced antibiotic prescribing when CRP (cut-off) guidance was provided (n = 2). Meta-analyses showed significantly higher rates of re-consultation within 30 days (n = 8, 1 significant). Clinical recovery, resolution of symptoms, and hospital admissions were not significantly different between CRP-POCT and usual care. CRP-POCT can reduce immediate antibiotic prescribing for RTIs in primary care (number needed to (NNT) for benefit = 8) at the expense of increased re-consultations (NNT for harm = 27). The increase in re-consultations and longer-term effects of CRP-POCT need further evaluation. Overall, the benefits of CRP-POCT outweigh the potential harms (NNTnet = 11).

Background Cardiovascular disease (CVD) remains the leading cause of mortality in individuals with type 2 diabetes mellitus (T2DM), driven by chronic hyperglycaemia, dyslipidaemia, and systemic inflammation. In Nigeria, genetic predispositions, ethnic and environmental factors may further modulate CVD risk. This study aimed to evaluate the association between high-sensitivity C-reactive protein (hsCRP) and CVD risk in Nigerian T2DM patients receiving standard care. Methods This cross-sectional hospital-based study was conducted over 13 months. Data on socio-demographic characteristics, medical history, clinical findings, and laboratory parameters were collected using a structured proforma. Serum hsCRP was measured by homogenous immunoassay, while 10-year CVD risk was estimated with the WHO CVD risk assessment chart validated for Western sub-Saharan Africa. Statistical analyses, including binary logistic regression to assess the association between hsCRP and CVD risk, were conducted using SPSS version 25, with significance set at p  < 0.05. Results Moderate-to-high CVD risk was prevalent in 51.5% of the study population. Longer diabetes duration (AOR = 1.345, 95% CI: 1.222–1.480, p  < 0.001), elevated HbA1c (OR = 1.438, 95% CI: 1.061–1.949, p  = 0.019), and co-morbid hypertension (OR = 14.498, 95% CI: 2.611–80.515, p  = 0.002) were significantly associated with higher CVD risk. Serum hsCRP levels were higher in moderate-to-high-risk individuals (median: 2.42 mg/L, IQR: 2.8; 2.71 mg/L, IQR: 1.8) compared to lower-risk individuals (median: 1.22 mg/L, IQR: 2.5; 1.48 mg/L, IQR: 2.6), p  = 0.012. However, it was not an independent predictor of CVD risk after adjusting for confounders ( p  = 0.369). Conclusion There is a high burden of increased CVD risk in this population despite ongoing management, with prolonged diabetes duration, poor glycaemic control and co-morbid hypertension as key predictors. Although hsCRP levels were elevated in higher-risk individuals, its clinical utility as an independent predictor of CVD risk may be limited. These findings emphasize the need to strengthen routine CVD risk assessment, prioritize modifiable risk factors, and optimize glycaemic control to reduce CVD burden in Nigerian T2DM patients.

The low-cost daily monitoring of C-reactive protein (CRP) levels is crucial for screening acute inflammation or infections as well as managing chronic inflammatory diseases. In this study, we synthesized novel 2-Methacryloyloxy ethyl phosphorylcholine (MPC)-based biomimetic nanoparticles with a large surface area to develop a visual CRP-quantification assay using affordable glass capillaries. The PMPC nanoparticles, synthesized via reflux precipitation polymerization, demonstrated multivalent binding capabilities, enabling rapid and specific CRP capture. In the presence of CRP, PMPC nanoparticles formed sandwich structures with magnetic nanoparticles functionalized with CRP antibodies, thereby enhancing detection sensitivity and specificity. These sandwich complexes were magnetically accumulated into visible and quantifiable stacks within the glass capillaries, allowing for the rapid, sensitive, and specific quantification of CRP concentrations with a detection limit of 57.5 pg/mL and a range spanning from 0 to 5000 ng/mL. The proposed visual distance-based capillary biosensor shows great potential in routine clinical diagnosis as well as point-of-care testing (POCT) in resource-limited settings.

High sensitivity C-reactive protein (hsCRP) is a marker of systemic inflammation that has been associated with persistent depressive symptoms. Depression and anxiety are frequently associated with a chronic inflammatory state, yet the nature of this relationship has not been rigorously examined in diverse Hispanic/Latino populations. We aimed to study the association of anxiety and depressive symptoms as well as comorbid presentations, with circulating high sensitivity C-reactive protein (hsCRP) levels in a large Latino cohort of diverse heritages. We hypothesized a significant positive associations of both anxiety and depressive symptoms and hsCRP levels and potential variations among the heritage groups. Depressive symptoms and anxiety were measured by the Center for Epidemiological Studies Depression Scale (CES-D) and State-Trait Anxiety Inventory (STAI), respectively. Serum hsCRP (hsCRP) levels of 15,448 participants (age 18 to 75 years; 52.3% women) from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) were measured and categorized based on the established cardiovascular disease (CVD) risk reference values (< 1mg/L, low; 1-<3 mg/L, intermediate; ≥ 3mg/L, high). Mean CES-D, STAI scores, and hsCRP levels were 7.0 (SD = 5.9), 17.0 (SD = 5.7), and 3.84 (SD = 7.85), respectively. Generalized linear modeling, adjusted for sociodemographic characteristics revealed significant associations between depression (exp(β) = 1.12; p<0.01) and anxiety symptoms (exp(β) = 1.10; p<0.05) with continuous hsCRP levels. For categorical values of hsCRP, one SD increase in CES-D and STAI scores was associated with a 10% and 8% increase in the RRRs of high vs. low hsCRP, respectively. However, these relationships between CES-D or STAI and hsCRP were no longer statistically significant after adjustment for CVD risk factors and medications. We found modest associations between anxiety and depressive symptoms and systemic inflammation measured by hsCRP among diverse Hispanics/Latinos that did not appreciably differ between heritage groups.

Background Competing risk method has not been used in a large-scale prospective study to investigate whether increased levels of high-sensitivity C-reactive protein (hs-CRP) elevate the risk of primary liver cancer (PLC). Our study aims to prospectively investigate the relationship between hs-CRP and new-onset PLC. Methods and results Ninety-five thousand seven hundred fifty-nine participants without the diagnosis of PLC, and who had their demographic characteristics and biochemical parameters recorded, were analyzed from the Kailuan Cohort study. Cox proportional hazards regression models and competing risk regression models were used to evaluate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) of PLC. During a median follow-up of 11.07 years, 357 incidental PLC cases were identified over a total of 1,035,039 person-years. The multivariable HRs (95%CI) for the association of hs-CRP of 1–3 mg/L group and hs-CRP>3 mg/L with PLC were 1.07(0.82 ~ 1.38), 1.51(1.15 ~ 1.98) in a Cox proportional hazard regression analysis adjusted for other potential confounders. In the cause-specific hazard model, the multivariable HRs (95%CI) for the association of hs-CRP of 1–3 mg/L group and hs-CRP>3 mg/L with PLC were 1.06(0.81 ~ 1.40), 1.50(1.14 ~ 1.99). Similar results were also observed in the sub-distribution hazard function model with corresponding multivariate HRs (95%CI) of 1.05(0.80 ~ 1.40), 1.49(1.13 ~ 1.98) in hs-CRP of 1–3 mg/L group and hs-CRP>3 mg/L group, respectively. Conclusions This prospective study found a significant association of higher levels of hs-CRP with new-onset PLC. The main clinical implications would be an increased awareness of hs-CRP and its correlation to the risk of PLC. This study should be a steppingstone to further research on chronic inflammation and PLC. Trial registration Registration number: ChiCTR–TNRC–11001489 .

Background Diagnosis of periprosthetic joint infection (PJI), especially chronic PJI, is very confusing and challenging. The value of C-reactive protein (CRP) in infectious diseases has been recognized, but the diagnostic value of CRP in chronic PJI is unknown. Our aim was to investigate the diagnostic value of synovial CRP in chronic PJI and to explore the role of combined serum and synovial CRP in distinguishing chronic PJI from aseptic failure after knee and hip arthroplasties. Methods We prospectively enrolled patients scheduled to have a revision surgery for chronic PJI or aseptic loosening from January 2019 to December 2020, in which synovial CRP was additionally measured along with routine preoperative diagnostic serum ((ESR, CRP) and synovial (PMN%) biomarkers. The receiver operating characteristic (ROC) curves and area under the curve (AUC) were analyzed for each biomarker to determine diagnostic efficacy. Results There were no statistically significant differences between the infection ( n  = 39) and aseptic ( n  = 58) groups, including 61 hips and 36 knees. The synovial CRP levels were significantly higher in the infection group than in the aseptic group (median: 9.93 mg/l vs 3.58 mg/l; p  < .001). The optimal cut-off value for detecting chronic PJI of Synovial fluid (SF) CRP was of 7.26 mg/l with a sensitivity of 84.62%, a specificity of 93.10%. The combined model I (Serum CRP > 10.2 mg/l OR SF CRP > 7.26 mg/l) had a negative predictive value (NPV) of 96.67%, and a sensitivity of 97.44%. The combined model II (Serum CRP > 10.2 mg/l AND Synovial CRP > 7.26 mg/l) led to a specificity of 1, and a positive predictive value (PPV) of 1. Conclusions The present study demonstrated that the combination of serum and synovial CRP can be used as an adjunct to the diagnosis of chronic PJI.