High C-reactive protein to albumin ratio and the short-term survival prognosis within 30 days in terminal cancer patients receiving palliative care in a hospital setting: A retrospective analysis.

Survival estimates are very important to patients with terminal cancer. The C-reactive protein (CRP)/albumin ratio is associated with cancer outcomes. However, few studies have investigated the dose-response association in terminal cancer patients. Therefore, we aimed to evaluate the association between the CRP/albumin ratio and mortality in terminal cancer patients using a longitudinal analysis. We retrospectively investigated the electronic medical records of 435 inpatients with terminal cancer admitted to the palliative care unit of Yeouido St. Mary's Hospital between October 8, 2015, and January 17, 2018. In total, 382 patients with terminal cancer were enrolled in the study. The serum CRP/albumin ratio measured at admission had a linear dose-response relationship with the risk of death among the terminal cancer patients (P for linearity = .011). The multivariate analyses showed that the CRP/albumin ratio was an independent prognostic factor (Model 1, CRP/albumin ratio >48.53 × 10: HR = 2.68, 95% CI = 1.82-3.93; Model 2, tertile 2: HR = 1.91, 95% CI = 1.31-2.82 and tertile 3: HR = 3.66, 95% CI = 2.24-5.97). The relationship between a high CRP/albumin ratio and poor survival was a flat L-shape for survival time with an inflection point at approximately 15 days, while the relationship was not significant in terminal cancer patients who survived beyond 30 days. This study demonstrated that high CRP/albumin ratios are significantly and independently associated with the short-term survival prognosis of terminal cancer patients within 30 days.

Comparison of C Reactive Protein and Procalcitonin Levels in Cerebrospinal Fluid and Serum to Differentiate Bacterial from Viral Meningitis.

GOALS: It is unclear whether C reactive protein (CRP) and procalcitonin (PCT) levels in cerebrospinal fluid (CSF) improve the accuracy compared to their serum levels for the differential diagnosis of infectious meningitis. The aim of this study was to compare the accuracy of CRP and PCT levels in CSF and serum in order to differentiate between bacterial and viral meningitis. PROCEDURES: CRP and PCT levels were measured in CSF and serum from patients with bacterial or viral meningitis. The diagnostic accuracy was determined using receiver operating characteristic curves (ROC), calculating the area under the ROC curve (AUC). RESULTS: Thirty patients were included in this study, 18 of whom had bacterial meningitis and 12 viral meningitis. The AUCs to differentiate bacterial from viral meningitis using serum CRP, CSF CRP, serum PCT and CSF PCT were 0.926; 0.898; 0.963; and 0.694 respectively. Serum CRP and PCT exhibited 100% and 88.9% sensitivity, 83.3% and 100% specificity with a cut-off =14.0 mg/L and 0.18 µg/L respectively. CONCLUSIONS: Levels of CRP and PCT in CSF did not present greater accuracy in differentiating bacterial from viral meningitis compared to serum levels. Serum CRP and PCT showed a high diagnostic accuracy, therefore its quantification is recommended in all patients with suspected infectious meningitis.

Causes and outcomes of markedly elevated C-reactive protein levels.

OBJECTIVE: To characterize the causes of marked elevation of C-reactive protein (CRP) levels, investigate patient outcomes, and examine factors that might influence the CRP response. DESIGN: Health records were used to retrospectively determine patient characteristics, diagnoses, and outcomes over a 2-year period (2012 to 2013). SETTING: A large referral centre in Moncton, NB. PARTICIPANTS: Adult inpatients and outpatients with a CRP level above 100 mg/L. MAIN OUTCOME MEASURES: Differences among the CRP distributions of various diagnosis categories were examined using Kruskal-Wallis tests, and factors affecting outcomes were examined using Fisher exact tests. RESULTS: Over the 2-year period, 1260 CRP levels (839 patients; 3.1% of all tests) were above 100 mg/L (range 100.1 to 576.0 mg/L). The mean age was 63 years (range 18 to 101) and 50.2% of patients were men. Infection was the most prevalent cause (55.1%), followed by rheumatologic diseases (7.5%), multiple causes (5.6%), other inflammatory conditions (5.4%), malignancy (5.1%), drug reactions (1.7%), and other conditions (2.0%). A diagnosis could not be established in 17.6% of cases. On average, infections caused higher peak CRP levels (W = 34 519, P < .001) and infection was present in 88.9% of cases with CRP levels greater than 350 mg/L. Rheumatologic causes were associated with only 5.6% of CRP levels above 250 mg/L. The overall mortality was 8.6% and was higher in patients with malignancy (37.0%), multiple diagnoses (21.0%), and leukopenia (20.7%, P = .002). CONCLUSION: Most patients had infections and the proportion of patients with infections increased with the level of CRP, although many diagnoses were associated with markedly elevated CRP levels. These data could help guide health care professionals in the evaluation and management of these patients.

Pentraxins: multifunctional proteins at the interface of innate immunity and inflammation.

Pentraxins are a family of multimeric pattern recognition proteins highly conserved in evolution. On the basis of the primary structure of the protomer, pentraxins are divided into two groups: short pentraxins and long pentraxins. C reactive protein, the first pattern recognition receptor identified, and serum amyloid P component are classic short pentraxins produced in the liver in response to IL-6. Long pentraxins, including the prototype PTX3, are expressed in a variety of tissues. PTX3 is produced by a variety of cells and tissues, most notably dendritic cells and macrophages, in response to Toll-like receptor (TLR) engagement and inflammatory cytokines. Through interaction with several ligands, including selected pathogens and apoptotic cells, pentraxins play a role in complement activation, pathogen recognition and apoptotic cell clearance. In addition, PTX3 is involved in the deposition of extracellular matrix and female fertility. Unlike the classic short pentraxins CRP and SAP, PTX3 primary sequence and regulation are highly conserved in man and mouse. Thus, gene targeting identified PTX3 (and presumably other members of the family) as multifunctional soluble pattern recognition receptors acting as a nonredundant component of the humoral arm of innate immunity and involved in tuning inflammation, matrix deposition, and female fertility. (c) 2009 International Union of Biochemistry and Molecular Biology, Inc.

Proteína C reactiva en cirugía ortopédica / C-Reactive protein in orthopedic surgery

C-reative protein is an acute phase protein, therefore its plasmatic curve will vary accorging to noxa. This variation of the curve is both in magnitude and form, making it easily detectable only a few hours after injury. This unique characteristic of CRP has led to different plasmatic curves for orthopedic surgeries. This curve pattern alteration should lead us to suspect some kind of complication, which is of great importance for opportune treatment.

Importancia de la hipercoagulabilidad en la cirugía de la isquemia crónica de extremidades inferiores / The importance of hypercoagulability in the surgery of chronic ischaemia of the lower limbs

Introducción. Se ha descrito una alta prevalencia de estados de hipercoagulabilidad en pacientes con isquemia crónica.Objetivo. Determinar la prevalencia e importancia de estados de hipercoagulabilidad en pacientes con patología oclusiva crónica de extremidades inferiores, que precisan revascularización. Pacientes y métodos. Estudio prospectivo octubre 1999-abril 2000. En 52 pacientes se determinó: antitrombina III, proteína C y S, anticuerpos anticardiolipina, plasminógeno, a2-antiplasmina y resistencia a la proteína C activada. Se registraron factores de riesgo, clínica, cirugía realizada y resultados, y se analizó su relación con alteraciones de hipercoagulabilidad. Resultados. El 6 por ciento presentaban déficit de antitrombina III; el 31 por ciento, déficit de proteína C; el 2 por ciento, déficit de proteína S; el 10 por ciento, anticuerpos anticardiolipina, y el 12 por ciento, resistencia a la proteína C activada (RPCA). El 29 por ciento de los pacientes presentaban una alteración; el 13 por ciento, más de una, y el 58 por ciento, ninguna. El 50 por ciento (3/6) de los pacientes con RPCA se trombosaron, frente al 13 por ciento (6/46) de los pacientes sin RPCA (p= 0,05). El 42 por ciento (3/7) de los pacientes con varias alteraciones se trombosaron, frente al 13 por ciento (6/45) del resto (p= 0,08). El 33 por ciento (2/6) de los pacientes con RPCA presentaron trombosis precoz, frente al 2,1 por ciento (1/46) del resto (p= 0,03). El 28 por ciento (2/7) de los pacientes con varias alteraciones presentaron trombosis precoz, frente al 2,2 por ciento (1/ 45) del resto (p= 0,04). Conclusiones. La prevalencia de estados de hipercoagulabilidad en isquémicos crónicos es elevada. Estos hallazgos inducen implicaciones terapéuticas. (AU)

Determination of the habitual low blood level of C-reactive protein in individuals.

In order to use C-reactive protein (CRP) in risk prediction in individuals, it is necessary to know how to obtain the habitual level of an individual and hence its biological variations: i.e. longitudinal variability within subjects and variability between individuals. This paper provides data on biological variability that is used to propose a strategy for assessing individual low levels of CRP. The longitudinal variability in individuals (intraindividual variability) is essential to know, but only reported in a very limited way. Additional data were calculated from in-house and requested databases for periods of follow-up from 5 days to 1 year. The intraindividual coefficient of variation (CVi) was found to be rather similar for several groups and periods and on average was approximately 30%. Reported analytical coefficients of variation of commercial and in-house methods generally are below 6%, which is well below the desired limit of half the CVi. The distribution of CRP in apparently healthy individuals is wide and skewed with interquartile values ranging between 150-250% of the median and an estimate of the composite coefficient of variation (CVc) of approximately 120%. The distribution is equally broad in several other groups studied such as type II diabetics and pregnant women. It is concluded that the coefficient of variation for the determination of CRP in a single blood sample is as high as approximately 30%, but that this is acceptable for the reliable positioning of individuals within the distribution of CRP in the group with a CVc as high as -120%. CRP can show unexpected outliers (increases) which can sometimes be explained by information from a short questionnaire and definitely identified by the analysis of a second blood sample after an interval of approximately 2 weeks. Similarly, to ascertain high values in a first sample a second blood sample can be analyzed. It should be noted that, in view of the significant intraindividual variability of CRP, the difference between the first and second values may reach 71%. The large intraindividual variability of CRP approximating 30% renders it difficult to position an individual reliably in smaller categories such as tertiles, quartiles or quintiles of the total distribution. It is suggested that it would be most practical to have a goal of a single decision level or threshold only. Positioning an individual into two groups with equally wide distribution is on the borderline of reliability for one blood sample. Multiple blood samplings are required for smaller categories and higher threshold levels. The use of a decision limit should further acknowledge the limited interclass stability of around r = approximately 0.5 for a single blood sample. The above considerations are summarized in a practical working scheme. This scheme can serve as a basis for further refinement, discussions and development of sampling and decision limits to be selected from medical and economical perspectives and tested in practice.

Lectin like properties and differential sugar binding characteristics of C-reactive proteins purified from sera of normal and pollutant induced Labeo rohita.

Different forms of C-reactive proteins (CRPs) have been purified to electrophoretic homogeneity from the sera of Labeo rohita confined in freshwater (CRP(N)) and water polluted with nonlethal doses of cadmium (CRP(Cd)) or mercury (CRP(Hg)). CRP(N), CRP(Cd), and CRP(Hg) show remarkable differences in their electrophoretic mobility but exhibit strong immunological cross reactivity. All these CRPs exhibit variable agglutination properties with erythrocytes from diverse sources in presence of Ca+2, which could be inhibited by a variety of sugars showing specificity for galactose. Inhibition results show that the potency of galactose as an inhibitor increases about 4 fold in the process of transformation of CRP(N) to CRP(Cd) and CRP(Hg). In case of CRP(N), Gal beta(1 --> 1) Gal and oNO2 phenyl beta-Gal show highest inhibitory potency while oNO2-phenyl beta-Gal is the most potent inhibitor for CRP(Cd) and CRP(Hg) but the potency of Gal beta(1 --> 1) Gal reduced drastically. 6-phosphate D-Gal and stachyose are 20 times weaker inhibitors than D-Gal for induced CRP mediated agglutination, in contrast, these sugars are only 6 times weaker for CRP(N). Dissociation constants of the binding of CRP(N) with phosphoryl choline (PC) and galactose are about 9 mM and PC binding causes a change in the alpha and beta conformations of these CRPs.

Expression, detection and assay of a neoantigen (Neo-CRP) associated with a free, human C-reactive protein subunit.

It has previously been reported that human C-reactive protein (CRP) can exist in at least two molecular conformations distinguished by antigenic, electrophoretic and ligand-binding reactivities. In the present study we describe the formation, detection and distinctiveness of a conformation expressing a CRP neoantigen (neo-CRP), and report that this form is characteristic in vitro of a free CRP subunit. Soluble native-CRP was found to express neo-CRP antigenicity upon treatment with acid; upon urea-chelation or heating in the absence of calcium; and upon adsorption onto uncoated polystyrene plates. Native-CRP bound by capture ELISA to phosphorylcholine-containing ligand or anti-native-CRP did not express neo-CRP antigenicity, suggesting that PC ligand- or antibody binding is not sufficient to induce expression of the neoantigen. Human CRP which expressed neo-CRP antigenicity had limited solubility and tended to aggregate in buffers of ionic strength 0.15, but remained soluble when the ionic strength was reduced to 0.015. Soluble urea-chelated or acid-treated CRP molecules expressing neo-CRP antigenicity chromatographed and electrophoresed as a single protein with a Mr of approx. 22,000, indicating that the CRP neoantigen can be expressed on free CRP subunits and this expression need not require proteolysis. Further, molecules expressing neo-CRP antigenicity were detected in the plasma of patients with rheumatoid arthritis. The identification and characterization of this CRP neoantigen should serve as a useful marker in studies of CRP subunits and biologically relevant forms of CRP, and should contribute to the elucidation of the role of CRP in the acute inflammatory response.