Serum Levels Of Acute Phase Reactants Research Articles

Correlation of Hematological Indices and Acute-Phase Reactants in Rheumatoid Arthritis Patients on Disease-Modifying Antirheumatic Drugs: A Retrospective Cohort Analysis.

Acute-phase markers are often used to evaluate the disease activity of rheumatoid arthritis (RA). Occasionally, the serum levels of acute-phase reactants remain normal in patients with obvious inflamed joints. Hematological indices derived from complete blood counts have been shown to correlate with disease activity. This provides a potential practical implementation in daily practice. Only a few studies have evaluated the relation between hematological indices and novel RA treatment (i.e., biological and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs); no research has examined the changes in hematological indices in RA treatments longitudinally. We conducted a retrospective study involving 273 RA patients with b/tsDMARD treatment and followed them for at least a year. Baseline, 3-month, and 6-month lab data were collected. The results indicated a reduction in the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), monocyte-lymphocyte ratio (MLR), and systemic immune-inflammation index (SII) post-treatment. Higher baseline PLRs and SIIs were associated with a more significant reduction in ESR at three months (η2 = 0.03/0.13, p = 0.21/0.023). NLR and SII correlated with CRP moderately at three months (r = 0.373/0.394, p < 0.001/< 0.001). A correlation comparison showed that the correlation of NLR and PLR with CRP differs during different periods (p = 0.037/0.004). Subgroup analysis revealed that the time effect on correlation is related to treatment with Janus kinase inhibitor and anti-interleukin-6 but not antitumor necrosis factors.

Clinical and Biologic Characteristics of Kingella kingae -Induced Septic Arthritis of the Knee in Young Children.

Septic arthritis of the knee is presumed to be the most frequent form of Kingella kingae -induced osteoarticular infection. This study aimed to report on the clinical course, biological parameters, and results of microbiological investigations among children with K. kingae -induced septic arthritis of the knee. It also assessed the modified Kocher-Caird criteria's ability to predict K. kingae -induced septic arthritis of the knee. The medical charts of 51 children below 4 years old with confirmed or highly probable K. kingae -induced arthritis of the knee were reviewed. Data were gathered on the five variables in the commonly-used Kocher-Caird prediction algorithm (body temperature, refusal to bear weight, leukocytosis, erythrocyte sedimentation rate, and C-reactive protein level). Patients with K. kingae -induced arthritis of the knee usually presented with a mildly abnormal clinical picture and normal or near-normal serum levels of acute-phase reactants. Data on all five variables were available for all the children: 7 children had zero predictors; 8, 20, 12, and 4 children had 1, 2, 3, and 4 predictors, respectively; no children had 5 predictors. This gave an average of 1.96 predictive factors and a subsequent probability of ≤ 62.4% of infectious arthritis in this pediatric cohort. Because the clinical features of K. kingae -induced arthritis of the knee overlap with many other conditions affecting this joint, the Kocher-Caird prediction algorithm is not sensitive enough to effectively detect K. kingae -induced septic arthritis of the knee. Excluding K. kingae -induced arthritis of the knee requires performing nucleic acid amplification assays on oropharyngeal swabs and joint fluid from those young children presenting with effusion of the knee, even in the absence of fever, leukocytosis, or a high Kocher-Caird score.

Impact of Obesity and Its Associated Comorbid Conditions on COVID-19 Presentation.

BackgroundThere is great variability in clinical presentation of COVID-19 worldwide. The current study evaluated the impact of obesity and its related complications on the course of COVID-19 in Egyptian patients.MethodsWe included 230 COVID-19 Egyptian patients from Tanta City. According to their body-mass index (BMI), patient were divided into three groups: normal weight (BMI <25 kg/m2), overweight (BMI >25–<30 kg/m2), and obese (BMI ≥30 kg/m2). Patients’ glycemic status, lipid profile, and serum levels of acute-phase reactants were assessed. The number of patients receiving intensive care and the number of deaths in each group were counted.ResultsMean values of random blood sugar, serum cholesterol, triglycerides, serum ferritin, erythrocyte-sedimentation rate, LDH, CRP, D-dimer levels, and blood pressure were significantly higher in obese patients (165.6, 129.5, 105, 1,873, 26, 403, 56.45, 977.16 and 142/87, respectively) than in normal-weight (97.2, 103.5, 70.4, 479, 17.4, 252, 23.2, 612.4, and 118.6/76.8, respectively) and overweight patients (111.4, 106.3, 78.13, 491.3, 19.8, 269.27, 25.42, 618.4, and 120.3/79.3, respectively). Lymphopenia was also significantly predominant in the obese group. Multivariate logistic regression analysis revealed that elevated serum triglycerides, total cholesterol, low density–lipoprotein cholesterol, blood pressure, ferritin, CRP, and low relative lymphocyte count were significant risk factors in obese COVID-19 patients.ConclusionObesity and its related complications increase the risk of presenting a more severe form of COVID-19 in Egyptian patients.

Evaluation of rituximab therapy in real clinical practice (according to the OREL registry of patients with rheumatoid arthritis

Objective:to analyze therapy with rituximab (RTM) in real clinical practice according to the data available in OREL registry of patients with active rheumatoid arthritis (RA).Subjects and methods. The analysis included 349 patients. All the patients received RTM: 340 – the original drug (MabThera®) and 9 – the biosimilar Acellbia®. 263 patients (75.4%) received RTM in combination with disease-modifying anti-rheumatic drugs (DMARDs) and 86 (24.6%) – RTM as monotherapy.Results and discussion. Of the 349 patients included in the analysis, 272 (77.9%) patients received RTM as the first biologic agent (BA) (263 patients were treated with the original drug and 9 – with the biosimilar) and 77 (22.1%) patients had previously used the BA. The majority of patients (n=205 (58.7%)) received three or more; 109 (31.2%) patients – one, and 35 (10%) – two RTM courses of RTM therapy. RTM caused a significant reduction in disease activity just after the first therapy course and in the levels of acute-phase reactants (C-reactive protein (CRP) and ESR); after the fifth therapy course, median CRP concentration decreased by 1.4 times and amounted to 7 [1.2; 17.9] mg/l and that of ESR reduced by 1.8 times and was 10 [5; 20] mm/hr (p&lt;0.05).Conclusion.The analysis of RTM therapy in RA patients in real clinical practice demonstrated that in most cases RTM was given as the first BA, in combination with DMARDs, the main agent of which was methotrexate. The use of RTM was accompanied by a significant reduction in disease activity and in the serum levels of acute-phase reactants and autoantibodies.

Association of Simvastatin and Hyperlipidemia With Periodontal Status and Bone Metabolism Markers

The objective of this study is to determine whether simvastatin consumption and hyperlipidemia are associated with a worse periodontal condition and specific bone activity biomarkers. This cross-sectional and analytic study includes 73 patients divided into three groups: 1) simvastatin-treated patients with hyperlipidemia (n = 29); 2) patients with hyperlipidemia treated by diet alone (n = 28); and 3) normolipidemic patients (controls, n = 16). The periodontal clinical variables of all participants were gathered, a blood sample was drawn from each to determine the lipid profile (total cholesterol, triglycerides, low-density lipoprotein, and high-density lipoprotein), serum levels of acute-phase reactants (C-reactive protein), erythrocyte sedimentation rate, and bone metabolism markers (osteoprotegerin [OPG], osteocalcin, procollagen type I N-terminal propeptide, and C-terminal telopeptide of type I collagen). The mean ESR was higher in the diet-treated patients with hyperlipidemia than in the normolipidemic controls (P = 0.04). Serum OPG concentrations were significantly higher in the simvastatin-treated patients with hyperlipidemia than in the diet-treated patients with hyperlipidemia (P = 0.05). Multivariable linear regression analysis adjusted for age, sex, tobacco, and alcohol revealed that, compared with the normolipidemic patients, the simvastatin-treated patients with hyperlipidemia showed a mean reduction of 0.8 mm (95% confidence interval = -1.5 to 0.0, P = 0.05) in clinical attachment loss. Within the limits of this study, the findings suggest that the intake of simvastatin is associated with increasing serum OPG concentrations, and this could have a protective effect against bone breakdown and periodontal attachment loss. The baseline systemic inflammatory state of patients with hyperlipidemia is indicated by their increased erythrocyte sedimentation rate.

Inflamed temporal artery: histologic findings in 354 biopsies, with clinical correlations.

We reviewed 888 temporal artery biopsies (TAB) performed in 871 patients in a single institution from January 1986 to December 2013. Forty-four biopsies (4.9%) were inadequate, 490 (55.2%) were devoid of inflammation and were considered negative, and 354 (39.9%) showed inflammation and were considered positive. On the basis of the localization of the inflammation, positive TABs were further classified into 4 categories: small vessel vasculitis (SVV), in which inflammation was limited to small periadventitial vessels devoid of muscular coat, with sparing of the temporal artery (32 cases, 9% of the positive biopsies); vasa vasorum vasculitis (VVV), in which inflammation was limited to the adventitial vasa vasorum (23 cases, 6.5% of the positive biopsies); inflammation limited to adventitia (ILA), in which inflammation extended from a strictly perivascular localization to the surrounding adventitia, without medial involvement (25 cases, 7% of the positive biopsies); and transmural inflammation (TMI), in which inflammation crossed the external elastic lamina and extended to the media (274 cases, 77.5% of the positive biopsies). In TMI, inflammation was generally more prominent between media and adventitia and mostly consisted of T lymphocytes and macrophages, with occasionally a significant number of plasma cells. Numerous eosinophils or neutrophils (with or without leucocytoclasia and suppurative necrosis), fibrinoid necrosis (limited to small branches of the temporal artery), and acute thrombosis were unusual, being present in 8%, 1.8%, 0.7%, and 9.5% of our biopsies with TMI, respectively. Giant cells, laminar necrosis, and calcifications prevailed along the internal elastic lamina and were present in 74.8%, 25.2%, and 20% of the biopsies with TMI, respectively. Among the 322 patients with positive TAB on whom we obtained clinical information, 317 had giant cell arteritis and 5 had a different disease: 3 (with SVV at histology) had ANCA-associated vasculitis, 1 (with SVV with amyloid deposits) had primary systemic amyloidosis, and 1 (with TMI limited to a small branch) had polyarteritis nodosa. In none of these cases the biopsy showed fibrinoid necrosis or significant numbers of eosinophils or neutrophils. Considering the 317 patients with giant cell arteritis, those with SVV and VVV compared with those with TMI had a significantly lower frequency of cranial manifestation (including headache, jaw claudication, and abnormalities of temporal arteries), lower serum levels of acute-phase reactants, and a reduced frequency of prednisone therapy at the time of TAB, of the "halo sign" at color duplex sonography of temporal arteries, and of systemic symptoms (for VVV). Polymyalgia rheumatica and blindness were equally represented in all patients groups, whereas there was a higher frequency of male sex and peripheral arthritis in patients with SVV. Patients with ILA were more similar to those with TMI, having a lower frequency of headache, of abnormalities of temporal arteries, and of a positive "halo sign" at color duplex sonography of temporal arteries. In conclusion, the histologic spectrum of inflammatory lesions that can be found in TAB is broad, and the differences have clinical implications.

Rhythm and Conduction Analysis of Patients With Acute Rheumatic Fever

Various rhythm and conduction abnormalities can develop in acute rheumatic fever. This study investigated rhythm and conduction abnormalities in children with acute rheumatic fever using a standard 12-lead electrocardiogram and 24-h rhythm Holter recordings. This multicenter retrospective study, performed between August 2011 and March 2012, enrolled 73 consecutive children with acute rheumatic fever. Standard electrocardiography was used to measure PR and corrected QT intervals. Holter recordings were evaluated for all the patients, and 52 of the patients (71.2 %) had carditis that was either isolated or together with other major criteria. A positive correlation was detected between carditis and the mean PR interval on standard electrocardiography, but this was not significant (p > 0.05). Standard electrocardiography showed a significant positive correlation between PR and corrected QT intervals (p = 0.03; r = 0.55). Standard electrocardiography showed only three patients (4.2 %) with premature contractions, whereas 24-h electrocardiography showed 26 patients (35.6 %) with premature contractions. Carditis was positively correlated with premature contractions (p < 0.01; r = 0.57). One patient with junctional rhythm and one patient with left bundle block were detected by standard electrocardiography. Whereas some patients with carditis exhibited no arrhythmic evidence on standard electrocardiograms, complete atrioventricular block, supraventricular tachycardia, and Mobitz type 1 block were observed on 24-h Holter recordings. A positive correlation also was observed between the presence of premature contractions and serum levels of acute-phase reactants (p = 0.03; r = 0.62). These findings led to the conclusion that rhythm and conduction disorders in acute rheumatic fever are more common than previously thought.

Interaction Between Periodontal Disease and Systemic Secondary Amyloidosis: From Inflammation to Amyloidosis

It has become increasingly clear in recent years that periodontal disease can cause a dramatic increase in the levels of markers of systemic inflammation, and that periodontal treatment can result in reduction in the levels of these markers. We have previously shown that the prevalence of moderate to severe periodontitis was significantly higher in patients with familial Mediterranean fever (FMF) with amyloidosis than in patients with FMF without amyloidosis. Thus, the aim of this study is to investigate if chronic periodontitis is associated with secondary amyloidosis in the Black Sea region of Turkey. A total of 112 patients with biopsy-proven secondary amyloidosis (59 patients with FMF, 40 patients who were either chronically infected or had malignant disease, 13 patients with periodontitis) and 22 healthy subjects, were included in this study. Periodontal health and disease were evaluated using gingival index (GI), papillary bleeding index (PBI), plaque index (PI), and periodontal disease index (PDI). The concentrations of serum acute phase reactants (APRs) were measured at baseline and at 4 to 6 weeks after completion of the non-surgical periodontal therapy. The prevalence of moderate to severe periodontitis was 47.5% in patients with FMF, 72.5% in patients who were either chronically infected or had malignant disease, and 84.6% in patients with periodontitis. Serum levels of APRs in patients with amyloidosis were reduced significantly after non-surgical periodontal therapy (P <0.01). Periodontitis can increase the levels of APRs and potentiate the development of amyloidosis either by themselves or association with traditional factors, such as FMF and other chronic inflammatory diseases. Thus, preventing or treating periodontitis might prevent or at least alleviate the progression of amyloidosis. Periodontal evaluation should be performed as part of a medical assessment and considered as an etiologic factor for secondary amyloidosis.

Periodontal disease in patients with familial Mediterranean fever: from inflammation to amyloidosis

Familial Mediterranean fever stimulates a very intense acute-phase reactants response and if left untreated eventually leads to amyloidosis. The aim of this study was to determine the prevalence of periodontal disease among patients with familial Mediterranean fever in the Black Sea region in Turkey and to evaluate whether periodontitis is related to amyloidosis in patients with familial Mediterranean fever. One-hundred and thirty three patients with familial Mediterranean fever and 50 healthy subjects were included in this study. Periodontal health and disease were evaluated using the gingival index, papillary bleeding index, plaque index and periodontal disease index. The concentrations of serum acute-phase reactants were measured at baseline and at 4-6 wk after completion of the nonsurgical periodontal therapy. Genetic testing for familial Mediterranean fever was performed using the familial Mediterranean fever StripAssay. Kidney biopsy was carried out on all proteinuric patients. The prevalence of moderate to severe periodontitis in familial Mediterranean fever patients with amyloidosis (80.6%) was significantly greater (p < 0.01) than in familial Mediterranean fever patients without amyloidosis (38%) and in controls (20%). Serum levels of acute-phase reactants in familial Mediterranean fever patients were reduced significantly following nonsurgical periodontal therapy (p < 0.01). Periodontal therapy seems to reduce the serum levels of acute-phase reactants in patients with familial Mediterranean fever. Therefore, treating periodontitis might help to alleviate the disease burden in patients with familial Mediterranean fever.

Neonatal-Onset Multisystem Inflammatory Disease Responsive to Interleukin-1β Inhibition

Goldbach-Mansky R, Dailey NJ, Canna SW, et al. N Engl J Med. 2006;355:581–592 PURPOSE OF THE STUDY. Neonatal-onset multisystem inflammatory disease (NOMID) is a chronic inflammatory disease that develops in infancy and is characterized by an urticarial rash, arthropathy, and central nervous system disease, including aseptic meningitis, cerebral atrophy, mental retardation, seizures, and vision and hearing loss. Approximately 60% of patients have a mutation in the cold-induced autoinflammatory syndrome 1 (CIAS1) gene, which is involved in the interleukin 1β (IL-1β) pathway. This study evaluated the effect of anakinra (Kineret, Amgen), an IL-1 receptor antagonist, on the various clinical and laboratory aspects of NOMID. STUDY POPULATION. A cohort of 18 patients aged 4 to 32 years with clinical NOMID (67% with mutations in CIAS1) who had active disease despite treatment with other antiinflammatory agents. METHODS. Patients were given a daily subcutaneous dose of anakinra. The drug was withdrawn from 11 patients at 3 months with the development of a clinical flare. Thereafter, all patients were continued on daily treatments up to 24 months. Clinical and laboratory assessments were made at 1, 3, and 6 months during therapy with anakinra. Primary end points included changes in a disease-specific daily diary score and changes in the serum levels of acute-phase reactants. RESULTS. All patients had an immediate response to anakinra with resolution of rash and conjunctivitis. There was an improvement in diary scores at 3 months that was maintained at 6 months. Serum amyloid A, C-reactive protein, and the erythrocyte sedimentation rate significantly declined with treatment. All the patients had headache at baseline, which resolved or improved with therapy, and cochlear and leptomeningeal lesions were improved on MRI. Serum levels of IL-1β, which were initially higher than those in healthy controls, decreased over the first 6 months of therapy. All the patients who underwent a treatment withdrawal experienced rapid improvement of their symptoms after resuming anakinra. Other than injection-site reactions, which resolved with continued treatment, there were no serious adverse events. CONCLUSIONS. Anakinra may be a safe and effective treatment for patients with NOMID. REVIEWER COMMENTS. This study suggests that anakinra may have a role in the treatment of other diseases in which IL-1β mediates inflammation (eg, systemic juvenile rheumatoid arthritis). Additional studies are needed to determine its long-term effects and clinical application. This study is an example of how specific immunomodulatory therapy may be useful in treating those diseases that have a defined molecular pathophysiologic profile.

Preprocedural serum levels of acute-phase reactants and prognosis after percutaneous coronary intervention

In this study we evaluate the value of baseline concentrations of acute-phase reactants on prognosis after percutaneous coronary intervention (PCI). Blood samples were drawn immediately before PCI to measure baseline concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), lipoprotein(a) (Lp(a)), and fibrinogen. Follow-up data were collected at 8 months. Repeat PCI, CABG, myocardial infarction, and death were recorded as major adverse clinical events (MACE). Furthermore the recurrence of angina pectoris was noted. The study included 600 consecutive patients after a successful PCI. Sixty-four percent of the patients were stented. The mean age was 61.6 years and 68.9% were male. CRP levels were significantly higher in patients who were to have repeat angina as compared with those who were not (P=0.0322). IL-6 levels were not correlated with angina or MACE. Lp(a) and fibrinogen concentrations were both significantly related to MACE (P=0.0337 and P=0.0253, respectively). Our study clearly supports the role of inflammation in restenosis after PCI as measured in statistically higher levels of Lp(a) and fibrinogen in patients with MACE and CRP in patients with repeat angina.

Acute-phase response after stent implantation in the carotid artery: association with 6-month in-stent restenosis.

To determine the prognostic importance of periintervention serum levels of acute-phase reactants in 6-month restenosis after stent implantation in the carotid artery. One hundred eight consecutive patients with 70% or greater stenosis of the internal carotid artery (ICA) according to the North American Symptomatic Carotid Endarterectomy Trial criteria underwent successful stent implantation in the ICA in a prospective cohort study. Six-month patency was evaluated at color-coded duplex ultrasonography. The association between in-stent restenosis (> or =50%, North American Symptomatic Carotid Endarterectomy Trial criterion) and C-reactive protein (CRP) and serum amyloid A levels at baseline and at 24 and 48 hours after intervention was assessed. Restenosis was found in 15 (14%) patients within 6 months. CRP level at 48 hours, exemplary for the postintervention acute-phase response, was significantly (P =.01) associated with 6-month restenosis by using multiple logistic regression analysis. Recurrent stenosis after prior stent implantation in the carotid artery (odds ratio, 9.2; 95% CI: 1.6, 53.2; P =.01) and residual stenosis of 10%-30% after stent implantation (odds ratio, 9.7; 95% CI: 1.6, 59.3; P =.01) were independent clinical predictors of restenosis. Extent of vascular inflammatory response after stent implantation in the carotid artery measured with acute-phase reactants is associated with 6-month patency. Recurrent stenosis after prior stent implantation and initial suboptimal technical result seem to be clinically relevant predictors of postangioplasty outcome.

Granzyme-positive cytotoxic cells are specifically increased in early rheumatoid synovial tissue.

To define the expression and the phenotype of granzyme (Gran) A and B positive cytotoxic cells in synovial tissue (ST) from patients with rheumatoid arthritis (RA) with respect to disease duration and activity. Using antibodies against GranA and GranB, which serve as markers of activated natural killer (NK) cells and cytotoxic T lymphocytes, ST sections from 10 patients with early RA, 10 patients with longstanding RA, and 10 patients with osteoarthritis were examined. The phenotype of Gran+ cells was determined with double-labeling techniques. Gran+ cells, the majority of which were NK cells, were found in ST from patients in all groups. Several of these cells did not express the surface markers CD16, CD56, and CD57. The highest ST expression of GranB was found in patients with early RA. In RA patients, there was a positive correlation of GranB expression with serum levels of acute-phase reactants, but not with histologic scores for inflammation. Gran+ cells are mainly NK cells, a substantial proportion of which do not express conventional NK cell surface markers. GranB expression is specifically increased in the synovial tissues of patients with RA of short duration.