Elevated C-reactive Protein Values Research Articles

FAILURE OF THE FIRST BIOLOGIC TREATMENT IN PATIENTS WITH SPONDYLOARTHRITIS: DATA FROM THE MOROCCAN REGISTRY OF BIOLOGICAL THERAPIES IN RHEUMATIC DISEASES (RBSMR)

Introduction:Spondyloarthritis is a group of chronic inflammatory rheumatic diseases that commonly affect young adults. The advent of biological background treatments has revolutionized the management of these conditions, although some patients may not respond adequately to these interventions. Objectives: To assess the prevalence of first biological treatment failure in spondyloarthritis and identify the factors associated with this outcome. Methods: Our study included patients with spondyloarthritis retained according to the ASAS criteria, aged over 18 years, treated with biological treatment, and providing written informed consent. The participants were sourced from the ten rheumatology departments in Morocco, utilizing data from the RBSMR registry, a multicenter historical-prospective registry. Primary failure was characterized by treatment inefficacy within the initial six months, while secondary failure concerns cases of ineffectivenessbeyond six months of treatment. Patients were assessed every six months with a scheduled follow-up period of three years. Inclusion began in June 2017 and ended in January 2019, when the database was first frozen. Results: A total of 194 patients were included in the study. The mean age was 40.23 years with a standard deviation of 13.68. The gender ratio was 1.73 (M/F). The average disease duration was 615.9 weeks with a standard deviation of 349.12. HLA-B27 antigen was positive in 66% of patients. Peripheral involvement was observed in 70% of patients, axial involvement in 96.4%, and enthesic involvement in 61.5%. Radiographic sacroiliitis was identified in 87.6% of patients, radiographic coxitis in 40.7%, and sonographic coxitis in 19.8%. Regarding extra-articular manifestations, 14.5% of patients experienced anterior uveitis, 6.9% had cutaneous psoriasis, and 10.7% had concomitant chronic inflammatory bowel disease. The ASDAS CRP indicated high activity in 50.9% of patients, and the BASDAI (spondyloarthritis activity index) exceeded 4 in 79.2% of patients. During the initial visit, 22.5% of patients were undergoing corticosteroid therapy, and 53.8% were receiving csDMARDs. Etanercept was the most commonly prescribed biological, accounting for 33%. Over the three-year follow-up, five primary failures and 17 secondary failures to the first biological treatment were observed (eight failures at the 12th month, six at the 18th month, and three at the 24th month), resulting in a prevalence of 11,85% for the failure of the first biological. In bivariate analysis, no statistically significant factors were found to be associated with the failure of the first biological at the 6th, 12th, or 24th month visits. However, at the 18th-month visit, both the average BASDAI and C-reactive protein (CRP) levels were statistically higher in patients who experienced failure with the first biological. Conclusion: The failure of the first biologicaltreatment is a rather rare situation in our study. Specific factors were notably linked to this failure and should be considered in patient management, particularly elevated BASDAI and CRP values. These factors have also been reported in the literature to be associated with first biological treatment failure, along with additional factors.

A cross-sectional study on clinical characteristics and severity of children with COVID-19 admitted to a teaching institute in North India.

SARS-CoV-2 infection presentation in children is usually milder than in adults but can be severe and fatal as well. Data on the pediatric population regarding severity and clinical presentation are still limited, and there is a need to have a better understanding of clinical features, severity, and laboratory parameters. To document clinical and laboratory characteristics and outcomes of children with SARS-CoV-2 in a low-middle-income country and to evaluate clinicodemographic factors and biochemical markers associated with severity and mortality. A hospital-based cross-sectional study was conducted among 112 COVID-19-positive children at a designated Level-3 center in North India. Clinical characteristics, laboratory parameters, and severity of COVID-19 cases as well as factors associated with the severity of the disease, were analyzed by descriptive statistics and a Chi-square test. The adolescent age group (age 12-18 years) was affected most (64.3%). Male patients accounted for 56.3% of total cases. Fever was the most common symptom (41.1%) followed by cough. Presenting complaints were highest from the respiratory system (32.1%) followed by the gastrointestinal (8.9%) and the neurological system (7.1%). Majority of patients had mild disease (87%) while 13% had the moderate-severe disease. Spo2 < 95% (P = 0.00001), neutrophilia (P < 0.000001), lymphopenia (P < 0.000001), elevated values of C-reactive protein (P < 0.00001), Interleukin-6 (P = 0.002), D- dimer (P = 0.00014) and respiratory symptoms as presenting complaints (P < 0.000001) were found to be significantly associated with severity of disease. The male and adolescent age group was affected most. Presenting complaints were highest from the respiratory system. Unusual presentation may have gastrointestinal or neurological presentation. Most children with COVID-19 had mild disease. Moderate to severe disease was not uncommon. Factors including neutrophilia, lymphopenia, elevated lab values of C-reactive protein, D-dimer, and interleukin-6 had a significant association with the severity of the disease. These biomarkers can help predict the severity of the disease.

Factors Associated with Length of Hospitalization in Patients with Diabetes and Mild COVID-19: Experiences from a Tertiary University Center in Serbia.

Background and Objectives: During the COVID-19 pandemic, there was an increased number of hospitalized COVID-19-positive patients suffering from type 2 diabetes mellitus (T2DM). The objective of this research study was to explore factors associated with the length of hospitalization of patients with T2DM and the mild form of COVID-19. Material and Methods: This retrospective cohort study involved all patients who tested positive for COVID-19 and those who were treated in the dedicated COVID-19 department of the University Clinical Center (UCC) in Nis between 10 September 2021 and 31 December 2021. Upon admission, patients underwent blood tests for biochemical analysis, including blood count, kidney and liver function parameters (C-reactive protein (CRP), creatinine kinase, and D-dimer), and glycemia and HbA1c assessments. Additionally, all patients underwent lung radiography. Univariate and multivariate regression analyses were employed to assess the impact of specific factors on the length of hospitalization among patients with T2DM. Results: Out of a total of 549 treated COVID-19-positive patients, 124 (21.0%) had T2DM, while 470 (79.0%) did not have diabetes. Among patients with T2DM, men were significantly younger than women (60.6 ± 16.8 vs. 64.2 ± 15.3, p < 0.01). The average hospitalization length of patients with diabetes was 20.2 ± 9.6 (5 to 54 days), and it was significantly longer than for patients without diabetes, at 15.0 ± 3.4, which ranged from 3 days to 39 (t-test ≈ 5.86, p < 0.05). According to the results of the univariate regression analysis, each year of age is associated with an increase in the length of hospital stay of 0.06 days (95% CI: 0.024 to 0.128, p = 0.004). Patients who received oxygen therapy were treated for 2.8 days longer than those who did not receive oxygen treatment (95% CI: 0.687 to 4988, p = 0.010), and each one-unit increase in CRP level was associated with a 0.02-day reduction in the length of hospitalization (95% CI: 0.004 to 0.029, p = 0.008). Based on the results of the multivariate regression analysis, each year of age is associated with an increase in the length of hospitalization by 0.07 days (95% CI: 0.022 to 0.110, p = 0.003). Patients who received oxygen therapy were treated for 3.2 days longer than those who did not receive oxygen therapy (95% CI: 0.653 to 5726, p = 0.014), and each unit increase in CRP level was associated with a 0.02-day reduction in the length of hospitalization (95% CI: 0.005 to 0.028, p = 0.004). Conclusions: Based on the presented results, COVID-19-positive patients with diabetes had, on average, longer hospitalizations than COVID-19 patients without diabetes. The hospital treatment of patients with T2DM and a milder form of COVID-19 was associated with older age, the use of oxygen therapy, and elevated CRP values. Patients who received oxygen therapy were treated approximately 3 days longer than those who did not receive this therapy.

Values of White Blood Cell Count and C-Reactive Protein in Diagnosis of Acute Appendicitis

Background and objectives. Acute appendicitis is one of the most common surgical emergencies. Accurate diagnosis of acute appendicitis is based on careful history, physical examination, and laboratory investigation. The purpose of this study is to investigate the value of white blood cells (WBC) and C-reactive protein (CRP) in the diagnosis of acute appendicitis. Methods. A retrospective analysis of 350 files of patients who underwent appendectomy was conducted. Selected files were those patients who were admitted to ALmasara clinic Tripoli Libya between Aug 2011 to July 2023, ages of patients ranged from 18 to 80 years. Statistical analysis was performed using SPSS version 26 software. A statistical procedure was implemented to compare the hematologic parameters in two groups (Males and Females) to determine if there was any significant difference between them. Means of WBC, Neutrophil, Lymphocyte and CRP were compared between two groups by an independent one-way analysis of variance (ANOVA). Results. This study consisted of 350 participants who were diagnosed with appendicitis. The results showed that about (69.4%) of appendicitis patients exhibited a high white blood cell count (leukocytosis). Slightly over half (52.6%) of the participants had an elevated neutrophil percentage (neutrophilia). Approximately (64.3%) of the appendicitis patients had decreased lymphocyte percentage (lymphopenia). In relation to CRP values, the study showed that most participants (76.5%) had positive CRP results. Conclusion. Individuals with appendicitis have higher levels of leukocytes, neutrophils, and C-reactive protein, and decreased lymphocyte counts. Elevated WBC and CRP values together provide a better specificity and positive predictive value than individual markers.

The Predictive Value of Plasma Sodium and Other Laboratory Parameters in Determining Complicating Appendicitis in Children

Objective: Finding a reliable preoperative predictor of complicated acute appendicitis (AA) has been a challenging diagnostic problem. The present study aimed to identify potential factors that may predict complicated AA in the pediatric emergency department (ED) based on routine, widely available laboratory tests on admission to the ED, including plasma sodium concentration. Methods: We retrospectively reviewed clinical and laboratory data of pediatric patients with AA who underwent emergency surgery at our department between January 2020 and December 2022. The patients were divided into two groups: histopathologically proven complicated AA (n = 80) and noncomplicated AA (n = 155). Results: Complicated AA was associated with reduced plasma sodium and chloride concentrations (p < 0.001, both), decreased values of lymphocytes (p = 0.002), elevated C-reactive protein (CRP) (p < 0.001), and elevated values of white blood cells (WBC) and neutrophils (p = 0.012 and 0.001, respectively). In binomial logistic regression, increased levels of CRP and WBC and decreased levels of sodium were predictors of complicated AA. The area under the receiver operating characteristic curve was 0.825 (95% confidence interval: 0.764, 0.886). Conclusion: We identified mild hyponatremia and elevated CRP and WBC values as potential markers for distinguishing complicated from uncomplicated pediatric AA with implications for surgical approaches for treating complicated AA and conservative approaches for treating uncomplicated AA.

Do Elevated Serum C-Reactive-Protein Levels Excuse Delayed Surgery for Femoral Neck Fractures?

In elderly patients with femoral neck fractures, preoperative serum C-reactive protein (CRP) values might be elevated due to active infections. Although there are limited data on CRP as a predictor of periprosthetic joint infection (PJI), out of concern, this could lead to delayed surgery. Therefore, we aim to investigate whether elevated serum-CRP levels justify delayed surgery for femoral neck fractures. A retrospective analysis was performed of the records of patients undergoing arthroplasty who were found to have an elevated CRP level of 5 mg/dL or more between January 2011 to December 2020. The patients were stratified to three groups, according to initial serum CRP levels at a cut off of 5 mg/dL and the time between admission and surgery (<48 vs. ≥48 h after admission). This study revealed that the patients with elevated serum CRP levels and delayed surgery showed a worse survival rate and significantly more postoperative complications than the patients on whom surgery was performed immediately. There were no significant differences in terms of PJI and prolonged wound healing in the inter-group comparison. Therefore, delays to surgery on the basis of elevated CRP values offer no benefits to patients with femoral neck fractures.

Role of Prognostic Markers as a Predictor of Mortality and Short-Term Prognosis in COVID.19

Introduction: As the world is slowly out of its second wave wrecked by the Delta strain, the world population is now struck once again with a new strain of COVID-19. As the outbreak is spreading, prognostic markers such as C-reactive protein (CRP), D-dimer, and ferritin levels can help the physician in predicting clinical outcomes at an early stage. Materials and Methods: Our study made an analysis of patients presented to the emergency medicine department with positive COVID antigen or reverse transcriptase–polymerase chain reaction (RT-PCR) results. Patient demographic data, clinical profile, and values of D-dimer, CRP, and serum ferritin were obtained. All the patients were subjected to standard treatment according to COVID protocol. Results: Our study population was comprised of 312 patients. Among them, 162 (51.9%) were male, and 150 (48.1%) were female. Our study found that among 45 patients, who had expired, 38 (84.4%) patients had elevated D-dimer values, 45 (100%) patients had elevated CRP values, and 41 (91.1%) patients had elevated ferritin values. P =001, which is statistically significant. Conclusion: Our study found that values of prognostic markers such as D-dimer, CRP, and serum ferritin at the time of presentation can be used as a predictor of mortality and risk stratification and predict the probable need for prolonged hospital and intensive care unit stay. These values also correlate well with the disease severity of the patients. They can also be used to predict the probable need for respiratory support during the course of a stay in the hospital.

The relationship between structural analysis of the hand and clinical characteristics in psoriatic arthritis

Up to now, there is only limited information available on a possible relationship between clinical characteristics and the mineralization of metacarpal bones and finger joint space distance (JSD) in patients with psoriatic arthritis (PsA). Computerized digital imaging techniques like digital X-ray radiogrammetry (DXR) and computer-aided joint space analysis (CAJSA) have significantly improved the structural analysis of hand radiographs and facilitate the recognition of radiographic damage. The objective of this study was to evaluate clinical features which potentially influence periarticular mineralization of the metacarpal bones and finger JSD in PsA-patients. 201 patients with PsA underwent computerized measurements of the metacarpal bone mineral density (BMD) with DXR and JSD of all finger joints by CAJSA. DXR-BMD and JSD were compared with clinical features such as age and sex, disease duration, C-reactive protein (CRP) as well as treatment with prednisone and disease-modifying antirheumatic drugs (DMARDs). A longer disease duration and an elevated CRP value were associated with a significant reduction of DXR-BMD, whereas JSD-parameters were not affected by both parameters. DXR-BMD was significantly reduced in the prednisone group (–0.0383 g/cm²), but prednisone showed no impact on finger JSD. Patients under the treatment with bDMARDs presented significant lower DXR-BMD (–0.380 g/cm²), JSDMCP (–0.0179 cm), and JSDPIP (–0.0121 cm) values. Metacarpal BMD was influenced by inflammatory activity, prednisone use, and DMARDs. In contrast, finger JSD showed only a change compared to baseline therapy. Therefore, metacarpal BMD as well as finger JSD represent radiographic destruction under different aspects.

C-Reactive Protein Levels in Children with Acute Bronchiolitis.

Results Of 287 patients, 229 (79.2%) were included. 132 (57.6%) were males. Median presentation age was 3.7 (interquartile range (IQR), 1.27-12.33) months. Median CRP level was 10.4 (IQR, 2.8-35.1) mg/L. CRP was high in 167 (72.9%) patients. 17.6% (33/187 patients) had confirmed bacterial coinfection. Respiratory syncytial virus (RSV) was detected in 84 (36.7%) patients. Mean CRP level was higher in RSV-negative compared to RSV-positive patients, 31.3 ± 44.3 versus 21.5 ± 27.7 mg/L, respectively (P = 0.042). Respiratory viral serology profile was positive in 34.7% (17/49 patients). 66.9% (107/160 patients) had positive chest X-ray. Antibiotics were used in 78.1% (179/227 patients). Thirteen (5.7%) patients required intensive care, five (2.2%) had surgical intervention, four (1.8%) required endotracheal intubation, and four (1.8%) died. Patients with high CRP were older at presentation (P < 0.0001) and had more fever (P < 0.0001) and cough (P = 0.002), but lower hemoglobin level (P < 0.0001) compared to those with normal CRP. Fever (P = 0.016) and hemoglobin level (P = 0.002) were independent factors. Conclusion Most children with acute bronchiolitis had high rate of elevated CRP values that did not correlate with the rate of bacterial coinfection. High CRP levels were found in older children, those presented with more fever and cough, and had a lower hemoglobin level despite that those factors were previously reported to be associated with disease severity and bacterial coinfection. This study also showed a high overall rate of antibiotic prescriptions in mostly viral disease.

C-reactive protein as an indicator of polymorbidity in patients with arterial hypertension

Aim of the study was to investigate the role of C-reactive protein as an indicator of multimorbidity in patients with arterial hypertension.Material and methods. A retrospective archival study of the data of 1958 patients with arterial hypertension who were examined and treated at the clinic of the Federal Research Center for Fundamental and Translational Medicine (Novosibirsk) was carried out. 2 groups of patients were allocated depending on the concentration of C-reactive protein in the blood serum: normal and elevated (&gt; 5 mg/l). A comparative analysis of the severity of polymorbidity, as well as clinical, laboratory and biochemical parameters in the selected groups were carried out.Results. It has been established that patients with arterial hypertension with elevated values of C-reactive protein had higher rates of transnosological and transsystemic polymorbidity, accompanied by changes in lipid, carbohydrate and purine metabolism (a decrease in high-density lipoprotein cholesterol, an increase in the concentration of glucose and uric acid in blood serum, an increase in the index atherogenicity), as well as an increase in the content of fibrinogen in the blood serum.Conclusions. The concentration of C-reactive protein in the blood serum can serve as a biochemical marker of polymorbidity in patients with arterial hypertension.

C-REACTIVE PROTEIN/ALBUMIN RATIO AND NEUTROPHIL-LYMPHOCYTE RATIO AS PREDICTORS OF COVID-19 SEVERITY

Coronavirus disease 2019 (COVID-19) was announced in early December 2019. By genome sequencing, the virus was recognised. From Wuhan City, the virus spread globally. The pandemic situation was declared by the World Health Organization.The first case of COVID-19 in Indiawas reported in Kerala on January 27, 2020.The clinical features varied with disease severity. Most COVID-19 patients have non-severe manifestations and show a good prognosis. However, patients with severe disease may progress to pulmonary dysfunction, multiple organ dysfunction, and death. COVID-19 related to a considerable mortality rate in older patients and cases had other morbidities. Studies suggested that the inflammatory storm is a common finding in other coronaviruses.Similarly, increases in the inflammatory markers like C-reactive protein (CRP),ferritin,interleukin-6 (IL-6) and were described in COVID-19 (1). Albumin levels decreased in the inflammatory conditions reduced levels were confirmed in severe COVID-19 patients. Hypoalbuminemia and high CRP/albumin ratio were previously linked to the mortality of various clinical conditions as critically ill patients.To avoid the unnecessary or inappropriate utilisation of the healthcare resources, early prediction of the severity of COVID-19 will be helpful. Severity prediction will also improve the prognosis by reducing the mortality rate.Thus, this study aimed to evaluate the role of inflammatory markers in estimating the severity and predicting the prognosis of COVID-19. This study hypothesised that elevated values of CRP/ albumin ratio and the neutrophil-lymphocyte ratio at the time of COVID-19 diagnosis are associated with COVID-19 severity and mortality.

Multiple intravenous antibiotics usage is associated with intravenous immunoglobulin resistance in Kawasaki disease

Kawasaki disease (KD) is a form of systemic vasculitis that primarily affects children under the age of 5 years old. Antibiotics are often prescribed for KD patients even before a diagnosis is made due to their prolonged fever and elevated inflammatory markers. Therefore, the purpose of this study was to investigate the impact of antibiotics usage on the disease outcome of KD. We carried out a retrospective chart review of children between 2005 and 2017 for initial immunoglobulin (IVIG) treatment of KD. KD children with initial IVIG treatment more than 10 days after the onset of symptoms were excluded. In total, 280 children were eligible for this study, among which 209 had been treated with antibiotic(s) and 71 had not been. The IVIG resistance rates were 5.6% (4/71), 8.9% (10/112), and 21.6% (21/97) in non-users, single-drug users, and multiple-drug users, respectively (r=0.205, p=0.003). The IVIG resistance rate of the multiple antibiotics drug users in KD patients was significantly higher than the other two groups. Furthermore, the likelihood of IVIG resistance was found to increase with elevated C-reactive protein (CRP) values (1.010/unit, p<0.001) but not with total white blood cell (WBC) count (p=0.466). The probability of IVIG resistance increases with elevated CRP values and the use of multiple IV antibiotics, thus indicating that physicians should be prudent in administering multiple IV antibiotics when treating assumed infections in KD children.

Cytokine Profile Elevations on Admission Can Determine Risks of Severe Acute Pancreatitis in Children

To utilize a Luminex platform to examine multiple cytokines simultaneously as well as clinical laboratory testing to identify markers that predict acute pancreatitis severity in the pediatric population on admission. Patients (<19years of age) prospectively enrolled over a 4-year period in a single institution acute pancreatitis database were included in separate derivation and validation cohorts. Plasma samples were obtained within 48hours of admission and stored for analysis. Samples from mild acute pancreatitis and severe acute pancreatitis (moderately severe and severe combined) were analyzed using Luminex panels and C-reactive protein (CRP) testing. The derivation cohort examined 62 cytokines in 66 subject samples (20 control, 36 mild acute pancreatitis, 10 severe acute pancreatitis) and identified interleukin 6 (IL-6) (P=.02) and monocyte chemotactic protein-1 (MCP-1) (P=.02) as cytokines that were differentially expressed between mild and severe acute pancreatitis. Our validation cohort analyzed 76 cytokines between 10 controls, 19 mild acute pancreatitis, and 6 severe acute pancreatitis subjects. IL-6 (P=.02) and MCP-1 (P=.007) were again found to differentiate mild acute pancreatitis from severe acute pancreatitis. CRP values were obtained from 53 of the subjects, revealing a strong association between elevated CRP values and progression to severe disease (P<.0001). This study identified and validated IL-6 and MCP-1 as predictors of severe acute pancreatitis using 2 distinct cohorts and showed that CRP elevation is a marker of progression to severe acute pancreatitis. These biomarkers have not been extensively studied in the pediatric acute pancreatitis population. Our data allows for risk-stratification of patients with acute pancreatitis, and represent novel insight into the immunologic response in severe acute pancreatitis.

AB0370 UTILITY OF CRP AND ESR IN THE DIAGNOSIS OF GIANT CELL ARTERITIS RELAPSE IN A PHASE 2 TRIAL OF MAVRILIMUMAB

Background:No universally accepted definition of flare currently exists in giant cell arteritis (GCA). Although relapses are defined mostly on clinical grounds (recurrence of GCA-related signs/symptoms), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) help clinicians assess disease activity. In fact, &gt;70% of patients on glucocorticoids (GCs) alone have increased CRP or ESR when the disease is active. In contrast, tocilizumab, given its IL-6-blockade effect in the liver, rapidly reduces CRP and ESR levels, rendering them unreliable for disease activity monitoring. Mavrilimumab – a GM-CSF receptor α inhibitor with demonstrated efficacy in a Phase 2 GCA trial1 – downregulates inflammation upstream of IL-6. We hypothesized that mavrilimumab would not interfere with the utility of CRP and ESR in monitoring disease activity and in identifying GCA relapse.Objectives:To analyze the relationship between CRP/ESR and clinical disease activity in GCA patients treated with mavrilimumab.Methods:New-onset and relapsing GCA patients with active disease were recruited. GC-induced remission (no GCA symptoms and CRP &lt;1 mg/dL or ESR &lt;20 mm/hr) was required by baseline. Patients were randomized 3:2 to mavrilimumab 150 mg or placebo subcutaneously every 2 weeks plus a protocol-defined 26-week prednisone taper. The primary efficacy endpoint was time to relapse by Week 26. Relapse (adjudicated) was defined as recurrent GCA-related signs/symptoms, including new/worsening vasculitis on imaging, concurrent with CRP ≥1 mg/dL and/or ESR ≥30 mm/hr. CRP and ESR were also measured periodically during the trial.This post hoc analysis assessed the association of recurrent GCA-related signs/symptoms with concurrent CRP or ESR elevation post-randomization by treatment arm. We also assessed the proportion of patients with CRP or ESR elevation without GCA-related signs/symptoms up to Week 26.Results:Seventy patients were enrolled (mavrilimumab, N=42; placebo, N=28). The association of CRP or ESR elevation with unequivocal GCA-related signs/symptoms post-randomization was consistent regardless of treatment arm: 8/8 in the mavrilimumab group and 13/13 in the placebo group (Table 1). During relapse, median (range) CRP was 1.8 (1.4 – 8.4) mg/dL (mavrilimumab group) and 1.8 (1.1 – 9.0) mg/dL (placebo group). Corresponding ESR values were 39.5 (30 – 102) mm/hr (mavrilimumab group) and 49 (31 – 101) mm/hr (placebo group). Four mavrilimumab recipients had self-limited, equivocal GCA-related signs/symptoms without concurrent CRP or ESR elevation; all 4 completed the prespecified GC taper by Week 26 without need for rescue GCs, so relapse was not confirmed. At least 1 elevated CRP or ESR value in the absence of GCA-related signs/symptoms was observed in 58.8% of mavrilimumab recipients and 93.3% of placebo recipients by Week 26.Conclusion:The observed association of CRP or ESR elevation with GCA-related signs/symptoms is consistent with the upstream mechanism and supports the utility of the stringent protocol definition of relapse. The frequency and magnitude of CRP and ESR elevations at relapse were similar in both treatment groups, suggesting that CRP and ESR remain useful in assessments of disease activity in mavrilimumab-treated patients. CRP and ESR elevations without GCA-related signs/symptoms occurred more often in placebo recipients.

Changes in the levels of some cytokines when using blood purification in COVID-19 patients

The use of high-adsorption membrane hemofiltration in COVID-19 positive patients to reduce the severity of a cytokine storm is clearly beneficial but at the same time, there are no certain procedures for its practical use.The objective:to study the change in the levels of IL-6 and IL-18 in response to prolonged (24-72 hours) high-adsorption membrane hemofiltration.Subjects and methods. We retrospectively analyzed the data on IL-6 and IL-18 levels and their changes in 69 patients who were COVID-19 positive and had different degrees of lung damage, they had received high-adsorption membrane hemofiltration during their stay at the intensive care unit. The extent of lung lesions was the following: 4 people had CT-2, 44 people had CT-3, and 21 patients had CT-4. 18 patients had an unfavorable outcome of the disease. High-adsorption membrane hemofiltration (Prismaflex) was used in the group of patients who had clinical signs of the rapid progression of the disease and also such laboratory findings as elevated values of C-reactive protein (above 100 mg/L), ferritin (more than 600 μg/L), and progression of lymphopenia. This intervention lasted for 24 hours at CT-2/3, and 48 hours at CT-4. The effluent dose was 30.0 ± 6.4 ml/kg/h. The levels of IL-6, IL-18, and procalcitonin were tested before and after the completion of the intervention, and the difference between their concentration before and after high-adsorption membrane hemofiltration was calculated. The potential association between received data (IL-6, IL-18, delta of IL-6, delta of IL-18) and degree of lung damage and outcomes was analyzed.Results.It was detected that the more the lungs were affected, the lower levels of IL-6 and IL-18 were and vice versa and this correlation was not associated with the use of tocilizumab (used in 44 people). The maximum decrease in the level of cytokines was observed in the group of patients with CT-2. There was a significant association between the delta of IL-6 (F = 6.69; p ≤ 0.05) and the outcome which was especially pronounced in people with a favorable outcome.Conclusion.As the inflammation progresses in the lungs, the levels of IL-6 and IL-18 decrease which may be a manifestation of the depletion of the cytokine storm. The use of prolonged high-adsorption membrane hemofiltration (24-48 h) allows reducing the level of cytokines. The delta value reflects a decrease in IL-6 concentration, it significantly correlates with the outcome which indicates the importance of using this method in a continuous mode.

Factors Associated With Elevated Inflammatory Markers Prior to Shoulder Arthroplasty.

Background: Preoperative erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) ranges for several shoulder arthroplasty indications are not well understood. Purpose: We sought to compare preoperative ESR and CRP values for a variety of shoulder arthroplasty indications and evaluate risk factors for elevated preoperative ESR and CRP values. Methods: We conducted a retrospective cohort study of shoulder arthroplasty cases performed at a single academic medical institution from 2013 to 2018. Preoperative ESR and CRP values for 235 shoulder arthroplasties with various indications were recorded. Independent risk factors for elevated values (CRP > 10.0 mg/L and ESR > 30.0 mm/h) were determined via multiple variable logistic regression. Results: Patients undergoing shoulder arthroplasty for osteoarthritis had an ESR (mean ± SD) of 22.6 ± 17.8, with 29.8% of patients elevated, and a CRP of 6.5 ± 6.4, with 25.5% of patients elevated. Arthroplasty for acute fracture and prosthetic joint infection (PJI) had higher preoperative ESR and CRP values. Multivariate analysis identified several predictors of elevated ESR, including infection, acute fracture, diabetes, and female sex. It also identified predictors of elevated CRP, including infection, acute fracture, and younger age. Conclusions: Preoperative ESR and CRP values may be elevated in 25% to 30% of patients undergoing primary shoulder arthroplasty. Arthroplasty for both acute fracture and PJI, along with several other patient factors, was associated with elevated preoperative ESR and CRP. Thus, routine collection of ESR and CRP preoperatively may not be of benefit, as elevated values are common. Further study is warranted.

Prognostic Value of Preoperative Inflammatory Markers in Melanoma Patients with Brain Metastases.

Background: Metastatic melanoma disease is accompanied by highly systemic inflammatory responses. The prognostic value of preoperative laboratory inflammation markers in brain metastatic melanoma patients has not been adequately investigated so far. Methods: Preoperative inflammatory blood parameters were correlated to overall survival (OS) rates in melanoma patients that underwent surgery for brain metastasis (BM) between 2013 and 2019 at the authors’ institution. Receiver operating characteristic (ROC) analyses were used for cutoff determination of routine laboratory parameters. Results: Median OS in the present cohort of 30 melanoma patients with surgically treated BM was 7 months (95% confidence interval (CI) 5.7–8.3). Initial elevated C-reactive protein (CRP) levels (>10 mg/L), neutrophil-to-lymphocyte ratio (NLR) ≥ 4, platelet-to-lymphocyte ratio (PLR) ≥ 145, and lymphocyte-to-monocyte ratio (LMR) < 2 were associated with significantly reduced OS rates. Conclusions: The present study identifies several preoperative peripheral inflammatory markers as indicators for poor prognosis in melanoma patients with BM undergoing neurosurgical treatment. Elevated initial CRP values, higher NLR and PLR, and lower LMR were associated with reduced OS and, thus, might be incorporated into preoperative interdisciplinary treatment planning and counseling for affected patients.

THE RELEVANCE OF PREDICTING RHEUMATOID ARTHRITIS SEVERITY: FACILITATING EARLY TREATMENT IN POOR PROGNOSIS AND PROGNOSTIC LABORATORY MARKERS OF JOINT DAMAGE

Simultaneous testing especially of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and rheumatoid factor (RF), which are reversible measures of inflammation, together with clinical variables of inflammatory synovitis are recommended for evaluation of disease activity. In this study 35 patients (pts) with early RA were included, while 35 pts were in the healthy control group. Pts were treated with Methotrexate at an average dose of 10 mg once weekly. RA was evaluated following the dynamics of changes of the mean values of ESR, CRP and RF. Statistical analysis showed statistically significant differences among mean values of ESR in the four time intervals (p=0.00002). Regarding CRP, there were statistically significant differences among mean values in all four time intervals (p=0.0428) (standard deviations were with great variations). There were no statistically significant differences of RF in the four time intervals (p=0.573). We found high values of CRP and RF in most of the patients. In spite of the therapy with Methotrexate, disease progression continues especially in patients with elevated values of ESR, CRP and RF, which are shown as predictors for aggressive course of disease. This enables selection of high risk groups of patients for aggressive course of disease and points to the need of early and aggressive treatment. Keywords: rheumatoid arthritis, reactants of the acute phase, rheumatoid factor

Risk Factors and Clinical Parameters Associated with the Severity of the Clinical Picture of Enteroviral Meningitis in Neonates Treated in the Tertiary Neonatal Unit in Slovenia

O bjective – To describe the clinical course of enteroviral meningitis in neonates in a tertiary neonatal unit. M aterials and M ethods – We analysed maternal and perinatal history, clinical and laboratory data, therapy and short-term outcomes in neonates who had enterovirus detected in the cerebrospinal fluid (CSF) and compared the group of neonates with early-onset (≤7 day of life (DOL)) meningitis to the group of neonates with late-onset (>7 DOL) meningitis. R esults – A total of 30 term neonates were included (63% male). Majority (73%) presented during the summer and autumn months, 57% were in contact with siblings who had signs of viral disease, 10% of mothers had signs of viral disease at delivery or shortly after. Neonates presented with irritability (97%), fever (83%), feeding intolerance (66%), diarrhoea (56%), nonspecific rash (23%), seizures (10%). Both the C-reactive protein (CRP) and pro-calcitonin (PCT) were elevated in 23% of patients; only CRP was elevated in 57%, only PCT in 37%. Twelve (40%) had elevated leukocyte count in the CSF. Antibiotics were initiated in 80% (median treatment 1.5 days). Majority of the neonates with early-onset meningitis had jaundice, higher urea and creatinine serum concentration, and lower thrombocyte numbers. Conclusion – Enteroviruses are an important cause of meningitis in neonates during summer and autumn months. Neonates in close contact with ill family members or carers are particularly at risk. Neonates present with fever, irritability, feeding intolerance, diarrhoea, normal or mildly elevated CRP and/or PCT values. Neonates with early-onset meningitis had a similar grade of infection and outcome as did the neonates with late-onset disease. Our findings confirm that enteroviral meningitis car- ries a good prognosis in the majority of neonates.

Does the Inion OTPSTM absorbable plating system induce higher foreign-body reaction than titanium implants? An experimental randomized comparative study in rabbits

Hardware removal after complete fracture healing is a laborious and traumatic procedure that bears the risks of refracture, infection, and soft tissue damage. Absorbable materials for fracture fixation have the advantage of eliminating the need for removal; however, they may stimulate a considerable inflammatory response. For that reason, we compared in a prospective randomized experimental animal model study the incidence of foreign-body reactions between Inion OTPSTM absorbable plate implants, consisting of carbon trimethylene, L-polylactic acid, and D, L-polylactic acid, and conventional titanium plates. Seventy rabbits were equally divided into two groups. Titanium (Group A) or absorbable (Group B) plates and screws were implanted in the femoral shaft of the rabbits. Wound reaction and laboratory tests including white blood cell count (WBC), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) values were measured and compared at different time points. Radiographs and histological analysis of tissue samples from all animals were also used to identify potential foreign-body reactions. WBC showed normal values in both groups. In Group A, ESR levels were higher at all time points but CRP values were normalized at 3 weeks postoperatively. In Group B, ESR and CRP levels reached a peak at 3 weeks and were above normal values throughout the whole experiment (p < 0.001). Radiologic examination revealed periosteal thickening and surrounding sclerosis in 23 out of 35 animals of Group B (66%). All Group A animals had normal radiographic findings. Histopathology showed a typical non-specific foreign-body reaction in all animals in Group B (100%) but none in Group A. However, only four of them (11.8%) developed non-infected wound complications and showed significantly elevated CRP and ESR values (p = 0.054). Although Inion OTPSTM Biodegradable Plating System stimulates a foreign-body reaction, only a small but not negligible percentage of almost 12% may lead to wound problems. However, this difference compared to titanium plates was of borderline not statistically significant. Future studies should focus on the development of absorbable implants with improved biocompatibility aiming to further decrease the potential of foreign-body reaction and eliminate the need for additional reoperative procedures.