C-reactive Protein Measurements Research Articles

Leucine-Rich Alpha-2 Glycoprotein Is Associated With Transmural Inflammation Assessed by Intestinal Ultrasound in Patients With Crohn's Disease.

Intestinal ultrasound (IUS) is a non-invasive tool for evaluating transmural inflammation in Crohn's disease (CD). However, its utility is constrained by operator dependency and limited accessibility. To explore the feasibility of serum biomarkers-specifically leucine-rich alpha-2 glycoprotein (LRG)-as an alternative to IUS for assessing transmural inflammation. This retrospective, single-centre study included patients with CD who underwent IUS and measurements of LRG and C-reactive protein (CRP). We assessed correlations between biomarkers and five IUS scores (Limberg score, Bowel Ultrasound Score (BUSS), International Bowel Ultrasound Segmental Activity Score (IBUS-SAS), Simple Ultrasound Score (Simple-US) and Simple Ultrasound Score for Crohn's Disease (SUS-CD)) using receiver operator characteristic curve analysis and Spearman's rank correlation coefficient. We conducted subgroup analyses for patients in clinical remission. We analysed 213 IUS examinations performed on 97 patients; 170 (80%) IUS were during clinical remission. The area under the curve for LRG for each IUS score (0.76, 0.80, 0.77, 0.75 and 0.69, respectively) was superior to that of CRP and was statistically significant, particularly for LS, BUSS, IBUS-SAS and Simple-US (p < 0.001, p = 0.018, p < 0.001 and p < 0.001, respectively). Predictive values remained consistent among patients in remission. LRG demonstrated excellent correlation with IUS scores in both the overall patient population and those in remission. LRG showed a robust correlation with IUS scores, suggesting its potential as a novel indicator for targeting transmural healing in patients with CD.

Impact of systemic inflammation and disease activity on the incidence of interstitial lung disease in patients with rheumatoid arthritis – a nested case-control study within the German biologics register RABBIT

BackgroundTo investigate the association between the development of incident interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA) and the disease activity of RA with its various components, especially C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR).MethodsWe analysed data from RA patients, observed in the German biologics register RABBIT between 2001 and 2021. In a nested case-control study, patients with a reported incident ILD diagnosis during follow-up were matched 1:5 to patients without ILD. Matching criteria were sex, age, RA duration, date of enrolment and observation time. Defined by a directed acyclic graph (DAG), we adjusted the conditional logistic regression models for rheumatoid factor, smoking, chronic obstructive pulmonary disease and tuberculosis/chronic viral infections to investigate the impact of disease activity/systemic inflammation. Mean and categorized values were analysed within 12 months prior to ILD and during the entire observation time. Additionally, two sensitivity analyses were performed, using validated ILD cases only and considering ILD cases with an observation time of more than 12 months.ResultsWe identified 139 RA patients with incident ILD and matched them to 686 controls. In 94 cases the diagnosis could be validated, and 98 cases had a follow-up of > 12 months. The averaged DAS28 composite score (including ESR or CRP) was not associated with developing RA-ILD (odds ratios 1.16 [95% confidence interval: 0.97–1.40] and 1.06 [0.86–1.29], respectively). However, single measures of inflammation, log ESR (1.86 [1.35–2.57]) and log CRP (1.55 [1.21–1.97]), were significantly associated with an increased RA-ILD risk. A higher risk for ILD was also revealed for persistently high inflammation. Other DAS28 components showed no significant associations with RA-ILD. These results were consistent for values over the entire observation time of a patient and within 12 months prior to the ILD. Sensitivity analyses confirmed these findings.ConclusionHigher levels of systemic inflammation, as indicated by ESR and CRP, but not joint counts or patient’s global assessment, were significantly associated with the occurrence of incident ILD in patients with RA. As possible predictor for the development of RA-ILD, systemic inflammation should be monitored closely and independently of joint count results.

Plasma ferritin, C-reactive protein, and adenosine deaminase levels in tuberculous lymphadenitis and pleuritis and their role in monitoring treatment response

BackgroundWe aimed to assess the plasma levels of ferritin, C-reactive protein (CRP), and adenosine deaminase (ADA) at baseline and their utility as biomarkers to monitor response to treatment in extrapulmonary tuberculosis (EPTB) patients.MethodsProspective measurements of ferritin, CRP, and ADA were done in unstimulated plasma samples of 92 EPTB (49 TB lymphadenitis and 43 TB pleuritis) patients registered for anti-TB treatment. Blood samples were taken at the start, 2, and 6 months of treatment, plasma levels of ferritin and CRP were measured by the enzyme-linked immunosorbent assay and ADA levels by kinetic chemistry method at each time point. Data was analyzed using SPSS version 22. Non-parametric tests were used for paired analysis and two groups’ comparison. Spearman’s rank test was used for correlation analysis. A Chi-square test was used for categorical variables. A p-value < 0.05 was considered statistically significant.ResultsBefore the start of treatment, plasma levels of ferritin were raised in 13% and 45%, CRP in 21% and 64%, and ADA in 70% and 60% of TB lymphadenitis and pleuritis cases respectively. Levels of all three biomarkers with raised values at baseline decreased significantly with treatment at both 2 and 6 months in all patients. [Ferritin (2 months p = 0.001, 6 months p < 0.001), CRP (2 months p < 0.001, 6 months p < 0.001), ADA (2 months p = 0.039, 6 months p < 0.004)]. Plasma levels of ferritin (median 300 ng/ml range = 145–758 ng/ml) and CRP (median 11.73 mg/L, range = 10.45–17.84 mg/L) were significantly higher in TB pleuritis patients, while the levels of ADA were not significantly different among the two groups. Biosignatures generated by different combinations showed that a combination of all three biomarkers could predict treatment response in 83% and 100% of all patients at 2 and 6 months of treatment respectively.ConclusionA combination of serum ferritin, CRP, and ADA shows a promising role in monitoring response to treatment in TB lymphadenitis and TB pleuritis patients. Similar studies in larger cohorts are needed to establish a definite role of these biomarkers in EPTB patients.

Elevated Interleukin-6 Levels as a Potential Marker of Neonatal Morbidity in Full-term Infants With Polycythemia: A Prospective Study.

To research and show that interleukin-6 (IL-6) and c-reactive protein (CRP), which can be used as infection markers, are also higher among newborns with polycythemia. The study took place in the neonatal intensive care unit of Zekai Tahir Burak Maternity Teaching and Research Hospital. Infants with a gestational age of >37 weeks were included in the study. Infants with chorioamnionitis, perinatal asphyxia, and positive blood culture were excluded from the study. Blood samples were obtained six hours after the delivery from the peripheral vein of the infants for measurements of central hematocrit, blood culture, IL-6, and CRP. Infants with a venous hematocrit value of >65% were grouped as the "polycythemia group," and the ones with a venous hematocrit value of <65% were designated as the "control group." Observation of significantly higher levels of CRP and IL-6 among newborns admitted to the neonatal intensive care unit due to different causes (such as respiratory distress, hypoglycemia, and feeding intolerance), but significantly higher IL-6 levels in newborns with polycythemia. Thirty-five newborns (18 infants in the polycythemia group and 17 infants in the control group) were enrolled in the study. The IL-6 values for the polycythemia group were higher than the upper normal limits (mean ± 2SD, 37.6 ± 55 vs 12 ± 5pg/dL, respectively; P = 0.00). The IL-6 values of the polycythemia group were found to be higher than the IL-6 values of the control group, with a mean ± 2SD of 37.6 ± 55 vs 6.3 ± 3.4pg/dL, respectively; this was significant (P = 0.00). Although the CRP values of the polycythemia group were found to be slightly higher than those of the control group (a mean ± 2SD of 3.06 ± 4.07 vs 1.54 ± 2.21mg/dL, respectively, P > 0.05), this was not significant. This study found a significant and robust statistical correlation between IL-6 and v. Hct values (P = 0.01, rs = 0.641). Contrary to IL-6 levels, however, a meaningful relationship was not found between CRP and v.htc values (P = 0.286; rs = 0.184).

Resolution of tuberculosis blood RNA signatures fails to discriminate persistent sputum culture positivity after 8 weeks of anti-tuberculous treatment.

Concerted efforts aim to reduce the burden of 6 months of anti-tuberculous treatment for tuberculosis (TB). Treatment cessation at 8 weeks is effective for most but incurs increased risk of disease relapse. We tested the hypothesis that blood RNA signatures or C-reactive protein (CRP) measurements discriminate 8-week sputum culture status, as a prerequisite for a biomarker to stratify risk of relapse following treatment cessation at this time-point. We identified blood RNA signatures of TB disease or cure by systematic review. We evaluated these signatures and CRP measurements in a pulmonary TB cohort, pre-treatment, at 2 and 8 weeks of treatment, and sustained cure after treatment completion. We tested biomarker discrimination of 8-week sputum culture status using area under the receiver operating characteristic curve (AUROC) analysis and, secondarily, assessed correlation of biomarker scores with time to culture positivity at 8 weeks of treatment. 12 blood RNA signatures were reproduced in the dataset from 44 individuals with sputum culture-positive pulmonary TB. These normalised over time from TB treatment initiation. 11 out of 44 cases with blood RNA, CRP and sputum culture results were sputum culture-positive at 8 weeks of treatment. None of the contemporary blood RNA signatures discriminated sputum culture status at this time-point or correlated with bacterial load. CRP achieved modest discrimination with AUROC 0.69 (95% CI 0.52-0.87). Selected TB blood RNA signatures and CRP do not provide biomarkers of microbiological clearance to support TB treatment cessation at 8 weeks. Resolution of blood transcriptional host responses in sputum culture-positive individuals suggests Mycobacterium tuberculosis may colonise the respiratory tract without triggering a detectable immune response.

Retrospective Evaluation of C-reactive Protein for Ruling Out Infection After Cesarean Section.

Infection after cesarean section is a major contributor to maternal morbidity. Measurement of C-reactive protein (CRP) is a laboratory test frequently conducted to rule out or confirm postoperative infection. The present study aimed to evaluate whether CRP is a suitable tool for ruling out infection after cesarean section and whether there are any reliable cut-off values. 2056 patients with cesarean section (CS) over a 3-year period were included in a retrospective analysis. Outcome parameters and risk factors for postoperative infection were collected. CRP values from preoperative and postoperative tests were compared. Cut-offs for ruling out infection were assessed. Among 2056 CSs, postoperative infection occurred in 78 cases (3.8%). The prevalence of infection in emergency CS was lowest, at four out of 134 (2.9%), and the highest prevalence was seen in secondary CS, at 42 of 903 (4.6%; p=0.35). CRP values in the infection group were significantly higher (preoperative, 1.01mg/dl vs. 0.62mg/dl; day 1 postoperative, 7.91mg/dl vs. 6.44mg/dl; day 4 postoperative, 8.44mg/dl vs. 4.09mg/dl; p=0.01). A suitable cut-off value for ruling out infection was not identified. Although CRP values were significantly higher in the infection group, the clinical relevance of this appears to be negligible. CRP testing does not appear to be a reliable tool for diagnosing or ruling out postoperative infection.

Diagnostic Accuracy of Combined Measurement of Serum Homocysteine, C-Reactive Protein, and Serum Ferritin in Mild Cognitive Impairments and Alzheimer's Disease.

Evaluation of the diagnostic accuracy of combined detection of serum homocysteine (Hcy), C-reactive protein (CRP), and serum ferritin (SF) levels in patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI). Descriptive study. Place and Duration of the Study: Clinical Laboratory Section, Affiliated Hospital of Hebei University, Baoding, Heibei, China, from May 2022 to June 2023. Data of 120 patients with memory decline were retrospectively collected. They were divided into an MCI group and an AD group. A further 50 healthy participants were used as a normal control (NC) group. Differences in the Hcy, CRP, and SF levels between the three groups were evaluated. The specificity, accuracy, and sensitivity of these three indices in the combined or single diagnosis of AD and MCI were compared. Their associations with the severity of AD and MCI were also compared. The AD group had the highest levels of Hcy, CRP, and SF (18.79 ± 4.50, 6.35 ± 2.04, and 355.69 ± 120.36), followed by MCI (16.75 ± 3.06, 4.58 ± 2.31, and 203.48 ± 12.76), and NC group (14.32 ± 2.06, 2.06 ± 0.76, and 98.46 ± 5.06), with statistically significant differences (all p <0.001). The diagnostic efficacy of AD for CRP was 98.50%, sensitivity was 96.00%, and specificity was 94.00%, which was higher than Hcy and SF. Tested together, the area under the ROC curve was 99.90%, specificity was 98.00%, and sensitivity was 98.00%. The diagnostic efficacy of SF for MCI had sensitivity of 100.00%, and specificity of 100.00%, which was higher than that of Hcy and CRP. When the three were combined for detection, the area under the curve of SF was 100.00%, sensitivity of 100.00%, and specificity of 100.00%. The levels of Hcy, CRP, and SF were positively correlated with the severity of AD (p <0.01), while negatively correlated with the mini-mental state examination (MMSE) score (p <0.01). The combined detection of Hcy, CRP, and SF improved the diagnostic accuracy of comorbid AD and MCI. Homocysteine, C-reactive protein, Cognitive impairment, Serum ferritin, Alzheimer's disease.

Diagnostic Accuracy of Combined Measurement of Serum Homocysteine, C-Reactive Protein, and Serum Ferritin in Mild Cognitive Impairments and Alzheimer's Disease.

Evaluation of the diagnostic accuracy of combined detection of serum homocysteine (Hcy), C-reactive protein (CRP), and serum ferritin (SF) levels in patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI). Descriptive study. Place and Duration of the Study: Clinical Laboratory Section, Affiliated Hospital of Hebei University, Baoding, Heibei, China, from May 2022 to June 2023. Data of 120 patients with memory decline were retrospectively collected. They were divided into an MCI group and an AD group. A further 50 healthy participants were used as a normal control (NC) group. Differences in the Hcy, CRP, and SF levels between the three groups were evaluated. The specificity, accuracy, and sensitivity of these three indices in the combined or single diagnosis of AD and MCI were compared. Their associations with the severity of AD and MCI were also compared. The AD group had the highest levels of Hcy, CRP, and SF (18.79 ± 4.50, 6.35 ± 2.04, and 355.69 ± 120.36), followed by MCI (16.75 ± 3.06, 4.58 ± 2.31, and 203.48 ± 12.76), and NC group (14.32 ± 2.06, 2.06 ± 0.76, and 98.46 ± 5.06), with statistically significant differences (all p <0.001). The diagnostic efficacy of AD for CRP was 98.50%, sensitivity was 96.00%, and specificity was 94.00%, which was higher than Hcy and SF. Tested together, the area under the ROC curve was 99.90%, specificity was 98.00%, and sensitivity was 98.00%. The diagnostic efficacy of SF for MCI had sensitivity of 100.00%, and specificity of 100.00%, which was higher than that of Hcy and CRP. When the three were combined for detection, the area under the curve of SF was 100.00%, sensitivity of 100.00%, and specificity of 100.00%. The levels of Hcy, CRP, and SF were positively correlated with the severity of AD (p <0.01), while negatively correlated with the mini-mental state examination (MMSE) score (p <0.01). The combined detection of Hcy, CRP, and SF improved the diagnostic accuracy of comorbid AD and MCI. Homocysteine, C-reactive protein, Cognitive impairment, Serum ferritin, Alzheimer's disease.

Bad company? The pericardium microbiome in people investigated for tuberculous pericarditis in an HIV-prevalent setting

BackgroundThe site-of-disease microbiome and predicted metagenome were evaluated in a cross-sectional study involving people with presumptive tuberculous pericarditis. We also explored the interaction between C-reactive protein (CRP) and the microbiome. MethodsPeople with effusions requiring diagnostic pericardiocentesis (n=139) provided pericardial fluid for sequencing and blood for CRP measurement. ResultsPericardial fluid microbiota differed in β-diversity among people with definite (dTB, n=91), probable (pTB, n=25), and non- (nTB, n=23) tuberculous pericarditis. dTBs were Mycobacterium-, Lacticigenium-, and Kocuria-enriched vs. nTBs. HIV-positive dTBs were Mycobacterium-, Bifidobacterium-, Methylobacterium-, and Leptothrix-enriched vs. HIV-negative dTBs. HIV-positive dTBs on ART were Mycobacterium- and Bifidobacterium-depleted vs. those not on ART. dTBs exhibited enrichment in short-chain fatty acid (SCFA) and mycobacterial metabolism pathways vs. nTBs. Additional non-pericardial involvement (pulmonary infiltrates) was associated with Mycobacterium-enrichment and Streptococcus-depletion. Mycobacterium reads were in 34% (31/91) of dTBs, 8% (2/25) of pTBs and 17% (4/23) nTBs. People with CRP above (vs. below) the median value had different β-diversity (Pseudomonas-depleted). No correlation was found between enriched taxa in dTBs and CRP. ConclusionsPericardial fluid microbial composition varies by tuberculosis status, HIV (and ART) status and dTBs are enriched in SCFA-associated taxa. The clinical significance, including mycobacterial reads in nTBs and pTBs, requires evaluation.

The role of fecal matrix metalloprotease-9 as a non-invasive marker in diagnosis and assessment of clinical activity in inflammatory bowel disease patients

BackgroundInflammatory bowel disease is characterized by chronic and relapsing inflammation of the gastrointestinal tract, including two prominent forms: Crohn’s disease and ulcerative colitis. Determining diagnostic biomarkers for predicting disease activity and treatment response remains a challenging aspect.Aim of the workThe purpose of our research was to compare fecal CP and fecal MMP-9, two non-invasive biomarkers for inflammatory bowel disease (IBD), and to find out how fecal MMP-9 levels relate to disease activity by looking at how they relate to clinical, endoscopic, and histologic scores of disease activity.Patients and methodsThis study was performed on 80 subjects divided into 3 groups: group A: 30 patients with Crohn’s disease evidenced by endoscopy ileocolonoscopy, upper GI endoscopy, and tissue biopsy (15 patients with active disease and 15 patients in remission). Group B: 30 patients with ulcerative colitis disease evidenced by colonoscopy and tissue biopsy (15 patients with active disease and 15 patients in remission). Group C: 20 age-matched and sex-matched healthy controls. All participants underwent a thorough history review, comprehensive physical examination, complete laboratory tests, and C-reactive protein measurements. A quantitative enzyme-linked immunosorbent assay was used to determine the levels of fecal matrix metalloproteinase MMP 9 for both the patients and the controls. Ulcerative colitis was evaluated using the Mayo score, Montreal classification, and the Riley histological score. Additionally, Crohn’s disease was assessed with the Crohn’s Disease Activity Index, the Simple Endoscopic Score for Crohn’s Disease, and the D’Haens histological score.ResultsComparing fecal MMP-9 with fecal calprotectin (FC), we found that fecal MMP-9 was superior to FC in differentiating active Crohn’s disease from inactive Crohn’s disease, although there was no significant difference between FC and MMP-9 (P-value = 0.561). However, in ulcerative colitis, FC was superior to MMP-9 in distinguishing active UC from inactive UC, but again, there was no significant difference between FC and MMP-9 (P-value = 0.0731).In both the ulcerative colitis and Crohn’s disease groups, fecal MMP-9 could discriminate between patients in remission and those with active disease. Fecal matrix metalloproteinase-9 (MMP-9) was discovered to be a significant marker for assessing the clinical activity of both Crohn’s disease (CD) and ulcerative colitis (UC), with an AUC of 0.998 for CD and 0.991 for UC. Fecal MMP-9 demonstrated great sensitivity (93.33%), specificity (100%), positive predictive value (PPV) of 100%, and negative predictive value (NPV) of 93.7% (with a P-value < 0.001) using cutoff values of > 0.34 ng/mL for CD and > 0.36 ng/mL for UC. There was a strong positive correlation between fecal MMP-9 and endoscopic and clinical scores of disease activity.ConclusionFecal MMP-9 has emerged as a promising biomarker for evaluating the clinical activity of both Crohn’s disease and ulcerative colitis. It demonstrated superior diagnostic performance compared to fecal calprotectin in distinguishing active from inactive disease, especially in Crohn’s disease. Although fecal calprotectin outperformed MMP-9 in identifying active ulcerative colitis, the differences between the two markers were not statistically significant, suggesting that they may complement each other in clinical practice. Furthermore, fecal MMP-9 is capable of assessing the activity of endoscopically visible inflammatory bowel disease (IBD), which could help reduce the need for invasive endoscopic procedures.

Systemic inflammation in patients with atherosclerotic cardiovascular and chronic kidney disease in Spain: a population-based study using electronic medical records from a primary care database

Abstract Background Systemic inflammation (SI) is recognized as a critical driver of atherosclerotic cardiovascular disease (ASCVD), and it is frequently observed in ASCVD patients with comorbid chronic kidney disease (CKD). Elevated C-reactive protein (CRP) levels, a common biomarker for SI, have been associated with poor prognosis in ASCVD and CKD patients, increased risk of major adverse cardiovascular events and renal disease progression, as well as greater mortality. Purpose To estimate the prevalence of SI in patients with ASCVD in Spain overall and by CKD status, and to describe patients’ clinical characteristics. Methods In this population-based observational study, data from THIN Spain, a database of electronic medical records from a large network of general practitioners, were used to identify adult patients with a diagnosis code of ASCVD (atherosclerotic coronary or cerebrovascular event, peripheral arterial disease, or other atherosclerotic vascular event) and ≥1 eligible CRP measurement between January 1st 2014 to July 31st 2023 (latest data available at time of data extraction).[Figure] SI was defined as CRP ≥ 2mg/L. Point prevalence of SI at the end of the study (among patients alive with ≥1 CRP in the prior 18 months) and the proportion of patients with evidence of SI during the study period (2014-2023) were estimated overall and by CKD status (defined as CKD stage 3+, or eGFR &amp;lt;60 mL/min/1.73m², or urinary albumin-to-creatinine ratio ≥30 mg/g). Patients’ comorbidities (defined using primary care diagnoses), and laboratory values were reported by SI status at first CRP measurement during the study period. Results Among 76,423 patients with ASCVD diagnosis, 15,798 patients (20.7%) were included in the study (mean age: 71.1 years; 43% females), of whom 5,111 (34%) had CKD at first eligible CRP (n=975 with unknown CKD status). Mean CRP in ASCVD patients with CKD was 24% higher than in those without CKD (4.36 vs 3.53 mg/L, p&amp;lt;0.001). The proportion of ASCVD patients with SI at first CRP measurement was 58% overall (65% among CKD patients; 55% among patients without CKD; p&amp;lt;0.001). The point prevalence of SI at the end of the study was 56% among ASCVD patients overall (62% among CKD patients; 52% among patients without CKD; p&amp;lt;0.001), while 64% of ASCVD patients had evidence of SI at any time during the study period (72% among CKD patients; 59% among patients without CKD; p&amp;lt;0.001). Compared to ASCVD patients without SI, higher proportion of SI patients were smokers and with comorbidities. Also, ASCVD patients with SI had lower baseline eGFR levels and higher levels of LDL-C and triglycerides than ASCVD patients without SI.[Table] Conclusions SI prevalence is high among patients with ASCVD in Spain, especially among patients with comorbid CKD. Strategies to target SI may have beneficial effects in prevention of cardiovascular events and mortality in ASCVD patients.

Characterization of individuals with atherosclerotic cardiovascular disease, with and without chronic kidney disease: results from a UK electronic health record database

Abstract Introduction Elevated C-reactive protein (CRP) levels are often present in individuals with atherosclerotic cardiovascular disease (ASCVD), including in those who also have chronic kidney disease (CKD), and are associated with an increased risk of major adverse cardiovascular events (MACE). To understand unmet needs in the identification and management of at-risk individuals, we characterized patients with ASCVD in a UK database, according to CKD stage and CRP levels. Methods This study comprised separate retrospective cross-sectional and longitudinal cohort analyses of patients in the Clinical Practice Research Datalink (CPRD) Aurum database, a representative UK database of anonymized primary care records. In the cross-sectional analysis, CPRD Aurum was linked with Hospital Episode Statistics (HES) and Index of Multiple Deprivation data to assess patient characteristics on 1 Jan 2021 (defined as index date). In the cohort analysis, CPRD Aurum was linked with HES and Office for National Statistics mortality data to determine the incidence of 3-point MACE (3P-MACE) over approximately 5 years of follow-up (index date: 1 Jan 2016). Both analyses included individuals ≥ 18 years old with an ASCVD diagnosis in both primary and secondary care in the 5 years pre-index. Data were analysed using descriptive statistics. Patient characteristics were assessed by CKD stage; for individuals with CKD stage 3–4, characteristics were also assessed by CRP levels. Results In total, 225,767 and 230,055 individuals were included in the cross-sectional and cohort analyses, respectively. The prevalence of CKD stage 3–4 among individuals with ASCVD was 24.3% (Table 1). The proportion of individuals with elevated CRP (CRP ≥ 2 mg/L) and anaemia increased for successively higher CKD severity groups; in addition, glycated haemoglobin (HbA1c) ≥ 7% and elevated blood pressure were generally more frequently observed in individuals with CKD than in those without (Table 1). Individuals with ASCVD, CKD stage 3–4 and elevated CRP had higher HbA1c and total cholesterol levels and a greater proportion had obesity, anaemia and elevated blood pressure, compared with individuals with CRP &amp;lt; 2 mg/L (Table 2). Over 5 years’ follow-up, the incidence of 3P-MACE increased with CKD severity (Table 1) and with increasing CRP levels in individuals with ASCVD and CKD stage 3–4 (Table 2). However, only 28% of individuals with ASCVD and CKD stage 3–4 had CRP measurements. Conclusion Adults with ASCVD, CKD and elevated CRP identified from primary and secondary UK care records had a higher disease burden than individuals with CRP levels &amp;lt; 2 mg/L. In the UK, testing CRP levels is not routinely recommended, resulting in a high proportion of missing CRP measurements in this study. Routine testing of CRP may help in identifying patients with residual cardiovascular risk and has the potential to support risk assessment and management of patients with ASCVD and CKD.

Inflammation and long-term outcomes after first-time direct current cardioversion for atrial fibrillation: a nationwide register study

Abstract Background Emerging evidence suggests that the pathogenesis of atrial fibrillation (AF) is affected by inflammatory processes which contribute to structural and electrical remodeling of the atria, creating a substrate for arrythmia. Aim To assess whether inflammation measured by C-reactive protein (CRP) is associated with readmission for direct current (DC) cardioversion, ablation, heart failure or stroke after discharge from 1st time DC cardioversion. Methods This nationwide retrospective cohort study included patients undergoing 1st DC cardioversion between 2011 and 2018. Exclusion criteria were death within one day of cardioversion and no available CRP at baseline. Primary outcome was readmission for DC cardioversion of AF. Secondary outcomes were AF ablation, new admission of stroke, new admission of heart failure (HF), and all-cause death. Absolute risk rates (ARR) of outcomes were calculated for patients with available 1-year follow-up data. CRP 20 mg/L was chosen as cutoff to establish a clinically relevant borderline for inflammation. The association between baseline CRP and outcome was assessed in Cox proportional hazards regression models with a follow-up period starting from 1st DC cardioversion, ending no later than 31st of December 2018, for the entire study population (n=9,977). Results After exclusion criteria the study population consisted of 9,977 patients Mean age for CRP &amp;gt; 20mg/L: 66.8 (IQR: 60.5-74.2). Mean age for CRP &amp;lt; 20mg/L 68.9 (IQR: 62.9-75.9)(p&amp;lt;0.001). In total, 68.9% were male and the most frequent comorbidities included hypertension (57.3%), ischemic heart disease (25.1%), HF (20.6%), and history of stroke (7.1%). Patients with available CRP measurement and 1yr follow up was 7,764. Compared to patients with low CRP (&amp;lt;20 mg/L), patients with elevated CRP (&amp;gt;20mg/L) had a higher 1-year ARR of HF, and all cause death (p&amp;lt;0.001). Compared to patients with low CRP, patients with elevated CRP had a lower 1-year ARR of all-ablation and new DC cardioversion (p&amp;lt;0.001), (Table 1). CRP &amp;gt; 20mg/L was associated with lower risk for new DC cardioversion (HR 0.72, 95% CI: 0.64-0.82, p&amp;lt;0.001). However, in patients &amp;lt;75 years of age with CRP &amp;gt; 20mg/L at baseline had an increased risk of stroke after multivariable adjustments (HR 1.92, 95% CI: 1.10-3.35; p = 0.02) (Fig.1), while CRP &amp;gt; 20 mg/L was not associated with an increased risk of stroke in patients &amp;gt; 75yrs of age (Cox regressions estimates) (p for interaction = 0.03). Conclusion However, elevated CRP was associated with an increased risk of stroke in patients &amp;lt;75 years of age, even after multivariable adjustments. These results suggest that CRP may not be a reliable predictor of readmission for DC-cardioversion, especially in older individuals, but might be a potential risk stratification tool in identifying AF patients at higher risk of stroke in young individuals. We suspect this is due to the population with elevated CRP has more comorbidities and are older.

Characterizing CRP dynamics during acute infections.

C-reactive protein (CRP) is a common proxy of inflammation, but accurate characterizations of its dynamics during acute infections are scant. The goal of this study was to examine C-reactive protein (CRP) trajectories in hospitalized patients with viral infections, confirmed bacteremia (stratified by Gram-negative or Gram-positive bacteria), and non-bacteremic infections/inflammations, considering antibiotic treatment. Electronic medical records from Tel Aviv Sourasky Medical Center (July 2007-May 2023) were analyzed. Patients with blood cultures or positive viral tests were included. CRP levels were modeled using generalized additive mixed-effects models (GAMMs) and observed up to 150h after initial infection diagnosis. Patients with initial CRP levels > 31.9 were excluded, to remove individuals already in a highly active inflammatory process. The shapes of the CRP curves were characterized and peak CRP as well as area under the CRP curve were the primary variables of interest. Viral infections had the lowest and flattest CRP curves. Non-bacteremic infections showed intermediate levels, while bacteremia (especially Gram-negative under antibiotic treatment) had the highest CRP peaks. For instance, peak CRP ranged from 15.4mg/L in viral infections without antibiotics to 140.9mg/L in Gram-negative bacteremia with antibiotics. CRP trajectories significantly differ based on infection type and antibiotic treatment. Frequent CRP measurement could be a valuable diagnostic and risk stratification tool in hospitalized patients.

Extracorporeal Photopheresis with 5-Aminolevulinic Acid in Crohn's Disease-A First-in-Human Phase I/II Study.

Background/Objectives: With the increasing prevalence of Crohn's disease (CD), treatment options for patients who fail conventional and advanced therapy are highly needed. Therefore, we explored the safety and efficacy of extracorporeal photopheresis (ECP) using 5-aminolevulinic acid (ALA) and blue light (405 nm). Methods: Patients with active CD who failed or were intolerant to biological therapy were eligible. Mononuclear cells (90 mL) were collected from each patient using a Spectra Optia® apheresis system and diluted with 100 mL of 0.9% sodium chloride in a collection bag. The cells were incubated with ALA at a concentration of 3 millimolar (mM) for 60 min ex vivo and illumination with an LED blue light (405 nm) source (BLUE-PIT®) before reinfusion to the patient. Recording of vital signs and adverse events were regularly performed. At week 13, we assessed the patients with colonoscopy, the Harvey Bradshaw Index (HBI), the Inflammatory Bowel disease Health Related Quality of Life Questionnaire, and the measurement of serum C-reactive protein and fecal calprotectin (FC) levels. Biopsies of the intestines were taken for immunohistochemistry. Results: Seven patients were included. Four patients completed the treatments, with a total of 24 treatments. Three of the four patients achieved a favorable response, including a lower HBI, lower FC levels, and/or endoscopic improvement. No significant adverse events were observed. The remaining three patients received only one, three, or five treatments due to technical difficulties, medical reasons, or the withdrawal of informed consent. Conclusions: ALA-based ECP appears safe and seems to give some clinical improvement for the patients with active CD who failed to respond to conventional and advanced therapies.

Application of hs-CRP in Assessment of Tissue Inflammation Following Implantation of Biodegradable Polymer in Experiment.

Implants made of biodegradable polymers are replaced by regenerating tissues through inflammation. The changes occurring in tissues and the organism are of practical interest for studying the biocompatibility of the material and searching for systemic markers in the blood that reflect inflammation in peri-implantation tissues. The highly sensitive C-reactive protein (hs-CRP) measurements in blood and morphometric studies of tissue surrounding the implant were carried out in the experiment within three months of implantation of a biopolymer consisting of polycaprolactone (PCL) and polytrimethylene carbonate (PTMC). During the first month, tissue inflammation decreased, and the blood level of hs-CRP did not increase. The polymer biotransformation began in the tissues after a month of implantation and was accompanied by inflammation moving deeper into the matrix. Proliferation of inflammatory cells in tissues was reflected in an increase in the hs-CRP level three months after polymer installation. The result achieved confirmed the polymer's bioinertness. The level of hs-CRP in the blood of the animals correlated with the level of inflammation in peri-implantation tissues, reflecting the activity of inflammation in the process of polymer biotransformation. This inflammation protein can be recommended for assessing tissue processes following implantation of biopolymers and their biocompatibility.

Study of CRP, ferritin, and D-dimer in COVID-19 RICU patients as per HRCT severity in assiut university hospitals

BackgroundInflammatory markers were found to be elevated in patients with coronavirus disease (COVID-19). C-reactive protein (CRP), serum ferritin, and D-dimer levels may predict morbidity and mortality in (COVID-19) patients. Radiology plays a key role in the diagnosis, management, and follow-up of this disease. This study aimed to describe the radiological features of (COVID-19) infection, measure C-reactive protein (CRP), D-dimer, and ferritin levels and to correlate them with patient’s outcome and to consider them as predictors of morbidity and mortality in (COVID-19) patients.MethodsThis prospective cross-sectional analytic study had been done on 159 patients aged ≥ 18 years old, admitted at Assiut University Hospital RICU from November 2021 to November 2022, diagnosed as COVID-19 by positive RT-PCR. All patients were categorized on bases of HRCT chest disease reporting and data system (CO-RADS) scoring system into non-severe (CO-RADS 1,2,3) and severe (CO-RADS 4,5) groups. Inflammatory markers such as CRP, ferritin, and D-dimer were measured. Age, sex, comorbidities, need to mechanical ventilation MV, and mortality rate were reported. Correlation between HRCT(CO-RADS) score, inflammatory markers, and patient’s outcome was assessed.ResultsHigher CRP and serum ferritin levels, lower lymphocytic count, and higher frequency of need for mechanical ventilation were significantly greater in the severe group (P < 0.0001). Predictors of morbidity and mortality were CRP ≥ 133 mg/dl, DM, presence of chronic chest disease (P < 0.0001). A higher mortality rate was in patients of the severe group (65%) versus (9%) in the non-severe group (P < 0.0001).ConclusionsHRCT scan and measurement of CRP and ferritin plasma levels can be considered significant predictors for future prognosis and can early identify patients at risk of death and need for MV. Male gender, presence of DM, and chronic chest diseases are risk factors for severe illness.

Growth Differentiation Factor 15 during pregnancy and postpartum as captured in blood, cerebrospinal fluid and placenta: A cohort study on associations with maternal mental health

IntroductionGrowth Differentiation Factor 15 (GDF15) increases substantially during pregnancy and is primarily produced by the placenta. Elevated levels of GDF15 have been associated with mental health problems in non-perinatal populations, higher corticosterone levels, and decreased estrogen receptor activity. However, the role of GDF15 in mental health during the perinatal transition remains unknown. This longitudinal study is the first to evaluate pregnancy levels of GDF15 in cerebrospinal fluid (cGDF15), plasma (pGDF15) and placenta GDF15 mRNA, along with mapping plasma GDF15 (pGDF15) level changes from late pregnancy to early postpartum. Moreover, we aimed to evaluate the association between pregnancy cGDF15 levels and cortisol early postpartum, evaluate the association between pregnancy cGDF15 levels and mental health in pregnancy and postpartum, and evaluate the association between pGDF15 and estrogens and high-sensitivity C-reactive protein (CRP). MethodsWe included data from 95 women scheduled for a planned cesarean section and obtained cerebrospinal fluid (CSF) and plasma levels of GDF15. We quantified GDF15 mRNA levels in placenta biopsies. Estrogens, high-sensitivity CRP, and mental health measures were further collected on the day or one day before the cesarean section. At five weeks postpartum, mental health measures and saliva samples for cortisol analyses were collected. Correlation analyses for GDF15 in CSF, plasma, and placenta mRNA were performed, along with association analyses for pregnancy cGDF15, Cortisol Awakening Response, and mental health outcomes. ResultsWe demonstrated a strong correlation between cGDF15 and pGDF15 (r=0.52; p<0.001) and found that both cGDF15 and pGDF15 correlated with placenta GDF15 mRNA*placental weight (r=0.62, p<0.001 and r=0.44, p=0.008, respectively). During late pregnancy, both estradiol (E2) and estriol (E3) were significantly associated with pGDF15 levels (E2: p=0.002; E3: p(corrected)<0.001). Finally, we found that cGDF15 levels were not associated with self-reported mental well-being or the Cortisol Awakening Response or absolute cortisol at awakening postpartum. ConclusionThis novel study points to the unique hormonal landscape during the perinatal transition and the specific role of GDF15 in pregnancy, which appears uncoupled with perinatal mental health and cortisol outcomes. Our data also strongly imply that the overall amount of circulating GDF15 in late pregnancy is closely related to placenta size.

The impact of femoral/internal jugular vein selection on postoperative infection in central vein cannulation of newborns undergoing cardiac surgery.

In the low-weight newborn patient group, the development of catheter related bloodstream infections after cardiac surgery significantly impacts morbidity and mortality. In our study, the effects of choosing femoral or internal jugular vein localization in newborns on postoperative infection will be examined. Our hypothesis is that there may be a higher risk of catheter related bloodstream infections in the femoral region. This study was conducted retrospectively on newborn cases who underwent congenital heart surgery between September 1, 2020, and March 1, 2022. The cases were divided into 2 groups: those with central catheters inserted in the femoral and in internal jugular veins. Postoperative infection parameters were examined and the results were statistically evaluated. The study was conducted with a total of 201 newborn cases, of which 61.2% (n = 123) were male and 38.8% (n = 78) were female. The age of the cases ranged from 0 to 1 month, with a mean of 12 ± 9 days. Weight measurements ranged from 1.8 to 5.5 kg, with a mean of 3.20 ± 0.66 kg. Central catheters were placed in the femoral vein (FV) region in 71.6% of the babies (n = 144) and in the internal jugular vein region in 28.4% (n = 57). When culture results were examined between postoperative days 3 to 14, blood culture tests were positive in 12.4% (n = 25). The most common bacteria in positive cases were Klebsiella spp. (n = 13) and methicillin-resistant Staphylococcus aureus (n = 5). There was no statistically significant difference in blood culture results between the groups (P > .05). Changes in white blood cells, C-reactive protein, and procalcitonin measurements between preoperative and postoperative day 3 did not show statistically significant difference between the groups (P > .05). According to the results of our study, the placement of FV and internal jugular vein in neonates undergoing cardiac surgery did not differ in terms of postoperative infection risk. With appropriate sterilization, preventive measures and care considerations, FV or internal jugular vein region may be preferred based on the practitioner's expertise and choice in this patient group.

A-246 Can CRP be used to rule in or rule out elevated procalcitonin concentrations in the emergency department?

Abstract Background C-reactive Protein (CRP) and procalcitonin (PCT) are commonly used sepsis biomarkers but have very different properties. PCT rises earlier, has a shorter half-life and is more specific for sepsis than CRP. It is however significantly more expensive. This study examined whether CRP measurement can be used to screen for the need for PCT measurement in emergency department patients. Methods This was a retrospective study of anonymized records of paired CRP and PCT requests from the emergency department during 2023. All testing was performed using Beckman Coulter AU 5800 (CRP) and Roche e601 (PCT). PCT results were interpreted using the 2023 AACC guidelines on PCT use (PCT&amp;lt;0.1 ug/L: strongly discourage antibiotic use; PCT 0.1-0.25: discourage antibiotic use; PCT 0.26-0.5: encourage antibiotic use; PCT&amp;gt;0.5: strongly encourage antibiotic use) and the ability of CRP to predict PCT exceeding the various cutoffs was calculated using Microsoft Excel and Analyse-It statistical add-on. Results There were 1645 paired results available. The CRP concentrations at 95% and 99% sensitivity and specificity levels for the various PCT cutoffs are shown in the table, together with the projected reductions in PCT testing volumes if PCT testing is restricted to samples with CRP within the ranges defined by the 95% or 99% sensitivity/specificity values. For example, from the table, for PCT&amp;gt;0.1 ug/L cutoff at 95% confidence, subsequent PCT measurement on the sample is only performed if CRP is between 3.4 and 90.5 mg/L. Conclusions Limiting PCT measurements to samples with CRP concentrations inside ranges based on the PCT cutoff of interest and the appropriate confidence level (95% or 99%) can potentially reduce PCT testing by 20-40% in emergency department patients. For laboratories which perform CRP and PCT analysis sequentially on different platforms, this approach allows significant reductions in PCT test volumes while ensuring testing is performed in equivocal cases.