Changes In C-reactive Protein Research Articles

Temporal and spatial effects on C-reactive protein's regulation of inducible nitric oxide synthase production in periodontal disease.

Inducible nitric oxide synthase (iNOS) is associated with inflammation and osteoclastic differentiation in periodontal disease. This study was conducted to compare the time-dependent variation in iNOS production between the gingiva and other periodontal tissues and to explore the potential association with C-reactive protein (CRP) in early periodontal disease. Ligature-induced periodontal disease models (0-14days) were established in wild-type and CRP knockout rats. Changes in CRP, iNOS, and autophagy levels were examined in the gingiva and other periodontal tissues. Macrophages were treated with lipopolysaccharide and chloroquine to explore the role of autophagy in iNOS production. iNOS, CRP, and autophagy-related proteins were analyzed using Western blotting, immunostaining, and enzyme-linked immunosorbent assays. mRNA expression was detected by quantitative real-time polymerase chain reaction. Hematoxylin and eosin staining was used for histological analysis. Cathepsin K immunostaining and microcomputed tomography of the maxillae were performed to compare alveolar bone resorption. iNOS and CRP levels increased rapidly in periodontal tissues, as observed on Day 2 of ligature, then decreased more rapidly in the gingiva than in other periodontal tissues. CRP deficiency did not prevent iNOS generation, but effectively accelerated iNOS reduction and delayed alveolar bone loss. The CRP effect on iNOS was accompanied by a change in autophagy, which was reduced by CRP knockout. The regulation of iNOS by CRP shows temporospatial variation in early periodontal disease and is potentially associated with autophagy. These findings may contribute to the early detection and targeted treatment of periodontal disease.

Metabolic Syndrome and Inflammation from Young to Mid-Adulthood and Subclinical Kidney Damage in Middle-Aged Australians.

Background: Relationships between metabolic syndrome (MetS), inflammation, and chronic kidney disease (CKD) have been reported, but long-term follow-up studies are limited. This study aimed to investigate whether MetS and C-reactive protein (CRP) from young adulthood associated with the risk of subclinical kidney damage (SKD), a surrogate measure for CKD, in mid-adulthood. Materials and Methods: One thousand fifteen participants from the Childhood Determinants of Adult Health study aged 26-36 years at baseline (2004-2006) were followed up at age 36-49 (2014-2019). Log-binomial regression was used to determine whether MetS and high CRP in young adulthood and from young to mid-adulthood predicted the risk of SKD (an estimated glomerular filtration rate [eGFR] of 30-60 mL/min/1.73 m2 or an eGFR >60 mL/min/1.73 m2 with a urine albumin-creatinine ratio ≥2.5 mg/mmol [males] or ≥3.5 mg/mmol [females]) in midlife. Results: Having MetS in young adulthood was associated with an increased risk of SKD in midlife (adjusted relative risk [aRR] = 2.67, 95% confidence interval [CI]: 1.24-5.76). Participants with MetS and high CRP as young adults had a greater risk of having SKD in midlife (aRR = 4.27, 95% CI: 1.61-11.30) compared with those without MetS and high CRP. Furthermore, for participants with persistent MetS, the aRR of SKD in midlife was 4.08 (95% CI: 1.84-9.05) compared with those without MetS from young to mid-adulthood. No significant associations were found between CRP in young adulthood, or change in CRP from young to mid-adulthood, and SKD in midlife. Conclusions: MetS in young adulthood, with and without high CRP, and persistent MetS were associated with an increased risk of SKD in middle midlife.

Role of Janus Kinase inhibitors in the management of pulmonary involvement due to Long COVID-19 disease: A case control study.

Ongoing symptomatic coronavirus disease 2019 (OSC) is defined as persistent symptoms beyond 4 weeks of acute illness. OSC leads to prolonged hospitalization and oxygen dependence. We aimed to find the outcome of Janus kinase inhibitors (JAKi) as a steroid-sparing agent to treat OSC. In this single-center case-controlled study comparing JAKi and corticosteroids in OSC cases, data of 41 cases out of 86 were included - 21 in the JAKi group and 20 in the corticosteroid group from 4 weeks of acute illness to the next 4 weeks. Clinical parameters and inflammatory markers were recorded. The primary outcome was to compare the proportion of patients who were able to maintain oxygen saturation ≥95% with any oxygen supplementation in the two groups. The baseline clinical and demographic characteristics were similar in the two groups. The age was 53.65 ± 9.8 years and 51.48 ± 14.0 years in the corticosteroid group and JAKi group, respectively. At the baseline, 85% of patients in the corticosteroid group and 85.8% in the JAKi group were on oxygen support. The most common symptom in both groups was breathlessness followed by cough. Twenty percent of patients in the JAKi group received baricitinib and the remaining were given tofacitinib. At the time of follow-up, the majority of cases had a significant reduction in C-reactive protein (CRP) and D-dimer; however, the change in CRP and D-dimer was similar in both groups. The number of patients off oxygen support at 4 weeks was higher in the JAKi group (85% in the corticosteroid group vs. 95.2% in the JAKi group, P = 0.269), and the median time to liberation from oxygen support was significantly lower in JAKi group (19 days in corticosteroid group vs. 9 days in JAKi group, P < 0.001). The frequency of any adverse event was also higher in the corticosteroid group (70% vs. 23.8%, P = 0.003). JAKi can be used as immunomodulatory drugs in hypoxic OSC cases having evidence of ongoing inflammation.

The correlations between C-reactive protein and MRI-detected inflammation in patients with axial spondyloarthritis: a systematic review and meta-analysis.

C-reactive protein (CRP) and magnetic resonance imaging (MRI) are widely used to monitor inflammation in patients with axial spondyloarthritis (axSpA), but the relationship between CRP and MRI-detected inflammation is incompletely understood. The present study was undertaken to assess correlations between CRP and MRI-detected inflammation in axSpA. A systematic literature search was performed (Medline, Embase, and Cochrane Library) to identify relevant studies concerning CRP and MRI-detected inflammation in axSpA patients. The MRI-detected inflammation was evaluated by MRI-based disease activity score (DAS). The correlation between CRP and MRI-based DAS was integrated by random-effect models. Eighteen studies reported a total of 1392 axSpA patients which were included in this meta-analysis. CRP was significantly associated with spinal MR DAS (r=0.226, 95%CI [0.149, 0.291], p<0.001, I2=23%). We also found a moderate correlation between CRP change and spinal MR DAS change (r[ASspiMRI-a]=0.354, 95%CI [0.282, 0.422], p<0.001, I2=48%; r[SPARCC]=0.544, 95%CI [0.345, 0.701], p<0.001, I2=19%). CRP at baseline was negatively associated with improvement in spinal MR DAS (r= - 0.327, 95%CI [-0.397, -0.264], p<0.001, I2=0%). However, no significant association was found between CRP and sacroiliac joint (SIJ) MR DAS. In axSpA patients, CRP is associated with MRI-detected inflammation in the spine but not in SIJ. We speculate that CRP could be a reasonable index to reflect spinal inflammation. Therefore, we suggest it is not essential to repeat spinal MRI in a short term, while SIJ MRI may be necessary to provide additional information on inflammation. Key Points • CRP is associated with MRI-detected inflammation in the spine but not in sacroiliac joints. • CRP at baseline was negatively associated with improvement in spinal MR DAS. • It was not essential to repeat spinal MRI frequently, while SIJ MRI may be necessary to provide additional information on inflammation.

The Change of Serum Interleukin-6 Fails to Identify Subsequent Periprosthetic Joint Infection in Patients Who Have Two-Stage Revision for Periprosthetic Joint Infection

BackgroundThe diagnosis of persistent infection prior to second-stage reimplantation in 2-stage exchanges for periprosthetic joint infection (PJI) can be challenging as there is no optimal diagnostic tool. This study investigates the usefulness of pre-reimplantation serum C-reactive protein (CRP) and interleukin-6 (IL-6) and its change between both stages to identify patients who have subsequent PJI. MethodsThere were 125 patients who underwent planned 2-stage exchange for chronic knee or hip PJI from a single center retrospectively identified. Patients were included if preoperative CRP and IL-6 were available for both stages. Subsequent PJI was defined as 2 positive microbiological cultures at reimplantation or subsequent surgery or death due to PJI during follow-up. ResultsPrior to reimplantation, the median serum CRP (total knee arthroplasties [TKAs]: 1.0 versus 0.5 mg/dL, P = .028; total hip arthroplasties [THAs]: 1.3 versus 0.5 mg/dL, P = .015) and median IL-6 (TKA: 8.0 versus 6.0 pg/mL, P = .052; THA: 7.0 versus 6.0 pg/mL, P = .239) were higher in patients who had subsequent PJI. The IL-6 and CRP values showed moderate sensitivity (TKA/CRP: 66.7%; THA/CRP: 58.8%; TKA/IL-6: 46.7%; THA/IL-6: 35.3%) and good specificity (TKA/CRP: 66.7%; THA/CRP: 81.0%; TKA/IL-6: 86.3%; THA/IL-6: 83.3%). The change in CRP and IL-6 between the stages did not differ between the groups, respectively. ConclusionsSerum CRP and IL-6 show low to moderate sensitivity and good specificity in the diagnosis of subsequent PJI prior to reimplantation, which questions their usefulness as a rule-out test. Furthermore, the change in between stages does not appear to identify subsequent PJI.

Incident racial discrimination predicts elevated C-Reactive protein in the Black Women’s experiences Living with Lupus (BeWELL) study

IntroductionRacial discrimination is a distinct health threat that increases disease risk among Black Americans. Psychosocial stress may compromise health through inflammatory mechanisms. This study examines incident experiences of racial discrimination and changes in the inflammatory biomarker C-reactive protein (CRP) over a two-year period among Black women with systemic lupus erythematosus (SLE)—an inflammatory autoimmune disease sensitive to psychosocial stress and characterized by stark racial inequities in outcomes. MethodsData are from the Black Women’s Experiences Living with Lupus (BeWELL) Study. Participants (n = 380) from metropolitan Atlanta, Georgia were enrolled from April 2015 to May 2017. Incident racial discrimination was assessed bi-annually via self-report using the Experiences of Discrimination measure. CRP was assessed annually over a two-year period. Latent change score analyses modeled longitudinal within-person associations between incident racial discrimination and change in log-transformed CRP from baseline to Year 2. ResultsIncident experiences of racial discrimination were associated with elevated log-CRP across the two-year study period (b = 0.039, SE = 0.017, 95% CI: 0.006, 0.071). For each domain of incident racial discrimination experienced, CRP increased 3.98%. ConclusionThis study contributes to growing evidence on the biological consequences of racism and is the first to document an association between incident racial discrimination and changes in inflammation among Black women with SLE. Racial inequities in SLE outcomes and other diseases driven by inflammatory pathways may be explained in part through experiences of racial discrimination.

Early postoperative CRP predicts major complications following cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC).

Cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) is associated with significant postoperative complications. Early detection of at-risk patients may lead to improved outcomes. The role of C-reactive protein (CRP) in predicting postoperative complications has only been recently investigated. Postoperative complications were categorized according to Clavien-Dindo classification and further divided into minor (Grade <3) and major complications (Grade≥3A). Absolute CRP counts (mg/L) on postoperative days (POD) 1-7, and proportional change in CRP was compared and the area under (AUC) receiver operating characteristics (ROC) curve was calculated. Univariate and multivariate analysis was performed. Significant findings were externally validated. Twenty-five percent of patients experienced one or more major complications. A CRP level of≥106 mg/L on POD 2 and 65.5 mg/L on POD 4 were significantly associated with an increased risk of major complications with an AUC of 0.658 and 0.672, respectively. The proportional increase in CRP between POD 1 and 4 (ΔCRP POD 1/4) at a cut-off of 30 % had the best AUC of 0.744 and was the only independent risk factor for major complications (p<0.0001) on multivariate analysis. ∆CRP had an AUC of 0.716 (p=0.002) when validated in an independent database. CRP can be used in a variety of ways to predict major complications after CRS and HIPEC. However, the ∆CRP POD 1/4>30 % is the best indicator of major complications. Serial CRP measurements in the early postoperative period may lead to early detection of patients at risk of major complications allowing for alternative management strategies to improve outcomes.

C-reactive protein as a response biomarker to immune checkpoint blockade: A meta-analysis.

2559 Background: Tumor-promoting inflammation is a hallmark of cancer pathogenesis and is associated with poor outcomes and treatment resistance. C-reactive protein (CRP) is a routinely measured acute phase reactant whose synthesis is stimulated by cytokines and may thereby represent a surrogate for tumor promoting inflammation. Pre-treatment CRP has been associated with resistance to immune checkpoint blockade (ICB) in several studies. However, whether post-treatment changes in CRP correlate with ICB outcomes has not been systematically examined. Methods: We performed a systematic review to identify cohort studies or clinical trials in solid tumor patients receiving ICB therapy with CRP response comparator pairs (high/low) available. We included studies that had hazard ratio (HR) of overall survival (OS), progression-free survival (PFS), or odds ratio (OR) of objective response rate (ORR) available. We performed a meta-analysis using a random-effect model to evaluate if post-treatment changes in CRP are associated with ORR, PFS, or OS. Subgroup analysis for primary cancer type was performed. Heterogeneity was assessed using the I-squared statistic. Results: We screened 691 eligible studies; 19 met inclusion criteria and 2,101 patients were included. Patients experiencing post-ICB declines in CRP had improved ORR HR=4.67 [95% CI] [2.81-7.78] (p&lt;0.0001, I2=42%), PFS HR=2.47 [1.98-3.09] (p&lt;0.0001, I2=18%), and OS HR=2.28 [1.68-3.08] (p&lt;0.0001, I2=56%). Heterogeneity among subgroups was low in ORR (I2=14.6%) and PFS analysis ( I2=0%), and moderate in OS analysis (I2=64.2%). Conclusions: In patients receiving ICB therapy, post-treatment declines in CRP were associated with improved ORR, PFS, and OS across multiple histologies. These findings support the integration of on-treatment CRP decline as a clinically relevant response biomarker for novel therapies directed at modulating tumor-promoting inflammation. A meta-regression analysis will help determine optimal post-treatment CRP cutpoints. Pooled OR of ORR [95%CI] and HR [95%CI] of PFS and OS with subgroup analysis results and heterogeneity assessment. [Table: see text]

C-reactive protein in solid tumors: Clinically meaningful change and prognosis.

e15036 Background: C-Reactive Protein (CRP) has been associated with overall survival (OS) in both solid and hematologic malignancies. CRP is used alone or in conjunction with other variables e.g., albumin to create prognostic scores, yet use in clinical practice is limited. One barrier is the lack of guidelines quantifying clinically relevant changes. The aim of this study was to determine important changes in CRP and any association with OS. Methods: This was a retrospective cohort study of electronic medical record data. Subjects were included if they had a solid tumor, ≥2 CRP measurements post diagnosis, ≥7 days apart, age ≥18. They were divided into Baseline High CRP (HCRP≥10 mg/L), and Baseline Normal CRP (NCRP &lt; 10 mg/L) groups and analyzed separately. Median (range) and counts (%) were reported. Variables compared with parametric or nonparametric tests. CRP change (∆ = (2nd CRP-1st CRP)/1st CRP) cut-off points were determined by Receiver Operator Curves or dividing groups into tertiles for sensitivity and specificity. We report the Kaplan-Meier survival plots and Cox Proportional Hazard Survival Models. Results: 4931 solid tumors were identified with CRP values; 1473 ≥2 CRP at least one week apart. N = 943 HCRP; N = 530 NCRP. HCRP were more likely to have gastrointestinal cancers, high white blood cell count, liver disease, metastatic disease, undergone surgery. NCRP were more likely breast or skin cancer, female, higher BMI, longer OS. 50% ↓ or 2-fold ↑ in CRP from baseline were statistically relevant cut-off points. In HCRP, estimated OS for ≥50% and &lt; 50% ↓ in CRP was, mean (SE), 87(2) and 81(4) months respectively; a six-month difference. In NCRP, estimated OS for ≥2 and &lt; 2-fold ↑ was 90(3) and 105(3) respectively; a fifteen-month difference. In the COX models, ≥ 50% CRP ↓ in HCRP was associated with 40% lower mortality risk; ≥ 2x CRP ↑ in NCRP was associated with 2-fold ↑ mortality risk. Conclusions: CRP level changes with cut-off points of either a 50% reduction or a 2-fold ↑ from baseline correlated with better and worse OS respectively, during follow up of solid tumors. This was both statistically and clinically important. CRP has the characteristics of an ideal tumor biomarker. This could aid in disease prognostication and impact treatment decision making in routine clinical practice. [Table: see text]

The clinical and prognostic role of changes in parameters of the hemostasis system and C-reactive protein in the development of thrombotic complications in oxygen-dependent patients with coronavirus disease (COVID-19)

Aim. The purpose of our work was to find out the clinical and prognostic role of changes in hemostasis parameters and C-reactive protein (CRP) in the development of thrombotic complications in oxygen-dependent patients with coronavirus disease (COVID-19). Materials and methods. 211 oxygen-dependent patients with COVID-19 were examined. To assess the prognostic role of changes in hemostasis parameters and CRP, patients were divided into groups: I group – 94 patients who recovered, II group – 117 patients who died. Subgroups: II-A subgroup – 35 patients with thrombotic complications and II-B subgroup – 82 patients without these complications. All patients were examined and received treatment according to the normative documents in force at the relevant time. Results. The frequency of thrombotic complications in oxygen-dependent patients with COVID-19 was 16.6 %, among which the most common were pulmonary embolism (6.6 %), myocardial infarction (6.2 %), and ischemic stroke (3.2 %). Lifetime diagnosis of thrombotic complications took place on the 18th [16.0; 24.0] day of illness in 45.9 % of cases. Deathtime diagnosis of thrombotic complications took place on the 24th [20.0; 28.0] day of illness in 54.1 % of cases. Lifetime pulmonary artery thromboembolism was diagnosed less frequently than ischemic stroke (p = 0.002) and myocardial infarction (p = 0.02). With the development of oxygen dependence and admission to the intensive care unit on the 9th [8.0; 11.0] day of illness, changes in the hemostasis system were characterized as prothrombotic with an increase above the reference values of fibrinogen and D-dimer in patients of all groups. CRP in patients with fatal outcomes of the disease, regardless of the development of thrombotic complications, was higher (p &lt; 0.05) than in patients who subsequently recovered, and was accordingly in patients of the I group – 67.65 [41.20; 139.95] mg/l, in the II-A group – 122.2 [61.2; 178.0] mg/l, and in patients of the II-B group – 109.8 [56.3; 180.0] mg/l. In the dynamics of complex treatment after 5–7 days, the level of fibrinogen, D-dimer and CRP had a diagnostic value in predicting the further development of thrombotic complications. With an increase in the level of fibrinogen &gt;4.6 g/l (AUC = 0.600, p = 0.042), D-dimer &gt;2.1 μg/ml (AUC = 0.704, p = 0.001) and CRP &gt;89.3 mg/l (AUC = 0.720, p &lt; 0.001) the probability of developing thrombotic complications was significant. Conclusions. In dynamics of complex treatment of oxygen-dependent patients after 5–7 days, the levels of fibrinogen, D-dimer and C-reactive protein had consistent diagnostic value in predicting further development of thrombotic complications. Increased fibrinogen &gt;4.6 g/l, D-dimer &gt;2.1 μg/ml, and CRP &gt;89.3 mg/l were important for predicting the risk of developing thrombotic complications.

Changes of serum NSE, lactate and CRP in patients with postoperative infection after acute craniocerebral injury and their predictive value for prognosis

ABSTRACT To investigate the changes of serum neuron-specific enolase (NSE), lactate and C-reactive protein (CRP) in patients with postoperative infection after acute craniocerebral injury and their predictive value for prognosis. 71 patients with postoperative infection after acute craniocerebral injury were selected as infection group, and 56 patients without postoperative infection were selected as non-infection group. NSE, CRP and blood lactic acid levels were detected in all patients. The relationship between each index and thecondition and prognosis of patients was analyzed. The levels of serum NSE, lactic acid and CRP in infected group were higher than those in non-infection group (P<0.05). The levels of serum NSE, lactic acid and CRP in severe group were higher than those in mild group (P<0.05). Serum levels of NSE, lactic acid and CRP were positively correlated with the severity of infection (P<0.05), the area under the curve (AUC) of the receiver operating characteristic curve (ROC) was greater than that of the NSE level (P<0.05). The levels of serum NSE, lactate and CRP in the good prognosis group were lower than those in the poor prognosis group (P<0.05). The area under the curve (AUC) of receiver operating characteristic curve (ROC) of lactate level in predicting the prognosis of patients with infection was higher than that of NSE and CRP (P<0.05). Serum NSE, lactic acid and CRP have predictive value in patients with acute craniocerebral injury.

Temporal changes in biomarkers in individuals with and without acute mountain sickness following rapid ascent

BackgroundField studies have reported conflicting results regarding changes in biomarkers at high altitude. This study measured temporal changes in biomarkers and compared the differences between individuals with and without acute mountain sickness (AMS). Materials and methodsThis study included 34 nonacclimatized healthy participants. Ten-milliliters of blood were collected at four time points: 3 days before ascent (T0), on two successive nights at 3150 m (T1 and T2), and 2 days after descent (T3). Participants were transported by bus from 555 m to 3150 m within 3 hours. AMS was diagnosed using the self-reported Lake Louise Scoring (LLS) questionnaire. ResultsCompared with T0, significant increases in E-selectin and decreases in vascular endothelial growth factor (VEGF) levels were observed at high altitude. Significantly increased C-reactive protein (CRP), monocyte chemoattractant protein-1 (MCP-1), and S100 calcium-binding protein B (S100B) levels were observed at T2, and significantly decreased vascular cell adhesion molecule-1 (VCAM-1) levels were observed at T3. Eighteen (53%) participants developed AMS. Changes in E-selectin, CRP, MCP-1, and S100B levels were independent of AMS. Relative to individuals without AMS, those with AMS had significantly higher atrial natriuretic peptide (ANP) and VCAM-1 levels and lower plasminogen activator inhibitor-1 (PAI-1) levels at T1 and higher brain natriuretic peptide and lower VEGF and PAI-1 levels at T3. LLSs were positively correlated with ANP and VCAM-1 levels and negatively correlated with PAI-1 levels measured at T1. ConclusionsAfter acute ascent, individuals with and without AMS exhibited different trends in biomarkers associated with endothelial cell activation and natriuretic peptides.

Diagnostic Utility and Thresholds for Commonly Obtained Serum and Synovial Markers Prior to Reimplantation in Periprosthetic Joint Infection

BackgroundAccurate diagnosis of persistent periprosthetic joint infection (PJI) during 2-stage exchange remains a challenge. This study evaluated the diagnostic performance and thresholds of several commonly obtained serum and synovial markers to better guide reimplantation timing. MethodsThis was a retrospective review of 249 patients who underwent 2-stage exchange with antibiotic spacers for PJI. Serum and synovial markers analyzed included white blood cell (WBC) count, polymorphonuclear percentage (PMN%), neutrophil-to-lymphocyte ratio (NLR), and absolute neutrophil count (ANC). Serum markers analyzed were erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), as well as percentage change in ESR and CRP from initial diagnosis to reimplantation. Area under the curve (AUC) analyses were performed to determine diagnostic accuracy of detecting PJI. ResultsIn TKAs, synovial ANC and WBC had the highest AUCs (0.76), with thresholds of 2,952 and 3,800 cells/μL, respectively. The next best marker was serum CRP (0.73) with a threshold of 5.2 mg/dL. In THAs, serum CRP had the highest AUC (0.84) with a threshold of 4.3 mg/dL, followed by synovial PMN% (0.80) with a threshold of 77%. Percentage change in serum ESR or CRP provided low diagnostic value overall. ConclusionRegarding serum markers, CRP consistently performed well in detecting persistent PJI in patients with antibiotic spacers. Absolute values of serum CRP and ESR had better diagnostic value than trends for guiding reimplantation timing. Diagnostic performance differed with joint type; however, synovial markers outperformed serum counterparts. No marker alone can be utilized to diagnose residual PJI in these patients, and further work is needed in this domain.

Effects of once-weekly semaglutide 2.4mg on C-reactive protein in adults with overweight or obesity (STEP 1, 2, and 3): Exploratory analyses of three randomised, double-blind, placebo-controlled, phase 3 trials.

Inflammation is a key driver of atherosclerotic cardiovascular disease. C-reactive protein (CRP), an established biomarker of inflammation, is commonly elevated in people with overweight/obesity. STEP 1, 2, and 3 were 68-week, placebo-controlled trials of semaglutide for weight management in participants with overweight/obesity, with (STEP 2) or without (STEP 1 and 3) type 2 diabetes. Change in serum CRP from baseline to week 68 was assessed as a prespecified secondary endpoint for semaglutide 2.4mg versus placebo (STEP 1, 2, and 3) and versus semaglutide 1.0mg (STEP 2). Post hoc assessments included change in CRP by baseline characteristics (bodyweight, body mass index [BMI], glycaemic status, CRP concentration); change in CRP-defined cardiovascular risk category (<1 [low], 1-3 [intermediate], and >3mg/L [high]); and correlation between change in CRP and change in bodyweight, waist circumference, fasting serum insulin (STEP1 and 3), fasting plasma glucose, and homeostatic model assessment of insulin resistance (HOMA-IR). The trials took place from June through November 2018 (STEP 1 and 2) and from August 2018 to April 2020 (STEP 3). In all trials, semaglutide 2.4mg reduced CRP at week 68 versus placebo (estimated treatment difference [ETD; 95% CI]-44% [-49 to-39] in STEP 1, -39% [-46 to-30] in STEP 2, and -48% [-55 to-39] in STEP 3; all p<0.05). In STEP 2, CRP reductions were greater with semaglutide 2.4mg (-49%) than with 1.0mg (-42%) but the difference did not reach statistical significance (ETD [95% CI]-12% [-23 to 1]; p=0.06). Reductions in CRP occurred in parallel with bodyweight loss and were consistent regardless of baseline BMI/bodyweight/glycaemic status. More semaglutide-treated participants had reductions in CRP-defined cardiovascular risk versus those on placebo. Reductions in CRP were positively correlated with reductions in bodyweight, waist circumference, fasting plasma glucose, fasting serum insulin, and HOMA-IR (data not shown). In people with overweight/obesity, once-weekly semaglutide 2.4mg and 1.0mg reduced CRP concentration irrespective of baseline BMI/bodyweight/glycaemic status compared with placebo. These data suggest a potential anti-inflammatory role of semaglutide in obesity. Novo Nordisk.

Impact of Atorvastatin on C-reactive Protein, Glycaemic Status and Liver Enzymes among Non Diabetic Patients: A Prospective Study

Introduction: Atorvastatin is one of the common drugs used for primary and secondary prevention of atherosclerotic cardiovascular diseases. Various studies have suggested variation in C-reactive Protein (CRP) value, glycaemic status and liver enzymes of patients following statin therapy. However, the adequate and exact data regarding the impact of atorvastatin on the above parameters in the population of Eastern India is still limited. Aim: To estimate the effect of atorvastatin on CRP, glycaemic status and haepatic enzymes of non diabetic patients. Materials and Methods: A prospective longitudinal observational study was conducted in the Outpatient Department (OPD) of Internal Medicine at Midnapore Medical College and Hospital, Paschim Medinipur, West Bengal, India. The duration of the study was one year six months, from June 2020- December 2021. A total of 150 non diabetic patients aged between 30- 75 years receiving atorvastatin were enrolled in the present study. Patients with known Diabetes Mellitus (DM), impaired fasting glucose, impaired glucose tolerance, pregnancy and lactation were excluded. CRP, Fasting Blood Sugar (FBS), Postprandial Blood Sugar (PPBS), haepatic enzymes and lipid profile of participants were monitored at baseline, at the end of one month, six months and 12 months. The data was analysed using Statistical Package for Social Sciences (SPSS) version 22.0, Microsoft Excel and GraphPad Prism. Results: The study population were predominantly males (69.6%), with mean age of 54±8.88 years and mean weight of 60±5.86 kg. Majority of the patients were on atorvastatin 40 mg (60.86%) followed by atorvastatin 20 mg (26.8%) and atorvastatin 10 mg (12.3%). There were statistical significant changes of mean CRP (1.502 mg/L), mean FBS (86.52 mg/dL), mean PPBS (113.57 mg/dL), mean Serum Glutamic-oxaloacetic Transaminase (SGOT) (22.84 IU/L), mean Serum Glutamic Pyruvic Transaminase (SGPT) (25.24 IU/L) and lipid profile levels at the end of one year. None of the patients developed new onset DM at the end of one year. A 5% of patients developed prediabetes at the end of 3rd follow-up. Conclusion: Atorvastatin usage showed that, there was a significant increase in blood glucose and haepatic enzymes level in non diabetic population. Hence, strict monitoring of blood glucose levels along with periodic monitoring of haepatic enzyme levels should be done in regular intervals.

Proactive anti-inflammatory therapy in the advanced stages of a new coronavirus infection. Main results of the inpatient phase of the COLORIT study (Colchicin vs. Ruxolitinib and secukinumab in an open, prospective, randomized trial in patients with novel coronavirus infection COVID-19).

Aim To evaluate clinical efficacy of the proactive anti-inflammatory therapy in patients hospitalized for COVID-19 with pneumonia and a risk of "cytokine storm".Material and methods The COLORIT study was a comparative study with randomization into 4 groups: colchicine (n=21) 1 mg for the first 3 days followed by 0.5 mg/day through day 12 or discharge from the hospital; secukinumab 300 mg/day, s.c., as a single dose (n=20); ruxolitinib 5 mg, twice a day (n=10); and a control group with no anti-inflammatory therapy (n=22). The effect was evaluated after 12±2 days of inpatient treatment or upon discharge, what comes first. For ethical reasons, completely randomized recruitment to the control group was not possible. Thus, for data analysis, 17 patients who did not receive any anti-inflammatory therapy for various reasons not related with inclusion into the study were added to the control group of 5 randomized patients. Inclusion criteria: presence of coronavirus pneumonia (positive PCR test for SARS-CoV-2 RNA or specific clinical presentation of pneumonia; IDC-10 codes U07.1 and U07.2); C-reactive protein (CRP) concentration &gt;60 mg/l or its threefold increase from baseline; at least 2 of 4 symptoms (fever &gt;37.5 °C, persistent cough, shortness of breath with inspiratory rate &gt;20 per min or blood saturation with oxygen &lt;94 % by the 7th-9th day of disease. The study primary endpoint was changes in COVID Clinical Condition Scale (CCS-COVID) score. The secondary endpoints were the dynamics of CRP and changes in the area of lung lesion according to data of computed tomography (CT) of the lungs from the date of randomization to 12±2 days.Results All three drugs significantly reduced inflammation, improved the clinical course of the disease, and decreased the disease severity as evaluated by the CCS score: in the ruxolitinib group, by 5.5 (p=0.004); in the secukinumab group, by 4 (p=0.096); in the colchicine group, by 4 (p=0.017), and in the control group, by 2 (р=0.329). In all three groups, the CCS-COVID score was 2-3 by the end of observation period, which corresponded to a mild process, while in the control group, the score was 7 (р=0.005). Time-related changes in CRP were significant in all three anti-inflammatory treatment groups with no statistical difference between the groups. By the end of the study, changes in CT of the lungs were nonsignificant.Conclusion In severe СOVID-19 with a risk of "cytokine storm", the proactive therapy with ruxolitinib, colchicine, and secukinumab significantly reduces the inflammation severity, prevents the disease progression, and results in clinical improvement.

Changes in Heparin-Binding Protein, Procalcitonin, and C-Reactive Protein Within the First 72 Hours Predict 28-Day Mortality in Patients Admitted to the Intensive Care Unit with Septic Shock.

BACKGROUND This study aimed to evaluate the possible associations of heparin-binding protein (HBP), procalcitonin (PCT), and C-reactive protein (CRP) levels with 28-day mortality in septic shock patients admitted to Intensive Care Units (ICUs). MATERIAL AND METHODS Blood samples were taken at ICU admission and measured again 72 h later to calculate changes in HBP (ΔHBP), changes in PCT (ΔPCT), changes in CRP (ΔCRP), and changes in Sequential Organ Failure Assessment (DSOFA) relative to baseline. RESULTS Variables included in the univariable logistic regression model for survival were age, Acute Physiology and Chronic Health Evaluation (APACHE) II scores, decreasing ΔSOFA, decreasing DHBP, decreasing ΔPCT, and decreasing ΔCRP. Survival was directly related to decreasing ΔHBP with odds ratio (OR)=9.95 (95% confidence interval [CI] 4.63 to 21.35; P<0.001), decreasing ΔPCT with OR=7.85 (3.74 to 16.49; P<0.001), decreasing ΔCRP with OR=5.83 (2.84 to 11.97; P<0.001), decreasing ΔSOFA with OR=1.93 (1.00 to 3.75; P=0.051) and APACHE II score with OR=1.93 (1.14 to 1.68; P=0.001). In a multivariable logistic regression model for survival, only decreasing DHBP with OR=7.18 (2.91 to 17.69; P<0.001), decreasing ΔPCT with OR=5.17 (2.12 to 12.56; P<0.001), and decreasing ΔCRP with OR=4.33 (1.77 to 10.61; P=0.001) remained significant. CONCLUSIONS Measuring changes in HBP, PCT, and CRP within 72 h of admission may aid in predicting 28-day mortality for patients with septic shock in ICUs.

The effect of targeted rheumatoid arthritis therapeutics on systemic inflammation and anemia: analysis of data from the CorEvitas RA registry

BackgroundTo evaluate the effects of tumor necrosis factor inhibitors (TNFi), interleukin-6 receptor inhibitors (IL-6Ri), and Janus kinase inhibitors (JAKi) on hemoglobin (Hb) and C-reactive protein (CRP) levels in adults enrolled in CorEvitas (formerly Corrona), a large US rheumatoid arthritis (RA) registry.MethodsPatients who initiated TNFi, IL-6Ri, or JAKi treatment during or after January 2010, had Hb and CRP measurements at baseline and 6-month follow-up (± 3 months) and had continued therapy at least until that follow-up, through March 2020, were included in the analysis. Changes in Hb and CRP were assessed at month 6. Abnormal Hb was defined as < 12 g/dL (women) or < 13 g/dL (men); abnormal CRP was ≥ 0.8 mg/dL. Differences in Hb and CRP levels were evaluated using multivariable regression.ResultsOf 2772 patients (TNFi, 65%; IL-6Ri, 17%; JAKi, 17%) evaluated, 1044 (38%) had abnormal Hb or CRP at initiation; an additional 252 (9%) had both abnormal Hb and CRP. At month 6, the IL-6Ri group had a greater Hb increase than the TNFi (mean difference in effect on Hb: 0.28 g/dL; 95% CI 0.19–0.38) and JAKi (mean difference in effect on Hb: 0.47 g/dL; 95% CI 0.35–0.58) groups, regardless of baseline Hb status (both p < 0.001). The CRP decrease at month 6 was greater with IL-6Ri compared with TNFi and JAKi, regardless of baseline CRP status (both p < 0.05).ConclusionThese real-world results align with the mechanism of IL-6R inhibition and may inform treatment decisions for patients with RA.

The Association of Prenatal C-Reactive Protein and Interleukin-8 Levels with Maternal Characteristics and Preterm Birth.

The determinants of preterm birth remain unknown. Excessive maternal inflammation during pregnancy may play an important role in the pathogenesis of preterm birth. Our objective was to describe the association of prenatal levels of proinflammatory C-reactive protein (CRP) and interleukin-8 (IL-8) with preterm birth in participants of the Vitamin D Antenatal Asthma Reduction Trial. Five hundred and twenty-eight patients with available samples of both first- and third-trimester plasma were included in this analysis. CRP and IL-8 were measured from maternal prenatal samples. We examined the association between prenatal CRP and IL-8 with maternal health characteristics and the outcome of preterm birth. We also described the patterns of change in CRP and IL-8 from first to third trimester and their association with preterm birth. A subgroup analysis comparing only those with a spontaneous preterm birth phenotype to those with term birth was also performed. Maternal characteristics including lower educational attainment, higher prepregnancy body mass index, gestational diabetes, lower vitamin D, and an unhealthy diet were associated with elevated levels of prenatal CRP and IL-8. Higher third trimester CRP and an increase in CRP from first to third trimester were associated with an increased odds of preterm birth when compared to lower levels of CRP (adjusted odds ratio [aOR] = 1.49, 95% confidence interval: 1.02, 2.23, p = 0.04) or a decrease in CRP over pregnancy (aOR = 3.06, 95% CI = 1.31,7.55, p = 0.01), after adjusting for potential confounders. These associations were strengthened when comparing only patients with spontaneous preterm birth (n = 22) to those with term births. Higher levels of the proinflammatory markers CRP and IL-8 are associated with indicators of poor maternal health and preterm birth. Prenatal CRP levels may reflect maternal prenatal health status and serve as a predictor of preterm birth, especially among those with spontaneous preterm birth. · Elevated prenatal CRP is associated with poor maternal health.. · High prenatal CRP may predict premature birth, especially spontaneous premature birth phenotypes.. · Vitamin D insufficiency may be a modifiable risk factor for prenatal inflammation..

Associations of liver fat content with cardiometabolic phenotypes and outcomes in a multi-ethnic population: Results from the Dallas Heart Study.

To evaluate the associations between liver fat content and cardiometabolic parameters to explore potential threshold values that define metabolically healthy liver fat content, and to examine the association of liver fat content with cardiovascular events as well as its longitudinal progression. Participants in the Dallas Heart Study underwent clinical evaluation, including laboratory testing, and liver fat quantification by magnetic resonance spectroscopy (MRS) at baseline (N=2287) and at follow-up (N=343) after a mean of 7.3 years. Cardiovascular events were adjudicated (>12 years). The mean age at study entry was 44 years, 47% of participants were men, and 48% were African American. The following cardiometabolic biomarkers worsened across liver fat quintiles (P < 0.0001): body mass index (BMI); waist circumference; prevalence of hypertension; prevalence of diabetes; cholesterol, triglyceride, high-sensitivity C-reactive protein (CRP), leptin and fasting glucose levels; homeostatic model assessment of insulin resistance index (HOMA-IR); coronary artery calcium score; visceral adipose tissue; abdominal subcutaneous adipose tissue; and lower body subcutaneous adipose tissue. Cardiovascular events were comparable across groups defined by tertile of baseline liver fat content. Change in BMI (R=0.40), waist circumference (R=0.35), CRP (R=0.31), alanine aminotransferase (R=0.27), HOMA-IR (R=0.26), aspartate transaminase (R=0.15) and triglycerides (R=0.12) significantly correlated with change in liver fat content (P < 0.01 for all). Clinically relevant metabolic abnormalities were higher across quintiles of liver fat, with increases noted well within normal liver fat ranges, but cardiovascular events were not associated with liver fat content. Longitudinal changes in metabolic parameters, especially adiposity-related parameters, were correlated with change in liver fat content.