Association of Three Novel Inflammatory Markers: Lymphocyte to HDL-C Ratio, High-Sensitivity C-Reactive Protein to HDL-C Ratio and High-Sensitivity C-Reactive Protein to Lymphocyte Ratio With Metabolic Syndrome.

OBJECTIVE: We aimed to compare the association of three novel inflammatory indicators with metabolic syndrome (MetS) among Mashhad stroke and heart atherosclerotic disorder (MASHAD) cohort participants. METHODS: According to the International Diabetes Federation (IDF) criteria, the cohort participants were divided into the MetS(+) and MetS(-) groups. The lymphocyte to high-density lipoprotein cholesterol (HDL-C) ratio (LHR), high-sensitivity C-reactive protein (hs-CRP) to HDL-C ratio (HCHR) and hs-CRP to lymphocyte ratio (HCLR) were calculated and were compared between the groups. Binary logistic regression (LR) analysis was performed to find the association of the indices with the presence of MetS among men and women. Receiver-operating characteristic (ROC) curve analysis was used to establish cut-off values in predicting MetS for men and women. p-Values <0.05 were considered as statistically significant. RESULTS: Among a total of 8890 participants (5500 MetS(-) and 3390 MetS(+)), LHR, HCHR and HCLR were significantly higher in the MetS(+) group than in MetS(-) group (p < 0.001). In LR analysis, after adjusting for multiple cofounders, LHR remained an independent factor for the presence of MetS among men (OR: 1.254; 95% CI: 1.202-1.308; p < 0.001) and women (OR: 1.393; 95% CI: 1.340-1.448; p < 0.001). HCHR also remained an independent factor for the presence of MetS only in women (OR: 1.058; 95% CI: 1.043-1.073; p < 0.001). ROC curve analysis showed that LHR had the higher AUC for predicting MetS in both men (AUC: 0.627; 95% CI: 0.611-0.643; p < 0.001) and women (AUC: 0.683; 95% CI: 0.670, 0.696; p < 0.001). CONCLUSION: This suggests that among both genders, the LHR as an inexpensive and easy-to-access marker has a better diagnostic performance and could be a promising alternative to the traditional expensive inflammatory markers such as hs-CRP for the evaluation of inflammation in patients with MetS.

Inhibition of neuronal pentraxin 2 relieved epileptic seizure via reducing GluA1 phosphorylation.

Neuronal pentraxin 2 (Nptx2), a member of the synaptic protein family linked to excitatory synaptic formation, is found to be upregulated in epileptic mice, yet its role in epilepsy has been unclear. In vivo, we constructed a mouse model of epilepsy by using kainic acid induction. In vitro experiments, a Mg2+-free medium was used to induce epileptiform discharges in neurons. The results showed that the Nptx2 was upregulated in epileptic mice. Moreover, Nptx2 knockdown reduced the number of seizures and seizure duration. Knocking down Nptx2 not only reduced the number and duration of seizures but also showed a decrease in electroencephalogram amplitude. Behavioral tests indicated improvements in learning and memory abilities after Nptx2 knockdown. The Nissl staining and Timms staining revealed that Nptx2 silencing mitigated epilepsy-induced brain damage. The immunofluorescence staining revealed that Nptx2 absence resulted in a reduction of apoptosis. Nptx2 knockdown reduced Bax, cleaved caspase3, and cleaved caspase9 expression, while increased Bcl-2 expression. Notably, Nptx2 knockdown inhibited GluA1 phosphorylation at the S831 site and reduced the GluA1 membrane expression. The PSD95 expression declined in the epilepsy model, while the Nptx2 knockdown reversed it. Collectively, our study indicated that Nptx2 silencing not only alleviated brain damage and neuron apoptosis but also improved learning and memory ability in epileptic mice, suggesting Nptx2 as a promising target for epilepsy treatment.

Advances in heart failure monitoring: Biosensors targeting molecular markers in peripheral bio-fluids.

Cardiovascular diseases (CVDs), especially chronic heart failure, threaten many patients' lives worldwide. Because of its slow course and complex causes, its clinical screening, diagnosis, and prognosis are essential challenges. Clinical biomarkers and biosensor technologies can rapidly screen and diagnose. Multiple types of biomarkers are employed for screening purposes, precise diagnosis, and treatment follow-up. This article provides an up-to-date overview of the biomarkers associated with the six main heart failure etiology pathways. Plasma natriuretic peptides (BNP and NT-proBNP) and cardiac troponins (cTnT, cTnl) are still analyzed as gold-standard markers for heart failure. Other complementary biomarkers include growth differentiation factor 15 (GDF-15), circulating Galactose Lectin 3 (Gal-3), soluble interleukin (sST2), C-reactive protein (CRP), and tumor necrosis factor-alpha (TNF-α). For these biomarkers, the electrochemical biosensors have exhibited sufficient sensitivity, detection limit, and specificity. This review systematically summarizes the latest molecular biomarkers and sensors for heart failure, which will provide comprehensive and cutting-edge authoritative scientific information for biomedical and electronic-sensing researchers in the field of heart failure, as well as patients. In addition, our proposed future outlook may provide new research ideas for researchers.

Childhood maltreatment influences adult brain structure through its effects on immune, metabolic, and psychosocial factors.

Childhood maltreatment (CM) leads to a lifelong susceptibility to mental ill-health which might be reflected by its effects on adult brain structure, perhaps indirectly mediated by its effects on adult metabolic, immune, and psychosocial systems. Indexing these systemic factors via body mass index (BMI), C-reactive protein (CRP), and rates of adult trauma (AT), respectively, we tested three hypotheses: (H1) CM has direct or indirect effects on adult trauma, BMI, and CRP; (H2) adult trauma, BMI, and CRP are all independently related to adult brain structure; and (H3) childhood maltreatment has indirect effects on adult brain structure mediated in parallel by BMI, CRP, and AT. Using path analysis and data from N = 116,887 participants in UK Biobank, we find that CM is related to greater BMI and AT levels, and that these two variables mediate CM's effects on CRP [H1]. Regression analyses on the UKB MRI subsample (N = 21,738) revealed that greater CRP and BMI were both independently related to a spatially convergent pattern of cortical effects (Spearman's ρ = 0.87) characterized by fronto-occipital increases and temporo-parietal reductions in thickness. Subcortically, BMI was associated with greater volume, AT with lower volume and CPR with effects in both directions [H2]. Finally, path models indicated that CM has indirect effects in a subset of brain regions mediated through its direct effects on BMI and AT and indirect effects on CRP [H3]. Results provide evidence that childhood maltreatment can influence brain structure decades after exposure by increasing individual risk toward adult trauma, obesity, and inflammation.

Transgenic human C-reactive protein affects oxidative stress but not inflammation biomarkers in the aorta of spontaneously hypertensive rats.

BACKGROUND: C-reactive protein (CRP) is an acute inflammatory protein detected in obese patients with metabolic syndrome. Moreover, increased CRP levels have been linked with atherosclerotic disease, congestive heart failure, and ischemic heart disease, suggesting that it is not only a biomarker but also plays an active role in the pathophysiology of cardiovascular diseases. Since endothelial dysfunction plays an essential role in various cardiovascular pathologies and is characterized by increased expression of cell adhesion molecules and inflammatory markers, we aimed to detect specific markers of endothelial dysfunction, inflammation, and oxidative stress in spontaneously hypertensive rats (SHR) expressing human CRP. This model is genetically predisposed to the development of the metabolic syndrome. METHODS: Transgenic SHR male rats (SHR-CRP) and non-transgenic SHR (SHR) at the age of 8 months were used. Metabolic profile (including serum and tissue triglyceride (TAG), serum insulin concentrations, insulin-stimulated incorporation of glucose, and serum non-esterified fatty acids (NEFA) levels) was measured. In addition, human serum CRP, MCP-1 (monocyte chemoattractant protein-1), and adiponectin were evaluated by means of ELISA, histological analysis was used to study morphological changes in the aorta, and western blot analysis of aortic tissue was performed to detect expression of endothelial, inflammatory, and oxidative stress markers. RESULTS: The presence of human CRP was associated with significantly decreased insulin-stimulated glycogenesis in skeletal muscle, increased muscle and hepatic accumulation of TAG and decreased plasmatic cGMP concentrations, reduced adiponectin levels, and increased monocyte chemoattractant protein-1 (MCP-1) levels in the blood, suggesting pro-inflammatory and presence of multiple features of metabolic syndrome in SHR-CRP animals. Histological analysis of aortic sections did not reveal any visible morphological changes in animals from both SHR and SHR-CRP rats. Western blot analysis of the expression of proteins related to the proper function of endothelium demonstrated significant differences in the expression of p-eNOS/eNOS in the aorta, although endoglin (ENG) protein expression remained unaffected. In addition, the presence of human CRP in SHR in this study did not affect the expression of inflammatory markers, namely p-NFkB, P-selectin, and COX2 in the aorta. On the other hand, biomarkers related to oxidative stress, such as HO-1 and SOD3, were significantly changed, indicating the induction of oxidative stress. CONCLUSIONS: Our findings demonstrate that CRP alone cannot fully induce the expression of endothelial dysfunction biomarkers, suggesting other risk factors of cardiovascular disorders are necessary to be involved to induce endothelial dysfunction with CRP.

C-reactive protein-complement factor H axis as a biomarker of activity in early and intermediate age-related macular degeneration.

Purpose: To determine and compare the serum levels of complement Factor H (FH), monomeric C-Reactive Protein (mCRP) and pentameric C-Reactive protein (pCRP) in patients with age-related macular degeneration (AMD) and to correlate them with clinical, structural and functional parameters. Methods: Cross-sectional observational study. One hundred thirty-nine individuals (88 patients and 51 healthy controls) from two referral centers were included and classified into three groups: early or intermediate AMD (n=33), advanced AMD (n=55), and age and sex matched healthy controls (n=51). Serum levels of FH, mCRP, and pCRP were determined and correlated with clinical and imaging parameters. Results: Patients with intermediate AMD presented FH levels significantly lower than controls [186.5 (72.1-931.8) µg/mL vs 415.2 (106.1-1962.2) µg/mL; p=0.039] and FH levels <200 µg/mL were associated with the presence of drusen and pigmentary changes in the fundoscopy (p=0.002). While no differences were observed in pCRP and mCRP levels, and mCRP was only detected in less than 15% of the included participants, women had a significantly higher detection rate of mCRP than men (21.0% vs. 3.8%, p=0.045). In addition, the ratio mCRP/FH (log) was significantly lower in the control group compared to intermediate AMD (p=0.031). Visual acuity (p<0.001), macular volume (p<0.001), and foveal thickness (p=0.034) were significantly lower in the advanced AMD group, and choroidal thickness was significantly lower in advanced AMD compared to early/intermediate AMD (p=0.023). Conclusion: Intermediate AMD was associated in our cohort with decreased serum FH levels together with increased serum mCRP/FH ratio. All these objective serum biomarkers may suggest an underlying systemic inflammatory process in early/intermediate AMD patients.

Impact of supplementation with iron-folic acid (IFA) and vitamin D3 compared with IFA alone on haemoglobin levels in elderly people with mild-to-moderate anaemia: protocol for the double-blind, randomised, placebo-controlled Iron and vitamin D trial in Elderly Anemia (IDEA).

INTRODUCTION: Anaemia in the elderly is often difficult to treat with iron supplementation alone as prevalence of anaemia of chronic disease (ACD) alone or mixed with iron-deficiency anaemia (IDA) is high in this age group. Hepcidin remains high in ACD, preventing utilisation of iron for heme synthesis. Vitamin D3 has shown hepcidin suppression activity in both in vitro and in vivo studies. As there is no study assessing the effect of iron-folic acid (IFA) with vitamin D3 on haemoglobin levels in the elderly in India, we want to conduct this study to estimate the impact of supplementation of a therapeutic package of IFA and vitamin D3 on haemoglobin levels in the elderly with mild-to-moderate anaemia in comparison with IFA only. The study will also assess the impact of the proposed intervention on ferritin, hepcidin, 25-hydroxyvitamin D, C reactive protein (CRP) and parathyroid hormone (PTH) levels. METHODS AND ANALYSIS: This study is a community-based, double-blind, placebo-controlled, randomised trial. The study will be done in the Kalyani municipality area. Individuals aged ≥60 years with mild-to-moderate anaemia and normal vitamin D3 levels will be randomised into the intervention (IFA and vitamin D3 supplementation) group or the control group (IFA and olive oil as placebo). All medications will be self-administered. Follow-up will be done on a weekly basis for 12 weeks. The calculated sample size is 150 in each arm. Block randomisation will be done. The primary outcome is change in haemoglobin levels from baseline to 12 weeks. Secondary outcome is change in serum ferritin, 25-hydroxyvitamin D, hepcidin, CRP and PTH levels from baseline to 12 weeks. ETHICS AND DISSEMINATION: Ethical approval from the Institutional Ethics Committee of All India Institute of Medical Sciences Kalyani has been obtained (IEC/AIIMS/Kalyani/Meeting/2022/03). Written informed consent will be obtained from each study participant. The trial results will be reported through publication in a reputable journal and disseminated through health talks within the communities. TRIAL REGISTRATION NUMBER: CTRI/2022/05/042775. PROTOCOL VERSION: Version 1.0.

[Magnetic resonance imaging T2 mapping could reflect disease status in patients with dermatomyositis or polymyositis].

This study aimed to explore the value of magnetic resonance imaging (MRI) T2 mapping in the assessment of dermatomyositis (DM) and polymyositis (PM). Thirty-three confirmed cases (myosin group) and eight healthy volunteers (healthy control group) at the Department of Rheumatology and Immunology, the First Affiliated Hospital of Kunming Medical University, from October 2016 to December 2017, were collected and analyzed. Multiple parameters of the myosin group were quantified, including creatine kinase (CK), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), complement C3, and complement C4. Disease status was evaluated using a panel of tools: myositis disease activity assessment tool-muscle (MDAAT-muscle), myositis disease activity assessment tool-whole (MDAAT-all), health assessment questionnaire (HAQ), medical outcomes study health survey short form-36 item (SF-36), hand muscle strength test (MMT-8) score, and MRI T2 mapping of muscle (22 muscles in the pelvis and thighs) T2 values. The results showed that in the myositis group, the measurements for CK, ESR, CRP, complement C3, and complement C4 were 457.2 (165.6, 1 229.2) IU/L, 20 (10, 42) mm/1h, 3.25 (2.38, 10.07) mg/L, 0.90 (0.83, 1.06) g/L, and 0.18 (0.14, 0.23) g/L, respectively. The scores for MMT-8, MDAAT-muscle, MDAAT-all, HAQ, and SF-36 were 57.12±16.23, 5.34 (4.00, 6.00), 34.63±12.62, 1.55 (0.66, 2.59), and 44.66±7.98, respectively. T2 values were significantly higher in all 22 muscles of the pelvis and thighs of patients with DM or PM compared with the healthy controls [(54.99±11.60)ms vs. (36.62±1.66)ms, P<0.001], with the most severe lesions in the satrorius, iliopsoas, piriformis, gluteus minimus, and gluteus medius muscles. The total muscle T2 value in the myositis group was positively correlated with CK, MDAAT-muscle, MDAAT-all, and HAQ (r=0.461, 0.506, 0.347, and 0.510, respectively, all P<0.05). There was a negative correlation between complement C4, SF-36, and MMT-8 scores (r=-0.424, -0.549, and -0.686, respectively, all P<0.05). Collectively, the findings from this study suggest that MRI T2 mapping can objectively reflect the disease status of DM and PM.

Can serum interleukin 34 levels be used as an indicator for the prediction and prognosis of COVID-19?

OBJECTIVE: Interleukin 34 (IL-34) is a molecule whose expression is increased in conditions such as autoimmune disorders, inflammation, and infections. Our study aims to determine the role of IL-34 in the diagnosis, follow-up, and prognosis of Coronavirus Disease-19 (COVID-19). METHOD: A total of 80 cases were included in the study as 40 COVID-19 positive patient groups and 40 COVID-19 negative control groups. The COVID-19-positive group consisted of 20 intensive-care unit (ICU) patients and 20 outpatients. Serum IL-34, c-reactive protein (CRP), ferritin, D-dimer, troponin I, hemogram, and biochemical parameters of the cases were studied and compared between groups. RESULTS: IL-34 levels were significantly higher in the COVID-19-positive group than in the negative group. IL-34 levels increased in correlation with CRP in predicting the diagnosis of COVID-19. IL-34 levels higher than 31.75 pg/m predicted a diagnosis of COVID-19. IL-34 levels did not differ between the outpatient and ICU groups in COVID-19-positive patients. IL-34 levels were also not different between those with and without lung involvement. CONCLUSION: While IL-34 levels increased in COVID-19-positive patients and were successful in predicting the diagnosis of COVID-19, it was not found to be significant in determining lung involvement, risk of intensive care hospitalization, and prognosis. The role of IL-34 in COVID-19 deserves further evaluation.

[A multicenter prospective study on early identification of refractory Mycoplasma pneumoniae pneumonia in children].

Objective: To explore potential predictors of refractory Mycoplasma pneumoniae pneumonia (RMPP) in early stage. Methods: The prospective multicenter study was conducted in Zhejiang, China from May 1st, 2019 to January 31st, 2020. A total of 1 428 patients with fever >48 hours to <120 hours were studied. Their clinical data and oral pharyngeal swab samples were collected; Mycoplasma pneumoniae DNA in pharyngeal swab specimens was detected. Patients with positive Mycoplasma pneumoniae DNA results underwent a series of tests, including chest X-ray, complete blood count, C-reactive protein, lactate dehydrogenase (LDH), and procalcitonin. According to the occurrence of RMPP, the patients were divided into two groups, RMPP group and general Mycoplasma pneumoniae pneumonia (GMPP) group. Measurement data between the 2 groups were compared using Mann-Whitney U test. Logistic regression analyses were used to examine the associations between clinical data and RMPP. Receiver operating characteristic (ROC) curves were used to analyse the power of the markers for predicting RMPP. Results: A total of 1 428 patients finished the study, with 801 boys and 627 girls, aged 4.3 (2.7, 6.3) years. Mycoplasma pneumoniae DNA was positive in 534 cases (37.4%), of whom 446 cases (83.5%) were diagnosed with Mycoplasma pneumoniae pneumonia, including 251 boys and 195 girls, aged 5.2 (3.3, 6.9) years. Macrolides-resistant variation was positive in 410 cases (91.9%). Fifty-five cases were with RMPP, 391 cases with GMPP. The peak body temperature before the first visit and LDH levels in RMPP patients were higher than that in GMPP patients (39.6 (39.1, 40.0) vs. 39.2 (38.9, 39.7) ℃, 333 (279, 392) vs. 311 (259, 359) U/L, both P<0.05). Logistic regression showed the prediction probability π=exp (-29.7+0.667×Peak body temperature (℃)+0.004×LDH (U/L))/(1+exp (-29.7+0.667×Peak body temperature (℃)+0.004 × LDH (U/L))), the cut-off value to predict RMPP was 0.12, with a consensus of probability forecast of 0.89, sensitivity of 0.89, and specificity of 0.67; and the area under ROC curve was 0.682 (95%CI 0.593-0.771, P<0.01). Conclusion: In MPP patients with fever over 48 to <120 hours, a prediction probability π of RMPP can be calculated based on the peak body temperature and LDH level before the first visit, which can facilitate early identification of RMPP.

Association of T Cell Subsets and Platelet/Lymphocyte Ratio with Long-Term Complications in Kidney Transplant Recipients.

BACKGROUND Infection and chronic rejection remain major issues for kidney transplant recipients (KTRs). The present study aimed to explore the association of CD4+/CD8+ T cell ratio (CD4+/CD8+) and platelet/lymphocyte ratio (PLR) with long-term infection and chronic renal insufficiency in KTRs. MATERIAL AND METHODS KTRs admitted to a single hospital from June 2014 to December 2021 were divided into infected (164) and non-infected (107) groups based on clinical data. The levels of CD4+/CD8+, PLR, neutrophil/lymphocyte ratio (NLR), and C-reactive Protein (CRP) in KTRs with long-term infection, and their correlation with chronic kidney insufficiency, were analyzed. Survival analysis was used to evaluate the risk factors for long-term infection and chronic kidney insufficiency. RESULTS Spearman correlation analysis showed that chronic kidney insufficiency was positively correlated with PLR, and negatively correlated with CRP and CD4+/CD8+ (P<0.05). PLR was positively correlated with CRP, procalcitonin, erythrocyte sedimentation rate, and NLR, but negatively with CD4+/CD8+. CD4+/CD8+ was correlated with CRP, NLR, and PLR (P<0.05). Survival analysis and survival curves showed that PLR and CD4+/CD8+ were risk factors for long-term infection and chronic kidney insufficiency in KTRs (P<0.05). CONCLUSIONS CD4+/CD8+ and PLR were associated with long-term complications, and were risk factors for long-term infection and chronic kidney insufficiency in KTRs.

Association of Dietary Fiber and Measures of Physical Fitness with High-Sensitivity C-Reactive Protein.

Dietary fiber intake and physical fitness are independently associated with high-sensitivity C-reactive protein (hs-CRP) levels. Nevertheless, the association between dietary fiber intake, measures of physical fitness, and hs-CRP levels has not yet been fully evaluated. We investigated the influence of a combination of dietary fiber intake and measures of physical fitness, including hand grip strength, resistance training, and metabolic equivalents of tasks, on hs-CRP levels. Data collected from the Korea National Health and Nutrition Examination Survey (KNHANES) spanning 2015 to 2018 were used in this study. A total of 16,934 participants (7434 men and 9500 women aged ≥19 years) were included in this study. After adjusting for confounding factors (age, education, income, marital status, smoking status, drinking habits, total energy intake, and aerobic physical activity), we employed a multivariable logistic model to examine the association of dietary fiber intake and measures of physical fitness with hs-CRP levels. Among women, the odds of high hs-CRP levels were lower in those with the highest dietary fiber intake and superior grip strength compared to in women with the lowest dietary fiber intake and weaker grip strength (odds ratio [OR] = 0.40, 95% confidence interval [CI] = 0.24-0.68). The highest dietary fiber intake who participated in resistance exercise at least three times per week had a reduced odds of high hs-CRP levels compared with those with the lowest dietary fiber intake who did not engage in resistance exercise in both men and women (OR = 0.53, 95% CI = 0.32-0.89; OR = 0.40, 95% CI = 0.19-0.84, respectively). Our findings indicate that dietary fiber intake and high levels of physical fitness were associated with reduced odds of elevated hs-CRP levels.

The relationship of neuropsychiatric symptoms with inflammatory markers in the hippocampus and cingulate cortex of bipolar disorder subjects: A post-mortem study.

Increased levels of inflammation markers have been found in the peripheral tissue of individuals with bipolar disorder (BD), especially during mood episodes. Previous studies found distinctive inflammatory profiles across different brain regions, but potential associations with clinical symptoms are still lacking. This study aims to evaluate the association of neuropsychiatric symptoms with inflammatory markers in the hippocampus and cingulate of individuals with BD. Levels of IL-1ß, IL-6, IL-17A, cortisol, and C-reactive protein (CRP) were measured in the hippocampus and anterior cingulate of 14 BD individuals and their non-psychiatric controls. Neuropsychiatric symptoms present in the three months before death were assessed using the Neuropsychiatric Inventory (NPI). In the BD group, greater NPI scores were associated with higher IL-6 in the hippocampus (p = 0.011) and cingulate (p = 0.038) and higher IL-1ß (p = 0.039) in the hippocampus. After adjusting for age, sex and CDR, IL-1ß and IL-6 were still associated with higher NPI in the hippocampus. In correlation analysis considering both BD and their controls, moderate positive associations were found between NPI and IL-6 and cortisol in the hippocampus (p < 0.001 and p = 0.006) and cingulate (p = 0.024 and p = 0.016), IL-1ß (p < 0.001) and IL-17A in the hippocampus (p = 0.002). No difference in inflammatory markers was found according to type of psychotropic medication used. Hence, in individuals with BD, neuropsychiatric symptoms were differently associated with specific inflammatory cytokines and CRP in the hippocampus and cingulate. These results suggest that the neuroinflammatory changes occurring in BD may be more complex than previously expected and could be associated with clinical manifestations.

Serum high-sensitivity C-reactive protein and dementia in a community-dwelling Japanese older population (JPSC-AD).

In recent years, the association between neuroinflammatory markers and dementia, especially Alzheimer's disease (AD), has attracted much attention. However, the evidence for the relationship between serum-hs-CRP and dementia including AD are inconsistent. Therefore, the relationships of serum high-sensitivity CRP (hs-CRP) with dementia including AD and with regions of interest of brain MRI were investigated. A total of 11,957 community residents aged 65 years or older were recruited in eight sites in Japan (JPSC-AD Study). After applying exclusion criteria, 10,085 participants who underwent blood tests and health-related examinations were analyzed. Then, serum hs-CRP levels were classified according to clinical cutoff values, and odds ratios for the presence of all-cause dementia and its subtypes were calculated for each serum hs-CRP level. In addition, the association between serum hs-CRP and brain volume regions of interest was also examined using analysis of covariance with data from 8614 individuals in the same cohort who underwent brain MRI. After multivariable adjustment, the odds ratios (ORs) for all-cause dementia were 1.04 (95% confidence interval [CI] 0.76-1.43), 1.68 (95%CI 1.08-2.61), and 1.51 (95%CI 1.08-2.11) for 1.0-1.9 mg/L, 2.0-2.9 mg/L, and ≥ 3.0 mg/L, respectively, compared to < 1.0 mg/L, and those for AD were 0.72 (95%CI 0.48-1.08), 1.76 (95%CI 1.08-2.89), and 1.61 (95%CI 1.11-2.35), for 1.0-1.9 mg/L, 2.0-2.9 mg/L, and ≥ 3.0 mg/L, respectively, compared to < 1.0 mg/L. Multivariable-adjusted ORs for all-cause dementia and for AD prevalence increased significantly with increasing serum hs-CRP levels (p for trend < 0.001 and p = 0.001, respectively). In addition, the multivariable-adjusted temporal cortex volume/estimated total intracranial volume ratio decreased significantly with increasing serum hs-CRP levels (< 1.0 mg/L 4.28%, 1.0-1.9 mg/L 4.27%, 2.0-2.9 mg/L 4.29%, ≥ 3.0 mg/L 4.21%; p for trend = 0.004). This study's results suggest that elevated serum hs-CRP levels are associated with greater risk of presence of dementia, especially AD, and of temporal cortex atrophy in a community-dwelling Japanese older population.

Higher C-Reactive Protein to Albumin Ratio Portends Long-Term Mortality in Patients with Chronic Heart Failure and Reduced Ejection Fraction.

Background and Objectives: In this study, we aimed to investigate the prognostic value of the C-reactive protein to albumin ratio (CAR) for all-cause mortality in patients with chronic heart failure with reduced ejection fraction (HFrEF). Materials and Methods: In total, 404 chronic HFrEF patients were included in this observational and retrospective study. The CAR value of each patient included in this analysis was calculated. We stratified the study population into tertiles (T1, T2, and T3) according to CAR values. The primary outcome of the analysis was to determine all-cause mortality. Results: The median follow-up period in our study was 30 months. In the follow-up, 162 (40%) patients died. The median value of CAR was higher in patients who did not survive during the follow-up [6.7 (IQR = 1.6-20.4) vs. 0.6 (IQR = 0.1-2.6), p < 0.001]. In addition, patients in the T3 tertile (patients with the highest CAR) had a higher rate of all-cause mortality [n = 90 cases (66.2%), p < 0.001]. Multivariate Cox regression analysis revealed that CAR was an independent predictor of mortality in patients with HFrEF (hazard ratio: 1.852, 95% confidence interval: 1.124-2.581, p = 0.005). In a receiver operating characteristic curve analysis, the optimal cut-off value of CAR was >2.78, with a sensitivity of 66.7% and specificity of 76%. Furthermore, older age, elevated N-terminal pro-brain natriuretic peptide levels, and absence of a cardiac device were also independently associated with all-cause death in HFrEF patients after 2.5 years of follow-up. Conclusions: The present study revealed that CAR independently predicts long-term mortality in chronic HFrEF patients. CAR may be used to predict mortality among these patients as a simple and easily obtainable inflammatory marker.

mCRP-Induced Focal Adhesion Kinase-Dependent Monocyte Aggregation and M1 Polarization, Which Was Partially Blocked by the C10M Inhibitor.

Monomeric C-reactive protein (mCRP) has recently been implicated in the abnormal vascular activation associated with development of atherosclerosis, but it may act more specifically through mechanisms perpetuating damaged vessel inflammation and subsequent aggregation and internalization of resident macrophages. Whilst the direct effects of mCRP on endothelial cells have been characterized, the interaction with blood monocytes has, to our knowledge, not been fully defined. Here we showed that mCRP caused a strong aggregation of both U937 cell line and primary peripheral blood monocytes (PBMs) obtained from healthy donors. Moreover, this increase in clustering was dependent on focal adhesion kinase (FAK) activation (blocked by a specific inhibitor), as was the concomitant adhesive attachment to the plate, which was suggestive of macrophage differentiation. Confocal microscopy confirmed the increased expression and nuclear localization of p-FAK, and cell surface marker expression associated with M1 macrophage polarization (CD11b, CD14, and CD80, as well as iNOS) in the presence of mCRP. Inclusion of a specific CRP dissociation/mCRP inhibitor (C10M) effectively inhibited PBMs clustering, as well as abrogating p-FAK expression, and partially reduced the expression of markers associated with M1 macrophage differentiation. mCRP also increased the secretion of pro-inflammatory cytokines Interleukin-8 (IL-8) and Interleukin-1ß (IL-1ß), without notably affecting MAP kinase signaling pathways; inclusion of C10M did not perturb or modify these effects. In conclusion, mCRP modulates PBMs through a mechanism that involves FAK and results in cell clustering and adhesion concomitant with changes consistent with M1 phenotypical polarization. C10M has potential therapeutic utility in blocking the primary interaction of mCRP with the cells-for example, by protecting against monocyte accumulation and residence at damaged vessels that may be predisposed to plaque development and atherosclerosis.

Clinical usefulness of a host signature based on TRAIL, IP10, and CRP (MeMed BV) as infection biomarkers in intensive care units' patients. A retrospective observational study.

INTRODUCTION: Infection complications are common in intensive care unit patients, and early detection remains a diagnostic challenge. Procalcitonin (PCT) and C-reactive protein (CRP) are commonly used biomarkers. A novel diagnostic approach focuses on the host immune response. One of the approaches, the MMBV index, is based on measuring in a blood sample three parameters: (i) tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), (ii) interferon-γ-induced protein-10 (IP10), and (iii) CRP. This study aimed to evaluate the usefulness of MMBV as an infection biomarker in an ICU cohort. PATIENTS AND METHODS: Forty-six patients treated in the University Clinical Center in Gdansk ICU were enrolled in the study, and their clinical data were retrospectively analyzed. In total, 91 MMBV results were analyzed. RESULTS: Most of the patients had high MMBV values, suggesting bacterial etiology. A weak correlation between PCT and MMBV was observed, and no correlation between parameter changes was noted. There was a correlation between CRP/MMBV and between changes in CRP / changes in MMBV. CONCLUSION: It seems that MMBV is not valuable for ICU patients neither in diagnosing nor monitoring infection. Higher MMBV values may predict unfavorable treatment outcomes.

The Use of Biomarkers to Quantify Clinical Response to Total Knee Arthroplasty Interventions: A Systematic Review.

The primary objective of this review was to determine whether the attenuation of the postoperative inflammatory response (PIR) after total knee arthroplasty (TKA) leads to a notable improvement in clinical outcome scores. The secondary objective of this review was to determine the optimal approach in using inflammatory biomarkers, clinical inflammatory assessments, and imaging to quantify the PIR. A systematic literature search of eight major databases was conducted using a predetermined search strategy. C-reactive protein (CRP), interleukin-6 (IL-6), erythrocyte sedimentation rate (ESR), knee surface temperature (KST), and clinical outcome data were collected and graphically displayed. Eighty-six percent of the studies that reported a statistically significant decrease in inflammatory biomarkers in their treatment group demonstrated a concordant notable improvement in clinical outcome scores. Mean CRP, IL-6, ESR, and KST values peaked on postoperative day (POD) 2, POD1, POD7, and POD 1-3, respectively. The PIR is correlated with early pain and function recovery outcomes. Future studies comparing TKA surgical methodologies and perioperative protocols should assess PIR by incorporating inflammatory biomarkers, such as CRP and IL-6, and clinical inflammatory assessment adjuncts, to provide a more comprehensive comparison.

The Association between Serum Level of Vitamin D and Inflammatory Biomarkers in Hospitalized Adult Patients: A Cross-Sectional Study Based on Real-World Data.

Objective: The association between vitamin D status and inflammation remains unclear in hospitalized patients. Materials and Methods: We performed the current study based on real-world data from two teaching hospitals. Serum level of vitamin D (assessed by 25-hydroxyvitamin D) was evaluated within 2 days after admission. All the patients were further classified into three groups: deficiency (<12 ng/mL), insufficiency (12-20 ng/mL), and adequate (≥20 ng/mL). White blood cell (WBC) count, serum level of C-reactive protein (CRP), and procalcitonin were also measured and used to evaluate inflammation. Other potential covariates were abstracted from medical records. Charlson comorbidity index (CCI) was calculated to assess the severity of disease. Results: A total number of 35,528 hospitalized adult patients (21,171 men and 14,357 women) were included. The average age and BMI were 57.5 ± 16.2 years and 23.4 ± 3.7 kg/m2, respectively, while medium vitamin D level was 16.1 ng/mL (interquartile range: 11.4 ng/mL, 21.6 ng/mL) and median CCI was one point (interquartile range: 0 point, two points). The prevalence of deficiency and insufficiency was 28.0% and 40.5%. Multivariate linear regression model showed that serum level of vitamin D was significantly associated with WBC and CRP but not associated with procalcitonin. Each standard deviation (≈7.4 ng/mL) increase in vitamin D was associated with a decrease in WBC by 0.13 × 109/mL (95% CI: 0.2 × 109/mL, 0.06 × 109/mL) and 0.62 mg/L (95% CI: 0.88 mg/L, 0.37 mg/L) for CRP. Subgroup analysis and sensitivity analysis (excluding those whose eGFR <60 ml/min/1.73 m2, those whose daily calorie intake <1,000 kcal, and those who were recruited from Xin Hua hospital) generated similar results. Conclusions: The deficiency and insufficiency of vitamin D in the hospitalized adult patients was very common. However, the results should be interpreted with caution for limited representation of the whole inpatients. Low level of vitamin D was associated with inflammatory biomarkers, which provide the evidences to early intervention for lower the risk of infection.

Impact of filgotinib on pain control in the phase 3 FINCH studies.

OBJECTIVE: This post hoc analysis of the FINCH 1-3 (NCT02889796, NCT02873936 and NCT02886728) studies assessed specific effects of filgotinib on pain control and their relationship with other aspects of efficacy in patients with rheumatoid arthritis (RA). METHODS: Assessments included: residual pain responses of ≤10 and ≤20 mm on a 100 mm visual analogue scale (VAS); the proportion of patients who achieved VAS pain responses in addition to remission or low disease activity by Disease Activity Score-28 with C-reactive protein (DAS28-CRP) or Clinical Disease Activity Index (CDAI) criteria. RESULTS: Across studies, filgotinib reduced pain from week 2, with responses sustained throughout the studies. In FINCH 1, at week 24, 35.8%, 25.0%, 24.6% and 11.6% of patients in the filgotinib 200 mg, filgotinib 100 mg, adalimumab and placebo arms (each plus methotrexate) achieved VAS pain ≤20 mm in addition to DAS28-CRP remission; 26.3%, 17.9%, 17.2% and 7.6% achieved VAS pain ≤10 mm in addition to DAS28-CRP remission. A similar pattern was seen for CDAI remission. Time during which VAS pain was ≤10 or ≤20 mm was longest with filgotinib 200 mg and comparable between adalimumab and filgotinib 100 mg. Similar findings were reported for filgotinib in FINCH 2 and 3. CONCLUSION: In all RA populations studied, pain improvements occurred from week 2 and were sustained over time. In FINCH 1, filgotinib 100 mg provided similar pain amelioration to adalimumab, whereas filgotinib 200 mg resulted in greater pain improvement and higher proportion of patients with residual pain ≤10 or ≤20 mm and meeting DAS28-CRP remission criteria.