Correlation study: Bone density and circulating inflammatory markers in postmenopausal patients.

OBJECTIVE: This study aims to investigate the correlation between changes in bone mineral density (BMD) in postmenopausal women and circulating inflammatory markers. METHODS: This retrospective study focused on postmenopausal women admitted to the orthopedic department of Suzhou Benq Medical Center from June 2022 to December 2023, following predetermined inclusion and exclusion criteria. We retrospectively collected data on initial blood routine test results and bone density measurements for all study subjects upon admission, including parameters such as white blood cell count (WBC), C-reactive protein, interleukin-6 (IL-6), and procalcitonin (PCT). Additionally, the systemic immune-inflammation index (SII) was calculated using neutrophil count, lymphocyte count, and platelet count. Statistical analyses using SPSS and GraphPad software were performed to assess the correlation between bone density and inflammatory markers. RESULTS: Patients were classified into three groups based on BMD results, including 60 individuals in the osteoporosis (OP) group, 127 individuals in the osteopenia group, and 37 individuals in the Normal group, respectively. Principal component analysis analysis suggested that WBC, SII, and postmenopausal OP (PMOP) held significant feature values. Correlation analysis indicated a correlation between WBC (p = 0.021), IL-6 (p = 0.044), SII (p = 0.034), and PMOP. One-way ANOVA analysis revealed significant differences in IL-6 (p = 0.0179), SII (p = 0.0210), and PCT (p = 0.0200) among the three groups. Finally, ROC curve analysis demonstrated that SII (area under the curve = 0.716) has predictive value for PMOP. CONCLUSION: This study identified a certain predictive value for PMOP through the assessment of inflammatory markers in peripheral blood using routine blood tests.

The value of FPR, FAR, CAR, CPR in the auxiliary diagnosis of colon cancer.

Chronic malnutrition, abnormal blood clotting, and systemic inflammation contribute to the occurrence and progression of colon cancer. This study aimed to assess the diagnostic utility of the 100fibrinogen-to-prealbumin ratio (FPR), 100fibrinogen-to-albumin ratio (FAR), 100C-reactive protein-to-albumin ratio (CAR), and 100C-reactive protein-to-prealbumin ratio (CPR) in aiding the diagnosis of colon cancer. A total of 129 patients with colon cancer were enrolled between April 2015 and August 2022. While 129 patients with colon adenoma were selected as the control group. The serum levels of FAR, FPR, CAR, CPR, CEA, and CA125 in the colon cancer group were significantly higher than those in the colon adenoma group (P < .05). In Logistic regression analysis, high FAR and high FPR were identified as independent risk factors for colon cancer. Receiver operating characteristic (ROC) curve analysis results showed that Among the combined measures, FAR, FPR, CAR, and CPR had the highest diagnostic efficacy in distinguishing colon cancer from colon adenomas (AUC = 0.886, Sen = 80.62%, Spe = 81.40%). Thus, FAR, FPR, CAR, and CPR may serve as valuable biomarkers for the diagnosis of colon cancer, and the combined detection of FAR, FPR, CAR, and CPR can enhance the diagnostic efficiency for both colon cancer and colon adenoma.

Association between high-sensitivity C-reactive protein and renal function in Korean adults: A sex-specific analysis of Korea National Health and Nutrition Examination Survey 2015 to 2018 data.

This study aimed to investigate the association between high-sensitivity C-reactive protein (hs-CRP) levels, as a surrogate marker of systemic inflammation, and renal function among Korean adults grouped by age, sex, and body mass index. This study analyzed data obtained from the Korea National Health and Nutrition Examination Survey 2015 to 2018, a cross-sectional and nationally representative survey conducted by the Korean Centers for Disease Control and Prevention. Of the 22,451 subjects included in this study, 19,607 (87.3%) and 2844 (12.7%) had normal kidney function and incident chronic kidney disease, respectively. Reduced renal function was more frequently observed in subjects with high hs-CRP levels than in those with low hs-CRP levels (odds ratio [OR], 1.438; 95% confidence interval [CI], 1.234-1.674). In the group aged ≥ 65 years, the odds of reduced renal function were higher among subjects with a high hs-CRP level compared to those with a low hs-CRP level (OR, 1.528; 95% CI, 1.191-1.960). The association between hs-CRP level and renal function was observed only in women (OR, 2.485; 95% CI, 1.779-3.470) and further stratified by age and sex, the odds of reduced renal function were likely higher in women aged ≥ 65 years with a high hs-CRP level (OR, 2.338; 95% CI, 1.622-3.369). Moreover, reduced renal function was more observed in subjects aged ≥ 65 years and those with a body mass index < 25 kg/m2 (OR, 1.502; 95% CI, 1.087-2.075). This study showed that a high hs-CRP level likely contributes to the increased prevalence of reduced renal function. This association may aid the identification of individuals at high risk for reduced renal function, especially elderly women, in clinical or public health practice.

Cardiovascular disease risk factors and their associations with inflammation among US adolescents: NHANES, 2015 to March 2020.

INTRODUCTION: The prevalence of obesity and glycemic dysfunction in adolescents has increased over the past several decades but less is known on how these conditions are associated with systemic inflammation in this population. This study determined the associations between cardiovascular disease (CVD) risk factors and inflammation among a nationally representative sample of US. adolescents. RESEARCH DESIGN AND METHODS: Cross-sectional analyses were conducted among 2693 adolescents aged 12-19 years who participated in the 2015 to March 2020 National Health and Nutrition Examination Surveys. Chronic inflammation was determined using laboratory measures for high-sensitivity C reactive protein (hs-CRP). Adjusted ORs (aOR, 95% CI) were calculated from logistic regression models to determine the association between CVD risk factors (obesity, overweight, dysglycemia, hypertension, hyperlipidemia) and elevated hs-CRP (>3.0 mg/L) while controlling for sociodemographic characteristics and other CVD risk factors. RESULTS: Overall, 15.3% of adolescents had elevated hs-CRP. Adolescents who were older (16-19 years vs 12-15 years), obese, had A1c ≥5.7% (≥39 mmol/mol), high total cholesterol, or low high-density lipoprotein had hs-CRP distributions that were more high risk (χ2 p value <0.001). Adolescents with obesity or A1c ≥5.7% had a sixfold and a nearly twofold higher odds of elevated hs-CRP compared those without obesity and A1c <5.7% after full adjustment (aOR=6.39, 4.64 to 8.79 and aOR=1.70, 1.05 to 3.06, respectively). Adolescents with hypertension or hyperlipidemia were significantly more likely to have elevated hs-CRP compared with those without these conditions after adjustment for sociodemographic characteristics (aOR=2.46, 1.08 to 5.60 and aOR=2.19, 1.36 to 3.54, respectively), but the association was not significant after further adjustment for obesity. CONCLUSIONS: Among US adolescents, obesity was strongly associated with elevated hs-CRP, a marker for future CVD risk. Given the obesity epidemic and the marked proportion with elevated CRP, concern should be given to future CVD risk in younger adults.

Causal relationship between inflammatory markers and left ventricle geometry and function: A 2-sample Mendelian randomization study.

Studies have shown that some inflammatory markers can predict the risk of cardiovascular disease (CVD) and affect the structure and function of the heart. However, a causal relationship between inflammatory markers and the cardiac structure and function has not yet been established. Thus, we conducted a 2-sample Mendelian randomization (MR) study to explore the potential causal relationship between inflammatory markers and prognostically-related left ventricular (LV) parameters. Instrumental variables (IVs) for C-reactive protein (CRP), interleukin-6 (IL-6), and myeloperoxidase (MPO) levels were selected from the databases of large genome-wide association studies (GWAS). Summary statistics for LV parameters, including LV mass, ejection fraction, end-diastolic and systolic volumes, and the ratio of LV mass to end-diastolic volume, were obtained from cardiovascular magnetic resonance studies of the UK Biobank (n = 16923). The inverse-variance weighted (IVW) method was the primary analytical method used, and was complemented with the MR-Egger, weighted median, simple mode, weighted mode, and MR pleiotropy residual sum and outlier (MR-PRESSO) methods. Sensitivity analysis was performed to evaluate the robustness of the results. CRP was significantly associated with the LV mass in the IVW method (ß = -0.13 g [95% confidence interval [CI], 0.78 g-1.00 g], P = .046). A higher standard deviation of genetically-predicted CRP levels was associated with a 0.13 ±â€…0.06 g lower LV mass. No causal relationships of IL-6 and MPO with LV parameters were found. No evidence of heterogeneity and pleiotropy was detected. Sensitivity analyses confirmed the robustness of the results. Two-sample MR analysis revealed a causal association between increased CRP level and decreased LV mass, whereas IL-6 and MPO levels did not influence the LV parameters. However, further research is required to validate our findings.

Research on cognitive impairment and potential risk factors in peritoneal dialysis patients: An observational study.

The objective of this study is to investigate the associated risk factors and their effects on cognitive impairment (CI) in patients undergoing peritoneal dialysis. A retrospective analysis was conducted on the basic information of 268 patients who underwent continuous ambulatory peritoneal dialysis (CAPD) at our hospital from January 2020 to September 2023. Cognitive function was assessed using the Montreal Cognitive Assessment Scale during their subsequent dialysis visits. Participants were categorized into a CI group and a cognitively normal group. Blood and other biological samples were collected for relevant biomarker analysis. Subsequently, we analyzed and compared the factors influencing CI between the 2 groups. The prevalence of CI among CAPD patients was 58.2%. Compared to the cognitively normal group, the CI group had a higher prevalence of alcohol consumption, lower levels of education, and reduced serum uric acid levels (P < .05). There was also a higher incidence of autoimmune diseases such as systemic lupus erythematosus in the CI group (P < .05). In terms of dialysis efficacy, the residual kidney Kt/V and residual kidney Ccr were significantly lower in the CI group compared to the cognitively normal group. In blood parameters, the CI group showed elevated total cholesterol levels and lower serum calcium concentrations (P < .05). Logistic regression analysis identified male gender, older age, lower educational attainment, hypercholesterolemia, and elevated high-sensitivity C-reactive protein levels as independent risk factors for CI in CAPD patients (P < .05). Additionally, in this patient cohort, dialysis duration and residual renal function were protective factors against CI (P < .05). CI is prevalent among PD patients. Elevated high-sensitivity C-reactive protein levels, male gender, older age, lower educational attainment, and hypercholesterolemia constitute an independent risk factor for CI in CAPD patients, whereas residual renal function acts as a protective element.

Predicting the Outcomes of In Vitro Fertilization Using Baseline Maternal Serum Inflammatory Markers: A Retrospective Cohort Study.

PROBLEM: Achieving pregnancy through in vitro fertilization (IVF) remains a challenge, with less than one-third of women succeeding. There is a pressing need for reliable predictive tools to assess the likelihood of post-IVF pregnancy. While some serum inflammatory biomarkers have been investigated for their predictive potential, substantial knowledge gaps persist. This study examined the utility of different inflammatory markers in predicting IVF outcomes. METHOD OF STUDY: Inflammatory markers including the white blood cell count, neutrophil-to-lymphocyte ratio (NLR), platelet count, mean platelet volume, platelet distribution width, platelet-to-lymphocyte ratio (PLR), C-reactive protein (CRP), erythrocyte sedimentation rate, and vitamin D3 were assessed. Study outcomes were chemical pregnancy (positive serum beta-human chorionic gonadotropin 2 weeks post-embryo transfer), clinical pregnancy (detection of pregnancy sac via transvaginal ultrasonography), and viable pregnancy (detection of fetal heart rate). Univariate and multivariate logistic regression analyses were conducted, with multivariate analysis incorporating age, body mass index, infertility duration, type, and etiology, as well as all studied serum inflammatory markers, embryo count, stage, quality, and endometrial thickness. RESULTS: Lower NLR (p < 0.001, odds ratio [OR] = 0.372 [0.247-0.559]) and CRP (p = 0.035, odds ratio = 0.956 [0.916-0.997]) predicted chemical pregnancy in univariate analysis, with NLR maintaining significance in multivariate analysis (p = 0.022, OR = 0.319 [0.120-0.848]). Lower NLR (p < 0.001, OR = 0.309 [0.198-0.482]) and PLR (p = 0.013, OR = 0.994 [0.990-0.999]) predicted clinical pregnancy, with NLR surviving multivariate analysis (p = 0.005, OR = 0.217 [0.075-0.626]). Lower NLR (p < 0.001, OR = 0.320 [0.198-0.516]) also predicted viable pregnancy, maintaining statistical significance in multivariate analysis (p = 0.002, OR = 0.177 [0.058-0.541]). Other studied inflammatory markers did not predict IVF outcomes. CONCLUSIONS: NLR emerged as a robust independent predictor of pregnancy attainment after IVF.

Relationship between C-reactive protein/albumin ratio and mucocutaneous symptom frequency and disease severity in Behçet's disease.

Background/aim: There is no specific marker that can be applied to determine the severity of Behçet's disease. The aim of this study is to investigate the potential of C-reactive protein (CRP)/albumin (CAR) ratio as a tool for assessing the severity of Behçet's disease. Materials and methods: A retrospective crosssectional study was conducted by examining hospital archives. The CRP and albumin levels of Behçet's disease patients who presented to our dermatology clinic over a three-year period from February 2020 to February 2022 were included, along with the identical laboratory parameters in the control group. The CAR ratio was calculated and statistically compared across different clinical features of the disease and with the control group. Results: Of the 97 patients with Behçet's disease, 70.1% (n = 68) were female and the median age was 36.0 years (IQR = 20.5), whereas of the 53 control subjects, 77.4% (n = 41) were female and the median age was 35.0 years (IQR = 19.0). There was no statistically significant difference in sex or age between the groups (p > 0.05). The levels of CRP and CAR were found to be significantly elevated in patients with Behçet's disease compared to the control group (both p < 0.001). According to the ROC analysis, the area under the curve (AUC) of CRP level and CAR were found to be 0.784 (95%CI: 0.710-0.859), and 0.786 (95%CI: 0.712-0.861), respectively. The cut-off value for CRP was determined as 1.485, whereas for CAR it was 0.324. As the severity of Behçet's disease increased, there was a statistically significant increase in the CAR level (p < 0.001). The severity of Behçet's disease was statistically significantly associated with a high CAR level. Conclusion: CAR can be used as a quick and easily calculated parameter to assess the severity of Behçet's disease.

Considerations in case of suspected anastomotic leakage in the lower GI tract.

Colorectal anastomotic leakage (CAL) remains a feared complication after colorectal surgery and requires prompt detection and proper treatment. With the upswing of fast-track recovery programs in recent years this challenge has increased, as clinical features may only arise after discharge. Therefore, identification of the best diagnostic tools is of utmost importance, also since early treatment is associated with high success rates. Diagnostic tools range from general screening tools to invasive procedures to assess the severity of the leak. Laboratory tests, in particular the inflammation biomarkers C-reactive protein and procalcitonin, have a significant role in the detection of CAL after colorectal surgery. As these biomarkers are unspecific for CAL, additional imaging should be performed when blood levels are elevated. The golden standard for the detection of AL after colonic resections is a computed tomography (CT-scan). If tolerated, a contrast medium should be administered rectally to enhance diagnostic accuracy. When suspicion of CAL remains high despite negative previous tests, further endoscopy examination should be conducted. However, endoscopic examinations become more suitable for the early diagnostic work-up after rectal resections. This review aims to provide an overview of current diagnostics for the screening and assessment of the severity of CAL after colorectal surgery.

Clinical characteristics, anti-SARS-CoV-2 IgG titers, and inflammatory markers in individuals with post-COVID-19 condition in Kenya: a cross-sectional study.

Background: Post-coronavirus disease 2019 (post-COVID-19) is associated with considerable morbidity and reduced quality of life. However, studies characterizing the post-COVID-19 condition in Kenya are limited. This study aimed to determine the prevalence of post-COVID-19 condition and determine the clinical characteristics, anti-SARS-CoV-2 IgG titers, and concentrations of inflammatory markers of individuals with post-COVID-19 condition in Kenya. Methods: This descriptive cross-sectional study was conducted at the Kenyatta University Health Unit, Kenya. Demographic and clinical data were collected using a questionnaire. The serum levels of anti-SARS-CoV-2 antibodies, interleukin 6 (IL-6), and C-reactive protein (CRP) were quantified by enzyme-linked immunosorbent assays. Independent samples t-test was used to compare the anti-SARS-CoV-2 IgG, IL-6, and CRP levels between the participants with and without post-COVID-19 symptoms. The case definition for post-COVID-19 condition was persistence of acute COVID-19 symptoms or emergence of new symptoms 3 months after COVID-19 diagnosis, symptoms lasting for ≥2 months, and absence of any other etiological basis to explain the symptoms. Results: A total of 189 volunteers were recruited in this study (median age: 21 years, range: 18-71 years; male, 49.2%). Forty participants reported having had at least one COVID-19 positive diagnosis in the past, of which 12 (30%) complained of post-COVID-19 symptoms. Significant differences in the number and duration of symptoms were observed between the individuals with and without post-COVID-19 symptoms (t-statistic = 2.87, p = 0.01; t-statistic = 2.39, p = 0.02, respectively). However, no significant differences in serum levels of anti-SARS-CoV-2 IgG, IL-6, and CRP were observed between the two groups (P = 0.08, 0.9, and 0.28, respectively). Conclusion: These findings suggest that post-COVID-19 condition is a health concern even for a relatively young population in Kenya and globally. This condition requires more attention and well-designed studies to better define it and identify clinical chemistry markers that can be used for its diagnosis.

Inflammation altered correlation between CYP2C19 genotype and CYP2C19 activity in patients receiving voriconazole.

Voriconazole is the cornerstone of the treatment and prevention of fungal infections. While there is a good correlation between CYP2C19 genotype and voriconazole exposure during prophylactic treatment, no correlation was found in patients with invasive aspergillosis. Proinflammatory cytokines result in inhibition of CYP2C19 enzyme activity (and may result in phenoconversion). Here we investigated the relationship between inflammation, CYP2C19 genotype-predicted-phenotype, and CYP2C19 activity in patients receiving voriconazole. Data were obtained from two prospective studies investigating voriconazole treatment (NCT02074462 and NCT00893555). Dose-corrected voriconazole plasma concentration and C-reactive protein (CRP) were used as proxies for CYP2C19 activity and inflammation, respectively. After data extraction and synthesis, data from 39 patients with paired voriconazole and CRP measurements were available. The distribution of CYP2C19 genotype-predicted metabolizer phenotypes was 31% intermediate (IM), 41% normal (NM), and 28% rapid metabolizer (RM). During inflammation, dose-corrected voriconazole levels were increased by 245%, 278%, and 486% for CYP2C19 NMs IMs and RMs, respectively. Patients with moderate or high CRP levels (>50 mg/L) were phenoconverted to a lower metabolizer phenotype irrespective of their CYP2C19 genotype. In a subgroup analysis of eight patients with longitudinal data available with and without inflammation, the pattern of the dose-corrected voriconazole and CRP measurements were similar, with CYP2C19 activity following decreasing or increasing CRP levels. In conclusion, voriconazole plasma concentrations increase during inflammation due to downregulation of CYP2C19 activity. While this effect appears largest for CYP2C19 RMs, no clinically relevant differences were observed between the CYP2C19 genotypes.

The Efficacy of C-Reactive Protein (CRP) to Albumin Ratio (CAR) and Fibrinogen to CRP Ratio (FCR) in Predicting the Latent Period of Preterm Labor.

OBJECTIVE: To investigate the role of inflammatory markers, including neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and monocyte to lymphocyte ratio (MLR), c-reactive protein (CRP) to albumin ratio (CAR), fibrinogen to albumin ratio (FAR), and fibrinogen to CRP ratio (FCR) in predicting the latency period (≤72 vs. >72 hours) before preterm birth. MATERIALS AND METHODS: In a retrospective study, we assessed 135 patients meeting the specified criteria with signs of preterm labor (<34 weeks). The patients were categorized into two groups: 71 patients giving birth within 72 h (latency ≤ 72 h) and 64 patients giving birth after 72 h (latency > 72 h). We examined the demographic and medical characteristics and perinatal outcomes of all participants. Categorical variables between groups were compared using the Chi-square test. The Student's t-test was utilized for normally distributed continuous variables, and the Mann-Whitney U test was applied for non-normally distributed data. Receiver operating characteristic (ROC) curve analysis was conducted to identify the optimal cut-off levels for inflammatory markers in predicting the latency period before birth. RESULTS: Among the parameters examined, significant differences were observed between the groups only in terms of CAR and FCR. While CAR showed a significantly higher value in the group with latency period ≤72 h (0.537 ± 1.239 vs. 0.247 ± 0.325, p = 0.022), FCR showed a significantly lower value in the group with latency period ≤72 h (63.58 (2.99-1165) vs. 88.93 (9.35-1165), p = 0.013). The identified cut-off value for CAR was 0.190, providing a sensitivity of 57.7% and a specificity of 56.3% (p = 0.022). The cut-off value for FCR was 71.67, with a sensitivity of 42.3% and a specificity of 42.2% (p = 0.013). CONCLUSIONS: The CAR and the FCR, serving as predictive markers for preterm labor, may offer a simple, cost-effective, and easily accessible approach, particularly in resource-limited settings.

Impact of inflammation on cognitive function in patients with highly inflammatory rheumatoid arthritis.

OBJECTIVE: To evaluate cognitive function in patients with rheumatoid arthritis (RA) and inflammatory activity. PATIENTS AND METHODS: We performed a cross-sectional study of a cohort of patients with RA initiating their first biological treatment due to moderate-to-high inflammation and a healthy control group (no inflammatory diseases) matched for age, sex and educational level. All participants underwent a comprehensive neuropsychological assessment, with cognitive impairment defined as a Montreal Cognitive Assessment (MoCA) score<26. Additional assessments included various cognitive tests (STROOP, forward and backward digit spans), anxiety and depression scales (Hospital Anxiety and Depression Scale), quality of life measures (Quality of Life-Rheumatoid Arthritis) and average inflammatory activity according to the 28-joint Disease Activity Score (DAS28)-C-reactive protein (CRP) into high activity (DAS28≥3.2) and low activity (DAS28<3.2) groups, also CRP levels and interleukin 6 (IL-6) levels were measured using an ELISA. RESULTS: The study population comprised 140 participants, 70 patients with RA and 70 controls. Patients more frequently experienced cognitive impairment than controls (60% vs 40%; p=0.019) and had lower mean (SD) values in the MoCA (23.6 (3.9) vs 25.1 (3.4); p=0.019. As for subtests of the MoCA, involvement was more marked in patients than in controls for the visuospatial-executive (p=0.030), memory (p=0.026) and abstraction (p=0.039) domains. Additionally, patients scored lower on executive function, as assessed by the backward digit span test (4.0 (1.7) vs 4.7 (1.9); p=0.039). Cognitive impairment is associated with age and a lower educational level in the general population, and among patients with RA with educational level, obesity and average inflammatory activity (DAS28, CRP, and IL-6). CONCLUSIONS: Patients with RA with high inflammatory activity are more susceptible to cognitive impairment, which specifically affects the domains of visuospatial, memory, abstraction and executive function.

Biological use influences the impact of inflammation on risk of major adverse cardiovascular events in rheumatoid arthritis.

OBJECTIVES: Chronic inflammation promotes cardiovascular risk in rheumatoid arthritis (RA). Biological disease-modifying antirheumatic drugs (bDMARDs) improve disease activity and cardiovascular disease outcomes. We explored whether bDMARDs influence the impact of disease activity and inflammatory markers on long-term cardiovascular risk in RA. METHODS: We studied 4370 participants without cardiovascular disease in a 10-country observational cohort of patients with RA. Endpoints were (1) major adverse cardiovascular events (MACE) encompassing myocardial infarction, stroke and cardiovascular death; and (2) any ischaemic cardiovascular events (iCVE) including MACE plus revascularisation, angina, transient ischaemic attack and peripheral arterial disease. RESULTS: Over 26 534 patient-years, 239 MACE and 362 iCVE occurred. The interaction between 28-joint Disease Activity Score with C-reactive protein (DAS28-CRP) and bDMARD use was significant for MACE (p=0.017), suggesting the effect of DAS28-CRP on MACE risk differed among bDMARD users (n=515) and non-users (n=3855). DAS28-CRP (per unit increase) is associated with MACE risk in bDMARD non-users (HR 1.21 (95% CI 1.07 to 1.37)) but not users (HR 0.69 (95% CI 0.40 to 1.20)). The interaction between CRP (per log unit increase) and bDMARD use was also significant for MACE (p=0.011). CRP associated with MACE risk in bDMARD non-users (HR 1.16 (95% CI 1.04 to 1.30)), but not users (HR 0.65 (95% CI 0.36 to 1.17)). No interaction was observed between bDMARD use and DAS28-CRP (p=0.167) or CRP (p=0.237) for iCVE risk. CONCLUSIONS: RA activity and inflammatory markers associated with risk of MACE in bDMARD non-users but not users suggesting the possibility of biological-specific benefits locally on arterial wall independently of effects on systemic inflammation.

Determinants of transthyretin levels and their association with adverse clinical outcomes among UK Biobank participants.

Transthyretin is a transport protein whose misfolding has been implicated in the development of cardiac amyloidosis. Here, we examine the clinical correlates of transthyretin levels, the differences in transthyretin levels according to the pathogenic V142I TTR variant carrier status, and the association of transthyretin levels with outcomes among 35,206 UK Biobank participants who underwent plasma profiling and were free from prevalent cardiovascular disease and chronic renal disease. Transthyretin levels are lower in females, decrease with increasing C-reactive protein levels, and increase with body mass index, systolic blood pressure, diastolic blood pressure, total cholesterol, albumin levels, triglyceride levels, and creatinine levels. V142I non-carriers [n = 35,167, mean: -0.1 (0.3)] have higher adjusted transthyretin levels compared with the carriers [n = 39, mean: -0.5 (0.3)] (p:<0.001). A standard deviation decrease in transthyretin levels increases the risk of heart failure [HRadj: 1.17 (95% Confidence Interval = 1.08-1.26)] and all-cause mortality [HRadj: 1.18 (95% Confidence Interval = 1.14-1.24)]. This study shows that individuals with low transthyretin levels, such as those carrying the V142I variant, are at a higher risk of heart failure and mortality.

Construction and application of fetal loss risk model in systemic lupus erythematosus patients with mild disease severity.

BACKGROUND: This dynamic nomogram model was developed to predict the probability of fetal loss in pregnant patients with systemic lupus erythematosus (SLE) with mild disease severity before conception. METHODS: An analysis was conducted on 314 pregnancy records of patients with SLE who were hospitalized between January 2015 and January 2022 at Shenzhen People's Hospital, and the Longhua Branch of Shenzhen People's Hospital. Data from the Longhua Branch of the Shenzhen People's Hospital were utilized as an independent external validation cohort. The nomogram, a widely used statistical visualization tool to predict disease onset, progression, prognosis, and survival, was created after feature selection using multivariate logistic regression analysis. To evaluate the model prediction performance, we employed the receiver operating characteristic curve, calibration curve, and decision curve analysis. RESULTS: Lupus nephritis, complement 3, immunoglobulin G, serum albumin, C-reactive protein, and hydroxychloroquine were all included in the nomogram model. The model demonstrated good calibration and discriminatory power, with an area under the curve of 0.867 (95% confidence interval: 0.787-0.947). According to decision curve analysis, the nomogram model exhibited clinical importance when the probability of fetal loss in patients with SLE ranged between 10 and 70%. The predictive ability of the model was demonstrated through external validation. CONCLUSION: The predictive nomogram approach may facilitate precise management of pregnant patients with SLE with mild disease severity before conception.

Effect of in-line filtration in newborns: study protocol of the Intravenous Neonatal Central Access Safety (INCAS) randomized controlled trial.

BACKGROUND: Particulate contamination due to infusion therapy (administration of parenteral nutrition and medications) carries a potential health risk for infants in neonatal intensive care units (NICUs). This particulate consists of metals, drug crystals, glass fragments, or cotton fibers and can be generated by drug packaging, incomplete reconstitution, and chemical incompatibilities. In-line filters have been shown to remove micro-organisms, endotoxin, air, and particles in critically ill adults and older infants, but its benefits in newborn remain to be demonstrated. Moreover, 50% of inflammatory episodes in the setting of NICUs are blood culture-negative. These episodes could be partly related to the presence of particles in the infusion lines. METHODS: A multicenter randomized single-blind controlled trial was designed. All infants admitted to NICUs for which prolonged infusion therapy is expected will be enrolled in the study and randomized to the Filter or Control arm. All patients will be monitored until discharge, and data will be analyzed according to a "full analysis set." The primary outcome is the frequency of patients with at least one sepsis-like event, defined by any association of suspected sepsis symptoms with a level of c-reactive protein (CRP) > 5 mg/L in a negative-culture contest. The frequency of sepsis, phlebitis, luminal obstruction, and the duration of mechanical ventilation and of catheter days will be evaluated as secondary outcomes. The sample size was calculated at 368 patients per arm. DISCUSSION: This is the first multicenter randomized control trial that compares in-line filtration of parenteral nutrition and other intravenous drugs to infusion without filters. Sepsis-like events are commonly diagnosed in clinical practice and are more frequent than sepsis in a positive culture contest. The risk of these episodes in the target population is estimated at 30-35%, but this data is not confirmed in the literature. If the use of in-line filters results in a significant decrease in sepsis-like events and/or in any other complications, the use of in-line filters in all intravenous administration systems may be recommended in NICUs. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05537389, registered on 12 September 2022 ( https://classic. CLINICALTRIALS: gov/ct2/show/results/NCT05537389?view=results ).

Associations between systemic inflammation indicators and nonalcoholic fatty liver disease: evidence from a prospective study.

Background: Although inflammation has been linked to nonalcoholic fatty liver disease (NAFLD), most studies have focused only on a single indicator, leading to inconsistent results. Therefore, a large prospective study that includes a variety of well-documented single and composite indicators of inflammation is needed. This study aimed to thoroughly investigate the potential associations between different systemic inflammatory indicators and NAFLD in the UK Biobank cohort. Methods: After excluding ineligible participants, 378,139 individuals were included in the study. Associations between systemic inflammatory indicators and hepatic steatosis were assessed using multivariate logistic regression. The relationships between systemic inflammatory indicators and nonalcoholic fatty liver disease were analysed using Cox proportional hazards models, and nonlinear associations were investigated using restricted cubic splines. Results: According to the cross-sectional analysis, systemic inflammatory indicators significantly correlated with hepatic steatosis. Over a median follow-up of 13.9 years, 4,145 individuals developed NAFLD. After sufficient adjustment for confounding factors, CRP levels were found to be nonlinearly positively associated with NAFLD risk (P<0.001), representing the strongest correlation among the tested relationships; lymphocyte count and the LMR showed an L-shaped correlation; monocyte count and neutrophil count showed a linear positive correlation (all P< 0.001); and the NLR, PLR, and SII showed a U-shaped correlation (all P<0.001). Conclusions: Multiple systemic inflammatory indicators are strongly associated with the development of NAFLD, and aggressive systemic inflammation management may have a favourable impact on reducing the burden of NAFLD; further randomized controlled studies are needed.

Anti-inflammatory therapy with nebulized dornase alfa for severe COVID-19 pneumonia: a randomized unblinded trial.

Background: Prinflammatory extracellular chromatin from neutrophil extracellular traps (NETs) and other cellular sources is found in COVID-19 patients and may promote pathology. We determined whether pulmonary administration of the endonuclease dornase alfa reduced systemic inflammation by clearing extracellular chromatin. Methods: Eligible patients were randomized (3:1) to the best available care including dexamethasone (R-BAC) or to BAC with twice-daily nebulized dornase alfa (R-BAC + DA) for seven days or until discharge. A 2:1 ratio of matched contemporary controls (CC-BAC) provided additional comparators. The primary endpoint was the improvement in C-reactive protein (CRP) over time, analyzed using a repeated-measures mixed model, adjusted for baseline factors. Results: We recruited 39 evaluable participants: 30 randomized to dornase alfa (R-BAC +DA), 9 randomized to BAC (R-BAC), and included 60 CC-BAC participants. Dornase alfa was well tolerated and reduced CRP by 33% compared to the combined BAC groups (T-BAC). Least squares (LS) mean post-dexamethasone CRP fell from 101.9 mg/L to 23.23 mg/L in R-BAC +DA participants versus a 99.5 mg/L to 34.82 mg/L reduction in the T-BAC group at 7 days; p=0.01. The anti-inflammatory effect of dornase alfa was further confirmed with subgroup and sensitivity analyses on randomised participants only, mitigating potential biases associated with the use of CC-BAC participants. Dornase alfa increased live discharge rates by 63% (HR 1.63, 95% CI 1.01-2.61, p=0.03), increased lymphocyte counts (LS mean: 1.08 vs 0.87, p=0.02) and reduced circulating cf-DNA and the coagulopathy marker D-dimer (LS mean: 570.78 vs 1656.96 µg/mL, p=0.004). Conclusions: Dornase alfa reduces pathogenic inflammation in COVID-19 pneumonia, demonstrating the benefit of cost-effective therapies that target extracellular chromatin. Funding: LifeArc, Breathing Matters, The Francis Crick Institute (CRUK, Medical Research Council, Wellcome Trust). Clinical trial number: NCT04359654.

Prognostic impact of the high-sensitivity modified glasgow prognostic score on patients undergoing radical surgery for hepatocellular carcinoma : Authorship.

OBJECTIVE: Our study aimed to assess the ability of high-sensitivity modified Glasgow prognostic Score (HS-mGPS) predicting survival in patients undergoing radical surgery for hepatocellular carcinoma (HCC) and to compare the impact with other Inflammation-Based prognostic scoring systems including Glasgow prognostic Score (GPS) and modified GPS (mGPS). METHODS: Our study evaluated 293 patients with HCC who had undergone hepatectomy at the Third Affiliated Hospital of Soochow University between 2010 and 2018. The HS-mGPS, mGPS, and GPS were calculated based on particular cut-off values of preoperative C-reactive protein and albumin, and the correlations between HS-mGPS and clinicopathological parameters were evaluated. Univariate and multivariate survival analyses were conducted by Kaplan-Meier method and Cox proportional hazards model. To evaluate the discrimination ability of each prognostic score, the receiver operating characteristic (ROC) curve were generated and the areas under the curve (AUC) were measured and compared. RESULT: The study results indicated a correlation between elevated HS-mGPS scores and adverse clinical factors, including higher BCLC stage, C-P grade, multiple tumors, and larger tumor diameter. Kaplan-Meier and univariate survival analyses revealed that higher scores of HS-mGPS, GPS, and mGPS were all associated with significantly reduced overall survival (OS) (all p < 0.001). In multivariate survival analysis, HS-mGPS emerged as an independent risk factor for poor OS in patients undergoing hepatectomy for HCC (p = 0.010), along with factors including maximal tumor diameter (p < 0.001), microvascular invasion (MVI) (p = 0.008), and BCLC stage (p = 0.001). The analysis of ROC curves and the AUC values indicated that HS-mGPS outperforms GPS and mGPS in predicting the long-term prognosis of patients with resectable HCC. CONCLUSION: Preoperative HS-mGPS proves superior in predicting adverse long-term outcomes in HCC patients undergoing radical surgery.