Marker Of Subclinical Inflammation Research Articles

#2684 Free light chains levels in ANCA associated vasculitis: a new potential inflammatory biomarker

Abstract Background and Aims Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a systemic disease characterized by an immune-mediated process where inflammation plays a central role. The widely available serum biomarkers of inflammation are not always able to detect ongoing disease activity in ANCA-associated vasculitis (AAV) patients. Free light chains (FLCs) expression levels have been proposed as new promising biomarker in some immune-mediated and inflammatory diseases. The aim of this study is to evaluate the expression levels of FLCs in patients affected by AAV and investigate the potential effect of rituximab treatment on FLCs levels. Method We conducted a retrospective multicenter study enrolling AAV patients in complete remission of AAV (defined as BVAS/GPA = 0); those with clinical suspicion of underlying hematologic malignancy were excluded. We analyzed κ and λ FLCs serum concentrations and evaluated their correlation with biomarkers of immune system activation, such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), serum immunoglobulin (Ig) levels, serum C3 and C4 complement and albumin levels (which has a negative correlation with acute inflammatory phase). We assessed impact of rituximab (RTX) therapy within the last 6 months on the same laboratory parameters. Results A total of 137 patients with AAV were recruited, who were gender balanced, had an average age of 68 years and an estimated glomerular filtration rate of 68 (43-89) mL/min/1.73 m2. Fifty-one patients received rituximab treatment (RTX group), while 86 patients were on other immunosuppressive maintenance therapies (non-RTX group). In comparison to non-RTX group, patients treated with RTX experienced higher complement C3 levels, lower ESR levels and lower FLCs κ (p = 0.063) and λ (p = 0.013) levels. The differences between RTX and non-RTX groups in terms of FLCs were even more prominent after correction to total Ig concentration (p = 0.004 for κ /Ig and p = 0.003 for λ /Ig, respectively). Both, serum free κ and λ levels were found to correlate significantly with ESR (R = 0.55 and p < 0.001 for κ; R = 0.53 and p < 0.001 for λ) and albumin (R = ‒0.38 and p < 0.001 for κ; R = ‒0.33 and p < 0.001 for λ). Additionally, serum free κ levels showed an inverse association with C3 (R = ‒0.18 and p = 0.041). Conclusion In subjects with AAV, FLC levels were found to be associated with markers of inflammation and complement activation; hence FLCs levels may represent a promising biomarker for detection of subclinical inflammation in AAV patients on maintenance therapy. Rituximab therapy showed a potential to reduce the levels of markers of subclinical inflammation, including FLCs.

Composition of Whole Grain Dietary Fiber and Phenolics and Their Impact on Markers of Inflammation.

Inflammation is an important biological response to any tissue injury. The immune system responds to any stimulus, such as irritation, damage, or infection, by releasing pro-inflammatory cytokines. The overproduction of pro-inflammatory cytokines can lead to several diseases, e.g., cardiovascular diseases, joint disorders, cancer, and allergies. Emerging science suggests that whole grains may lower the markers of inflammation. Whole grains are a significant source of dietary fiber and phenolic acids, which have an inverse association with the risk of inflammation. Both cereals and pseudo-cereals are rich in dietary fiber, e.g., arabinoxylan and β-glucan, and phenolic acids, e.g., hydroxycinnamic acids and hydroxybenzoic acids, which are predominantly present in the bran layer. However, the biological mechanisms underlying the widely reported association between whole grain consumption and a lower risk of disease are not fully understood. The modulatory effects of whole grains on inflammation are likely to be influenced by several mechanisms including the effect of dietary fiber and phenolic acids. While some of these effects are direct, others involve the gut microbiota, which transforms important bioactive substances into more beneficial metabolites that modulate the inflammatory signaling pathways. Therefore, the purpose of this review is twofold: first, it discusses whole grain dietary fiber and phenolic acids and highlights their potential; second, it examines the health benefits of these components and their impacts on subclinical inflammation markers, including the role of the gut microbiota. Overall, while there is promising evidence for the anti-inflammatory properties of whole grains, further research is needed to understand their effects fully.

The inflammatory potential of diet is associated with the risk of age‐related eye diseases

Aims/Purpose: Inflammation is involved in the pathogenesis of cataract, age‐related macular degeneration (AMD) and possibly open‐angle glaucoma (OAG). We assessed whether the inflammatory potential of diet (quantified using the dietary inflammatory index; DII) affects the incidence of these eye diseases. Serum inflammation markers were investigated as possible mediators.Methods: Participants aged >45 years were derived from the Rotterdam Study. From 1991 onwards, every 4–5 years, participants underwent extensive eye examinations. At baseline, blood samples and dietary data were collected. The DII was adapted (aDII) based on data availability. Of the 7436 participants free of eye diseases at baseline, 4036 developed incident eye diseases over time (cataract = 2895, early‐intermediate AMD = 891, late AMD = 81, OAG = 169).Results: A higher aDII was significantly associated with increased inflammation. A higher neutrophil‐lymphocyte ratio (NLR) was associated with an increased risk of cataract and AMD. Additionally, complement component 3c (C3c) and systemic immune‐inflammation index (SII) were associated with increased risks of cataract and late AMD, respectively. Every point increase in the aDII was associated with a 9% increased risk of cataract (Odds ratio [95% confidence interval]: 1.09 [1.04–1.14]). The NLR and C3c partly mediated this association. We also identified associations of the aDII with risk of AMD (early‐intermediate AMD, OR [95% CI]: 1.11 [1.03–1.19]; late AMD, OR [95% CI]: 1.24 [1.02–1.53]). The NLR partly mediated these associations. The aDII was not associated with OAG.Conclusions: We observed an unfavourable association between the aDII and cataract. More importantly, we found an association between the aDII and risk of AMD. Especially the NLR, a marker of subclinical inflammation, seems to be involved. These findings are relevant for patients with AMD and substantiate the current recommendations to strive for a healthy lifestyle to prevent blindness.

The inflammatory potential of diet is associated with the risk of age-related eye diseases

Inflammation is involved in the pathogenesis of cataract, age-related macular degeneration (AMD), and possibly open-angle glaucoma (OAG). We assessed whether the inflammatory potential of diet (quantified using the dietary inflammatory index; DII) affects the incidence of these common blinding age-related eye diseases. Serum inflammation markers were investigated as possible mediators. Participants aged >45 years were selected from the prospective, population-based Rotterdam Study. From 1991 onwards, every 4-5 years, participants underwent extensive eye examinations. At baseline, blood samples and dietary data (using food frequency questionnaires) were collected. The DII was adapted based on the data available. Of the 7436 participants free of eye diseases at baseline, 4036 developed incident eye diseases during follow-up (cataract=2895, early-intermediate AMD=891, late AMD=81, OAG=169). The adapted DII (aDII) ranged from-4.26 (i.e., anti-inflammatory) to 4.53 (i.e., pro-inflammatory). A higher aDII was significantly associated with increased inflammation. A higher neutrophil-lymphocyte ratio (NLR) was associated with an increased risk of cataract and AMD. Additionally, complement component 3c (C3c) and systemic immune-inflammation index (SII) were associated with increased risks of cataract and late AMD, respectively. Every point increase in the aDII was associated with a 9% increased risk of cataract (Odds ratio [95% confidence interval]: 1.09 [1.04-1.14]). The NLR and C3c partly mediated this association. We also identified associations of the aDII with risk of AMD (early-intermediate AMD, OR [95% CI]: 1.11 [1.03-1.19]; late AMD, OR [95% CI]: 1.24 [1.02-1.53]). The NLR partly mediated these associations. The aDII was not associated with OAG. A pro-inflammatory diet was associated with increased risks of cataract and AMD. Particularly the NLR, a marker of subclinical inflammation, appears to be implicated. These findings are relevant for patients with AMD and substantiate the current recommendations to strive for a healthy lifestyle to prevent blindness.

The prognostic value of neutrophile/lymphocyte ratio and serum chemerin to predict maternal-fetal complications in pregnant systemic lupus erythematosus patients.

Pregnancy in SLE continues to be a challenge. The neutrophil-to-lymphocyte ratio (NLR) and chemerin are predictors of preeclampsia in the general population; however, their role as predictors of maternal-fetal complications in pregnant SLE patients has not been analyzed. To investigate the prognostic value of NLR and serum chemerin, to predict maternal-fetal complications in pregnant SLE patients, and compare both biomarkers among three study groups. Design: Analytical cross-sectional study of cases and controls with the following study groups: systemic lupus erythematosus (SLE), preeclampsia, and healthy. NLR and chemerin serum were determined between 20 and 25weeks of gestation. Patients were evaluated every 4-6weeks until pregnancy resolution. Maternal and fetal outcomes were registered. We employed Receiver Operating Characteristic (ROC) curves to validate prognostic values. Seventy pregnant patients were included: 20 with SLE, 20 with preeclampsia, and 30 healthy pregnant women; NLR values were 4 (2.3-5.6) in SLE, 6 (4.6-9.2) in preeclampsia, and 2.8 (2.1-2.9) in the group of healthy women (p = .0001). Chemerin levels were: 26 (15.3-56.2) in SLE, 96 (37.3-146.2) in preeclampsia, and 24.6ng/mL (15.3-47.4) in the healthy group (p = .007) Maternal complications were observed in 11 (55%), 20 (100%), and 8 (26%) per group, respectively. Thrombocytopenia was the most frequent complication in all pregnant women, followed by hypertensive disorders. Fetal complications were registered in 12 (60%), 16 (80%), and 2 (6.7%), respectively. Congenital malformations and prematurity were the most frequent fetal complications. NLR had good diagnostic accuracy in predicting maternal-fetal complications (AUROC 0.715) p = .015, CI 95% 0.56-0.86, cut-off point level: 2.9, sensitivity 61%, specificity 78%, positive predictive value (PPV) 65%, negative predictive value (NPV) 75%. Regarding chemerin, a cut-off point level >43ng/mL had a sensitivity of 75%, specificity of 72% AUROC 0.75, p = .001, CI 95% 0.61-0.89, PPV 51.7% NPV 87.8%, meaning that 51.7% of patients with chemerin levels >43ng/mL have or will have preeclampsia. The NLR may help predict maternal-fetal complications in SLE pregnancy, constituting a marker of subclinical inflammation. Chemerin levels may be associated with preeclampsia. These biomarkers could improve the care of SLE patients with timely intervention of potential complications during pregnancy.

Correlation between Serum High-Sensitivity C-Reactive Protein Level and Severity of Albuminuria Measured by Urine Albumin-to-Creatinine Ratio in Type 2 Diabetic Patients

Introduction: One of complications in type 2 diabetes mellitus (DM) that require high treatment cost is diabetic kidney disease (DKD), which is characterized by the presence of albuminuria, decrease in glomerular filtration rate, or both. Researches show a positive correlation between type 2 DM and serum high-sensitivity C-reactive protein (hs-CRP) level, a sensitive marker of subclinical inflammation. This study aimed to analyze the correlation between serum hs-CRP level and severity of albuminuria measured by urine albumin-to-creatinine ratio (ACR).Methods: The study was conducted at the Endocrinology Outpatient Clinic of Dr. Soetomo General Academic Hospital, Surabaya, on June-July 2020.Results: The study included 50 patients with type 2 DM, consisting of 25 (50%) men and 25 (50%) women, with median age of 58.0 (42-68) years and mean body mass index (BMI) of 21.91 ± 1.310 kg/m2. Median duration of DM was 12.0 (6-22) years, median HbA1c level was 7.20% (5.7%-12.3%), mean serum crEatinine level was 0.83 ± 0.180 mg/dL, and median estimated glomerular filtration rate (eGFR) value was 92.85 (61.6-121.2) mL/minute/1.73 m2. Median serum hs-CRP level was 1.20 (0.1-4.0) mg/L and median urine ACR value was 49.570 (7.78-426.00) mg/g. Normoalbuminuria was detected in 28% of subjects, microalbuminuria in 66% of subjects, and macroalbuminuria in 6% of subjects. This study showed positive and significant correlation between serum hs-CRP level and severity of albuminuria (r = 0.701; p = <0.001).Conclusion: There was positive and significant correlation betweeen serum hs-CRP level and severity of albuminuria in type 2 diabetic patients.

Ultra-High Frequency UltraSound (UHFUS) Assessment of Barrier Function in Moderate-to-Severe Atopic Dermatitis during Dupilumab Treatment.

Atopic dermatitis (AD) is a chronic multifactorial inflammatory disease characterized by intense itching and inflammatory eczematous lesions. Biological disease-modifying drugs, such as dupilumab are recommended for patients with moderate-to-severe AD, refractory to systemic immunosuppressive therapies. Disease monitoring is performed by clinical scores. Since 1970, however, the use of ultrasound and particularly high-frequency ultrasound (HFUS), has identified alterations in dermal echogenicity, called the subepidermal low-echogenic band (SLEB), that correlates with disease severity and response to treatment. We enrolled 18 patients with moderate-to-severe AD, divided into two groups: twelve patients in the dupilumab treatment (Group A) and six patients in standard treatment, from February 2019 to November 2019. We performed ultra-high frequency ultrasound (UHFUS) evaluation of lesional and non-lesional skin, focusing on SLEB average thicknesses measurement, epidermal thickness, and vascular signal in correlation with objective disease scores (EASI, IGA), patient's reported scores (Sleep Quality NRS and Itch NRS), and TEWL and corneometry at baseline (T0), after 1 month (T1) and 2 months (T2). The SLEB average thickness measurement, vascular signal, and epidermal thickness showed a statistically significant reduction in lesional skin of the biological treatment group and no significant reduction in non-lesional skin in both groups. In the lesional skin of the standard treatment group, only epidermal thickness showed a statistically significant reduction. Our study demonstrates that SLEB measurement, vascular signals, and epidermal thickness could be used as objective parameters in monitoring the AD treatment response, while the presence of SLEB in non-lesional skin could be used as a marker of subclinical inflammation and could predict development of clinical lesions, suggesting a pro-active therapy. Further follow-up and research are needed to clarify the association of SLEB decrease/disappearance with a reduction of flares/prolongment of the disease remission time.

#6368 PLATELET TO LYMPHOCYTE RATIO AND SICKLE CELL NEPHROPATHY

Abstract Background and Aims Platelet-to-lymphocyte ratio (PLR) was introduced as cheap and readily assessed biologic markers of subclinical inflammation in sickle cell disease. Microalbuminuria and hyperfiltration, early markers of Sickle cell nephropathy (SCN) have been reported to be associated with platelet-to-lymphocyte ratio (PLR). This association has not yet been assessed in Congolese Sickle cell disease (SCD) children. Therefore, the aim of the present study was to assess the association between PLR and early markers of kidney disease in SCD children living in the Democratic Republic of Congo (DRC). Method In this cross-sectional study, we have investigated 175 SCD children from four centers (Kinshasa university clinics, CMMASS, CMD Diamand, and Biamba Marie Mutumbo Dikembe) that give a comprehensive care to SCD patients. The PLR were calculated from full blood count. Elevated albuminuria and hyperfiltration, as the main outcomes of the study, were defined by urinary albumin/creatinine ratio (ACR) ≥30 mg/g and estimated glomerular filtration ratio (eGFR) >130 ml/min per 1.73 m2 for females and >140 ml/min per 1.73 m2 for males, respectively. Logistic regression analysis was used to assess the relationship between RPL and early sickle cell nephropathy. Results Of the 175 SCD children enrolled, 41(23.4%) and 67(38.3%) of them presented with abnormal albuminuria and hyperfiltration, respectively. RPL >130 was observed in 90 (51.4%) patients. RPL was strongly, significantly and independently associated with both abnormal albuminuria (aOR 3,381; IC95% 2, 22-1, 63; p = 0,000) and hyperfiltration (aOR 2, 19; 95%IC 2, 98 - 22, 25; p = 0,010). Conclusion The present study has shown that nearly fifty two out of one hundred SCD children bear a high platelet to lymphocyte ratio that is strongly and significantly associated with early markers of kidney disease.

Age-related Differences in T-cell Subsets and Markers of Subclinical Inflammation in Aging Are Independently Associated With Type 2 Diabetes in the Health and Retirement Study

ObjectivesAge-related changes in adaptive immunity and subclinical inflammation are both important risk factors for diabetes in older adults. We evaluated the independent association between T-cell subsets, subclinical inflammation, and diabetes risk in the Health and Retirement Study (HRS). MethodsWe measured 11 T-cell subsets, 5 pro-inflammatory markers, and 2 anti-inflammatory markers from the 2016 wave of the HRS (baseline). Diabetes/prediabetes status was estimated at the 2016, 2018, and 2020 waves of HRS, based on levels of blood glucose/glycated hemoglobin in plasma or self-reported status. We used survey generalized logit models to evaluate the cross-sectional associations and Cox proportional hazard models to evaluate longitudinal associations. ResultsAmong 8,540 participants (56 to 107 years of age), 27.6% had prevalent type 2 diabetes and 31.1% had prediabetes in the 2016 survey. After adjusting for age, sex, race/ethnicity, education, obesity, smoking, comorbidity index, and cytomegalovirus seropositivity, individuals with type 2 diabetes had lower naive T cells and higher memory and terminal effector T cells as compared with normoglycemic individuals. Among 3,230 normoglycemic participants in the 2016 survey, the incidence of diabetes was 1.8% over 4 years of follow-up. The baseline percentage of CD4+ effector memory T cells was associated with a lower risk of incident diabetes (hazard ratio [HR]=0.63, 95% confidence interval [CI] 0.49 to 0.80, p=0.0003) after adjustment for covariates. Baseline level of interleukin-6 (IL-6) was associated with risk of incident diabetes (HR=1.52, 95% CI 1.18 to 1.97, p=0.002). The associations between age-related changes in CD4+ effector memory T cells and risk of incident diabetes remained unchanged after adjustment for subclinical inflammation, although adjusting for CD4+ effector memory T cells nullified the association between IL-6 and incident diabetes. ConclusionsThis study showed that the baseline percentage of CD4+ effector memory T cells was inversely associated with incident diabetes independent of subclinical inflammation, but CD4+ effector memory T-cell subsets affected the relationship between IL-6 and incident diabetes. Further studies are needed to confirm and investigate mechanisms by which T-cell immunity affects diabetes risk.

Neutrophil-to-Lymphocyte Ratio Is an Independent Risk Factor for Coronary Artery Disease in Central Obesity.

Several inflammatory biomarkers were found to be associated with an increased risk of cardiovascular disease. Neutrophil-to-lymphocyte ratio (NLR) is a marker of subclinical inflammation that increases with the stress response. Visceral adiposity index (VAI) calculated as a combination of anthropometric and metabolic parameters reflects both the extent and function of visceral adipose tissue. Given the association of subclinical inflammation with both obesity and cardiovascular diseases, it is plausible that the inflammation-CVD association is modulated by the amount and function of adipose tissue. Thus, our aim was to examine the association between NLR and coronary artery calcium score (CACS), an intermediate marker of coronary artery disease in asymptomatic patients across VAI tertiles. Methods: Data from 280 asymptomatic participants of a cardiovascular screening program were analysed. In addition to the collection of lifestyle and medical history, a non-contrast cardiac CT scan and laboratory tests were performed on all participants. Multivariate logistic regression was conducted with CACS > 100 as the outcome and with conventional cardiovascular risk factors and NLR, VAI, and NLR by VAI tertile as predictors. Results: We found an interaction between VAI tertiles and NLR; NLR values were similar in the lower VAI tertiles, while they were higher in the CACS > 100 in the 3rd VAI tertile (CACS ≤ 100: 1.94 ± 0.58 vs. CACS > 100: 2.48 ± 1.1, p = 0.008). According to multivariable logistic regression, the interaction between NLR and VAI tertiles remained: NLR was associated with CACS > 100 in the 3rd VAI tertile (OR = 1.67, 95% CI 1.06-2.62, p = 0.03) but not in the lower tertiles even after adjustment for age, sex, smoking, history of hypertension, hyperlipidaemia, and diabetes mellitus, as well as high-sensitivity C-reactive protein. Our findings draw attention to the independent association between subclinical, chronic, systemic inflammation and subclinical coronary disease in obesity.

Association of High sensitivity C-reactive protein (Hs-CRP) with poor Glycaemic control and Coronary Heart Disease in Type 2 Diabetes Mellitus

High sensitivity C-reactive protein (Hs-CRP) is a sensitive marker of subclinical inflammation associated with atherosclerosis. Uncontrolled diabetes mellitus (DM) is one of the important risk factors of coronary heart disease (CHD). The aim of this study was to evaluate the association between Hs-CRP levels and both glycaemic control and CHD in Syrian type 2 diabetes mellitus (T2DM) patients. A random sample of 108 subjects was selected from T2DM and/or CHD patients seen in the National Centre for Diabetes, and the outpatient clinic of cardiology department at Tishreen University Hospital in Latakia. Four groups were formed: Group 1 [T2DM (+) CHD (-), N=29], Group 2 [T2DM (-) CHD (+), N=25], Group 3 [T2DM (+) CHD (+), N=29], and Group 4 (T2DM (-) CHD (-), N=25). Serum Hs-CRP and glycated haemoglobin (HBA1C) were determined. The SPSS 25.0 program was used for the statistical analysis. Probability (P) value less than 0.05 was considered statistically significant. Mean Hs-CRP level was higher in T2DM subjects with (5.23±1.56mg/l) or without (2.29±0.78mg/l) CHD compared to T2DM (-) CHD (-) patients (0.16±0.04mg/l), (p<0.0001 for both). Mean Hs-CRP level in T2DM with CHD was not only higher than T2DM patients without CHD (p<0.0001), but also than non-diabetic subjects with CHD (2.56±0.45mg/l) (p<0.0001). There was a positive correlation between serum Hs-CRP and HBA1C in T2DM patients with CHD (r=0.781, P<0.0001), Similarly, Hs-CRP levels were positively and significantly correlated with HBA1C in T2DM patients without CHD (r=0.800, p<0.0001). We also noticed that for every 1.0% increase in HbA1c there was an 77% increase in the likelihood of having an elevated Hs-CRP. We concluded that Hs-CRP was strongly correlated with glycaemic control in T2DM patients. The highest Hs-CRP level was observed in T2DM with CHD patients. Hs-CRP could predict the incidence of coronary heart disease in T2DM patients.

Subclinical inflammation markers in Abortus Imminens and their relation with obstetric outcomes. A case-control study

Background: In recent years, studies reveal that subclinical inflammatory markers can be used as an indicator of the inflammatory process in many diseases. Few studies have evaluated indicators of inflammation and postpartum outcomes in abortion immune patients. Objectives: The aim of the study is to investigate the relationship of subclinical inflammatory factors (Platelet crit (PCT), Neutrophil-lymphocyte ratio(NLR), Monocyte-lymphocyte ratio(MLR), Platelet-lymphocyte ratio(PLR)) obtained from complete blood count(CBC) with Abortion Immunes(AI) and obstetric results.. Material method: The study was conducted between January 2020 and January 2021. A total of 429 pregnant women, 203 of whom were pregnant with AI and 226 were healthy, were included in the study. Results: PCT, NLR, and MLR values were significantly higher and PLR values were low in the AI group (p<0.05). PCT > 0.22, NLR > 2.29, and MLR > 0.20 were significantly associated with increased risk of AI (P<0.05). PLR value above 135.5 was associated with the normal group. There was a significant difference between the group whose pregnancy was terminated by abortion and the group who gave birth in terms of PCT, NLR, MLR, and PLR values. PCT, NLR, and MLR values were high in the abortion group, and PLR values were low (p<0.05). Premature birth was developed in 11.3% (n=15) of AI patients. There was a significant difference between the preterm and term pregnancy in terms of PCT, NLR, MLR, and PLR levels (p<0.005). PCT, NLR, and MLR values were high and PLR levels were low in pregnant women who gave birth prematurely. Conclusion: We think that close follow-up of abortion imminence patients with high levels of these inflammatory factors is appropriate.

Maternal serum ischemia-modified albumin (IMA), total-sulphydryl concentrations, and some subclinic inflammatory markers in hyperemesis gravidarum (HG)

ObjectiveThis study investigates the relationship between Ischemia Modified Albumin and Total-Sulphydryl levels with some subclinical inflammatory markers in patients with hyperemesis gravidarum. Materials and methodsA total of 258 pregnant women, 137 with hyperemesis gravidarum and 121 low-risk pregnancies, were included in this case–control study. The patients were divided into three groups according to the severity of hyperemesis gravidarum as mild (n = 53), moderate (n = 41) and severe (n = 43). ResultsSerum Ischemia Modified Albumin levels were statistically different from the control group (P < 0.001). Among the subgroups, the highest Ischemia Modified Albumin value was observed in the severe hyperemesis gravidarum group, and the highest Total-Sulphydryl level was observed in the mild hyperemesis gravidarum group (P < 0.001). Serum potassium levels were higher in the control group (P < 0.001). While a negative correlation was observed between Ischemia Modified Albumin and Total-Sulphydryl, a positive correlation was observed in Platelet crit, C-reactive protein, and ketonuria. As the severity of the disease increases, Ischemia Modified Albumin, which is an oxidative stress factor, increases, and Total-Sulphydryl levels decrease (p < 0.001). Logistic regression analysis revealed that a one-unit increase in Ischemia Modified Albumin resulted in a statistically significant 1.9-fold increase in the risk of Severe hyperemesis gravidarum (OR 1.92, 95% CI 1.008–1.956; P = 0.01) ConclusionThis study shows that there is a condition in the pathophysiology of hyperemesis gravidarum, with an increase in Ischemia Modified Albumin and a decrease in Total-Sulphydryl levels, and oxidative stress occurs. It was important to detect increased Ischemia Modified Albumin and decreased antioxidant values in relation to the inflammatory factors that were effective in the severe hyperemesis gravidarum group.

Clinical correlates of R1 relaxometry and magnetic susceptibility changes in multiple sclerosis: a multi-parameter quantitative MRI study of brain iron and myelin

ObjectivesThe clinical impact of brain microstructural abnormalities in multiple sclerosis (MS) remains elusive. We aimed to characterize the topography of longitudinal relaxation rate (R1) and quantitative susceptibility (χ) changes, as indices of iron and myelin, together with brain atrophy, and to clarify their contribution to cognitive and motor disability in MS.MethodsIn this cross-sectional study, voxel-based morphometry, and voxel-based quantification analyses of R1 and χ maps were conducted in gray matter (GM) and white matter (WM) of 117 MS patients and 53 healthy controls. Voxel-wise between-group differences were assessed with nonparametric permutation tests, while correlations between MRI metrics and clinical variables (global disability, cognitive and motor performance) were assessed both globally and voxel-wise within clusters emerging from the between-group comparisons.ResultsMS patients showed widespread R1 decrease associated with more limited modifications of χ, with atrophy mainly involving deep GM, posterior and infratentorial regions (p < 0.02). While R1 and χ showed a parallel reduction in several WM tracts (p < 0.001), reduced GM R1 values (p < 0.001) were associated with decreased thalamic χ (p < 0.001) and small clusters of increased χ in the caudate nucleus and prefrontal cortex (p < 0.02). In addition to the atrophy, χ values in the cingulum and corona radiata correlated with global disability and motor performance, while focal demyelination correlated with cognitive performance (p < 0.04).ConclusionsWe confirmed the presence of widespread R1 changes, involving both GM and WM, and atrophy in MS, with less extensive modifications of tissue χ. While atrophy and χ changes are related to global and motor disability, R1 changes are meaningful correlates of cognition.Key Points• Compared to healthy controls, multiple sclerosis patients showed R1 and χ changes suggestive of iron increase within the basal ganglia and reduced iron and myelin content within (subnuclei of) the thalamus.• Thalamic volume and χ changes significantly predicted clinical disability, as well as pulvinar R1 and χ changes, independently from atrophy.• Atrophy-independent R1 and χ changes, suggestive of thalamic iron and myelin depletion, may represent a sensitive marker of subclinical inflammation.

Can RDW be used as a screening test for subclinical inflammation in children with FMF? Is RDW related to MEFV gene mutations?

Subclinical inflammation, an insidious feature of familial Mediterranean fever (FMF), can lead to life-threatening amyloidosis. We aimed to investigate acute phase reactants and complete blood count parameters to identify a useful marker for subclinical inflammation in children with FMF. A secondary aim was to identify an association between subclinical inflammation and specific Mediterranean fever (MEFV) gene mutations. This study included 420 pediatric patients with FMF. Laboratory parameters of patients during the attack-free period and MEFV gene mutation analyses were recorded. Of the 420 patients, 88 (21%) had subclinical inflammation. Of those with subclinical inflammation, 48 (55%) had mutations in exon 10, 36 (41%) had M694V mutation, and 10 (11%) had M694V homozygous mutation. Red cell distribution width (RDW) value was higher in exon 10, M694V, and M694V homozygous mutations compared to other mutations. RDW was positively correlated with serum amyloid A (SAA) (r = 0.390, p = 0.0001). Analysis of a receiver-operating characteristic curve of RDW revealed that its optimal cut-off value for subclinical inflammation was 12.69%, its sensitivity was 64.10%, and its specificity was 50.90%. The area under the curve was 0.616 (p = 0.004, 95% confidence interval = 0.538-0.695). We suggest that RDW can be used as a screening test as a marker of subclinical inflammation. A high RDW value should alert the clinician about subclinical inflammation in FMF children's patients with M694V (heterozygous, homozygous, compound heterozygous) mutation. Key Points • Subclinical inflammation in FMF patients can lead to amyloidosis. • RDW can be a predictor of subclinical inflammation. • RDW can be used as a screening test for subclinical inflammation in FMF patients with M694V mutation.

Evaluation of progression in metabolic parameters along with markers of subclinical inflammation and atherosclerosis among normoglycemic first degree relatives of type 2 diabetes mellitus patients

Evaluation of progression in metabolic parameters along with markers of subclinical inflammation and atherosclerosis among normoglycemic first degree relatives of type 2 diabetes mellitus patients

Subclinical inflammation as a predictor for erectile dysfunction after brachytherapy for localized prostate cancer

PURPOSE: Neutrophil-to-lymphocyte ratio (NLR), a marker for subclinical inflammation, has been previously shown to be associated with erectile dysfunction (ED). We studied the potential predictive value of the NLR on ED after prostate brachytherapy (PB) for PCa.METHODS AND MATERIALS: Between July 2005 and January 2021, 842 patients were included in this retrospective study of a prospectively maintained database. ED was assessed using the Common Terminology Criteria for Adverse Events (CTCAE) physician-reported scale. ED was defined as a Grade 2 or 3 function. NLR count was determined 1–2 months before PB and separated into values PB <2 and ≥2. Patient characteristics and erectile function at last follow-up were compared for patients with a Univariate and multivariate analyses were performed to evaluate the predictive value of baseline NLR ≥2 on post-PB ED.RESULTS: Baseline NLR ≥2 was found to be a statistically significant predictor of post-PB ED on both univariate (p = 0.002) and multivariate analyses (p = 0.008). Furthermore, the difference in ED prevalence between the NLR <2 and NLR ≥2 groups became more pronounced with longer follow-up after PB. The ED rate at 5 years post-PB was 43% for the NLR ≥2 groups, compared to 29% for the NLR <2 groups.CONCLUSIONS: Subclinical systemic inflammation is a potentially important factor for predicting sexual toxicity after pelvic radiotherapy. NLR may be used as a proxy for predicting post-PB ED.

Гематологические индексы – возможный маркер субклинического воспаления у больных ишемической болезнью сердца старческого возраста и долгожителей

Aim. To study the possibility of using hematological indices as markers of subclinical inflammation in very elderly patients and centenarians with coronary artery disease (CAD). Materials and Methods: The cross-sectional study enrolled 127 patients; 93 patients with CAD – in the study group, 34 patients without CAD – in the control group. The mean age of patients reached 88.2±5.3 years (76–98 years); 48.8% were over 90 years of age. The ratio of the number of neutrophils to lymphocytes (NLR), neutrophils to monocytes (NMR), platelets to lymphocytes (PLR), lymphocytes to monocytes (LMR) and the systemic immune-inflammation index (SII) were determined. Interleukin-6 (IL-6) was determined in all patients, tumor necrosis factor (TNF)-α – in 49 patients. Results. In patients with coronary artery disease, the mean content of leukocytes was significantly higher than in the control group (6.1±1.5 and 5.4±1.5×109/l, respectively, p=0.02), and platelets were less (212±60 and 243±78×109/l, respectively, p=0.02). The platelet-lymphocyte ratio (139±54 and 185±87, p=0.001), neutrophils-monocytes ratio (12.4±13.4 and 20.8±22.0; р=0.04) and systemic immune-inflammatory index (554±345 and 762±616; p=0.02) were lower in patients with CAD. In patients with heart failure, a significantly higher content of leukocytes was revealed (6.5±1.7 and 5.7±1.4×109/l, respectively, p=0.009). A direct correlation was established between NLR and the concentration of IL-6 (r=0.26; p=0.003), as well as an inverse correlation with the content of TNF-α (r=-0.3; p=0.03). Inverse correlation was registered between the NLR and functional abilities of patients (for Barthel index: r=-0.35; p&lt;0.0001; for IADL scale: r=-0.34; p&lt;0.0001). There was a direct correlation between NLR and the risk of falls by the Morse scale (r=0.38; p=0.001). Direct relationships between TLR and IL-6 (r=0.18; p=0.04), ESR (r=0.20; p=0.02) and the values of the Morse Fall Scale (r=0.43; p&lt;0.0001) were observed. An inverse correlation was registered between TLR and TNF-α (r=-0.43; p=0.002), Barthel index (r=-0.20; p=0.02), IADL scale (r=-0.21; p=0.01) and bone mineral density in the femur (r=-0.2; p=0.03). A direct correlation of systemic immune-inflammation index with IL-6 (r=0.24; p=0.006) and the values of the Morse Fall Scale (r=0.49; p&lt;0.0001), as well as an inverse relationship with TNF-α (r=-0.36; p=0.01), Barthel index (r=-0.26; p=0.02) and IADL scale (r=-0.3; p=0.001) were observed. Conclusion. Various hematological indices can be used as markers of subclinical inflammation in patients with coronary artery disease in old age and in centenarians.

Seasonal residual activity in adult familial Mediterranean fever: a longitudinal observational study.

Although it is assumed that cold exposure triggers inflammation in patients with familial Mediterranean fever (FMF), seasonal differences in FMF have not yet been investigated. This study aims to investigate the association of seasonal changes with the frequency of attacks, disease severity, and subclinical inflammation in FMF. This longitudinal study examined adult patients with FMF on an established treatment followed up for at least 1year in Istanbul. Clinical characteristics, medications, intraseasonal attacks counts, arthralgia and arthritis, disease severity, and the subclinical inflammation parameters were recorded covering four seasons. Friedman's and Cochran's Q tests were used to analyze changes in the above-mentioned data over seasons. Additionally, all attacks experienced in each season were added, and interseasonal differences were compared with the Chi-square goodness-of-fit test. Data for 240 observations (60 patients) were analyzed. The mean age and disease duration were 39.78 (SD 11.91) and 10 (IQR 6-22.75) years, respectively. The comparison of medians for four seasons did not show any statistical differences in terms of attack frequency, disease severity parameters, markers of subclinical inflammation, and the presence of arthralgia and arthritis. The total number of intraseasonal attacks experienced by patients differed among the seasons (p = 0.023), with a higher count in winter. Adult individuals with established FMF are more likely to experience attacks in winter than summer, but this difference may not be seen in the general parameters of disease activity/severity. This result supports the notion that there is a pronounced residual activity in winter.

A Potential Interplay between HDLs and Adiponectin in Promoting Endothelial Dysfunction in Obesity.

Obesity is an epidemic public health problem that has progressively worsened in recent decades and is associated with low-grade chronic inflammation (LGCI) in metabolic tissues and an increased risk of several diseases. In particular, LGCI alters metabolism and increases cardiovascular risk by impairing endothelial function and altering the functions of adiponectin and high-density lipoproteins (HDLs). Adiponectin is an adipokine involved in regulating energy metabolism and body composition. Serum adiponectin levels are reduced in obese individuals and negatively correlate with chronic sub-clinical inflammatory markers. HDLs are a heterogeneous and complex class of lipoproteins that can be dysfunctional in obesity. Adiponectin and HDLs are strictly interdependent, and the maintenance of their interplay is essential for vascular function. Since such a complex network of interactions is still overlooked in clinical settings, this review aims to highlight the mechanisms involved in the impairment of the HDLs/adiponectin axis in obese patients to predict the risk of cardiovascular diseases and activate preventive countermeasures. Here, we provide a narrative review of the role of LGCI in altering HDLs, adiponectin and endothelial functions in obesity to encourage new studies about their synergic effects on cardiovascular health and disease.