Soluble Receptor Levels Research Articles

Dysregulation of ACE (Angiotensin-Converting Enzyme)-2 and Renin-Angiotensin Peptides in SARS-CoV-2 Mediated Mortality and End-Organ Injuries.

ACE (angiotensin-converting enzyme)-2 as the target for SARS-CoV-2 also negatively regulates the renin-angiotensin system. Pathological activation of ADAM17 (A disintegrin and metalloproteinase-17) may potentiate inflammation and diminish ACE2-mediated tissue protection through proteolytic shedding, contributing to SARS-CoV-2 pathogenesis. We aim to examine plasma soluble ACE2 and angiotensin profiles in relation to outcomes by enrolling consecutive patients admitted for COVID-19 with baseline blood collection at admission and repeated sampling at 7 days. The primary outcome was 90-day mortality, and secondary outcomes were the incidence of end-organ injuries. Overall, 242 patients were included, the median age was 63 (52-74) years, 155 (64.0%) were men, and 57 (23.6%) patients reached the primary end point. Baseline soluble ACE2 was elevated in COVID-19 but was not associated with disease severity or mortality. In contrast, an upward trajectory of soluble ACE2 at repeat sampling was independently associated with an elevated risk of mortality and incidence of acute myocardial injury and circulatory shock. Similarly, an increase in soluble tumor necrosis factor receptor levels was also associated with adverse outcomes. Plasma Ang I, Ang 1-7 (angiotensin 1-7) levels, and the Ang 1-7/Ang II (angiotensin II) ratio were elevated during SARS-CoV-2 infection related to downregulation of ACE activity at baseline. Moreover, patients having an upward trajectory of soluble ACE2 were characterized by an imbalance in the Ang 1-7/Ang II ratio. The observed dysregulation of ACE2 and angiotensin peptides with disease progression suggest a potential role of ADAM17 inhibition and enhancing the beneficial Ang 1-7/Mas axis to improve outcomes against SARS-CoV-2 infection.

Increased Plasma GDF15 Is Associated with Altered Levels of Soluble VEGF Receptors 1 and 2 in Symptomatic Multiple Myeloma

Introduction: In multiple myeloma, there is an increase in bone marrow microvascular density and enhanced renal lymphangiogenesis. Increased levels of the proangiogenic protein growth differentiation factor-15 (GDF15) have previously been reported to be associated with poor prognosis in myeloma. A possible association between GDF15 and the soluble forms of vascular endothelial growth factor receptors (sVEGFR) 1 and 2 has not yet been investigated, and a role for these receptors in pathological angiogenesis in myeloma is still to be defined. Methods: Plasma levels of GDF15 and sVEGFR1 and 2 were determined by ELISA in patients with smouldering multiple myeloma (sMM), patients with symptomatic multiple myeloma (abbreviated as MM), and healthy controls. The levels were compared between the three groups, and correlation coefficients were calculated, as were Kaplan-Meier curves for GDF15 and sVEGFR1 and sVEGFR2. Results: Levels of GDF15 were significantly higher in MM than in both patients with sMM and controls. A gradual decrease in mean sVEGFR1 concentration was observed, with MM > sMM > controls. Mean sVEGFR2 was lower in patients with MM than in controls. There was a positive correlation between GDF15 and sVEGFR1, and GDF15 correlated negatively with sVEGFR2. High GDF15 (>3 ng/mL) was associated with poor prognosis. Conclusion: In multiple myeloma, increased expression of GDF15 correlates positively with sVEGFR1 and negatively with sVEGFR2. It is possible that the altered levels of sVEGFR1 and 2 contribute to the increased angio- and lymphangiogenesis observed in myeloma.

Hemodialysis Patients with Higher Serum Levels of Soluble Receptor for Advanced Glycation End Products Have an Increased Risk for Arteriovenous Fistula Failure

Background: Arteriovenous fistula (AVF) failure due to thrombosis is a major cause of morbidity in patients undergoing regular hemodialysis (HD). Advanced glycation end products (AGEs) and their receptor (RAGE) might contribute to inflammation, neointimal hyperplasia, and thrombosis. RAGE has a C-truncated secretory receptor form, called soluble RAGE (sRAGE). In this study, we aimed to evaluate the association of serum sRAGE with AVF failure due to thrombosis in HD patients. Methods: Eighty-eight prevalent HD patients with functional AVF were included in the study. The presence of stenosis, clinical and laboratory data, and serum sRAGE was evaluated at inclusion. sRAGE concentration was measured by a competitive enzyme-linked immunosorbent assay, and stenosis was detected by ultrasound. Patients were prospectively followed up for 36 months. During this period, AVF failure (defined as the absence of blast or palpable thrill and impossible cannulation with 2 needles because of complete thrombosis) was noted and thrombosis was certified by ultrasound examination. Results: During follow-up, 16 (18.18%) patients lost their vascular access due to thrombosis. In multivariate Cox regression analysis, sRAGE was a significant predictor of vascular access thrombosis (hazard ratio = 1.15, 95% confidence interval: 1.03–1.25, p = 0.012). Kaplan-Meier analysis showed a significantly lower AVF patency time in patients with sRAGE >16.78 ng/mL than those with sRAGE <16.78 ng/mL (p = 0.02). In the subgroup of patients with stenosis at baseline, sRAGE, serum albumin, obesity, and ischemic heart disease were associated with thrombosis. Conclusion: In our study, baseline, systemic sRAGE is associated with the occurrence of thrombosis of AVF, and this marker has a significant impact on AVF survival.

Differences in Inflammation, Treatment, and Outcomes Between Black and Non-Black Patients Hospitalized for COVID-19: A Prospective Cohort Study

PurposeRacial disparities in coronavirus disease 2019 (COVID-19) outcomes have been described. We sought to determine whether differences in inflammatory markers, use of COVID-19 therapies, enrollment in clinical trials, and in-hospital outcomes contribute to racial disparities between Black and non-Black patients hospitalized for COVID-19. MethodsWe leveraged a prospective cohort study that enrolled 1325 consecutive patients hospitalized for COVID-19, of whom 341 (25.7%) were Black. We measured biomarkers of inflammation and collected data on the use COVID-19-directed therapies, enrollment in COVID-19 clinical trials, mortality, need for renal replacement therapy, and need for mechanical ventilation. ResultsCompared to non-Black patients, Black patients had a higher prevalence of COVID-19 risk factors including obesity, hypertension, and diabetes mellitus and were more likely to require renal replacement therapy (15.8% vs 7.1%, P < .001) and mechanical ventilation (37.2% vs 26.6%, P < .001) during their hospitalization. Mortality was similar between both groups (15.5% for Blacks vs 14.0% for non-Blacks, P = .49). Black patients were less likely to receive corticosteroids (44.9% vs 63.8%, P< .001) or remdesivir (23.8% vs 57.8%, P < .001) and were less likely to be enrolled in COVID-19 clinical trials (15.3% vs 28.2%, P < .001). In adjusted analyses, Black race was associated with lower levels of C-reactive protein and soluble urokinase receptor and higher odds of death, mechanical ventilation, and renal replacement therapy. Differences in outcomes were not significant after adjusting for use of remdesivir and corticosteroids. ConclusionsRacial differences in outcomes of patients with COVID-19 may be related to differences in inflammatory response and differential use of therapies.

Association of Proinflammatory Cytokine Levels with Stroke Severity, Infarct Size, and Muscle Strength in the Acute Phase of Stroke

ObjectivePatterns of cytokine levels and their association with stroke severity, infarct size, and muscle strength are obscure. We aimed to analyze the immune mediators linked to T helper (Th)1, Th2, Th17, and regulatory T cell patterns and their association with stroke severity, infarct size, and muscle strength. Materials and methodsWe included patients with acute stroke (n = 15) and healthy non-disabled individuals (n = 20) aged > 18 years. The dependent variables were stroke severity according to the National Institute of Health Stroke Scale (NIHSS), infarct size on computed tomography, handgrip strength by dynamometry, and global muscle strength according to the Medical Research Council (MRC) scale. The independent variables were the circulating cytokine levels. The cytokine levels were compared between the groups, and correlations between the clinical data were verified. ResultsThe stroke group had higher interleukin (IL)-6 (p < 0.0001) and IL-10 (p < 0.0001) levels, but lower tumor necrosis factor (TNF)-α (p = 0.036) levels than the control group. IL-10 and soluble tumor necrosis factor receptor (sTNF-RII) levels were correlated with each other (r = 0.533; p = 0.042) and infarct size (r = 0.653; p = 0.033 and r = 0.689; p = 0.018, respectively). MRC scores were positively and negatively correlated with handgrip strength of the affected side (r = 0.78; p = 0.001) and NIHSS scores (r = -0.87; p < 0.0001), respectively. ConclusionsPlasma levels of some cytokines were associated with changes in the acute phase of stroke, and IL-10 and sTNF-RII levels are potential biomarkers of infarct size.

Elevated preoperative suPAR is a strong and independent risk marker for postoperative complications in patients undergoing major noncardiac surgery (SPARSE)

BackgroundPatients undergoing major surgery are often at risk of developing postoperative complications. We investigated whether a preoperative marker of chronic inflammation, soluble urokinase plasminogen activator receptor, can aid in identifying patients at high risk for postoperative complications, morbidity, and mortality. MethodsIn this prospective observational study (ClinicalTrials.gov identifier: NCT03851965), EDTA blood was collected from consecutive adult White patients scheduled for major noncardiac surgery with expected duration ≥2 hours under general anesthesia. Inclusion criteria were age ≥18 years and American Society of Anesthesiologists physical status I to IV. Plasma soluble urokinase plasminogen activator receptor levels were determined using the suPARnostic quick triage lateral flow assay. The primary endpoint was postoperative complications defined as presence of any complication and/or admission to intensive care unit and/or mortality within the first 90 postoperative days. ResultsPreoperative soluble urokinase plasminogen activator receptor had an odds ratio of 1.50 (95% confidence interval: 1.24–1.82) for every ng/mL increase. When including age, sex, American Society of Anesthesiologists score, C-reactive protein, and grouped soluble urokinase plasminogen activator receptor in multivariate analysis, patients with soluble urokinase plasminogen activator receptor between 5.5 and 10 ng/mL had an odds ratio of 11.2 (confidence interval: 3.1–40.8) and patients with soluble urokinase plasminogen activator receptor >10 ng/mL had an odds ratio of 19.9 (95% confidence interval: 4.3–92.9) compared to patients with soluble urokinase plasminogen activator receptor ≤5.5 ng/mL, respectively. Receiver operating characteristic analysis of soluble urokinase plasminogen activator receptor showed an area under the curve of 0.82 (confidence interval: 0.72–0.91). Receiver operating characteristic analysis combining age, sex, C-reactive protein levels, and American Society of Anesthesiologists score and had an area under the curve of 0.71 (95% confidence interval: 0.61–0.82). Adding soluble urokinase plasminogen activator receptor to this model increased the area under the curve to 0.83 (95% confidence interval: 0.74–0.92) (P = .033). ConclusionPreoperative soluble urokinase plasminogen activator receptor provided strong and independent predictive value on postoperative complications in White patients undergoing major noncardiac surgery.

Insulin sensitivity variations in apparently healthy Arab male subjects: correlation with insulin and C peptide

IntroductionDecreased insulin sensitivity occurs early in type 2 diabetes (T2D). T2D is highly prevalent in the Middle East and North Africa regions. This study assessed the variations in insulin sensitivity...

Exploring low grade inflammation by soluble urokinase plasminogen activator receptor levels in schizophrenia: a sex-dependent association with depressive symptoms

BackgroundThere is evidence of increased low grade inflammation (LGI) in schizophrenia patients. However, the inter-individual variation is large and the association with demographic, somatic and psychiatric factors remains unclear. Our aim was to explore whether levels of the novel LGI marker soluble urokinase plasminogen activator receptor (suPAR) were associated with clinical factors in schizophrenia and if such associations were sex-dependent.MethodIn this observational study a total of 187 participants with schizophrenia (108 males, 79 females) underwent physical examination and assessment with clinical interviews (Positive and Negative Syndrome Scale (PANSS), Calgary Depression Scale for Schizophrenia (CDSS), Alcohol Use Disorder Identification Test (AUDIT), and Drug Use Disorder Identification Test (DUDIT)). Blood levels of suPAR, glucose, lipids, and high sensitivity C-reactive protein (hsCRP) were determined and body mass index (BMI) calculated. Multivariable linear regression analyses were used adjusting for confounders, and sex interaction tested in significant variables.ResultsAdjusting for sex, age, current tobacco smoking and BMI, we found that levels of hsCRP and depressive symptoms (CDSS) were positively associated with levels of suPAR (p < 0.001). The association between suPAR and CDSS score was significant in females (p < 0.001) but not in males. Immune activation measured by hsCRP was not associated with depressive symptoms after adjusting for BMI.ConclusionOur findings indicate that increased suPAR levels are associated with depressive symptoms in females with schizophrenia, suggesting aberrant immune activation in this subgroup. Our results warrant further studies, including longitudinal follow-up of suPAR levels in schizophrenia and experimental studies of mechanisms.

Impact of cardiopulmonary bypass and surgical complexity on plasma soluble urokinase-type plasminogen activator receptor levels after cardiac surgery

Background Circulating soluble urokinase plasminogen activator receptor (suPAR) is a marker of inflammation with prognostic value for elevated risk of morbidity and mortality. It has not yet been shown how the inflammatory process induced by cardiac surgery affects suPAR concentrations postoperatively Methods In a prospective observational study, plasma suPAR levels were measured in 30 patients undergoing cardiac surgery with cardiopulmonary bypass (CPB), pre-, peri, post-operatively, and 3–5 days after surgery. Fifteen patients underwent coronary artery bypass grafting (CABG) and 15 underwent complex procedures with longer CPB duration. Concentrations of suPAR at each time point were compared to the preoperative levels and compared between the two groups. Results In both groups, plasma suPAR concentrations were significantly higher on the first postoperative day (3.27 (interquartile range (IQR) 2.75–3.86) µg/L compared to baseline (2.62 (1.98–3.86)) µg/L, p < .001. There were no significant differences in suPAR concentrations between the groups at any time point. Preoperatively, the median suPAR concentration was 2.57 (2.01–3.60) µg/L in the CABG group versus 2.67 (1.89–3.97) µg/L in the complex group (p = .567). At ICU arrival 2.48 (2.34–3.23) µg/L versus 2.73 (2.28–3.44) µg/L in CABG and complex patients, respectively (p = .914). There was no difference in suPAR concentrations between the groups on postoperative day 1 (3.34 (2.89–3.89) versus 3.19 (2.57–3.62) p = .967) or 3–5 days after surgery (2.72 (1.98–3.16) versus 2.96 (2.39–4.28) p = .085. Conclusions After a transient rise on the first postoperative day, the suPAR levels returned to the preoperative levels by the third postoperative day. There was no significant difference in suPAR levels between the routine CABG and complex group with longer CPB time.

Periodontal Clinicoradiographic Status and Whole Saliva Soluble Urokinase Plasminogen Activation Receptor and Tumor Necrosis Factor Alpha Levels in Type-2 Diabetic and Non-diabetic Individuals.

The authors hypothesise that whole saliva soluble-urokinase-type plasminogen-activator receptor (suPAR) and tumor necrosis factor-alpha (TNF-α) levels are higher in patients with poorly-controlled than well-controlled type-2 diabetes mellitus (DM) and non-diabetic controls. The aim was to assess the periodontal clinicoradiographic status and whole-salivary suPAR and TNF-α levels in type-2 diabetic and non-diabetic individuals. Patients with and without type-2 DM were included. In all patients, hemoglobin A1c (HbA1c) levels were measured. Participants were divided into 4 groups. Group 1: patients with poorly controlled type-2 DM; group 2: patients with well-controlled type-2 DM; group 3: non-diabetic patients with periodontitis; group 4: non-diabetic patients without periodontitis. Clinicoradiographic periodontal parameters (plaque index [PI], gingival index [GI], clinical attachment loss [AL], probing depth [PD] and mesial and distal marginal bone loss [MBL]) were measured. The whole saliva total protein concentration (TPC) and suPAR as well as TNF-α levels were measured. The level of statistical significance was set at p < 0.01. One hundred patients (25 patients per group) were included. Scores of PI (p < 0.01), GI (p < 0.01), clinical AL (p < 0.01), PD (p < 0.01), number of missing teeth and mesial (p < 0.01) and distal (p < 0.01) MBL were statistically significantly higher in group 1 than in groups 2-4. Scores of PI, GI, clinical AL, PD, mesial and distal MBL, and numbers of missing teeth were higher in group 3 (p < 0.01) than in groups 2 and 4. The whole saliva TPC, suPAR and TNF-α levels were statistically significantly higher among patients in group 1 (p < 0.01) than in groups 2-4. Patients with poorly-controlled type-2 DM presented with poorer clinicoradiographic periodontal status and increased whole saliva levels of suPAR, TNF-α and TPC compared with patients with well-controlled type-2 DM and non-diabetic individuals.

Дифференцированный подход к диагностике раннего неонатального сепсиса у преждевременно рожденных детей

Актуальность. Ранний неонатальный сепсис остается ведущей причиной заболеваемости и смертности недоношенных детей. Проблема своевременной диагностики обусловливает необходимость внедрения новых эффективных мониторинговых биомаркеров сепсиса новорожденных. Цель: совершенствование диагностики раннего неонатального сепсиса у преждевременно рожденных детей на основании определения диагностической значимости сывороточного уровня sTREM-1, разработка комплексного алгоритма и оценка эффективности подхода. Материалы и методы. Был проведен анализ клинико-лабораторных наблюдений 70 недоношенных детей с ранним неонатальным сепсисом (n = 22) и внутриутробной пневмонией (n = 48) с определением содержания sTREM-1 сыворотки крови. Результаты. У новорожденных с ранним неонатальным сепсисом выявлено достоверное снижение уровня sTREM-1 по сравнению с новорожденными с внутриутробной пневмонией (97,1 ± 4,5 пг/мл против 134,00 ± 7,73 пг/мл). При использовании неоднородной последовательной процедуры Вальда — Генкина установлены ранговые структуры диагностических показателей и разработана эффективная мультимаркерная диагностическая модель. Выводы. Определено, что содержание sTREM-1 в сыворотке крови детей из группы риска реализации внутриутробной инфекции &lt; 148 пг/мл в первые сутки жизни достоверно ассоциируется с неонатальным сепсисом. Использование разработанного мультимаркерного алгоритма способствует совершенствованию диагностики раннего неонатального сепсиса.

Pretreatment Levels of Soluble Tumor Necrosis Factor Receptor 1 and Hepatocyte Growth Factor Predict Toxicity and Overall Survival After 90Y Radioembolization: Potential Novel Application of Biomarkers for Personalized Management of Hepatotoxicity.

Liver function may be negatively affected by radiation for treatment of hepatic malignancy. Pretreatment blood cytokine levels are biomarkers for prediction of toxicity and survival after external-beam radiation therapy. We hypothesized that cytokines may also predict outcomes after radioembolization, enabling a biomarker-driven personalized approach to treatment. Methods: Pretherapy blood samples from patients enrolled on a prospective protocol evaluating 90Y radioembolization for management of intrahepatic malignancy were analyzed for 2 cytokines selected on the basis of prior studies in stereotactic body radiotherapy, soluble tumor necrosis factor receptor 1 (sTNFR1) and hepatocyte growth factor (HGF), via enzyme-linked immunosorbent assay, and key dosimetric parameters were derived from posttreatment 90Y PET/CT imaging. Toxicity was defined as a change in albumin-bilirubin score from baseline to follow-up (3-6 mo after treatment). Associations of cytokine levels, dose metrics, and baseline liver function with toxicity and overall survival were assessed. Results: Data from 43 patients treated with 90Y radioembolization for primary (48.8% [21/43]) or secondary (51.2% [22/43]) malignancy were assessed. Examined dose metrics and baseline liver function were not associated with liver toxicity; however, levels of sTNFR1 (P = 0.045) and HGF (P = 0.005) were associated with liver toxicity in univariate models. Cytokines were the only predictors of toxicity in multivariable models including dose metrics and prior liver-directed therapy. sTNFR1 (hazard ratio, 12.3; 95% CI, 3.5-42.5, P < 0.001) and HGF (hazard ratio, 7.5; 95% CI, 2.4-23.1, P < 0.001) predicted overall survival, and findings were similar when models were controlled for absorbed dose and presence of metastatic disease. Conclusion: Pretreatment cytokine levels predict liver toxicity and overall survival. These pathways can be targeted with available drugs, an advantage over previously studied dose metrics and liver function tests. Interventions directed at the TNFα-axis should be considered in future studies for prevention of liver toxicity, and HGF should be explored further to determine whether its elevation drives toxicity or indicates ongoing liver regeneration after prior injury.

The levels of soluble urokinase plasminogen activator receptor (suPAR) in saliva are influenced by acute stress

Although elevations in systemic suPAR levels have been associated with inflammatory conditions and with exposure to life stress and adversity, it is not yet clear whether acute psychological stress influences suPAR levels, either systemically and/or in saliva. The aim of this study was to investigate whether salivary suPAR levels are increased following exposure to acute psychological stress. Healthy subjects, aged 18–40 years, completed a laboratory psychological stressor and provided saliva samples before and after the stress test (60 min apart). Levels of suPAR as well as those of cytokines increased in the post-stress samples (all ps < .001). Baseline and post-stress IL-1β and TNF-α as well as post-stress IL-6 correlated significantly with suPAR (all ps < .01), but IL-10 and baseline IL-6 did not. These results show that suPAR levels in saliva are stress-reactive and suggest a potential application as stress biomarkers in saliva, particularly given the advantage of easily detectable concentrations.

Serum soluble (pro)renin receptor level as a prognostic factor in patients undergoing maintenance hemodialysis

The (pro)renin receptor [(P)RR)] is a multifunctional protein that is cleaved to generate the soluble (P)RR [s(P)RR], reflecting the status of the tissue renin-angiotensin system and/or activity of the (P)RR. The serum s(P)RR level is associated with arteriosclerosis, independent of other risk factors, in patients undergoing hemodialysis (HD). This study was conducted to investigate whether the s(P)RR level was associated with new-onset cardiovascular events or malignant diseases and poor prognosis in patients undergoing HD. Overall, 258 patients [70 (61–76) years, 146 males] undergoing maintenance HD were prospectively followed up for 60 months. We investigated the relationships between s(P)RR levels and new-onset cardiovascular events/ malignant diseases and mortality during the follow-up period using Cox proportional hazard analyses. The cumulative incidence of new-onset cardiovascular events (P = 0.009) and deaths (P < 0.001), but not of malignant diseases, was significantly greater in patients with higher serum s(P)RR level (≥ 29.8 ng/ml) than in those with lower s(P)RR level (< 29.8 ng/ml). A high serum s(P)RR level was independently correlated with cardiovascular mortality (95% CI 1.001–1.083, P = 0.046). The serum s(P)RR level was associated with cardiovascular events and mortality, thus qualifying as a biomarker for identifying patients requiring intensive care.

Serum estrogen and its soluble receptor levels in Egyptian patients with acute leukemia: case-control study

BackgroundAcute leukemias are malignant neoplastic diseases that arise from either lymphoid [ALL] or myeloid [AML] cell lines that are distinguished by the proliferation of BM non-functional immature cells and subsequently released into the bloodstream. ALL is prevalent malignancy in young, while AML in older. Diagnosis is usually routinely performed through peripheral blood count and smear then confirmed by BM aspirate. It is remarkable to notice that leukemia can be manifested at high, low, and even at normal leucocyte count. While treatment results have improved steadily over the last decades in younger and adults, limited changes have been in survival among subjects of age > 60 years. Aim of the work is to measure the serum estrogen [E2] and its soluble receptor [ER] levels in acute leukemia patients and extrapolate its possible clinical significance. This study included 40 [20 females and 20 males] healthy volunteers clinically free from any disease, 40 [20 females and 20 males] AML patients, and 40 [20 females and 20 males] ALL. To all subjects, serum E2 and its soluble ER level were investigated by ELISA.ResultsSerum E2 [pg/ml] level was lower in AML and ALL female and male patients groups than control group. Serum ER [ng/ml] level was lower in AML and ALL female and male patients groups than control group.ConclusionEstimation of serum E2 and its soluble ER level is of edifying diagnostic value. Determination of serum E2 and its soluble ER level in AML and ALL patients is of value in deciding treatment therapeutic target protocol.

Associations between childhood victimization, inflammatory biomarkers and psychotic phenomena in adolescence: A longitudinal cohort study

Exposure to victimization in childhood has been linked to the development of psychosis. However, little is known about how childhood victimization is translated into biological risk for psychosis. One possibility is via increased inflammation. This study aimed to investigate the association between childhood victimization, psychotic experiences (PEs) in adolescence and inflammatory markers using data from a general population cohort. Participants were 1,419 British-born children followed from birth to age 18 years as part of the Environmental Risk Longitudinal Twin Study. Childhood victimization was measured prospectively using multiple sources from birth to age 12 years. PEs were assessed during private interviews with participants at age 18 years for the period since age 12. Plasma C-reactive protein (CRP), interleukin-6 (IL-6), and soluble urokinase plasminogen activator receptor (suPAR) levels were measured from plasma samples collected from participants at 18 years. Young people with both PEs and childhood victimization were more likely to belong to a group with elevated suPAR, CRP and IL-6 levels at 18 years of age (OR = 3.34, 95% CI 1.69–6.59, p = 0.001) than those with no childhood victimization and without PEs. However, this association was attenuated when adjusted for other risk factors for elevated inflammation at age 18 (OR = 1.94, 95% CI 0.94–4.04, p = 0.075). In contrast, presence of PEs without childhood victimization was not significantly associated with age-18 inflammatory markers and neither was childhood victimization without PEs (all p’s greater than 0.05). The current study highlights that inflammatory dysregulation is mostly present in adolescents reporting PEs who also experienced childhood victimization, though this seemed to be largely due to concurrent inflammation-related risk factors.

DIAGNOSTICS AND TREATMENT OF ANEMIC SYNDROME IN PATIENTS WITH BREAST CANCER ON THE BACKGROUND OF NEOADJUVANT CHEMOTHERAPY

Introduction. In recent years, a separate publications have appeared indicating that interleukin 6 (IL-6) and the protein hepcidin 25 (GP25) play a significant role for the development of functional iron deficiency (FID) in oncological patients with a widespread tumor process. It is important to differentiate between FID and iron deficiency anemia (IDA), since they have the same morphological characteristics, but their treatment is fundamentally different.The aim of this study was to study the main metabolites of ferrokinetics, IL-6 and C-reactive protein (CRP) expression parameters in patients with breast cancer on the background of neoadjuvant chemotherapy to develop individual approaches to the diagnosis and treatment of anemic syndrome (AS), prediction, early detection of anemia and its adequate correction.Materials and methods. The study was conducted in 31 breast cancer patients, during of 6 cycles of chemotherapy. The main metabolites of ferrokinetics were studied: GP25, ferritin, soluble transferrin receptors, transferrin, iron, erythropoietin, IL-6 and CRP indices. The control group consisted of 29 apparently healthy women.Results. AS was detected in 14 (45.1 %) of breast cancer patients. IDA prevailed with microcytic, hypochromic characteristics of erythrocytes, a low concentration of ferritin, iron, GP25, IL-6, CRP, and a high level of transferrin and soluble transferrin receptors. A some patients were diagnosed with FID, mainly with the III and IV stages of the disease. Unlike IDA, they had a high concentration of ferritin, CRP and significant production of GP25, IL-6. Erythropoietin level was not optimal for the majority of patients with AS. A few patients on the background of treatment with recombinant erythropoietins revealed a deficiency of vitamins B12 (cyanocobalamin) and folic acid.Conclusion. Early diagnosis, a personalized approach to the prescription of iron preparations, recombinant erythropoietins, vitamins B12 and folic acid in patients with AS allowed for 6 cycles neoadjuvant chemotherapy without a significant decrease in erythrocytes, hemoglobin and hematocrit in most of them. The data obtained on IL-6, GP25, and CRP indicate relationship between them in the development of FID in breast cancer patients with a widespread tumor process and require further study.

Recombinant human thrombomodulin for pneumonia-induced severe ARDS complicated by DIC in children: a preliminary study.

PurposeRecombinant human soluble thrombomodulin (rTM) has been used to treat disseminated intravascular coagulation (DIC). Recent studies have shown the efficacy of rTM through its anti-inflammatory effects for treatment of adults with acute respiratory distress syndrome (ARDS). However, the safety and efficacy of rTM in children with severe ARDS complicated by DIC have not been reported. In this preliminary study, we reported the feasibility of using rTM for the treatment of pneumonia-induced severe ARDS complicated by DIC in children.MethodsSix children (age: median 10 months old) with pneumonia-induced severe ARDS complicated by DIC were enrolled in this preliminary study. rTM (380 U/kg) was administered for a maximum of 6 days, in addition to conventional therapies after diagnosis of severe ARDS complicated by DIC. After administration of rTM, we measured changes in the plasma TM concentration and evaluated the clinical course, status of DIC and ARDS, and other laboratory findings, including levels of cytokines, chemokines, and biomarkers.ResultsIn all six children, the plasma concentration of TM increased and DIC scores decreased after administration of rTM. Four of the six children recovered from the severe ARDS complicated by DIC after treatment, and were discharged from the hospital with no complications. In survived children, levels of soluble receptors for advanced glycation end products, interleukin-6, interleukin-8 and monocyte chemotactic protein-1 decreased after administration of rTM compared to those before rTM.ConclusionsThe rTM administration is feasible as an adjunctive therapeutic strategy for children over 2 months with pneumonia-induced severe ARDS complicated by DIC.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00540-021-02971-3.

The immunoregulatory function of peripheral blood CD71+ erythroid cells in systemic-onset juvenile idiopathic arthritis

CD71+ erythroid cells (CECs) are recognized to have an immunoregulatory function via direct cell–cell interaction and soluble mediators. Circulating CECs appear in newborns or patients with hemolytic and cardiopulmonary disorders. To assess the biological role of CECs in systemic inflammation, we studied the gene expression and function in systemic-onset juvenile idiopathic arthritis (SoJIA). Peripheral blood mononuclear cells of SoJIA patients expressed upregulated erythropoiesis-related genes. It represented the largest expansion of CECs during active phase SoJIA among other inflammatory diseases. Despite the opposing roles of erythropoietin and hepcidin in erythropoiesis, both serum levels were in concert with the amounts of SoJIA-driven CECs. Circulating CECs counts in inflammatory diseases were positively correlated with the levels of C-reactive protein, IL-6, IL-18, or soluble TNF receptors. Co-culture with active SoJIA-driven CECs suppressed secretions of IL-1β, IL-6, and IL-8 from healthy donor monocytes. The top upregulated gene in SoJIA-driven CECs was ARG2 compared with CECs from cord blood controls, although cytokine production from monocytes was suppressed by co-culture, even with an arginase inhibitor. CECs are driven to the periphery during the acute phase of SoJIA at higher levels than other inflammatory diseases. Circulating CECs may control excessive inflammation via the immunoregulatory pathways, partly involving arginase-2.

Sex Differences in the Association Between Inflammation and Event-Free Survival in Patients With Heart Failure.

Heart failure (HF) is associated with chronic inflammation, which is adversely associated with survival. Although sex-related differences in inflammation have been described in patients with HF, whether sex-related differences in inflammation are associated with event-free survival has not been examined. The aim of this study was to determine whether the association between inflammation as indicated by tumor necrosis factor-α and event-free survival differs between men and women with HF after controlling for demographic and clinical variables. This was a secondary analysis of data from 301 male (age, 61.0 ± 11.4 years) and 137 female (age, 60.3 ± 12.1 years) patients with HF. Serum levels of soluble tumor necrosis factor receptor 1 were used to indicate inflammatory status. Patients were grouped according to median split of soluble tumor necrosis factor receptor 1 level and sex into male with low inflammation (≤1820 pg/mL) (n = 158) or high inflammation (>1820 pg/mL) (n = 143), and female with low inflammation (n = 63) or high inflammation (n = 74). Cox regression models were run separately for men and women to determine whether inflammation contributed to differences in event-free survival between sexes with HF. There were 84 male (27.9%) and 27 female (19.7%) patients who had an event. Event-free survival in women did not differ by the severity of inflammation in the Cox regression analysis. In contrast, men with high inflammation had 1.85 times higher risk for an event compared with men with low inflammation. These data provide evidence that inflammation contributed to differences in event-free survival in men but not women with HF. Clinicians should be aware that men who have higher inflammation may be at a greater risk of HF or cardiac-related events than others with HF.