Subclinical Systemic Inflammation Research Articles

Sub-clinical systemic inflammation as a determinant of admission duration in psychosis.

The immune system may play an important role in the aetiology of psychotic disorders and there is increasing interest in the relationship between immune markers and clinical outcomes in psychosis. The present study investigated whether subclinical systemic inflammation was associated with length of stay in individuals with psychosis admitted to a psychiatric hospital. We tested the hypothesis that a higher level of subclinical systemic inflammation, as measured by the neutrophil-to-lymphocyte ratio (NLR) would be associated with a longer period in hospital. Retrospective cohort study based on electronic health records. We included patients with a psychosis spectrum disorder (ICD10: F20-F29) who had a routine blood test upon being admitted to a psychiatric hospital within the South London and Maudsley NHS Foundation Mental Health Trust, London, UK between 2013 and 2019. Multiple linear regression was used to determine the association between the NLR at the time of admission and the duration of the corresponding hospital stay, adjusting for covariables. Data from 1683 individuals with psychosis were analyzed. The median admission duration was 31days (interquartile range=48days). Higher neutrophil-to-lymphocyte ratio (NLR) was significantly associated with longer admission (B = 0.07, p<0.003) after adjusting for covariates. An association between a NLR and a longer admission, whilst controlling for relevant covariables, was observed highlighting the potential utility of inflammatory markers as prognostic marker in clinical settings.

P0326 Environmental factors, genetic predisposition and subclinical inflammation in the development of perinuclear-antineutrophil cytoplasmic antibody (P-ANCA)-positive ulcerative colitis: A European twin study

Abstract Background Perinuclear-antineutrophil cytoplasmic antibodies (P-ANCAs) have been identified in familial ulcerative colitis (UC), but the precise mechanism underlying their expression remains elusive. We assessed the role of genetic predisposition, environmental factors and systemic subclinical inflammation in the development of P-ANCA in a twin cohort with UC. Methods A total of 48 twin pairs (Leuven, Belgium n=4, Maastricht, The Netherlands n=6 and Örebro, Sweden n=38) with UC were included. Among these, 18 were monozygotic (3 concordant and 15 discordant for UC) and 30 were dizygotic (1 concordant and 29 discordant for UC). P-ANCA was detected through standardised ELISA, an indirect immunofluorescence assay and DNase treatment. In addition to high sensitivity C-reactive protein (hs-CRP), 92 inflammatory protein markers were measured in serum by proximity extension assay (Olink proteomics). Results P-ANCA was present in 16/52 (31%) of UC twins vs. 4/44 (9%) healthy twin siblings (p=0.01). No agreement in the presence of P-ANCA or their levels was observed between twin siblings in monozygotic pairs discordant for UC [intraclass correlation coefficient (ICC)=0.09] or dizygotic pairs (ICC=-0.20). Female sex was associated with an increased likelihood of P-ANCA (odds ratio, OR 5.49; 95% confidence interval, CI 1.47-20.57) and higher ANCA levels (ratio of geometric means 1.80; 95% CI 1.12-2.88). Active smoking was associated with lower concentrations of ANCA (ratio of geometric means 0.33; 95% CI 0.15-0.75) and potentially reduced the likelihood of P-ANCA (OR 0.23; 95% CI 0.02-2.21) in twins with UC but not in their healthy siblings. In twin siblings without UC, significant correlations between ANCA levels and hs-CRP, CDCP1, IL17A, CXCL9 and IL5 (correlation coefficients 0.36-0.41, p-values &amp;lt;0.05) were observed. Conclusion Female sex and tobacco smoking outweighed genetics regarding the generation and levels of P-ANCA and ANCA antibodies. The correlations between ANCA levels and inflammatory markers in healthy twin siblings suggest that P-ANCA may result from subclinical inflammation in these healthy siblings.

Red Blood Cell Distribution Width May Predict Drug-Induced Anemia and Prognosis in Patients Affected by Primary/Secondary Myelofibrosis Treated with Ruxolitinib.

Myelofibrosis (MF) is often characterized by a multifactorial anemia determined, in part, by bone marrow (BM) fibrosis, extramedullary erythropoiesis and splenomegaly. Ruxolitinib (RUX) is the first-in-class janus kinase 2 (JAK2) inhibitor approved for treatment of MF, proved to reduce spleen volume and decrease symptom burden. The red cell distribution width (RDW) is the measure of erythrocyte volume variability (anisocytosis). RDW has been recognized as a marker of clinical and subclinical systemic inflammation, and its elevation has also been associated with poor outcome in a wide spectrum of benign disorders and in different types of neoplasms. We retrospectively evaluated RDW in a single-center series of 200 consecutive patients with primary and secondary MF at RUX treatment initiation and examined any possible correlation with adverse MF features or drug-related anemia and any prognostic impact. We suggested 20.5% as the optimal cutoff point in RDW values at start of RUX to dichotomize patients in receiver operating characteristic (ROC) analysis for spleen response and for survival. Higher RDW values at RUX start were associated with clinical and laboratory features of an aggressive MF phenotype. Lower spleen response (p < 0.001) and greater odds of drug-related anemia at 3 (p = 0.006) and 6 months (p < 0.001) were alsoseen in patients with higher RDW. Both increased RDW (considered as a continuous variable) and RDW ≥ 20.5% were associated with shorter overall survival (OS) from RUX initiation in univariate and multivariate analysis: HR 1.25 (95% confidence interval [CI], 1.12-1.40) (p < 0.001) and HR 3.01 (95% CI 1.81-4.99) (p < 0.001), respectively. RDW ≥ 20.5% at RUX start seems to possibly improve patients' sub-stratification along with anemia and conventional prognostic scoring systems. RDW at RUX start might represent a good indirect measure of MF features and might have prognostic significance for RUX-treated patients affected by MF, aiding in the rapid detection of patients with poor prognosis.

Obesity and iron deficiency: what is the connection and how to treat?

The article presents a review of the literature and our own data on the etiology and pathogenesis of iron deficiency and iron deficiency anemia in patients with obesity. Obesity is considered as a subclinical systemic chronic inflammation, which is associated with an increase in the level of hepcidin, which is a key mediator of anemia during inflammation. Patients with obesity should undergo periodic screening of iron status and ferrokinetic parameters. Today, new oral iron preparations with increased tolerability and improved absorption are used in clinical practice. These include sucrosomial iron preparations. Sucrosomial iron (SI) is an innovative oral iron-containing carrier in which iron pyrophosphate is enclosed in a phospholipid matrix coated with sucrester, which protects sucrosomial iron from the effects of gastric juice, excluding contact with the mucous membrane of the gastrointestinal tract. Resistance to the action of gastric juice allows intact sucrosomes to reach the mucous membrane of the small intestine, where they are absorbed through special M cells, followed by the release of iron in liver cells. This allows prescribing SI to patients with iron deficiency and inflammatory bowel diseases, celiac disease, cancer and patients with obesity. Sucrosomial iron should be considered as an alternative treatment for iron deficiency in obese women. SI is innovative, allowing to bypass the “hepcidin barrier”, convenient for administration, effective for treatment, well tolerated than traditional oral iron salts.

Maternal Salivary miR-423-5p Is Linked to Neonatal Outcomes and Periodontal Status in Cardiovascular-High-Risk Pregnancies.

Periodontal disease (PD) during pregnancy may trigger systemic inflammation, increasing the risk of developing cardiometabolic disease (CMD). As a consequence, PD may result in the activation of cellular and molecular pathways, affecting the disease course and pregnancy outcome. Although microRNAs (miRNAs) are considered ideal biomarkers for many diseases, few studies have investigated salivary miRNAs and their role in pregnancy or neonatal outcomes. In this study, we sought to investigate the associations between salivary miRNAs of pregnant women with oral diseases and their effects on neonatal outcomes. Eleven (n = 11) salivary miRNAs from a cohort of pregnant women with oral diseases (n = 32; oral health, H; gingivitis, G; and periodontitis, P) were detected using a previous profiling analysis with an FDR < 0.20 and a fold change (FC) < 0.5 or FC > 2 for the most highly expressed miRNAs. Spearman correlations were performed for 11 salivary microRNAs associated with oral-derived inflammation, which could affect neonatal outcomes during pregnancies at risk for cardiometabolic disease (CMD), defined by the presence of a high pregestational BMI. In addition, ROC curves demonstrated the diagnostic accuracy of the markers used. Upregulation of miR-423-5p expression and a decrease in miR-27b-3p expression were detected in the P-group (p < 0.05), and ROC analysis revealed the diagnostic accuracy of miR-423-5p for discriminating oral diseases, such as gingivitis versus periodontitis (P vs. G, AUC = 0.78, p < 0.05), and for discriminating it from the healthy oral cavity (P vs. H, AUC = 0.9, p < 0.01). In addition, miR-27b-3p and miR-622 were also able to discriminate the healthy group from the P-group (AUC = 0.8, p < 0.05; AUC = 0.8, p < 0.05). miR-483-5p was able to discriminate between the G-group (AUC = 0.9, p < 0.01) and the P-group (AUC = 0.8, p < 0.05). These data support the role of salivary miRNAs as early biomarkers for neonatal outcomes in pregnant women with periodontal disease at high risk for CMD and suggest that there is cross-talk between salivary miRNAs and subclinical systemic inflammation.

The Skin and Inflamm-Aging.

With its unique anatomical location facing both the external and internal environment, the skin has crucial functions, including shielding the body from damage caused by ultraviolet radiation and chemicals, preventing water loss, acting as a primary barrier against pathogens, participating in metabolic processes like vitamin D production and temperature control and relaying information to the body through sensory and proprioceptor nerves. Like all organ systems, skin is known to undergo multiple changes with aging. A better understanding of the mechanisms that mediate aging-related skin dysfunction may allow the creation of targeted therapeutics that have beneficial effects not only on aged skin but also on other organs and tissues that experience a loss of or decline in function with aging. The skin is the largest organ of the body and can contribute to serum inflammatory mediator levels. One alteration known to occur with age is an impairment of skin barrier function; since disruption of the barrier is known to induce inflammation, skin may be a major contributor to the sustained, sub-clinical systemic inflammation associated with aging. Such "inflamm-aging" may underlie many of the deleterious changes observed in aged individuals. This review explores the role of age-related skin changes, skin inflammation and inflamm-aging.

The Potential Link between Obesity, Synbiotics Intake and Inflammasomes in an Animal Model

Abstract Background Obesity is one of the major public health problems worldwide, being considered a global epidemic. A growing body of evidence highlights the relevance of inflammasomes as a consequence of metabolic disorders and obesity. NLRP3 is the most studied component of the inflammasomes. Gut microbes contribute to the subclinical systemic inflammation that ultimately leads to the development of pathologies such as obesity, insulin resistance. Therefore, the use of intestinal microbiota modulators (e.g probitoics, prebiotics, or both as synbiotics) may improve several metabolic and immune functions. Recently, the link between these modulators and NLRP3 in obesity is less investigated. Aim of the Work to study the potential involvement of inflammasomes as an indicator for the efficacy of synbiotics in alleviating diet-induced obesity. Materials and Methods Thirty adult male Wistar rats were randomly divided into four groups (7 rats /group): normal control group (receiving normal diet), HFD (high fat diet) group, normal group receiving synbiotics, and HFD rats receiving synbiotics. After eight weeks, all rats were sacrificed then WAT (visceral, subcutaneous), brown adipose tissue, and liver were obtained. The body weight of each rat was measured weekly. The expression of NLRP3 was performed by real-time PCR. Results HFD induced a significant weight gain compared to normal diet (p &amp;lt; 0.05). However, synbiotics administration could not affect such weight gain in rats receiving HFD with synbiotics (p &amp;gt; 0.05). The expression of NLRP3, pre-inflammatory marker, is elevated in adipose and liver tissues in HFD group compared to normal diet group (p &amp;lt; 0.05). However, synbiotics successfully reduced the expression of NLRP3 in all previous tissues (p &amp;lt; 0.05). Conclusion the intake of synbiotics could disrupt the inflammatory consequences of obesity through targeting the expression of NLRP3. Thereby, synbiotics might be a promising potential therapeutic agent in treatment of obesity.

The role of nutraceuticals in heart failure muscle wasting as a result of inflammatory activity. The International Lipid Expert Panel (ILEP) Position Paper.

Muscle wasting is one of the main causes for exercise intolerance and ventilatory inefficiency in patients with heart failure and a strong predictor of frailty and reduced survival. The prevalence of sarcopenia is at least 20% in patients with heart failure. Patients with heart failure often have subclinical systemic inflammation, which may exert sustained effects on skeletal muscle. Besides exercise, nutrition should also be carefully evaluated as an appropriate diet with selected nutraceuticals may be able to stimulate muscle anabolism and inhibit muscle catabolism. This review summarizes the epidemiological and clinical trial evidence supporting the recommendations for the use of nutraceuticals with anti-inflammatory properties in heart failure and provides an overview of the state of the evidence for nutraceutical supplementation to prevent and/or mitigate heart failure muscle wasting.

Trends in the prevalence of atrophic gastritis and Helicobacter pylori infection over a 10‑year period in Japan: The ROAD study 2005‑2015.

Few large population-based studies have examined the prevalence of atrophic gastritis (AG) and Helicobacter pylori infection in Japan. The purpose of the present study was to estimate the prevalence of AG and H. pylori infection by age, in addition to investigating their change rates from 2005 to 2016 in Japan using data from a large population-based cohort. A total of 3,596 participants [1,690 in the baseline survey (2005-2006) and 1,906 at the fourth survey (2015-2016)] aged 18 to 97 years were included in the cohort. The prevalence of AG and H. pylori infection were examined at baseline and in the fourth survey based on serological tests for the H. pylori antibody titer and pepsinogen levels. The prevalence of AG and H. pylori infection were 40.1% (men, 44.1%; women, 38.0%) and 52.2% (men, 54.8%; women, 50.8%), respectively, at baseline. AG seropositivity rates showed a significant decrease from 40.1 to 25.8% in 10 years. H. pylori seropositivity rates decreased significantly from 52.2 to 35.5% in 10 years. Stratified for age, the prevalence of AG showed an increasing trend with age, whereas the prevalence of H. pylori infection increased with aging, except for in the elderly group, showing an inverted U-shaped association. In this population-based, cross-sectional study with a 10-year interval survey, the prevalence of AG and H. pylori infection decreased significantly. This change may influence the prevalence of H. pylori-related diseases, including extra-gastric disorders associated with H. pylori-induced systemic subclinical inflammation and hypochlorhydria, such as colorectal neoplasia and arteriosclerosis.

The role of cytokines in the development of systemic inflammation in chronic obstructive pulmonary disease and obesity

Patients with chronic obstructive pulmonary disease (COPD) are characterized by a variety of comorbid conditions, including both somatic (arterial hypertension, atherosclerosis, coronary heart disease, bronchial asthma, malignant neoplasms, diabetes mellitus, obesity, etc.) and mental (depressive disorders, suicide attempts). Against the background of various chronic diseases of the respiratory system, endocrine, metabolic disorders, the risks of exacerbations of COPD increase. The leading unifying mechanism of these conditions is systemic subclinical inflammation. Its excessive activity leads to the loss of the physiological functions of inflammation, which is accompanied by an imbalance in the endocrine system and the release of high concentrations of hormones and neurotransmitters. The result of this response is the uncoupling of cytokine mechanisms, which leads to an imbalance in the system of pro- and anti-inflammatory cytokines. The article describes the role of the pro-inflammatory chemokine IL-8 (interleukin 8), which is responsible for the migration of neutrophils to the site of inflammation. This is how the neutrophilic type of inflammation is formed. IL-4 and IL-10 are considered, which occupy a leading position in the formation of CD4+ type of immunoreactivity, which is observed in bronchial asthma. Attention is focused on the significance of IL-6, because it is an integral component of local and systemic inflammation. An increase in its concentration and, as a result, a potential risk of damage to the respiratory epithelium is the remodeling of the bronchial tree, resulting in a decrease in the elasticity of the epithelium of the respiratory tract. This mechanism leads to the formation of pulmonary emphysema and further potentiation of pathophysiological processes in patients with COPD. Since IL-6 is a cytokine with anti-inflammatory properties, its molecular activity is achieved by interacting with a special receptor complex consisting of two subunits: IL-6R and gp130. The former mediates IL-6 binding, while the latter triggers the JAK/STAT or MAPK signaling cascade pathways. The result of the reaction of IL-6 with the effector cell directly depends on the type of signaling. The paper describes three mechanisms of signal transduction into the target cell: classical, cluster, and transsignaling. Thus, by studying the role of cytokines in the systemic inflammatory response, we have shown the cross-talk between adipose tissue and the lungs in obesity, highlighting the main inflammatory mediators, which may indicate new therapeutic targets for preventing pulmonary dysfunction.

Impact of Oral Health on Rheumatoid Arthritis

This is a narrative review describing how oral infections and diseases associate with rheumatoid arthritis. From the voluminous oral microbiom, bacteria can get access to circulation through inflamed periodontal tissue, oral mucosa, and carious teeth. This results in upregulation of a number of chemokines and cytokines that often cause chronic, subclinical systemic inflammation with consequent organ pathology. The periodontal pathogen Porphyromonas gingivalis was observed to cause citrullination of proteins that play a role in the development of arthritis by generating of specific autoantibodies such as anti-citrullinated peptide antibody. These migrate and form immune complexes at the synovial membrane of joints. In general, patients with rheumatoid arthritis should have a healthy mouth. Dry mouth is a symptom seen among many patients with rheumatic diseases, also rheumatoid arthritis. Because saliva is one of the principal defense factors of the mouth, hyposalivation renders the patient liable to oral diseases. Consequently, the patients must drink enough daily and use saliva substitutes when necessary, and, above all, maintain good oral hygiene daily. In rheumatoid arthritis, manual dexterity may be impaired, however, causing cleaning the teeth difficult. Hence, patients with rheumatic diseases like rheumatoid arthritis need counseling and individual oral health care instructions by oral health care professionals for implementation at home. An electric toothbrush should be recommended. Regular oral health examinations by dentists are needed more often than among the healthy.

Helicobacter pylori-Related Extraintestinal Manifestations—Myth or Reality

It is well documented that Helicobacter pylori (H. pylori) can cause both gastrointestinal and extraintestinal manifestations. The latter one represents a major burden in terms of diagnosis and treatment. H. pylori-associated systemic subclinical inflammation is mostly responsible for the development of extraintestinal manifestations, and its early eradication might result in preventing all adverse events related to their occurrence. Thus, it was suggested that H. pylori might be associated with iron deficiency anemia, thrombocytopenia (immune thrombocytopenic purpura), Schonlein Henoch purpura, failure to thrive, vitamin B12 deficiency, diabetes mellitus, body mass index, cardiovascular diseases, as well as certain neurological conditions. Nevertheless, studies showed both pros and cons in terms of the role of H. pylori in the development of previously mentioned clinical entity underlining the crucial need for further studies on these topics. Although most of these extraintestinal manifestations occur during adulthood, we must not forget that H. pylori infection is acquired mainly during childhood, and thus its early diagnosis and eradication might represent the cornerstone in the prevention of H. pylori-induced inflammatory status and consequently of all related extraintestinal conditions.

The human long noncoding RNAs CoroMarker, MALAT1, CDR1as, and LINC00460 in whole blood of individuals after controlled short-term exposure with ultrafine metal fume particles at workplace conditions, and in human macrophages in vitro

BackgroundShort-term inhalation of occupationally relevant ultrafine zinc/copper (Zn/Cu) containing welding fumes has been shown to induce subclinical systemic inflammation, associated with an elevated risk for cardiovascular diseases. The involvement of noncoding RNAs (lncRNAs) in this setting is currently unknown. However, lncRNAs have been reported to fulfill essential roles in, e.g., cardiovascular diseases, inflammation, infectious diseases, and pollution-related lung disorders.MethodsIn this study, the specific lncRNAs levels of the 4 lncRNAs CoroMarker, MALAT1, CDR1as and LINC00460 were determined by RT-qPCR in THP-1 macrophages exposed to Zn/Cu metal fume suspensions for 1, 2, and 4 hours in vitro. Furthermore, 14 subjects were exposed to Zn/Cu containing welding fumes (at 2.5 mg/m3) for 6 hours. Before, 6, 10, and 29 hours after exposure start, whole blood cell lncRNAs levels were determined by RT-qPCR.ResultsIn THP-1 macrophages, we observed a 2.3-fold increase of CDR1as at 1 h (Wilcoxon p = 0.03), a non-significant increase of CoroMarker at 1 h, and an increase of LINC00460 at 2 h (p = 0.03) and at 4 h (p = 0.06). In whole blood cells, we determined a non-significant upregulation of CDR1as at 6 h (p = 0.2), a significant downregulation of CoroMarker at 6 h (p = 0.04), and a significant upregulation of LINC00460 levels at 10 h (p = 0.04) and 29 h (p = 0.04). MALAT-1 remained unchanged in both settings.ConclusionThe orientation of regulation of the lncRNAs is (except for CoroMarker) similar in the in vitro and in vivo experiments and in line with their described functions. Therefore, these results, e.g. the upregulation of the potential risk marker for cardiovascular diseases, CDR1as, contribute to understanding the underlying mechanisms of Zn/Cu-induced subclinical inflammation in metal workers.

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.

1412-P: Preexisting Nonalcoholic Steatohepatitis Attenuates Improvement of Adipose Tissue OXPHOS Capacity after Weight-Loss Surgery

Impaired adipose tissue (AT) function closely associates with obesity, type 2 diabetes and nonalcoholic fatty liver disease (NAFLD) . Mitochondrial oxidative phosphorylation (OXPHOS) capacity of AT improves after weight loss surgery. However, it is not clear if the improvement is affected by the presence of NAFLD before surgery. We examined 52 severely obese people exhibiting no histological liver disease (OBE_CON) , simple steatosis (OBE_NAFL) or steatohepatitis (OBE_NASH) before (0 weeks) , 12 and 52 weeks after bariatric surgery. Whole-body insulin sensitivity was measured by hyperinsulinemic euglycemic clamps. OXPHOS capacity of subcutaneous AT was assessed by high-resolution respirometry. Transcript levels of TNFα in AT were quantified by RT-PCR. Before surgery, OBE_NASH presented with lower insulin sensitivity and higher HbA1c compared to OBE_CON and OBE_NAFL (all p&amp;lt;0.05) whereas OXPHOS capacity in AT was comparable between the groups. Maximum coupled respiration declined at week 12 by 17% from week 0 in OBE_CON only (p&amp;lt;0.05) . From 12 to 52 weeks, AT maximum coupled respiration markedly increased by 82 and 49% in OBE_CON and OBE_NAFL (both p&amp;lt;0.001) but only by 28% in OBE_NASH (p=0.05; maximum coupled OXPHOS at week 52: OBE_CON vs. OBE_NASH p&amp;lt;0.05) . The changes in AT maximum coupled respiration from 12 to 52 weeks correlated negatively with changes in AT TNFα levels in OBE_CON (β=-0.83, p&amp;lt;0.001) and negatively with changes in systemic C-reactive protein levels in OBE_NASH (β=-0.34, p&amp;lt;0.05) . Maximal noncoupled OXPHOS yielded similar changes and correlations. In conclusion, in severe obesity, weight loss-related improvements in AT OXPHOS capacity may be mediated to a great extent by reduced AT inflammation in people without liver disease; however, with pre-surgery manifestation of NASH and worsening of metabolic control, residual systemic subclinical inflammation may attenuate the improvement of AT OXPHOS capacity after bariatric surgery. Disclosure S.Kahl: None. G.Heilmann: None. I.Esposito: None. M.Schlensak: None. M.Roden: Advisory Panel; Eli Lilly and Company, Research Support; Boehringer Ingelheim International GmbH, Nutricia, Speaker's Bureau; Novo Nordisk. K.Strassburger: None. S.Gancheva: None. N.Saatmann: None. C.Granata: None. C.Herder: Research Support; Sanofi. K.Pafili: None. J.Puetzer-furmanczak: None. T.Sarabhai: None. Funding German Federal Ministry of Health; Ministry of Culture and Science of the State North Rhine-Westphalia;German Federal Ministry of Education and Research;European Funds for Regional Development (EFRE-0400191) ;EUREKA Eurostars-2 (E!113230DIA-PEP) ;German Science Foundation (CRC/SFB1116/2 B12; RTG/GRK 2576 vivid, Project 3) ;Schmutzler Stiftung

Outcomes of Acute Coronary Syndrome in Hospitalized Patients with Celiac Disease, a United States Nationwide Experience

Background: Cardiovascular disease remains the leading cause of death in the United States. Coronary artery disease alone accounted for approximately 13% of deaths in the US in 2016. Some studies have suggested an increased prevalence of coronary artery disease (CAD) in chronic inflammatory conditions, such as celiac disease (CD). Chronic subclinical systemic inflammation, decreased absorption of cardio-protective nutrients and drugs have all been postulated as the driving mechanisms for this increased risk of CAD. Methods: We reviewed a Nationwide Inpatient Sample from 2007 to 2017, using Acute Coronary syndrome as a principal diagnosis with CD as the secondary diagnosis, utilizing validated ICD-9-CM and ICD-10 codes. We examined the annual trends in the number of cases and hospitalization charges yearly and used survey regression to calculate adjusted odds ratios (aOR) for hospital mortality and other outcomes. Results: We identified a total of 8,036,307 ACS hospitalizations from 2007 to 2017, of which 5917 (0.07%) had a diagnosis for CD. The proportion of patients with CD in ACS hospitalizations increased from 0.015% in 2007 to 0.076% in 2017. These patients were significantly older (70.3 vs. 67.4 years, p &lt; 0.02), more likely female (51.9% vs. 39.5%, p &lt; 0.01), and more likely to be white (93.8% vs. 76.6%; p &lt; 0.01) than ACS patients without CD. After adjusting for age, gender, race, Charlson Comorbidity index and hospital level characteristics, ACS hospitalizations for CD patients had a lower odds ratio for hospital mortality (aOR = 0.39; 95% CI = 0.23–0.67; p &lt; 0.01). Additionally, length of stay in this patient population was shorter (4.53 vs. 4.84 days, p &lt; 0.01) but the mean hospitalization charges were higher (USD 64,058 vs. USD 60,223, p &lt; 0.01). Conclusion: We found that the number of ACS-related admissions in CD patients has risen more than five-fold between 2007 and 2017. However, the odds of in-hospital mortality in these patients is not higher than patients without CD. The results of our study demonstrate that although the systemic inflammation related to CD is associated with an increasing prevalence of ACS hospitalizations, on the contrary, the mortality rate is significantly higher in patients without celiac disease.

Longitudinal association of inflammatory markers with markers of glycaemia and insulin resistance in European children.

Subclinical systemic inflammation may lead to development of type 2 diabetes, but there has been no investigation into its relationship with early progression of glycaemic deterioration and insulin resistance, especially in younger population. In this study we assessed longitudinal associations of pro- and anti-inflammatory markers with markers that evaluate glycaemia and insulin resistance. This study includes 6537 initially nondiabetic children (mean age at baseline=6.2years) with repeated measurements from the IDEFICS/I.Family cohort study (mean follow-up=5.3years) from eight European countries. Markers of inflammation were used as independent variables and markers of glycaemia/insulin resistance as dependent variables. Associations were examined using two-level growth model. Models were adjusted for sex, age, major lifestyle, metabolic risk factors, early life markers, and other inflammatory markers in final model. Children with 6years of follow-up showed that a one-unit increase in z-score of leptin level was associated with 0.38 (95% CI=0.32 to 0.44) unit increase in HOMA-IR z-scores. Leptin continued to be associated with HOMA-IR even when analysis was limited to children with no overall obesity, no abdominal obesity, and low to normal triglyceride levels. An inverse association was observed between IL-15 and HOMA-IR (β=-0.11, 95% CI=-0.15 to -0.07). IL-15 should be evaluated further in the prevention or treatment of prediabetes whereas leptin may prove to be useful in early detection of prediabetes via their association with markers of insulin resistance in European children.

Evaluation of Inflammatory Hematological Ratios (NLR, PLR, MLR and Monocyte/HDL-Cholesterol Ratio) in Obese Adolescents

Introduction: Obesity is a gradually more important multifactorial disease in both children and adults. Obese children and adolescents are at higher risk of becoming obese in adulthood, which is associated with an increased risk of mortality and morbidity. There is subclinical systemic inflammation in obesity. The study aimed to evaluate the hematological parameters as an indicator of inflammation in obese adolescents and to show the relationship of monocyte/HDL-cholesterol ratio, having a lipid component, with other inflammatory hematological parameters. Materials and methods: We retrospectively reviewed the medical files of 60 patients, 30 obese and 30 healthy controls, aged between 11 and 16 years, who applied to the pediatric outpatient clinic. Laboratory tests, hematological parameters, gender, age, and BMI were compared between the groups. Correlations between monocyte/HDL-cholesterol ratio and other laboratory parameters in the obese group were examined. Results: BMI, Alanine aminotransferase (ALT), C-reactive protein (CRP), triglyceride, insulin, and HOMA-IR levels of the obese adolescent group were statistically significantly higher than the control group (p&lt;0.05). There was no statistically significant difference between the obese and control groups in terms of inflammatory hematological ratios (NLR, PLR, MLR, and monocyte/HDL-cholesterol ratio) (p&gt;0.05). There was no statistically significant relationship between monocyte/HDL-cholesterol and other inflammatory hematological rates (p&gt;0.05). There was a positive, moderate (48.6%), and statistically significant relationship between monocyte/HDL-cholesterol and MLR (p&lt;0.05). Conclusions: In our study, the NLR, PLR, MLR, and monocyte/HDL-cholesterol values of the obese adolescent group were similar to the control group. There was correlation between monocyte/HDL-cholesterol and monocyte/lymphocyte values. There was no correlation between other rates. Our data do not support the utility of inflammatory hematological rates as a biomarker in adolescent obesity. However, we believe that our study can shed light on other studies to be conducted.

Stingless bee honey: An overview of health benefits and main market challenges.

This review aimed to evaluate the nutraceutical and medicinal effects of stingless bee honey (SBH) by bringing a discussion focused on the main known in vitro/in vivo health-promoting effects. SBH has a high-water content, slight sweetness, acidic flavor, fluid texture, and slow crystallization. The type and concentration of phenolic compounds and consequent antioxidant activity were mainly associated with the floral sources, geographical location, bee species, and processing steps. SBH has anti-inflammatory, antimicrobial (against spoilage and pathogenic microorganisms), anti-diabetic, and skin aging delay activities in in vitro tests. It has also shown antioxidant and hypolipidemic effects, can protect from injuries caused by dyslipidemia, possess anti-inflammatory activity against chronic subclinical systemic inflammation and anti-diabetic properties, and can control and prevent Staphylococcus aureus infection on infected wound healings in in vivo tests (rats). However, clinical trials are crucial for the probation of the medicinal and nutraceutical properties of SBH. Despite this, there are still no general norms and/or quality standards for this type of honey. The information summarized in this review is important to add value to this little-consumed food, providing helpful information to spread knowledge about its benefits, assisting future studies, and raising perspectives for its recognition as a functional food. Furthermore, it may encourage the creation of standard quality for the production and marketing of SBH. PRACTICAL APPLICATIONS: Previous studies have already summarized the chemical profile and physicochemical properties of stingless bee honey (SBH) and its potential health properties. However, no study has performed an overview of the potential nutraceutical and medicinal effects of SBH, presenting results from in vitro and in vivo investigations. Therefore, this review is the first study to overview the potential nutraceutical and medicinal effects of SBH, showing results of in vitro/in vivo health-promoting effects. The bioactivity of SBH is related to bee species and floral sources. The SBH has anti-inflammatory, antimicrobial, anti-diabetic, and antioxidant in vitro activity. It has also shown hypolipidemic effects and protection from injuries caused by dyslipidemia in rats.

Acute-phase proteins and diabetic indices in type 2 diabetesmellitus and their predictive values

Context Diabetes mellitus consists of a group of metabolic disorders that share a common phenotype of hyperglycemia. Chronic systemic subclinical inflammation has also been identified as a driving force for insulin resistance, metabolic syndrome, and type 2 diabetes mellitus (T2DM). Iron overload is a risk factor for diabetes. The link between iron and diabetes was first recognized in pathologic conditions such as hereditary hemochromatosis and thalassemia. Aims The research is approached with the idea of detecting any association between basal C-reactive protein (CRP) or serum ferritin levels with one of most valuable diabetic indices which is HbA1c as a clinical trial to establish an inflammatory role responsible to develop insulin resistance. Settings and design This comparative cross-sectional study was conducted on T2DM patients who attended the Outpatient Department at Assiut University Hospitals. Patients and methods Totally, 67 participants were enrolled for the study, out of which 47 were cases and 20 were age and sex controls. Fasting blood sugar, postprandial blood sugar, HbA1c, serum ferritin, and CRP were estimated. Statistical analysis used Statistical Package for the Social Sciences software version 19.0 was used for statistical analysis. Results There is statistically significant decrease in serum ferritin level after 3 months of follow-up and glucose control, which means that serum ferritin would decrease with reducing serum fasting blood sugar and postprandial BS (P Conclusion From our study point of view, persistent elevated serum ferritin levels in patients with T2DM tend to exhibit a certain degree of inflammation that, in one way or another, is likely to increase their risk of developing cardiovascular complications or may be have a role in the development of insulin resistance.