Levels Of Systemic Inflammation Research Articles

GALECTIN-3 AS A BIOMARKER OF CARDIOVASCULAR FIBROSIS IN RHEUMATOID ARTHRITIS PATIENTS WITH SUPPRESSED INFLAMMATION

Objective: Galectin-3 has emerged as a biomarker of cardiovascular fibrosis in high cardiovascular risk individuals. Increased levels of galectin-3 have been previously reported in patients with immune-mediated inflammatory diseases. Nevertheless, it has not been elucidated whether this finding is secondary to the presence of cardiovascular comorbidities and/or the pronounced inflammatory burden of the populations most commonly included in relevant studies. We investigated whether patients with rheumatoid arthritis (RA), a disease characterized by excess cardiovascular risk, present increased levels of galectin-3 even in the absence of cardiovascular comorbidities and pronounced inflammatory load. Design and method: We recruited patients with RA who presented low levels of systemic inflammation and were free from cardiovascular comorbidities including hypertension, diabetes mellitus and established CVD, and non-RA individuals matched for age, sex and office systolic/diastolic blood pressure. Galectin-3 and high-sensitivity C-reactive protein (hsCRP) were measured with enzyme-linked immunosorbent assay using commercially available kits. Carotid-femoral pulse wave velocity (PWV) was estimated with applanation tonometry (SphygmoCor AtCor Medical, Sidney, Australia). Results: In a total of 48 individuals (mean age 53.4±8.6 years, 83.3% females), hsCRP did not significantly differ between RA patients (n = 24) and controls (n = 24) [2.0 (5.6) vs 1.7 (2.4) μg/ml), p = 0.718]. By contrast, significantly increased levels of galectin-3 were observed in the RA group compared to controls [6.9 (6.7) vs 4.6 (4.7)] ng/dl, p = 0.015]. Galectin-3 was associated with PWV (r = 0.390, p = 0.009), but this association was rendered non-significant after adjustment for age and sex. Conclusions: Patients with RA present increased levels of galectin-3. These findings were observed even in a meticulously selected population such as ours, characterized by suppressed inflammation and the absence of hypertension and cardiovascular comorbidities. Further studies are warranted to investigate the potential role of galectin-3 as a potential prognostic marker or therapeutic target in patients with immune-mediated inflammatory diseases.

ASSESSMENT OF ENDOTHELIAL FUNCTION BY FLOW-MEDIATED DILATION IN WELL-CONTROLLED PATIENTS WITH RHEUMATOID ARTHRITIS

Objective: Endothelial dysfunction is considered as the primary pathophysiological process towards the development of cardiovascular disease (CVD). Patients with rheumatoid arthritis (RA) are at increased CVD risk attributed to the synergistic effect of chronic inflammation and traditional cardiovascular risk factors. However, it is uncertain whether endothelial function in RA is impaired even in the absence of cardiovascular comorbidities and pronounced inflammatory load. Design and method: Patients with RA who presented low levels of systemic inflammation and were free from cardiovascular comorbidities including hypertension, diabetes mellitus and established CVD, were studied. Non-RA individuals matched for age, sex and office systolic/diastolic blood pressure comprised the control group. Endothelial function was evaluated with the gold-standard flow-mediated dilation (FMD) in the brachial artery (Aloka ProSound A7 Ultrasound System). Results: A total of 22 female individuals were included in the study, of whom 10 were RA patients aged 57±13 years and 12 healthy volunteers aged 56±9 years. All patients with RA were at remission or low disease activity. Traditional CVD risk factors (age, systolic and diastolic blood pressure, smoking, body mass index and lipids) did not significantly differ between RA patients and controls. By contrast, significantly lower FMD values were observed in the RA group compared to controls [6.4 (5.0) vs 11.8 (5.2) %, p = 0.003]. The association between RA and FMD levels remained significant even after adjustment for age and systolic blood pressure (beta = 0.562, p = 0.009). Conclusions: Endothelial dysfunction is present in RA, even in a population characterized by the absence of hypertension and cardiovascular comorbidities and with relatively low systemic inflammatory burden. Further studies are warranted to verify the findings of this pilot study and delineate the role of endothelial dysfunction as a potential prognostic marker or therapeutic target.

The relationship between sleep and salivary and serum inflammatory biomarkers in adolescents.

Poor sleep behavior can trigger an inflammatory response and contribute to the development of inflammatory diseases. Cytokines can act as indicators of inflammation and may precede the onset of inflammatory diseases. This study aimed to determine the association between sleep timing parameters (bedtime, sleep duration, sleep debt, and social jetlag) and the levels of nine serum and salivary inflammatory and metabolic biomarkers. Data were collected from 352 adolescents aged 16-19 years enrolled in Kuwait's public high schools. The levels of C-reactive protein (CRP), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), vascular endothelial growth factor (VEGF), monocyte chemoattractant protein-1 (MCP-1), adiponectin, leptin, and insulin were measured from saliva and serum samples. We conducted mixed-effect multiple linear regression modeling to account for the school variable as a random effect to assess the relationship between the sleep variables and salivary and serum biomarkers. Mediation analysis was conducted to check if BMI was a mediator between bedtime and the biomarkers. There was a statistically significant elevation in serum IL-6 level associated with later bedtime (0.05 pg./mL, p = 0.01). Adolescents with severe sleep debt of ≥2 h had an increase in salivary IL-6 biomarker levels (0.38 pg./mL, p = 0.01) compared to those who had sleep debt of <1 h. Adolescents with sleep debt of ≥2 h had significantly higher levels of serum CRP (0.61 μg/mL, p = 0.02) than those without sleep debt. Additionally, we found that the inflammatory biomarkers (CRP, IL-6, IL-8, IL-10, VEGF, and MCP-1) and metabolic biomarkers (adiponectin, leptin, and insulin) had more statistically significant associations with the bedtime variables than with sleep duration variables. CRP, IL-6, and IL-8 were associated with sleep debt, and IL-6, VEGF, adiponectin, and leptin levels were associated with social jetlag. BMIz was a full mediator in the relationship between late bedtime and increased serum levels of CRP, IL-6, and insulin. Adolescents who go to bed at or later than midnight had dysregulated levels of salivary and serum inflammatory biomarkers, suggesting that disrupted circadian rhythm can trigger higher levels of systemic inflammation and potentially exacerbate chronic inflammation and the risk of metabolic diseases.

An impaired pituitary–adrenal signalling axis in stable cirrhosis is linked to worse prognosis

Background & AimsInadequate adrenal function has been described in patients with cirrhosis. We investigated (i) the pituitary–adrenal axis at different clinical stages and (ii) the clinical impact of decreased serum cortisol levels in stable patients with advanced chronic liver disease (ACLD). MethodsWe included 137 outpatients with ACLD undergoing hepatic venous pressure gradient (HVPG) measurement in the prospective VICIS study (NCT03267615). Patients were stratified into six clinical stages: S0: subclinical portal hypertension (PH) (HVPG 6–9 mmHg), S1: clinically significant PH (HVPG ≥10 mmHg) without varices, S2: presence of varices, S3: previous variceal bleeding, S4: previous non-bleeding decompensation, and S5: further decompensation. ResultsFifty-one patients had compensated ACLD (S0: n = 13; S1: n = 12; S2: n = 26), whereas 86 patients had decompensated ACLD (S3: n = 7; S4: n = 46; S5: n = 33). Serum total cortisol (t-Cort) showed a strong correlation with estimated serum free cortisol (f-Cort; Spearman’s ρ: 0.889). With progressive clinical stage, median ACTH levels (from S0: 44.0 pg/ml to S5: 20.0 pg/ml; p = 0.006), t-Cort (from S0: 13.9 μg/dl to S5: 9.2 μg/dl; p = 0.091), and cortisol binding globulin (from S0: 49.3 μg/ml to S5: 38.9 μg/ml; p <0.001) decreased, whereas f-Cort (p = 0.474) remained unchanged. Lower t-Cort levels independently predicted bacterial infections (asHR: 1.11; 95% CI: 1.04–1.19; p = 0.002), further decompensation (asHR: 1.08; 95% CI: 1.02–1.12; p = 0.008), acute-on-chronic liver failure (ACLF; asHR: 1.11; 95% CI: 1.04–1.19; p = 0.002), and liver-related death (asHR: 1.09; 95% CI: 1.01-1.18; p = 0.045). ConclusionsThe pituitary–ACTH–adrenal–cortisol axis is progressively suppressed with increasing severity of cirrhosis. Lower t-Cort is an independent risk factor for bacterial infections, further decompensation of ACLF, and liver-related mortality—even in stable outpatients with cirrhosis. Clinical trial numberVienna Cirrhosis Study (VICIS; NCT: NCT03267615). Impact and ImplicationsIn a cohort of stable outpatients, we observed progressive suppression of the pituitary–adrenal axis with increasing clinical stage of advanced chronic liver disease (ACLD). Increased levels of bile acids and systemic inflammation (assessed by interleukin-6 levels) could be involved in this suppression. Serum total cortisol (t-Cort) was strongly correlated with serum free cortisol (f-Cort) and lower t-Cort levels were independently associated with a higher risk of adverse clinical outcomes, including bacterial infections, further decompensation, acute-on-chronic liver failure, and liver-related death.

Neuropeptide Y potentiates T-Lymphocyte inflammation after psychological trauma

Post-traumatic stress disorder (PTSD) is a psychiatric disorder characterized by severe behavioral alterations, but also demonstrates elevated levels of systemic inflammation, sympathoexcitation, and a potentiated risk for autoimmune and cardiovascular diseases. These physiological changes suggest perturbations to the immune system, however, the signaling mechanisms linking psychological trauma to the immune system are not well understood. Utilizing a pre-clinical mouse model of PTSD known as repeated social defeat stress (RSDS), we previously demonstrated that psychological trauma causes robust T-lymphocyte-driven inflammation in the spleen as evidenced by increased pro-inflammatory cytokine production (primarily interleukin 17A, IL-17A), inflammatory polarization, and enhanced mitochondrial reactive oxygen species. Moreover, targeted denervation of the spleen was able to completely ablate this T-lymphocyte inflammatory response after psychological trauma, suggesting the signal was autonomic and neural in nature. Given that the splenic nerve possesses only sympathetic neurons (no direct parasympathetic innervation), we hypothesized that psychological trauma mediates splenic T-lymphocyte inflammation via enhanced release of sympathetic neurotransmitters. To test this, we first exposed naïve primary T-lymphocytes to various sympathetic catecholamines, including dopamine, norepinephrine, and epinephrine. Contrary to our original hypothesis, we observed no significant changes in IL-17A expression or mitochondria reactive oxygen species. Next, we assessed the physiological response of naïve T-lymphocytes exposed to neuropeptide Y (NPY) given its role in both sympathoexcitation as well as in PTSD. Interestingly, naïve T-lymphocytes treated with NPY also demonstrated no effect, but when NPY was given in combination of norepinephrine, we observed both an increase in IL-17A gene expression (~2 fold) and intracellular redox (~2 fold). To further investigate this effect, we examined NPY levels in our RSDS mouse model over-time. Circulating NPY levels spiked immediately after only one day of RSDS (~4.5 fold, p=0.0317) but steadily declined over the remaining 10 day psychological trauma induction. Intriguingly, NPY levels were strongly correlated with both circulating IL-17A and T-lymphocyte mitochondrial reactive oxygen species levels after RSDS, supporting our in vitro observations. Overall, these data suggest NPY may be playing a critical role in shaping the inflammatory milieu after psychological trauma, which may enhance the likelihood of inflammatory comorbidities. NIH R01HL158521 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Dl-3-n-butylphthalide improves intestinal microcirculation disorders in septic rats by regulating the PI3K/AKT signaling pathway and autophagy.

Sepsis has complex pathophysiological mechanisms that bring new challenges in the treatment of sepsis at a time when the intestinal microcirculation in sepsis is receiving increasing attention. Dl-3-n-butylphthalide (NBP), which is a drug that can improve multiorgan ischemic diseases, is also worth examining to improve the intestinal microcirculation in sepsis. In this study, male Sprague-Dawley rats were divided into the sham group (n=6), CLP group (n=6), NBP group (n=6) and NBP+LY294002 group (n=6). The rat model of severe sepsis was established by cecal ligation and puncture (CLP). Abdominal wall incisions and sutures were performed in the first group, and CLP was performed in the latter three groups. Normal saline/NBP/NBP+LY294002 solution was injected intraperitoneally 2h or 1h before modeling. Hemodynamic data (blood pressure and heart rate) were recorded at 0, 2, 4 and 6h. Sidestream dark field (SDF) imaging and the Medsoft System were used to observe the intestinal microcirculation of rats and obtain data at 0, 2, 4, and 6h. Six hours after the model was established, the serum levels of TNF-α and IL-6 were measured to evaluate the level of systemic inflammation. Pathological damage to the small intestine was evaluated by electron microscopy and histological analysis. The expression levels of P-PI3K, PI3K, P-AKT, AKT, LC3 and p62 in the small intestine were analyzed by Western blotting. The expressions of P-PI3K, P-AKT, LC3 and P62 in small intestine were detected by immunohistochemical staining. NBP improved intestinal microcirculation disturbances in septic rats, alleviated the systemic inflammatory response, reduced the destruction of the small intestinal mucosa and the disruption of microvascular endothelial cells, and alleviated autophagy in vascular endothelial cells. NBP increased the ratio of P-PI3K/total PI3K, P-AKT/total AKT, and P62/β-actin and decreased the ratio of LC3 II/LC3 I. NBP ameliorated intestinal microcirculation disturbances and the destruction of small intestinal vascular endothelial cells in septic rats by activating the PI3K/Akt signaling pathway and regulating autophagy.

The pro-inflammatory response to influenza A virus infection is fueled by endothelial cells.

Morbidity and mortality from influenza are associated with high levels of systemic inflammation. Endothelial cells play a key role in systemic inflammatory responses during severe influenza A virus (IAV) infections, despite being rarely infected in humans. How endothelial cells contribute to systemic inflammatory responses is unclear. Here, we developed a transwell system in which airway organoid-derived differentiated human lung epithelial cells were co-cultured with primary human lung microvascular endothelial cells (LMECs). We compared the susceptibility of LMECs to pandemic H1N1 virus and recent seasonal H1N1 and H3N2 viruses and assessed the associated pro-inflammatory responses. Despite the detection of IAV nucleoprotein in LMEC mono-cultures, there was no evidence for productive infection. In epithelial-endothelial co-cultures, abundant IAV infection of epithelial cells resulted in the breakdown of the epithelial barrier, but infection of LMECs was rarely detected. We observed a significantly higher secretion of pro-inflammatory cytokines in LMECs when co-cultured with IAV-infected epithelial cells than LMEC mono-cultures exposed to IAV. Taken together, our data show that LMECs are abortively infected by IAV but can fuel the inflammatory response.

Applications of Lifestyle Medicine in the Management of Hidradenitis Suppurativa: A Literature Review

Introduction: Hidradenitis Suppurativa (HS) is an inflammatory skin condition characterized by the formation of pus-discharging abscesses under the skin in axillary, inguinal, gluteal, and perianal body sites. Modifiable risk factors such as obesity and smoking have been associated with exacerbation of HS severity. Despite this, research on the clinical application of lifestyle medicine for the improvement of HS symptoms remains scarce. The goal of this review was to evaluate benefits of lifestyle medicine in improving HS symptoms. Methods: A total of 8 articles that examined the associations of smoking cessation, diet modification and weight-loss with HS improvement were investigated. These publications came from cohort studies and intervention trials and were appraised using the Critical Appraisal Skills Programme checklist. Results: HS patients following a brewer’s yeast free diet reported significant decrease in HS abscesses and a severe immune reaction to the substance. The Paleolithic and Anti-Inflammatory diet alongside the reduction of foods high in carbohydrates, sugars, and dairy were also associated with improved HS symptoms. Zinc gluconate supplementation demonstrated improved inflammatory nodules and decreased boil count in patients. No correlation between HS and weight-loss or smoking cessation were observed. Discussion: Based on the results, eating patterns resembling the Paleolithic and Anti-Inflammatory diets may lower levels of systemic inflammation in HS patients by reducing the production of TNF- α cytokines present in HS lesions. Increased levels of antioxidants paired with fewer levels of pro-oxidant properties present in both diets are suggested to help improve the course of the disease in some patients. Conclusion: Further intervention trials and cohort studies must be conducted investigating the effects of smoking cessation, weight-loss and diet in HS severity to determine the integration of lifestyle medicine pillars in clinical practice. No correlations between smoking cessation and weight-loss with HS were established due to limited clinical evidence. Intervention trials beyond exclusionary diets need to be conducted to elucidate the role of nutrition in HS exacerbation and alleviation.

Correlation between mismatch repair and survival of patients with gastric cancer after 5-FU-based adjuvant chemotherapy.

Almost all adjuvant chemotherapy regimens for gastric cancer recommended by guidelines are fluorouracil (5-FU) based, and 5-FU-based adjuvant chemotherapy plays an important role in reducing the recurrence of gastric cancer after surgery. However, the effect of mismatch repair (MMR) status on survival after 5-FU-based adjuvant chemotherapy in patients with gastric cancer remains controversial. We prospectively included patients with gastric cancer who underwent radical gastrectomy between March 14, 2017 and September 30, 2021. The included patients received 5-FU-based adjuvant chemotherapy or surgery alone. The MMR status of patients was divided into MMR proficient (pMMR) and MMR defective (dMMR) according to four MMR proteins. Peripheral blood was collected for systemic inflammation analysis. The main purpose of this study was to analyze the effect of MMR status on survival after 5-FU-based adjuvant chemotherapy in patients with gastric cancer. We also analyzed the differences in systemic inflammation levels in different MMR status and their impact on survival. A total of 479 patients were enrolled, with a median follow-up period of time was 36months. In the surgery alone group, dMMR gastric cancer had better disease-free survival (DFS) (hazard ratio [HR] = 4.33, 95% confidence interval [CI] 1.25-15.02, p = 0.02) than pMMR, and in the adjuvant chemotherapy group, there was no significant difference in DFS (HR = 1.16, 95% CI 0.65-2.07, p = 0.61) between dMMR and pMMR gastric cancer. The same results were seen for overall survival (OS). In addition, the result show that in the dMMR group, there was no difference in DFS (HR = 1.62, 95% CI 0.46-5.77, p = 0.45) between patients receiving adjuvant chemotherapy and those receiving surgery alone. In the pMMR group, the DFS values (HR = 0.59, 95%CI 0.35-0.99, p = 0.04) of patients receiving adjuvant chemotherapy were better than those of patients receiving surgery alone, and the same results were observed for OS. In addition, among pMMR patients, patients with a low platelet lymphocyte ratio (PLR) who received 5-FU adjuvant chemotherapy and those with a low neutrophil lymphocyte ratio (NLR) and systemic immune-inflammation index (SII) who received surgery alone had better DFS and OS. To our knowledge, this is the first prospective study to specifically explore the correlation between MMR and survival of patients with gastric cancer after 5-FU-based adjuvant chemotherapy. The results showed that gastric cancer patients with pMMR can benefit from 5-FU-based adjuvant chemotherapy, but those with dMMR cannot. Among pMMR patients, lower PLR and SII values with surgery alone and lower NLRs in those receiving 5-FU-based adjuvant chemotherapy were associated with higher DFS and OS.

Enhanced mitochondrial oxidative metabolism in peripheral blood mononuclear cells is associated with fatty liver in obese young adults

Systemic inflammation underlies the association between obesity and nonalcoholic fatty liver disease (NAFLD). Here, we investigated functional changes in leukocytes’ mitochondria in obese individuals and their associations with NAFLD. We analyzed 14 obese male Japanese university students whose body mass index was > 30 kg/m2 and 15 healthy age- and sex-matched lean university students as controls. We observed that the mitochondrial oxidative phosphorylation (OXPHOS) capacity with complex I + II-linked substrates in peripheral blood mononuclear cells (PBMCs), which was measured using a high-resolution respirometry, was significantly higher in the obese group versus the controls. The PBMCs’ mitochondrial complex IV capacity was also higher in the obese subjects. All of the obese subjects had hepatic steatosis defined by a fatty liver index (FLI) score ≥ 60, and there was a positive correlation between their FLI scores and their PBMCs’ mitochondrial OXPHOS capacity. The increased PBMCs’ mitochondrial OXPHOS capacity was associated with insulin resistance, systemic inflammation, and higher serum levels of interleukin-6 in the entire series of subjects. Our results suggest that the mitochondrial respiratory capacity is increased in the PBMCs at the early stage of obesity, and the enhanced PBMCs’ mitochondrial oxidative metabolism is associated with hepatic steatosis in obese young adults.

Stress induced proinflammatory adaptations: Plausible mechanisms for the link between stress and cardiovascular disease.

Initiating from Hans Selye's conceptualization of stress physiology, to our present understanding of allostatic load as the cumulative burden of chronic psychological stress and life events, investigators have sought to identify the physiological mechanisms that link stress to health and disease. Of particular interest has been the link between psychological stress and cardiovascular disease (CVD), the number one cause of death in the United States. In this regard, attention has been directed toward alterations in the immune system in response to stress that lead to increased levels of systemic inflammation as a potential pathway by which stress contributes to the development of CVD. More specifically, psychological stress is an independent risk factor for CVD, and as such, mechanisms that explain the connection of stress hormones to systemic inflammation have been examined to gain a greater understanding of the etiology of CVD. Research on proinflammatory cellular mechanisms that are activated in response to psychological stress demonstrates that the ensuing low-grade inflammation mediates pathways that contribute to the development of CVD. Interestingly, physical activity, along with its direct benefits to cardiovascular health, has been shown to buffer against the harmful consequences of psychological stress by "toughening" the SAM system, HPA axis, and immune system as "cross-stressor adaptations" that maintain allostasis and prevent allostatic load. Thus, physical activity training reduces psychological stress induced proinflammation and attenuates the activation of mechanisms associated with the development of cardiovascular disease. Finally, COVID-19 associated psychological stress and its associated health risks has provided another model for examining the stress-health relationship.

Physical performance of patients with chronic kidney disease stage 5D and coronary heart disease

BACKGROUND. Assessment of physical performance in patients is usually based on the results of the 6-minute walk test, which is primarily associated with heart or respiratory failure. THE AIM: to analyze the results of the 6-minute walk test with clinical and laboratory parameters of patients with CKD 5D, including criteria for protein-energy malnutrition. PATIENTS AND METHODS. 67 people with CKD 5D were examined, including 42 men and 25 women, mean age 49.0 ± 14.9 and 57.2 ± 15.5 years, respectively, p = 0.036. The duration of RRT in men was 96.1 ± 80.3 months, in women 100.7 ± 66.1 months, p = 0.810. The diagnosis of coronary heart disease was established in 22 people, 7 of them had AMI. The muscle strength of the skeletal muscles was assessed using a hand dynamometer, the performance of the skeletal muscles – during a test with a 6-minute walk. All patients filled out food diaries, where they indicated the qualitative and quantitative composition of the food which they consumed for 3 days. RESULTS. Walking load was most easily tolerated by patients without clinical manifestations of CAD. Between patients with and without AMI in history, the number of points on the Borg scale was comparable and reached the maximum values. The highest concentration of C-reactive protein and the lowest concentration of serum albumin were observed in patients who had had AMI. Relationships were found between serum albumin with C-reactive protein and the results of the 6-minute walk test, as well as between the mass index of the left ventricular myocardium with the results of the 6-minute walk test. CONCLUSION. Left ventricular hypertrophy masks the clinical signs of reduced physical performance, but increases the risk of cardiovascular complications. The results of the 6-minute walk test in patients with CAD should be evaluated in more detail. A number of studies are needed to clarify how dietary recommendations should be modified depending on the level of systemic inflammation in CKD.

The Mediating Role of Systemic Inflammation in the Effects of Fetal Famine Exposure on Cardiovascular Disease in Adults: A Cohort Study

BackgroundA few studies have reported the association between famine exposure during fetal development and risk of CVD, but no mechanisms have been explored. ObjectivesThe objective of this study was to examine risk of CVD in adulthood after exposure to famine during the fetal stage and explore the mediating role of systemic inflammation. MethodsA total of 59,416 participants of the Kailuan Study without CVD were included. All participants were divided into 3 groups based on date of birth, including the unexposed group (1963–1974), the fetal-exposed group (1959–1962), and the childhood-exposed group (1949–1958). Systemic immune-inflammation index (SII) (neutrophils × platelets / lymphocytes) and systemic inflammatory response index (SIRI) (neutrophils × monocytes / lymphocytes) are 2 novel systemic inflammation indexes that represent the level of systemic inflammation. Time-weighted Cox regression was used to test the effect of famine exposure on risk of CVD, and a mediation model was used to calculate the role of systemic inflammation. ResultsDuring a median follow-up period of 12.36 (12.69, 13.16) y, a total of 3772 cases of CVD were documented. Compared with unexposed participants, the fetal-exposed group had an increased risk of CVD (HR: 1.19; 95% CI: 1.04, 1.38) and stroke (HR: 1.28; 95% CI: 1.09, 1.51) but not MI. No association was observed in the childhood-exposed group.In mediation analysis, SII mediated an estimated 24.43% of the association between fetal exposure and CVD (24.61% for stroke and 23.27% for MI). For SIRI, this percentage was 30.20% for CVD (29.94% for stroke and 31.25% of MI). ConclusionsFetal exposure to famine may increase risk of CVD in adulthood. Systemic inflammation may play an intermediary role in the effect of fetal famine exposure on CVD.

Diagnosis of coronary layered plaque by deep learning

Healed coronary plaques, morphologically characterized by a layered phenotype, are signs of previous plaque destabilization and healing. Recent optical coherence tomography (OCT) studies demonstrated that layered plaque is associated with higher levels of local and systemic inflammation and rapid plaque progression. However, the diagnosis of layered plaque needs expertise in OCT image analysis and is susceptible to inter-observer variability. We developed a deep learning (DL) model for an accurate diagnosis of layered plaque. A Visual Transformer (ViT)-based DL model that integrates information from adjacent frames emulating the cardiologists who review consecutive OCT frames to make a diagnosis was developed and compared with the standard convolutional neural network (CNN) model. A total of 237,021 cross-sectional OCT images from 581 patients collected from 8 sites were used for training and internal validation, and 65,394 images from 292 patients collected from another site were used for external validation. In the five-fold cross-validation, the ViT-based model provided better performance (area under the curve [AUC]: 0.860; 95% confidence interval [CI]: 0.855–0.866) than the standard CNN-based model (AUC: 0.799; 95% CI: 0.792–0.805). The ViT-based model (AUC: 0.845; 95% CI: 0.837–0.853) also surpassed the standard CNN-based model (AUC: 0.791; 95% CI: 0.782–0.800) in the external validation. The ViT-based DL model can accurately diagnose a layered plaque, which could help risk stratification for cardiac events.

Effects of hemicellulose on intestinal mucosal barrier integrity, gut microbiota, and metabolomics in a mouse model of type 2 diabetes mellitus.

Impaired gut barrier contributes to the progression of type 2 diabetes mellitus (T2DM), and the gut microbiota and metabolome play an important role in it. Hemicellulose, a potential prebiotics, how its supplementation impacted the glucose level, the impaired gut barrier, and the gut microbiota and metabolome in T2DM remained unclear. In this study, some mice were arranged randomly into four groups: db/db mice fed by a compositionally defined diet (CDD), db/db mice fed by a CDD with 10% and 20% hemicellulose supplementation, and control mice fed by a CDD. Body weight and fasting blood glucose levels were monitored weekly. The gut barrier was evaluated. Fresh stool samples were analyzed using metagenomic sequencing and liquid chromatography-mass spectrometry to detect gut microbiota and metabolome changes. Systemic and colonic inflammation were evaluated. Better glycemic control, restoration of the impaired gut barrier, and lowered systemic inflammation levels were observed in db/db mice with the supplementation of 10 or 20% hemicellulose. The gut microbiota showed significant differences in beta diversity among the four groups. Fifteen genera with differential relative abundances and 59 significantly different metabolites were found. In the db/db group, hemicellulose eliminated the redundant Faecalibaculum and Enterorhabdus. The increased succinate and ursodeoxycholic acid (UDCA) after hemicellulose treatment were negatively correlated with Bifidobacterium, Erysipelatoclostridium, and Faecalibaculum. In addition, hemicellulose reduced the colonic expressions of TLR2/4 and TNF-α in db/db mice. Hemicellulose may serve as a potential therapeutic intervention for T2DM by improving impaired intestinal mucosal barrier integrity, modulating gut microbiota composition, and altering the metabolic profile.

The Impact of Post COVID Rehabilitation on the Level of Systemic Inflammation in Patients with Post COVID Syndrome

Low-grade inflammation is a risk factor for adverse cardiovascular events including death from cardiovascular disease. Cardiovascular events are one of the most common manifestations of post covid syndrome, impacting the mortality in the post covid period.

Systemic Inflammation but not Oxidative Stress Is Associated with Physical Performance in Moderate Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) patients manifest muscle dysfunction and impaired muscle oxidative capacity, which result in reduced exercise capacity and poor health status. The aim of this study was to compare the physical performance, systemic inflammation, and oxidative stress of patients with moderate COPD, and to associate physical performance with inflammatory and oxidative stress plasma markers. Twenty CONTROL (n=10) and moderate COPD (n=10) patients participated in this study. Systematic inflammation and oxidative stress plasma markers, maximal aerobic capacity (VO2peak), and maximal isometric strength (MVIC) of the knee extensor (KE) muscles were measured. VO2peak was 31.3% greater in CONTROL compared to COPD (P=0.006). The MVIC strength of the KE was 43.9% greater in CONTROL compared to COPD (P=0.002). Tumor necrosis factor-alpha (TNF-α) was 79.6% greater in COPD compared to CONTROL (P<0.001). Glutathione peroxidase activity (GPx) activity was 27.5% lesser in COPD compared to CONTROL (P=0.05). TNF-α concentration was correlated with KE MVC strength (R=-0.48; P=0.045) and VO2peak (R=-0.58; P=0.01). Meanwhile, malondialdehyde (MDA) and GPx activity were not associated with KE strength or VO2peak (P=0.74 and P=0.14, respectively). COPD patients showed lesser muscle strength and aerobic capacity than healthy control individuals. Furthermore, patients with COPD showed greater systemic inflammation and lesser antioxidant capacity than healthy counterparts. A moderate association was evident between levels of systemic inflammation and physical performance variables.

Associations of Particulate Matter Exposures With Brain Gray Matter Thickness and White Matter Hyperintensities: Effect Modification by Low-Grade Chronic Inflammation.

Numerous studies have shown the effect of particulate matter exposure on brain imaging markers. However, little evidence exists about whether the effect differs by the level of low-grade chronic systemic inflammation. We investigated whether the level of c-reactive protein (CRP, a marker of systemic inflammation) modifies the associations of particulate matter exposures with brain cortical gray matter thickness and white matter hyperintensities (WMH). We conducted a cross-sectional study of baseline data from a prospective cohort study including adults with no dementia or stroke. Long-term concentrations of particulate matter ≤ 10 µm in diameter (PM10) and ≤ 2.5 µm (PM2.5) at each participant's home address were estimated. Global cortical thickness (n = 874) and WMH volumes (n = 397) were estimated from brain magnetic resonance images. We built linear and logistic regression models for cortical thickness and WMH volumes (higher versus lower than median), respectively. Significance of difference in the association between the CRP group (higher versus lower than median) was expressed as P for interaction. Particulate matter exposures were significantly associated with a reduced global cortical thickness only in the higher CRP group among men (P for interaction = 0.015 for PM10 and 0.006 for PM2.5). A 10 μg/m3 increase in PM10 was associated with the higher volumes of total WMH (odds ratio, 1.78; 95% confidence interval, 1.07-2.97) and periventricular WMH (2.00; 1.20-3.33). A 1 μg/m3 increase in PM2.5 was associated with the higher volume of periventricular WMH (odds ratio, 1.66; 95% confidence interval, 1.08-2.56). These associations did not significantly differ by the level of high sensitivity CRP. Particulate matter exposures were associated with a reduced global cortical thickness in men with a high level of chronic inflammation. Men with a high level of chronic inflammation may be susceptible to cortical atrophy attributable to particulate matter exposures.

Алгоритм клинико-иммунологической диагностики вариантов патологических иммунофенотипов, ассоциированных с атипичными хроническими активными герпесвирусными инфекциями

An imbalance of different parts of the antiviral immune response system associated with deficits of type I and type II interferons (IFN) is commonly observed in atypical chronic active herpesvirus infections (ACA-HVI). Objective. To develop a clinical and immunological diagnostic algorithm for detecting the pathological immunophenotypes of ACA-HVI. Patients and methods. A total of 263 male and female patients aged 23–70 years with ACA-HVI were examined. The study included the following methods for herpesvirus detection: serodiagnostics and a real-time polymerase chain reaction (RT-PCR). The cytokine profile (interleukins IL-1β, IL1Ra, IL-6, IL-17, TNFα) and the IFN system were analyzed by an enzyme-linked immunosorbent assay (ELISA). The study was approved by the Ethics Committee, and an informed consent was obtained from all patients. Results. To assess the clinical signs of immunosuppression in patients with ACA-HVI, we formulated de novo clinical criteria of class I and class II and used them in the study. Based on the three main pathological immunophenotypes identified, we created an algorithm for the clinical and laboratory diagnosis of ACA-HVI. It was shown that determining the serum levels of cytokines IL-1β, IL-6, IL1Ra and tumor necrosis factor-α is the most optimal option to assess the level of systemic inflammation and neuroimmune inflammation. Conclusion. The findings of the immunological study allowed us to identify variants of pathological immunophenotypes, which are characterized by the variability of the detected disorders. The revealed disorders in the immune system and IFN system in each pathological immunophenotype are associated with certain ACA-HVI manifestations, typical of study groups 1, 2, 3. Key words: herpesvirus infections, neutrophil granulocytes, interferon system, pathological immunophenotypes

Cluster analysis identifies six clinical subtypes of hidradenitis suppurativa characterised by distinct comorbidities, inflammatory and metabolic profiles, patient‐reported outcomes and treatment patterns

AbstractBackgroundSub‐classification of hidradenitis suppurativa (HS) may allow for a better understanding of disease aetiology and disease burden, and eventually permit a more personalised treatment for patients.ObjectiveTo identify patient subtypes of HS based on comorbidity patterns and clinical characteristics, and to examine their inflammatory and metabolic blood profiles and associated levels of experienced distress, pain, quality of life, employment status and prescribed treatments.MethodsCluster analysis of clinical data from consecutive, newly referred adult HS patients attending a dermatological hospital department.ResultsA total of 534 patients (338 women and 196 men) with a mean age of 40.5 years (SD = 13.7) were included; 35.4% had Hurley stage I, 50.4% had Hurley stage II, and 14.8% had Hurley stage III. In total, six disease subtypes were identified: ‘female subtype’ (n = 182, 34.1%), ‘familial subtype’ (n = 144, 27.0%), ‘diabetes subtype’ (n = 107, 20.0%), ‘psychiatric disease subtype’ (n = 49, 9.2%), ‘Crohn's disease subtype’ (n = 29, 5.4%) and ‘asthma subtype’ (n = 23, 4.3%). Patients with ‘Crohn's disease subtype’ and ‘diabetes subtype’ had highest levels of systemic inflammation (C‐reactive protein, erythrocyte sedimentation rate, leucocytes and neutrophils), blood glucose and lipids (triglycerides), p &lt; 0.001. The highest boil‐associated pain score, p &lt; 0.001, overall disease‐related distress, p = 0.008 and lowest quality of life, p = 0.015, was reported by patients with ‘familial subtype’, whereas highest rates of unemployment were observed among patients with ‘diabetes subtype’ and ‘psychiatric disease subtype’, p &lt; 0.001. Treatment patterns differed significantly between the subtypes, with biologics being most often prescribed to patients with ‘Crohn's disease subtype’ (21.1%), p &lt; 0.001.ConclusionThis study identified six subtypes of HS based on comorbidity patterns, clinical characteristics, blood profiles, patient‐reported outcomes and treatment patters, supporting the concept of heterogeneity within HS.