Non-inflammatory Group Research Articles

Correlation between neutrophil to lymphocyte ratio and C-reactive protein in diverse disease states in hospitalized patients.

This study aims to find if any significant correlation exists between C-reactive protein and Neutrophil to Lymphocyte Ratio as an indirect measure of inflammation. We selected 983 patients with any inflammatory condition who presented to a tertiary care hospital and were admitted in medical wards or Intensive Care Units (ICUs) of KRL Hospital Islamabad from December 2021 to December 2022. The study was a cross sectional study and convenience sampling was done. The patients were categorized into five groups depending upon their pathophysiology. Kolmogorov Smirnov test was used to assess the normality of the data, and Spearman's coefficient was used to calculate the correlation between NLR and CRP. A total of 983 patients were included. Mean CRP and NLR levels were 89.9±3.2 and 7.06±0.24, respectively. There was a significant positive correlation between CRP-NLR in the infectious, non-infectious non-inflammatory, and malignancy groups (0.420, 0.381, 0.642, p <0.01), and inflammatory group (0.322, p <0.05), and no correlation with chronic diseases. A significant correlation was shown to exist between CRP and NLR in patients with malignancies, non-infective non-inflammatory, inflammatory, and infective conditions and can therefore be used interchangeably to detect the presence of inflammation. Further exploration of these associations may contribute to a more nuanced understanding of the intricate relationships between different markers of inflammation and response to treatment.

Noninflammatory 97-amino acid High Mobility Group Box 1 derived polypeptide disrupts and prevents diverse biofilms

Bacterial biofilm communities are embedded in a protective extracellular matrix comprised of various components, with its' integrity largely owed to a 3-dimensional lattice of extracellular DNA (eDNA) interconnected by Holliday Junction (HJ)-like structures and stabilised by the ubiquitous eubacterial DNABII family of DNA-binding architectural proteins. We recently showed that the host innate immune effector High Mobility Group Box 1 (HMGB1) protein possesses extracellular anti-biofilm activity by destabilising these HJ-like structures, resulting in release of biofilm-resident bacteria into a vulnerable state. Herein, we showed that HMGB1's anti-biofilm activity was completely contained within a contiguous 97 amino acid region that retained DNA-binding activity, called 'mB Box-97'. We engineered a synthetic version of this 97-mer and introduced a single amino acid change which lacked any post-translational modifications, and tested its activity independently and in combination with a humanised monoclonal antibody that disrupts biofilms by the distinct mechanism of DNABII protein sequestration. mB Box-97 disrupted and prevented biofilms, including those formed by the ESKAPEE pathogens, and importantly reduced measurable proinflammatory activity normally associated with HMGB1 in a murine lung infection model. Herein, we discuss the value of targeting the ubiquitous eDNA-dependent matrix of biofilms via mB Box-97 used singly or in a dual host-augmenting/pathogen-targeted cocktail to resolve bacterial biofilm infections. This work was supported by NIH/NIDCD R01DC011818 to L.O.B. and S.D.G. and NIH/NIAID R01AI155501 to S.D.G.

Efficacy and safety of ketamine for pediatric and adolescent super-refractory status epilepticus and the effect of cerebral inflammatory conditions

ObjectiveTo investigate the short-term benefits and adverse effects of ketamine in the treatment of pediatric and adolescent super-refractory status epilepticus (SRSE), with a focus on the inflammatory etiology. MethodsThis retrospective observational cohort study included a consecutive series of 18 pediatric to adolescent patients with SRSE admitted between 2008 and 2023 and treated with ketamine. Seizure frequency per hour before and after ketamine administration and response rate were calculated. Neurological decline, catecholamine administration, and adverse effects were also assessed. The patients were divided into inflammatory and non-inflammatory etiology groups. ResultsThe median age at SRSE onset was 1 year 5 months (range: 11 days-24 years), and 78% of the patients were male individuals. The median duration of treatment was 7.5 days (interquartile range: 2.8–15.5 days). Fifteen (83%) patients achieved >50% seizure reduction. The median seizure frequency before and after ketamine treatment was 5.9 and 0.9, respectively, showing a significant reduction in seizure frequency (p < 0.0001). Ten patients had inflammatory etiologies including bacterial meningitis (n = 2), viral encephalitis (n = 3), and febrile infection related epilepsy syndrome (n = 5). The inflammatory etiology group required a longer treatment duration (p = 0.0453) and showed lower seizure reduction (p = 0.0264), lower response rate (p = 0.0044), and higher neurological decline (p = 0.0003) than the non-inflammatory etiology group. Three (17%) patients experienced transient adverse events requiring intervention within 24 h of initiating ketamine administration. ConclusionsKetamine administration was associated with fewer serious adverse events and a reduced seizure frequency. Additionally, inflammatory conditions may weaken the efficacy of ketamine in patients with SRSE.

Efficacy of Homoeopathic Medicine in the Treatment of Osteoarthritis: A Systematic Review

Introduction: Osteoarthritis is a non-inflammatory heterogeneous group of degenerative joint disease. Homoeopathic remedy has encountered rheumatological problems very well. The main aim of this systemic review was to evaluate, specify and pinpoint the findings of all relevant individualised studies, thereby making the available evidence more accessible to decision-makers. Materials &amp; Methods: An intensive search of RCT clinical research manuscripts published between 2000 and 2022 was done under various databases and it ensured that all papers belong to peer-reviewed journals. The data items were extracted by following points like publication years, population, interventions and comparator (Verum vs control), outcomes, methods, overall result and manufacturer of Verum. The five-point Jadad scoring system was used to assess the methodological quality of the selected trials with increasing scores indicating a higher quality. Whereas the null hypothesis in this systematic review was that individualized homoeopathic medicine had no impact. Results: A total of 56 experimental and controlled clinical trials were identified to be screened. After complete screening, the proper number of eligible papers was 12 and finally selected 08 RCT with a double-blind peer-review published paper. The studies maintain total number of patients of 1,891 and after dropping out 1,628 patients eagerly continued. The 08 studies focused on knee joints and lower back pain. Conclusion: In this study, we clearly understood that homoeopathic combination formulas work well on OA. Individualized Homoeopathic remedy was not effective due to insufficient trial reports. It’s also noticeable that homoeopathic combinations may have some adverse drug reactions. So, we need proper evidence for individualized homoeopathic medicine to say it works properly. It’s our duty to uptake trial testing continuously for the betterment of homoeopathy. However, more research is needed to completely evaluate and validate the efficacy or inadequacy of therapy with OA.

Mechanism of intestinal injury induced by WNT2B high-expressed fibroblasts in Crohn's disease

Objective: To explore the mechanism of intestinal tissue damage induced by macrophages activated by WNT2B high-expressed fibroblasts. Methods: This study involved biological information analysis, pathological tissue research and cell experimental research. The biological information of the colon tissue from the children with inflammatory bowel disease in previous study was analyzed again with single-cell sequencing. The pathological tissues were collected by colonoscopy from 10 children with Crohn's disease treated in the Department of Gastroenterology of Guangzhou Women and Children's Medical Center from July 2022 to September 2022. According to the findings of colonoscopy, tissues with obvious inflammation or ulceration were classified as the inflammatory group, while tissues with slight inflammation and no ulceration were classified as the non-inflammatory group. HE staining was performed to observe the pathological changes of the colon tissues. Macrophage infiltration and CXCL12 expression were detected by immunofluorescence. In terms of cell experiments, fibroblasts transfected with WNT2B plasmid or empty plasmid were co-cultured with salinomycin treated or non-treated macrophages, respectively; the expression of proteins through Wnt classical pathway were detected by western blotting. Macrophages treated with SKL2001 were used as the experimental group, and those with phosphate buffer as the control group. The expression and secretion of CXCL12 in macrophages were detected by quantitative Real-time PCR and enzyme-linked immunosorbent assay (ELISA). T-test or rank sum test were used for the comparison between groups. Results: Single-cell sequencing analysis suggested that macrophages were the main cells in inflammatory bowel disease colon tissue, and there was interaction between WNT2B high-expressed fibroblasts and macrophages. HE staining of the 10 patients ((9.3±3.8) years old, 7 males and 3 females) showed that the pathological score of colon tissue in the inflammatory group was higher than that in the non-inflammatory group (4 (3, 4) vs. 2 (1, 2) points, Z=3.05, P=0.002). Tissue immunofluorescence indicated that the number of infiltrating macrophages in the inflammatory group was significantly higher than that in the non-inflammatory group under high power field of view (72.8±10.4 vs.8.4±3.5, t=25.10, P<0.001), as well as the number of cells expressing CXCL12 (14.0±3.5 vs. 4.7±1.9, t=14.68, P<0.001). In cell experiments, western blotting suggested an elevated level of glycogen synthase kinase-3β phosphorylation in macrophages co-cultured with fibroblast transfected with WNT2B plasmid, and salinmycin could reverse this change. Real-time PCR suggested that the transcription level of CXCL12 in the experimental group was higher than that in the control group (6.42±0.04 vs. 1.00±0.03, t=183.00, P<0.001), as well as the expression and secretion of CXCL12 by ELISA ((465±34) vs. (77±9) ng/L, t=13.21, P=0.006). Conclusion: WNT2B high-expressed fibroblasts can secrete WNT2B protein and activate the Wnt classical signaling pathway thus enhancing the expression and secretion of CXCL12 in macrophages, inducing the development of intestinal inflammation of Crohn's disease.

Intestinal Microbiota Reduction Followed by Fasting Discloses Microbial Triggering of Inflammation in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) synovitis is dominated by monocytes/macrophages with inflammatory patterns resembling microbial stimulation. In search of triggers, we reduced the intestinal microbiome in 20 RA patients (open label study DRKS00014097) by bowel cleansing and 7-day fasting (≤250 kcal/day) and performed immune monitoring and microbiome sequencing. Patients with metabolic syndrome (n = 10) served as a non-inflammatory control group. Scores of disease activity (DAS28/SDAI) declined within a few days and were improved in 19 of 20 RA patients after breaking the fast (median ∆DAS28 = -1.23; ∆SDAI = -43%) or even achieved remission (DAS28 < 2.6/n = 6; SDAI < 3.3/n = 3). Cytometric profiling with 46 different surface markers revealed the most pronounced phenomenon in RA to be an initially increased monocyte turnover, which improved within a few days after microbiota reduction and fasting. Serum levels of IL-6 and zonulin, an indicator of mucosal barrier disruption, decreased significantly. Endogenous cortisol levels increased during fasting but were insufficient to explain the marked improvement. Sequencing of the intestinal microbiota indicated that fasting reduced potentially arthritogenic bacteria and changed the microbial composition to species with broader metabolic capabilities. More eukaryotic, predominantly fungal colonizers were observed in RA, suggesting possible involvement. This study demonstrates a direct link between the intestinal microbiota and RA-specific inflammation that could be etiologically relevant and would support targeted nutritional interventions against gut dysbiosis as a causal therapeutic approach.

The Association of IFN-γ, TNF-α, and Interleukins in Bronchoalveolar Lavage Fluid with Lung Cancer: A Prospective Analysis.

Lung cancer is a leading cause of cancer-related mortality worldwide. Identifying novel diagnostic and prognostic biomarkers is essential for improving patient outcomes. This study aimed to investigate the predictive role of cytokines from bronchoalveolar lavage fluid (BALF) in lung cancer diagnosis and prognosis. A prospective study was conducted on 33 patients with suspected lung cancer, divided into inflammatory and non-inflammatory BALF groups. Inflammatory markers in BALF were assessed, and their association with lung cancer risk was analyzed using receiver operating characteristic (ROC) plot analysis, sensitivity and specificity percentages, and regression analysis. Statistically significant differences were observed between the inflammatory and non-inflammatory groups for several inflammatory markers, including IFN-gamma, IL-1b, IL-2, IL-6, IL-10, and IL-12p70. In the follow-up analysis, significant differences persisted for IFN-gamma, IL-1b, IL-2, IL-4, and IL-6. ROC plot analysis revealed that IL-12p70 had the highest area under the curve (AUC) value (0.702), followed by IL-2 (0.682), IL-6 (0.620), IL-4 (0.611), TNF-alpha (0.609), IL-10 (0.604), IL-1b (0.635), and IFN-gamma (0.521). IL-6 showed the highest sensitivity (73%), and IL-1b had the highest specificity (69%). Regression analysis demonstrated that IL-6 (cut-off = 25 pg/mL) and IL-12p70 (cut-off = 30 pg/mL) had the highest odds ratios for lung cancer risk, at 5.09 (95% CI: 2.38-9.24, p < 0.001) and 4.31 (95% CI: 1.85-8.16, p < 0.001), respectively. Cytokines from BALF, particularly IL-6 and IL-12p70, show potential as diagnostic and prognostic biomarkers for lung cancer. Further studies with larger cohorts are warranted to confirm these findings and elucidate the clinical implications of these markers in lung cancer management.

A dual covariant biomarker approach to Kawasaki disease, using vascular endothelial growth factor A and B gene expression; implications for coronary pathogenesis

IntroductionKawasaki disease (KD) is the most common vasculitis in young children, with coronary artery lesions (CALs) and coronary aneurysms (CAAs) being responsible for most KD-related deaths. ObjectiveWe hypothesized that Vascular Endothelial Growth Factors (VEGFs) are pivotal in KD inflammation and coronary artery lesions. This study assessed VEGF-A and VEGF-B gene expression (GE) as potential biomarkers in KD inflammation. Study designWe analyzed NCBI-GEO datasets, categorizing gene expression patterns as "inflammatory" or "non-inflammatory". We focused on TNF-, NFKB1, VEGF-A, and VEGF-B GEs. Datasets were filtered based on differential changes in TNF and NFKB1 levels to isolate those with inflammatory shifts. ResultsInflammatory datasets (GSE63881, GSE73464, and GSE68004) displayed elevated TNF, NFKB1, and VEGF-A GE levels during acute KD. VEGF-B GE exhibited a distinctive trend: an initial drop and subsequent rise during recovery, a pattern that was missing in the non-inflammatory group. The treatment response was also studied, with intravenous immunoglobulin (IVIG) responders showing significant downregulation of NFKB1 GE after treatment: GSE16797 [IVIG ± methylprednisolone; p = 8.6443-03], GSE48498 [IVIG; p = 6.618e-02, infliximab; p = 3.240e-03], and GSE18606 [IVIG; p = 3.518e-02]. Considering the similar binding of VEGF-A and VEGF-B to the VEGFR1 receptor, a co-variate and inverse relationship is suggested. ConclusionTemporal VEGF-A, VEGF-B, and GE changes show promise as new post-inflammatory biomarkers for KD. Novelty results with the biomarker approach, with the potential for a dual temporal relationship between VEGF-A and VEGF-A. A comprehensive exploration of VEGF-A and VEGF-B genes and protein analysis in KD is warranted to understand the functional aspects of these changes and how best to utilize the pattern of changes for therapeutic benefit.

Unveiling the causes of pericardial effusion in a contemporary case series of pericardiocentesis in Latin America

Pericardial effusions requiring pericardiocentesis have multiple causes that vary among geographical regions and health contexts. This procedure can be performed for diagnostic or therapeutic indications. The purpose of this study was to identify the principal causes of pericardial effusions and indications for pericardiocentesis, exploring differences among groups. This was a retrospective case series of patients who underwent pericardiocentesis for pericardial effusion in a single center in Latin America. Demographic, clinical, echocardiographic, and procedural variables were recorded and analyzed. The primary outcome was to determine the causes of pericardial effusions in these patients and the indication (diagnostic, therapeutic, or both). The results are presented in two groups (inflammatory and noninflammatory) according to the cause of the pericardial effusion. One hundred sixteen patients with pericardial effusion underwent pericardiocentesis. The median age was 58 years (IQR 46.2–70.7), and 50% were male. In the noninflammatory pericardial effusion group, there were 61 cases (53%), among which neoplastic pericardial effusion was the most frequent cause (n = 25, 40.9%). In the inflammatory group, there were 55 cases (47%), and the main cause was postpericardiectomy syndrome after cardiac surgery (n = 31, 56.4%). The principal indication for pericardiocentesis was therapeutic (n = 66, 56.8%). Large pericardial effusion without hemodynamic effect of cardiac tamponade was significantly more frequent in the inflammatory group (p = 0.03). In conclusion, the principal cause of pericardial effusion in patients who underwent pericardiocentesis was postpericardiectomy syndrome after cardiac surgery, followed by neoplastic pericardial effusion. Pericardiocentesis is mainly a therapeutic procedure.

Analytical performance of a canine ELISA monocyte chemoattractant protein-1 assay for use in cats and evaluation of circulating levels in normal weight and obese cats

BackgroundIn human and murine obesity, adipose tissue dwelling macrophages and adipocytes produce monocyte chemoattractant protein-1 (MCP-1) leading to systemic low-grade inflammation. The aim of the study was to validate a canine MCP-1 ELISA assay for use in cats and to investigate whether a difference in MCP-1 concentrations could be detected between: a) cats having normal or elevated circulating serum amyloid A (SAA) levels and b) normal weight and obese cats. Serum obtained from 36 client-owned cats of various breed, age and sex with normal (n = 20) to elevated SAA (n = 16) was used for the validation of the canine MCP-1 ELISA assay. As no golden standard exists for measurement of inflammation, circulating MCP-1 concentrations were compared to SAA measurements, as an indicator of systemic inflammation. Analytical precision, dilution recovery and detection limit were calculated. A possible correlation between MCP-1 concentrations and obesity related measures (body fat percentage (BF%), insulin sensitivity and cytokine expression) were investigated in another population of 73 healthy, lean to obese, neutered domestic short-haired cats.ResultsIntra- (2.7–4.1%) and inter-assay (2.2–3.6%) coefficient of variation and dilution recovery were acceptable, and the detection limit was 27.1 pg/mL. MCP-1 did not correlate with SAA, and there was no difference between the inflammatory (SAA > 20 mg/L) and non-inflammatory group, due to a marked overlap in MCP-1 concentrations. Circulating MCP-1 concentrations were unaffected by BF% (r2 = 2.7 × 10–6, P = 0.21) and other obesity-related markers.ConclusionsThe present canine ELISA assay seems to be able to measure circulating feline MCP-1. However, further studies are needed to determine its possible use for detecting inflammation in relation to disease processes or obesity-related low-grade inflammation in cats.

Critical view of safety in laparoscopic cholecystectomy: A prospective investigation from both cognitive and executive aspects.

BackgroundThe achievement rate of the critical view of safety during laparoscopic cholecystectomy is much lower than expected. This original study aims to investigate and analyze factors associated with a low critical view of safety achievement.Materials and MethodsWe prospectively collected laparoscopic cholecystectomy videos performed from September 2, 2021, to September 19, 2021, in Sichuan Province, China. The artificial intelligence system, SurgSmart, analyzed videos under the necessary corrections undergone by expert surgeons. Also, we distributed questionnaires to surgeons and analyzed them along with surgical videos simultaneously.ResultsWe collected 169 laparoscopic cholecystectomy surgical videos undergone by 124 surgeons, among which 105 participants gave valid answers to the questionnaire. Excluding those who conducted the bail-out process directly, the overall critical view of safety achievement rates for non-inflammatory and inflammatory groups were 18.18% (18/99) and 9.84% (6/61), respectively. Although 80.95% (85/105) of the surgeons understood the basic concept of the critical view of safety, only 4.76% (5/105) of the respondents commanded all three criteria in an error-free way. Multivariate logistic regression results showed that an unconventional surgical workflow (OR:12.372, P < 0.001), a misunderstanding of the 2nd (OR: 8.917, P < 0.05) and 3rd (OR:8.206, P < 0.05) criterion of the critical view of safety, and the don't mistake “fundus-first technique” as one criterion of the critical view of safety (OR:0.123, P < 0.01) were associated with lower and higher achievements of the critical view of safety, respectively.ConclusionsThe execution and cognition of the critical view of safety are deficient, especially the latter one. Thus, increasing the critical view of safety surgical awareness may effectively improve its achievement rate.

Long-term Follow-up of 254 Ceramic Coated Implant (CCI) Evolution Total Ankle Replacements.

The ceramic coated implant (CCI) Evolution was a third-generation implant design used in approximately 2000 total ankle replacements (TARs) between 2003 and 2016. Because this implant was abandoned, long-term follow-up studies are lacking. All patients undergoing TAR using a CCI prosthesis between 2004 and 2012 were included for analysis. Preoperatively the tibiotalar alignment was measured, and postoperatively the patients were followed up clinically, with radiographs and by questionnaire. The primary outcome was implant survival at 10 years of follow-up. Implant survival was also compared for (1) inflammatory joint disease vs noninflammatory joint disease and (2) preoperative tibiotalar neutral vs varus or valgus alignment. The secondary outcomes were complications, reoperations, and function (assessed by patient-reported outcome measures). Two hundred fifty-four TARs were performed in 237 patients. Two hundred twelve additional procedures were performed to achieve stable ankles. At 10-year follow-up, the survival was 67.5%, with an average time to revision of 4.5 years. The 10-year survival of the inflammatory joint disease group was 76.8% and of the noninflammatory joint group 63.1% (P = .44). In 248 TARs, the preoperative tibiotalar alignment was measured; (62% neutral, 25% varus, and 13% valgus), these showed 10-year survival rates of 74.7%, 48.2%, and 68.9% respectively (P = .07). The complication rate was 54%; 37% of patients underwent reoperation. At a mean of 8.5 years, postoperative satisfaction scored an average of 7.0 (SD 2.26) on a 0- to 10-point numeric rating scale. The mean Foot and Ankle Ability Measure sports subscore was 24.7, the mean Foot and Ankle Outcome Score (FAOS) sports subscore was 42.8, and the mean 36-Item Short Form Health Survey score was 40.0. Regarding daily activities, the mean FAOS was 81.0. This is currently the sole study reporting the long-term results of the CCI prosthesis. The survival and functional outcomes were inferior to other third-generation mobile-bearing ankle implants.

IL-1 receptor antagonist, MIS-C, and the peculiar autoimmunity of SARS-CoV-2

IL-1 receptor antagonist, MIS-C, and the peculiar autoimmunity of SARS-CoV-2

Abstract 9057: Anti-inflammatory Effect of Biologic Therapy in Patients With Psoriatic Disease: A Prospective Cohort Fdg-pet Study

Introduction: Psoriatic arthritis (PsA) and cutaneous psoriasis (PsO) are linked with an increased risk of adverse cardiovascular events. Hypothesis: Central vascular inflammation (VI) as measured on F-18-fluorodeoxyglucose (FDG) positron emission tomography (PET) in the ascending aorta will improve in patients following therapy with biologic agents compared to PsO patients receiving non-biologic therapy and controls. We also postulate that in patients responding to biologics, there will be an improvement in coronary microvascular dysfunction as measured by myocardial blood flow reserve (MFR) determined by rubidium-82 (82Rb) PET. Methods: We studied 3 patient cohorts (patients with PsA and/or PsO started on biologic agents, patients with PsO managed on non-biologic therapy, and patients with non-inflammatory arthritis). The primary outcome of our study was the change in VI, estimated as the target-to-background ratio by FDG PET in the most diseased segment of the ascending aorta at baseline compared to 6-month follow-up (TBRmax). We also performed 82Rb PET studies at baseline and 6-month follow-up to determine any changes on left ventricular MFR. Results: 34 participants were enrolled in the study (11 PsA and/or PsO patients on biologic agents, 13 patients in PsO group managed on non-biologic therapy, and 10 in the non-inflammatory control group). A significant drop in the thoracic aorta uptake was observed in the biologic-treated group (change in TBRmax: -0.46±0.55) when compared to the the PsO group treated with non-biologic therapy (change in TBRmax: 0.23±0.67). The group with imaging evidence of a response to biologic agents (i.e. TBRmax drop greater than median value) maintained MFR (change in MFR of 0.05±0.19) when compared to the group with a response on TBRmax that was below the median, which had a drop in MFR (-2.9±0.8) (P=0.03). Conclusions: VI in the thoracic aorta decreased compared to psoriasis patients treated with non-systemic therapies and controls. Psoriasis patients treated with biologics who demonstrated a significant response on FDG PET imaging, maintained their MFR compared to non-responders. There is a positive impact of immune therapies on VI and microvascular disease in patients with chronic inflammation.

Long term outcomes of patients with chronic inflammatory diseases after percutaneous coronary intervention

Abstract Introduction Patients with chronic inflammatory diseases are at increased risk for coronary artery disease. Aim We aimed to assess the long-term outcomes of patients with chronic inflammatory diseases who underwent percutaneous coronary intervention. Methods A Retrospective cohort study of all adult (&amp;gt;18 years) patients who underwent PCI in a large [1000 bed] tertiary care centerfrom January 2002 to August 2020. Results A total of 12,951 patients underwent PCI during the study period and were included in the cohort. The population of chronic inflammatory diseases includes 247/12,951 [1.9%]; 70 with IBD and 173 with AIRD. The composite endpoint of mortality, ACS or CHF admission was more frequent in the inflammatory disease group (77.5% in AIRD group, 72.9% in the IBD group and 59.6% in the non-inflammatory group, p&amp;lt;0.001). The adjusted cox regression model found a statistically significant increased risk of the composite primary endpoints of around 40% for patients both with AIRD and IBD. The increased risk for ACS was 61% for AIRD patients and 37% for IBD patients. Patients with inflammatory diseases were found to have a significant increased risk CHF admission, while both IBD and AIED patients had a non-significant increased risk for mortality. Conclusion Patients with AIRD and IBD are at higher risk for cardiovascular events also in long term follow up once diagnosed with CAD and treated with PCI. Funding Acknowledgement Type of funding sources: None.

ANTI-INFLAMMATORY EFFECT OF BIOLOGIC THERAPY IN PATIENTS WITH PSORIATIC DISEASE COMPARED WITH TREATMENT WITH NON-BIOLOGIC DMARDS: A PROSPECTIVE COHORT FDG-PET STUDY

<h3>BACKGROUND</h3> Psoriatic arthritis (PsA) and cutaneous psoriasis (PsO) are linked with an increased risk of adverse cardiovascular events. We hypothesized that central vascular inflammation on F-18-fluorodeoxyglucose (FDG) positron emission tomography (PET) in the ascending aorta would improve in these patients following therapy with biologic agents compared to PsO patients receiving non-biologic therapy and non-inflammatory control patients. We also postulated that in patients responding to biologics, there would an improvement in coronary microvascular dysfunction as measured by myocardial blood flow reserve (MFR) determined by rubidium-82 (82Rb) PET. <h3>METHODS AND RESULTS</h3> We studied 3 patient cohorts (patients with PsA and/or PsO started on biologic agents, patients with PsO managed on non-biologic therapy, and control patients with non-inflammatory arthritis). The primary outcome of our study was the change in vascular inflammation, estimated as the target-to-background ratio (TBR) by FDG PET in the most diseased segment of the ascending aorta at baseline compared to 6-month follow-up (TBRmax). We also performed 82Rb PET studies at baseline and 6-month follow-up to determine any changes on left ventricular MFR. A total of 34 participants were enrolled in the study (11 PsA and/or PsO patients on biologic agents, 13 patients in PsO group managed on non-biologic therapy, and 10 in the non-inflammatory control group). The majority (64.7%) of participants were men and the median age was 62 years (IQR: 48, 69). A significant drop in the thoracic aorta uptake was observed in the biologic-treated group (thoracic aorta change in TBRmax: -0.46±0.55) when compared to the change in the thoracic aorta FDG uptake of the PsO group treated with non-biologic therapy (thoracic aorta change in TBRmax: 0.23±0.67). Furthermore, the group with imaging evidence of a response to biologic agents (i.e. TBRmax drop > median value of 7%) maintained MFR (3.40±1.23 MFR to 3.5±1.2 MFR over 6 months) when compared to the group with a below median response on TBRmax which had a drop in MFR (2.9±0.8 MFR to 2.2±0.6 over 6 months) (P=0.03). <h3>CONCLUSION</h3> In a cohort of psoriasis patients treated with biologics, the FDG uptake in the thoracic aorta decreased over the study period compared to psoriasis patients treated with non-systemic therapies as well as controls. Additionally, psoriasis patients treated with biologics who demonstrated a significant anti-inflammatory response on FDG PET imaging, maintained their MFR compared to non-responders. This study supports the notion that there is a positive impact of immune therapies on vascular inflammation and microvascular disease in patients with chronic inflammation.

Skin Microbiota in Non-inflammatory and Inflammatory Lesions of Acne Vulgaris: The Underlying Changes within the Pilosebaceous Unit.

Acne vulgaris is a common chronic inflammatory skin disease of the pilosebaceous unit. Clinical manifestations include seborrhea, non-inflammatory lesions, inflammatory lesions, or scar formation. Fourteen eligible participants of either sex, aged 18-28years old, with mild to moderate acne lesions, were recruited in this observational study. The contents of 10 pilosebaceous units of non-inflammatory (comedones) and inflammatory lesions (papules and pustules) were collected from each participant's face and examined by amplicon metagenomics sequencing and real-time Polymerase Chain Reaction (PCR). Male participants, participants with a higher body mass index (BMI) than normal, and participants younger than 20years old, were revealed to have a higher proportion of Malassezia in their non-inflammatory lesions than that in inflammatory lesions. There was an increased abundance of Malassezia restricta (M. restricta) and Cutibacterium acnes (C. acnes) in the non-inflammatory group. Correlation analysis indicated that Staphylococcus epidermidis (S. epidermidis) and M. restricta have similar proliferation trends with C. acnes during the transformation from non-inflammatory to inflammatory lesions. M. restricta probably involve in the microecological balance within the pilosebaceous unit.

The incidence rate of herpes zoster in inflammatory bowel disease: A meta-analysis of cohort studies.

Inflammatory bowel disease is associated with an increased risk of opportunistic infections. This study aimed to investigate the incidence rate of herpes zoster in patients with inflammatory bowel disease.A meta-analysis was conducted by searching PubMed literature published from January 2000 to July 2019. The main outcome was the incidence rate of a new diagnosis of herpes zoster in patients previously diagnosed with inflammatory bowel disease. The incidence rate ratio (IRR) and 95% confidence interval (95% CI) for herpes zoster associated with inflammatory bowel disease was measured.A total of 6 eligible cohort studies matching the entry criteria were included in the meta-analysis, providing 216,552 participants with inflammatory bowel disease and 790 events of herpes zoster among these participants with inflammatory bowel disease. The pooled incidence rate of developing herpes zoster was 10.41 per 1000 person-years in the inflammatory bowel disease group and 6.10 per 1000 person-years in the non-inflammatory bowel disease group, respectively. The meta-analysis demonstrated that patients with inflammatory bowel disease were associated with 1.68-fold increased risk of developing herpes zoster when compared to those without inflammatory bowel disease (IRR = 1.68, 95% CI = 1.53–1.84). Crohn disease and ulcerative colitis were associated with an increased risk of developing herpes zoster (IRR = 1.67, 95% CI = 1.40–1.98 for Crohn disease and IRR = 1.49, 95% CI = 1.34–1.65 for ulcerative colitis, respectively).Patients with inflammatory bowel disease are at increased risk of developing herpes zoster. We suggest that the vaccination should be considered at the time of inflammatory bowel disease being diagnosed.

Single nucleotide polymorphisms, gene expression and serum profile of immune and antioxidant markers associated with postpartum disorders susceptibility in Barki sheep

The objective of this study was to explore the immunological and antioxidant alterations associated with ovine postpartum disorders. Blood samples were collected from 90 adult Barki ewes and allocated into three equal-sized groups (30 ewes each): control group (CG), inflammatory postpartum disorders group (IPG) and non-inflammatory postpartum disorders group (NIPG). PCR-DNA sequencing approach was carried out for TLR4 (256-bp) and SOD (456-bp) genes, and nucleotide sequence variations were noticed to be associated with postpartum disorders resistance/susceptibility. Gene expression profile was also evaluated and levels of IL5, IL6, IL1-ß, TNF alpha, TLR4 and Tollip were significantly up-regulated in ewes affected with postpartum disorders than resistant ones, while SOD and CAT genes pattern elicited an opposite trend. Exploring serum profile also showed a significant increase of IL-1α, IL-1β, IL-6, TNF-α, MDA and NO in IPG compared to their correspond values in NIPG and CG. However, serum levels of IL-10, CAT, GSH and GPx were significantly decreased. This study highlights that SNPs in TLR4 and SOD genes could be genetic markers for postpartum disorders resistance/susceptibility in Barki ewes. Gene expression alongside serum profiles of antioxidant markers could also be used to follow-up the immune status of ewes to build up an effective management protocol.

Comparison of brain-derived neurotrophic factor (BDNF) serum level in inflammatory and non-inflammatory acne vulgaris

Background: Acne vulgaris is a chronic and self-limiting inflammation disorder of the pilosebaceous unit, generally manifested in adolescents with polymorphic lesions, such as comedones, papules, nodules, and cyst. Brain-derived neurotrophic factor (BDNF) is a member of neurotrophins that can be downregulated because of stress. It is suspected that a lower BDNF level is induced inflammatory process, although its relationship with acne vulgaris has not been widely studied. This study compared BDNF serum levels in the inflammatory and non-inflammatory type of acne vulgaris.Methods: This is analytical observational research with a cross-sectional design that involved 31 acne vulgaris patients with inflammatory lesions and 31 acne vulgaris patients with non-inflammatory lesions. Each subject was interviewed and going through dermatology examinations, followed by blood sampling to assessed their BDNF serum levels through the ELISA test. The collected data were analyzed statistically using an independent T-test. P&lt;0.05 was significant.Result: The mean BDNF serum levels in acne vulgaris patients were 32,53±6,32 ng/ml. In subjects with inflammatory-type lesions, the mean BDNF level is 27,55±3,31 ng/ml. While, in the non-inflammatory type lesions group, the mean BDNF is 37,51±4,37 ng/ml. The BDNF serum level is significantly lower in inflammatory-type subjects than in non-inflammatory type (p &lt; 0,001).Conclusion: There was a significant difference in serum BDNF levels between the inflammatory and non-inflammatory type acne groups.