Progressive Inflammatory Disease Research Articles

Endometriosis epidemiology, features of risk factors and aetiology: literature review

Augustina Zaveriuchaitė1, Geistė Tubutytė1 1 Vilnius University, Faculty of Medicine, Vilnius, Lithuania Abstract Background. Endometriosis is a progressive chronic hormone-dependent inflammatory disease, often affecting women in child-bearing age. During its course the endometrium tissue forms outside of the uterine cavity. Due to delayed diagnostics the epidemiology of this disease is not known exactly. Aim. To review scientific literature about endometriosis epidemiology, risk factors and aetiological aspects. Materials and methods. The literature search was conducted in the international database PubMed. Keywords such as ,,endometriosis‘‘, ,,endometriosis epidemiology‘‘, ,,endometriosis risk factors‘‘, ,,endometriosis aetiology‘‘ and their combinations were used. 717 publications were found in the search results, of which 653 articles were rejected that did not match the topic. The literature review includes 64 articles in English, published between 1986 and 2022. Results. It has been proven that this disease is diagnosed more often to women that have a higher social-economical status, are working night shifts, have encountered misbehavior in their childhood, have a family history of endometriosis in first-degree relatives, had an early menarche and/or the menstruation cycle is shorter than 27 days. Diet is also of an important role to this disease while alcohol increases the risk of having endometriosis. Conclusions. The prevalence of endometriosis is not known exactly. Despite lack of understanding of its aetiology, it is assumed that various factors are of influence. That includes the genetic profile, inflammation, hormonal activity, menstruation cycles, metabolism of prostaglandines and imunological elements. Keywords: endometriosis, risk factors, aetiology, epidemiology.

The research progress of anti-inflammatory and anti-fibrosis treatment of chronic pancreatitis.

Chronic pancreatitis (CP) is a chronic progressive inflammatory disease of the pancreas, caused by multiple factors and accompanied by irreversible impairment of pancreatic internal and external secretory functions. Pathologically, atrophy of the pancreatic acini, tissue fibrosis or calcification, focal edema, inflammation, and necrosis are observed. Clinical manifestations include recurrent or persistent abdominal pain, diarrhea, emaciation, and diabetes. In addition, CP is prone to develop into pancreatic cancer(PC) due to persistent inflammation and fibrosis. The disease course is prolonged and the clinical prognosis is poor. Currently, clinical treatment of CP is still based on symptomatic treatment and there is a lack of effective etiological treatment. Encouragingly, experiments have shown that a variety of active substances have great potential in the etiological treatment of chronic pancreatitis. In this paper, we will review the pathogenesis of CP, as well as the research progress on anti-inflammatory and anti-fibrotic therapies, which will provide new ideas for the development of subsequent clinical studies and formulation of effective treatment programs, and help prevent CP from developing into pancreatic cancer and reduce the prevalence of PC as much as possible.

Glycobiology of rheumatic diseases.

Glycosylation has a profound influence on protein activity and cell biology through a variety of mechanisms, such as protein stability, receptor interactions and signal transduction. In many rheumatic diseases, a shift in protein glycosylation occurs, and is associated with inflammatory processes and disease progression. For example, the Fc-glycan composition on (auto)antibodies is associated with disease activity, and the presence of additional glycans in the antigen-binding domains of some autoreactive B cell receptors can affect Bcell activation. In addition, changes in synovial fibroblast cell-surface glycosylation can alter the synovial microenvironment and are associated with an altered inflammatory state and disease activity in rheumatoid arthritis. The development of our understanding of the role of glycosylation of plasma proteins (particularly (auto)antibodies), cells and tissues in rheumatic pathological conditions suggests that glycosylation-based interventions could be used in the treatment of these diseases.

Analysis of Pediatric Rasmussen Encephalitis: Experience from A Tertiary Care Hospital in Bangladesh

Background: Rasmussens encephalitis (RE) is rare progressive cerebral inflammatory disease predominantly affecting pediatric population. The key clinical features are seizure and hemiparesis. Seizure is mostly focal with or without epileptia partialis continua (EPC). Diagnosis is established by EEG showing epileptic discharges with focal slowing, focal cortical atrophy in neuroimaging and T cell dominated encephalitis in biopsy or autopsy. This study was done to describe the clinical, laboratory features and treatment of RE in Bangladesh perspective.
 Materials & Methods: This study was done in Department of Pediatric Neurology, IPNA, BSMMU, Dhaka, Bangladesh. Four admitted children who were diagnosed as RE from January 2016 to July 2019 were included in this study. Retrospective detail data of the all four patients were collected and analyzed.
 Results: The age ranging was 3-12 years, all were male. Cognitive decline, speech disorder, hemiparesis were observed in all the patients. Among them 1 had prodrome of fever. All the patients had seizure, mostly focal onset. Among them 2 had EPC. Treatment was given mainly with immune modulatory drugs (Intravenous methyl prednisolone, IV immunoglobulin, oral steroids) and antiepileptic drugs. On follow up all the patients had consequences in the form of hemiparesis, epilepsy, dysphasia, cognitive disorder etc.
 Conclusion: Cognitive decline, speech disorder, focal seizure and hemiparesis were the common presentation. EPC was observed in 50% of cases and consequences on follow up in all cases.
 BANGLADESH J CHILD HEALTH 2021; VOL 45 (3) : 147-154

Epimedii Herba: An ancient Chinese herbal medicine in the prevention and treatment of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic, progressive inflammatory and systemic autoimmune disease resulting in severe joint destruction, lifelong suffering and considerable disability. Diverse prescriptions of traditional Chinese medicine (TCM) containing Epimedii Herba (EH) achieve greatly curative effects against RA. The present review aims to systemically summarize the therapeutic effect, pharmacological mechanism, bioavailability and safety assessment of EH to provide a novel insight for subsequent studies. The search terms included were "Epimedii Herba", "yinyanghuo", "arthritis, rheumatoid" and "Rheumatoid Arthritis", and relevant literatures were collected on the database such as Google Scholar, Pubmed, Web of Science and CNKI. In this review, 15 compounds from EH for the treatment of RA were summarized from the aspects of anti-inflammatory, immunoregulatory, cartilage and bone protective, antiangiogenic and antioxidant activities. Although EH has been frequently used to treat RA in clinical practice, studies on mechanisms of these activities are still scarce. Various compounds of EH have the multifunctional traits in the treatment of RA, so EH may be a great complementary medicine option and it is necessary to pay more attention to further research and development.

MicroRNA-155 acts as a potential prognostic and diagnostic factor in patients with ankylosing spondylitis by modulating SOCS3.

Ankylosing spondylitis (AS) is a progressive inflammatory disease. Our primary objective was to explore the role of miR-155 and its targeted factors in AS pathogenesis. PBMCs were isolated from 30 AS patients and 30 healthy individuals using the Ficoll-hypaque isolation approach. The expression of miR-155 and its associated targets, including Suppressor Of Cytokine Signaling 3 (SOCS3), STAT3, and IL-21, were determined using qT-qPCR. Then, PBMCs were cultured, and the effect of miR-155, SOCS3 siRNA (to suppress its expression), pEFSOCS3 (enforced expression), and their combination were investigated by qRT-PCR and western blotting. We also treated the cultured PBMCs with Brefeldin A, a potent inhibitor of cytokine secretion, to determine its effect on IL-21 expression and secretion. In addition, the association between miR-155 and patients' clinicopathological features was examined. The results showed that miR-155, IL-21, and STAT3 were increased in patients with AS, while SOCS3 had decreasing expression trend. It was also determined that miR-155 alleviates SOCS3 expression and increases IL-21 and STAT3 expression; it had a prominent effect when combined with SOCS3 siRNA. Besides, we showed that simultaneous transfection of miR-155 and pEFSOCS3 had no significant effect on IL-21 and STAT3 expression, revealing that miR-155 could alleviate the enforced expression of SOCS3. It was also proven that Brefledine A led to IL-21 up-regulation or accumulation while relieving its secretion. Also, a significant correlation between miR-155 and pathological features of AS patients was found. miR-155 acts as a potential prognostic and diagnostic biomarker. Its up-regulation leads to the down-regulation of SOCS3 and increased expression of IL-21 and STAT3 as characteristic of TH-17 lymphocytes, leading to worsening inflammatory conditions in patients with AS.

An overview of psoriatic arthritis including clinical manifestations, assessment, diagnostic criteria, investigations, drug management and GRAPPA guidelines.

Psoriatic arthritis (PsA) is a chronic and often progressive inflammatory disease, occurring in up to 30% of patients with psoriasis. Assessment of patients with PsA requires consideration of all disease domains, including peripheral arthritis, axial disease, enthesitis, dactylitis, skin psoriasis, psoriatic nail disease, uveitis and inflammatory bowel disease. Co-morbidities and related conditions should all be considered including: obesity, metabolic syndrome, cardiovascular disease, anxiety/depression, liver disease, chronic infections, malignancy, osteoporosis, fibromyalgia and reproductive health.

Alcoholic liver disease and intestinal microbiota in an experimental model: Biochemical, inflammatory, and histologic parameters

ObjectivesAlcoholic liver disease (ALD) is the leading cause of alcohol-related deaths worldwide. Experimental ALD models are expensive and difficult to reproduce. A low-cost, reproducible ALD model was developed, and liver damage compared with the gut microbiota. The aims of this study were to develop an experimental model of ALD, through a high-fat diet, the chronic use of ethanol, and intragastric alcohol binge; and to evaluate the composition of the gut microbiota and its correlation with markers of inflammatory and liver disease progression in this model. MethodsAdult male Wistar rats were randomized (N = 24) to one of three groups: control (standard diet and water + 0.05% saccharin), ALC4 and ALC8 (sunflower seed, 10% ethanol + 0.05% saccharin for 4 and 8 wk, respectively). On the last day, ALC4/8 received alcoholic binge (5 g/kg). Clinical, nutritional, biochemical, inflammatory, pathologic, and gut microbiota data were analyzed. ResultsALC4/8 animals consumed more alcohol and lipids (P < 0.01) and less total energy, liquids, solids, carbohydrates, and proteins (P < 0.01), and gained less weight (P < 0.01) than controls. ALC8 had lower Lee index scores than controls and ALC4 (P < 0.01). Aminotransferases increased and albumin diminished in ALC4/8 but not in the control group (P < 0.03 for all). Glucose and aspartate transaminase/alanine aminotransaminase ratios were higher in the ALC8 rats than in the controls (P < 0.03). Cholesterol was higher in ALC4 and lower in ALC8 compared with controls (P < 0.03). Albumin and high-density lipoprotein cholesterol levels were lower in ALC8 (P < 0.03). Hepatic concentration of triacylglycerols was higher in ALC8 than in ALC4 and controls (P < 0.05). ALC4/8 presented microvesicular grade 2 and 3 steatosis, respectively, and macrovesicular grade 1. No change in the gene expression of inflammatory markers between groups was seen. ALC4/8 had lower fecal bacterial α-diversity and relative abundance of Firmicutes (P < 0.005) and greater Bacterioidetes (P < 0.0007) and Protobacteria (P < 0.001) than controls. Gut microbiota correlated with serum and liver lipids, steatosis, albumin, and aminotransferases (P < 0.01 for all). ConclusionThe model induced nutritional, biochemical, histologic, and gut microbiota changes, and appears to be useful in the study of therapeutic targets.

The utility of wearable devices in assessing ambulatory impairments of people with multiple sclerosis in free-living conditions

Background and objectivesMultiple sclerosis (MS) is a progressive inflammatory and neurodegenerative disease of the central nervous system affecting over 2.5 million people globally. In-clinic six-minute walk test (6MWT) is a widely used objective measure to evaluate the progression of MS. Yet, it has limitations such as the need for a clinical visit and a proper walkway. The widespread use of wearable devices capable of depicting patients’ activity profiles has the potential to assess the level of MS-induced disability in free-living conditions. MethodsIn this work, we extracted 96 features in different temporal granularities (from minute-level to day-level) from wearable data and explored their utility in estimating 6MWT scores in a European (Italy, Spain, and Denmark) MS cohort of 337 participants over an average of 10 months’ duration. We combined these features with participants’ demographics using three regression models including elastic net, gradient boosted trees and random forest. In addition, we quantified the individual feature's contribution using feature importance in these regression models, linear mixed-effects models, generalized estimating equations, and correlation-based feature selection (CFS). ResultsThe results showed promising estimation performance with R2 of 0.30, which was derived using random forest after CFS. This model was able to distinguish the participants with low disability from those with high disability. Furthermore, we observed that the minute-level (≤ 8 minutes) step count, particularly those capturing the upper end of the step count distribution, had a stronger association with 6MWT. The use of a walking aid was indicative of ambulatory function measured through 6MWT. ConclusionsThis study demonstrates the utility of wearables devices in assessing ambulatory impairments in people with MS in free-living conditions and provides a basis for future investigation into the clinical relevance.

Polyguanine alleviated autoimmune hepatitis through regulation of macrophage receptor with collagenous structure and TLR4-TRIF-NF-κB signalling.

Autoimmune hepatitis (AIH) is a progressive and chronic inflammatory disease in the liver. MARCO is a surface receptor of macrophage involving in tissue inflammation and immune disorders. Moreover, polyguanine (PolyG) is considered to bind to macrophage receptor with collagenous structure (MARCO). However, the role of MARCO and PolyG in the development and treatment of AIH still remains unclear. Therefore, this study explores the expression of MARCO and therapeutic activity of PolyG in both S100-induced AIH in mouse and Lipopolysaccharide (LPS)-treated macrophage (RAW264.7 cells). Moreover, there were significant increases in inflammatory factors and MARCO, as well as decrease in I-kappa-B-alpha (Ik-B) in the liver of AIH mice and LPS-induced cells. However, PolyG treatment significantly reversed the elevation of inflammatory cytokins, MARCO and reduction of Ik-B. In addition, PolyG treatment could downregulate the expression of Toll-like receptor 4 (TLR4) and TIR-domain-containing adaptor inducing interferon-β (TRIF), decrease macrophage M1 polarization and increase macrophage M2 polarization. When hepatocytes were co-cultured with different treatment of macrophages, similar expression profile of inflammatory cytokines was observed in hepatocytes. The research revealed that MARCO expression was elevated in AIH mice. PolyG treatment and inhibition of MARCO significantly reduced inflammatory cytokines expression in the liver as well as hepatocytes and macrophages. Therefore, MARCO could be a target for the treatment of AIH.

Enhanced Label-Free Nanoplasmonic Cytokine Detection in SARS-CoV-2 Induced Inflammation Using Rationally Designed Peptide Aptamer.

Rapid and precise serum cytokine quantification provides immense clinical significance in monitoring the immune status of patients in rapidly evolving infectious/inflammatory disorders, examplified by the ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. However, real-time information on predictive cytokine biomarkers to guide targetable immune pathways in pathogenic inflammation is critically lacking, because of the insufficient detection range and detection limit in current label-free cytokine immunoassays. In this work, we report a highly sensitive localized surface plasmon resonance imaging (LSPRi) immunoassay for label-free Interleukin 6 (IL-6) detection utilizing rationally designed peptide aptamers as the capture interface. Benefiting from its characteristically smaller dimension and direct functionalization on the sensing surface via Au-S bonding, the peptide-aptamer-based LSPRi immunoassay achieved enhanced label-free serum IL-6 detection with a record-breaking limit of detection down to 4.6 pg/mL, and a wide dynamic range of ∼6 orders of magnitude (values from 4.6 to 1 × 106 pg/mL were observed). The immunoassay was validated in vitro for label-free analysis of SARS-CoV-2 induced inflammation, and further applied in rapid quantification of serum IL-6 profiles in COVID-19 patients. Our peptide aptamer LSPRi immunoassay demonstrates great potency in label-free cytokine detection with unprecedented sensing capability to provide accurate and timely interpretation of the inflammatory status and disease progression, and determination of prognosis.

Three Major Gastrointestinal Cancers Could Be Distinguished through Subclass-Specific IgG Glycosylation.

Esophageal cancer (EC), gastric cancer (GC), and colorectal cancer (CRC) are three major digestive tract tumors with higher morbidity and mortality due to significant molecular heterogeneity. Altered IgG glycosylation has been observed in inflammatory activities and disease progression, and the IgG glycome profile could be used for disease stratification. However, IgG N-glycome profiles in these three cancers have not been systematically investigated. Herein, subclass-specific IgG glycosylation in CRC, GC, and EC was comprehensively characterized by liquid chromatography-tandem mass spectrometry. It was found that IgG1 sialylation was decreased in all three cancers, and the alterations in CRC and EC may be subclass-specific. IgG4 mono-galactosylation was increased in all three cancers, which was a subclass-specific change in all of them. Additionally, glycopeptides of IgG1-H5N5, IgG2-H4N3F1, and IgG4-H4N4F1 could distinguish all three cancer groups from controls with fair diagnostic performance. Furthermore, bioinformatics verified the differential expression of relevant glycosyltransferase genes in cancer progression. Significantly, those three gastrointestinal cancers could be distinguished from each other using subclass-specific IgG glycans. These findings demonstrated the spatial and temporal diversity of IgG N-glycome among digestive cancers, increasing our understanding of the molecular mechanisms of EC, GC, and CRC pathogenesis.

Platelet-Derived Exosomes in Atherosclerosis.

Atherosclerosis (AS), the main cause of many cardiovascular diseases (CVDs), is a progressive inflammatory disease characterized by the accumulation of lipids, fibrous elements, and calcification in the innermost layers of arteries. The result is the thickening and clogging of these vessel walls. Several cell types are directly involved in the pathological progression of AS. Among them, platelets represent the link between AS, inflammation, and thrombosis. Indeed, besides their pivotal role in hemostasis and thrombosis, platelets are key mediators of inflammation at injury sites, where they act by regulating the function of other blood and vascular cell types, including endothelial cells (ECs), leukocytes, and vascular smooth muscle cells (VSMCs). In recent years, increasing evidence has pointed to a central role of platelet-derived extracellular vesicles (P-EVs) in the modulation of AS pathogenesis. However, while the role of platelet-derived microparticles (P-MPs) has been significantly investigated in recent years, the same cannot be said for platelet-derived exosomes (P-EXOs). For this reason, this reviews aims at summarizing the isolation methods and biological characteristics of P-EXOs, and at discussing their involvement in intercellular communication in the pathogenesis of AS. Evidence showing how P-EXOs and their cargo can be used as biomarkers for AS is also presented in this review.

Overrepresentation of Enterobacteriaceae and Escherichia coli is the major gut microbiome signature in Crohn's disease and ulcerative colitis; a comprehensive metagenomic analysis of IBDMDB datasets.

ObjectivesA number of converging strands of research suggest that the intestinal Enterobacteriaceae plays a crucial role in the development and progression of inflammatory bowel disease (IBD), however, the changes in the abundance of Enterobacteriaceae species and their related metabolic pathways in Crohn’s disease (CD) and ulcerative colitis (UC) compared to healthy people are not fully explained by comprehensive comparative metagenomics analysis. In the current study, we investigated the alternations of the Enterobacterales population in the gut microbiome of patients with CD and UC compared to healthy subjects.MethodsMetagenomic datasets were selected from the Integrative Human Microbiome Project (HMP2) through the Inflammatory Bowel Disease Multi’omics Database (IBDMDB). We performed metagenome-wide association studies on fecal samples from 191 CD patients, 132 UC patients, and 125 healthy controls (HCs). We used the metagenomics dataset to study bacterial community structure, relative abundance, differentially abundant bacteria, functional analysis, and Enterobacteriaceae-related biosynthetic pathways.ResultsCompared to the gut microbiome of HCs, six Enterobacteriaceae species were significantly elevated in both CD and UC patients, including Escherichia coli, Klebsiella variicola, Klebsiella quasipneumoniae, Klebsiella pneumoniae, Proteus mirabilis, Citrobacter freundii, and Citrobacter youngae, while Klebsiella oxytoca, Morganella morganii, and Citrobacter amalonaticus were uniquely differentially abundant and enriched in the CD cohort. Four species were uniquely differentially abundant and enriched in the UC cohort, including Citrobacter portucalensis, Citrobacter pasteurii, Citrobacter werkmanii, and Proteus hauseri. Our analysis also showed a dramatically increased abundance of E. coli in their intestinal bacterial community. Biosynthetic pathways of aerobactin siderophore, LPS, enterobacterial common antigen, nitrogen metabolism, and sulfur relay systems encoded by E. coli were significantly elevated in the CD samples compared to the HCs. Menaquinol biosynthetic pathways were associated with UC that belonged to K. pneumoniae strains.ConclusionsIn conclusion, compared with healthy people, the taxonomic and functional composition of intestinal bacteria in CD and UC patients was significantly shifted to Enterobacteriaceae species, mainly E. coli and Klebsiella species.

AN UNCOMMON PRESENTATION OF ANTISYNTHETASE SYNDROME-RELATED INTERSTITIAL LUNG DISEASE IN A YOUNG INDIAN MALE

AN UNCOMMON PRESENTATION OF ANTISYNTHETASE SYNDROME-RELATED INTERSTITIAL LUNG DISEASE IN A YOUNG INDIAN MALE

S982 The Progression of Crohn’s Disease: Results From an Observational Study Using U.S. Claims Data

Introduction: Crohn’s disease (CD) is a chronic progressive inflammatory disease of the gastrointestinal tract. Disease progression is characterized by the occurrence of CD complications, including fistula, intestinal stenosis, and abscess. The aim of this study was to characterize progression among patients with CD without complications. Methods: This cohort study used data from the Optum claims database from 01/2016 to 06/2020. Patients without a previous CD diagnosis between 01/2017 and 06/2019 were considered as newly diagnosed cases; those with a previous CD diagnosis prior to the index date (CD diagnosis date) or 01/2017 were considered as existing cases. Patients with a history of CD progression were excluded. The primary objective was to estimate the risk of and time to progression from the time of CD diagnosis in patients newly diagnosed with CD without complications at baseline. Risk of progression (proportion of patients at risk who progressed) was estimated for both newly diagnosed and existing CD cases at 6 months and 1, 2, and 3 years. Kaplan–Meier estimates for time to progression (duration between index date and first progression event) were generated for newly diagnosed CD cases. Other outcomes e.g., demographic characteristics, were assessed over the follow-up period (between index date and 06/2020) using descriptive statistics. Results: In total, 23,241 patients (mean age 47.1 years [standard deviation 18.7]; 42.3% female) with CD were identified; 29.3% (n=6804) were newly diagnosed and 70.7% (n=16,437) were existing cases. The most common comorbidities in newly diagnosed and existing cases were obesity (25.4%; 18.4%), anxiety (24.5%; 21.9%), and depression (22.1%; 18.7%); extraintestinal manifestations (2.4%; 3.8%). The most common CD-related medication was antibiotics for newly diagnosed (25.2%; 18.3% existing) and acetylsalicylic acid for existing cases (27.5%; 13.1% newly diagnosed). Risk of CD progression over time ranged from 19.3% to 26.6% in newly diagnosed and 8.2% to 21.4% in existing cases (Table). A total of 6804 patients with newly diagnosed CD progressed with a median time to progression of 709 days (interquartile range: 415–987) (Figure). Conclusion: Over 20% of all patients with CD experienced progression during the follow-up period. Intestinal stenosis was a more common complication than fistula or abscess.Figure 1.: Time to Crohn’s disease progression events for newly diagnosed cases Time from CD diagnosis to progression event was assessed for the entire follow-up period for newly diagnosed cases only and was estimated as the time from the index date (date of the first CD diagnosis) to the progression date. If no such progression event was observed in the available follow-up period, the patient was censored. CD, Crohn’s disease; IQR, interquartile range. Table 1. - Risk of Crohn’s disease progression Period post-index date* Total follow-up period 6 months 1 year 2 years 3 years Newly diagnosed cases Existing cases Newly diagnosed cases Existing cases Newly diagnosed cases Existing cases Newly diagnosed cases Existing cases Newly diagnosed cases Existing cases Patients at risk of CD progression, n 6804 16,437 6117 15,182 5503 13,720 3875 11,238 1668 7856 Patients with CD progression†, n (%) 1714 (25.2) 3288 (20.0) 1183 (19.3) 1241 (8.2) 1188 (21.6) 1622 (11.8) 953 (24.6) 1879 (16.7) 444 (26.6) 1680 (21.4) CD fistula (diagnosis or surgery) 430 (6.3) 990 (6.0) 270 (4.4) 327 (2.2) 293 (5.3) 456 (3.3) 259 (6.7) 535 (4.8) 125 (7.5) 499 (6.4) Intestinal stenosis (stricture diagnosis or surgery) 1227 (18.0) 2211 (13.5) 843 (13.8) 798 (5.3) 845 (15.4) 1050 (7.7) 655 (16.9) 1224 (10.9) 320 (19.2) 1106 (14.1) Intestinal abscess (diagnosis or drainage procedure) 443 (6.5) 729 (4.4) 275 (4.5) 259 (1.7) 293 (5.3) 372 (2.7) 269 (6.9) 464 (4.1) 112 (6.7) 411 (5.2) Patients who underwent CD-related surgery, n (%) 354 (5.2) 684 (4.2) 198 (3.2) 214 (1.4) 217 (3.9) 305 (2.2) 206 (5.3) 417 (3.7) 95 (5.7) 384 (4.9) *Date of the first CD diagnosis. †A patient was considered to have CD progression if they had a diagnosis CD-related fistula, intestinal stenosis, or abscess, or underwent a CD-related surgery after the index date, whichever event occurred first. The date of the first of these progression events was considered the progression date. CD, Crohn’s disease.

A 4-Year Retrospective Claims Analysis of Oral Corticosteroid Use and Health Conditions in Newly Diagnosed Medicare FFS Patients with COPD.

PurposeWe analyzed population-level administrative claims data for Medicare fee-for-service (FFS) beneficiaries to provide insights on systemic oral corticosteroid (OCS) use patterns and associated health conditions and acute events among patients newly diagnosed with chronic obstructive pulmonary disease (COPD).BackgroundCOPD is a progressive inflammatory disease of the lungs, characterized by acute exacerbations that may lead to increased mortality. Short courses of systemic corticosteroids (SCS) are recommended to reduce recovery time from exacerbations, although SCS use has been associated with increased risk of adverse events.MethodsThis study used 2013–2019 Medicare 100% FFS research identifiable files, which contain all Medicare Parts A, B, and D paid claims incurred by 100% of Medicare FFS beneficiaries. Descriptive statistics for patients newly diagnosed with COPD were analyzed, including OCS use, select health conditions and acute events, and COPD exacerbations. Statistical models were used to analyze the relationship between the incidence of select health conditions and events and cumulative OCS dosage.ResultsOf Medicare FFS patients newly diagnosed with COPD, 36% received OCS in the 48 months following diagnosis, and 38% of OCS episodes lasted longer than the recommended 5–7 days. Patients had a variety of health conditions or acute events in the 24-month period prior to new COPD diagnosis, such as hypertension, depression/anxiety, type 2 diabetes, or osteoporosis, that could heighten the risks of OCS use. Patients treated with >1000 mg of prednisolone equivalent OCS in the 48 months following COPD diagnosis had a higher incidence of new conditions or events, including cardiovascular disease, heart failure, hypertension, obesity, dyspepsia, infections, and depression/anxiety, than patients with no OCS use.ConclusionThese results highlight the potential risks of OCS in COPD treatment, including prolonged use among complex Medicare patients, and reinforce the importance of preventive treatment strategies and therapy optimization early in the disease course.

Insight into the Relationship between Oral Microbiota and the Inflammatory Bowel Disease.

Inflammatory bowel disease has been a growing concern of lots of people globally, including both adults and children. As a chronic inflammatory disease of the intestine, even though the etiology of inflammatory bowel disease is still unclear, the available evidence from clinic observations has suggested a close association with microorganisms. The oral microbiota possesses the characteristics of a large number and abundant species, second only to the intestinal microbiota in the human body; as a result, it successfully attracts the attention of researchers. The highly diverse commensal oral microbiota is not only a normal part of the oral cavity but also has a pronounced impact on the pathophysiology of general health. Numerous studies have shown the potential associations between the oral microbiota and inflammatory bowel disease. Inflammatory bowel disease can affect the composition of the oral microbiota and lead to a range of oral pathologies. In turn, there are a variety of oral microorganisms involved in the development and progression of inflammatory bowel disease, including Streptococcus spp., Fusobacterium nucleatum, Porphyromonas gingivalis, Campylobacter concisus, Klebsiella pneumoniae, Saccharibacteria (TM7), and Candida albicans. Based on the above analysis, the purpose of this review is to summarize this relationship of mutual influence and give further insight into the detection of flora as a target for the diagnosis and treatment of inflammatory bowel disease to open up a novel approach in future clinical practice.

Cross-regional homeostatic and reactive glial signatures in multiple sclerosis

Multiple sclerosis (MS) is a multifocal and progressive inflammatory disease of the central nervous system (CNS). However, the compartmentalized pathology of the disease affecting various anatomical regions including gray and white matter and lack of appropriate disease models impede understanding of the disease. Utilizing single-nucleus RNA-sequencing and multiplex spatial RNA mapping, we generated an integrated transcriptomic map comprising leukocortical, cerebellar and spinal cord areas in normal and MS tissues that captures regional subtype diversity of various cell types with an emphasis on astrocytes and oligodendrocytes. While we found strong cross-regional diversity among glial subtypes in control tissue, regional signatures become more obscure in MS. This suggests that patterns of transcriptomic changes in MS are shared across regions and converge on specific pathways, especially those regulating cellular stress and immune activation. In addition, we found evidence that a subtype of white matter oligodendrocytes appearing across all three CNS regions adopt pro-remyelinating gene signatures in MS. In summary, our data suggest that cross-regional transcriptomic glial signatures overlap in MS, with different reactive glial cell types capable of either exacerbating or ameliorating pathology.

Expanding role of deoxyribonucleic acid-sensing mechanism in the development of lifestyle-related diseases.

In lifestyle-related diseases, such as cardiovascular, metabolic, respiratory, and kidney diseases, chronic inflammation plays a causal role in their pathogenesis; however, underlying mechanisms of sterile chronic inflammation are not well-understood. Previous studies have confirmed the damage of cells in these organs in the presence of various risk factors such as diabetes, dyslipidemia, and cigarette smoking, releasing various endogenous ligands for pattern recognition receptors. These studies suggested that nucleic acids released from damaged tissues accumulate in these tissues, acting as an endogenous ligand. Undamaged DNA is an integral factor for the sustenance of life, whereas, DNA fragments, especially those from pathogens, are potent activators of the inflammatory response. Recent studies have indicated that inflammatory responses such as the production of type I interferon (IFN) induced by DNA-sensing mechanisms which contributes to self-defense system in innate immunity participates in the progression of inflammatory diseases by the recognition of nucleic acids derived from the host, including mitochondrial DNA (mtDNA). The body possesses several types of DNA sensors. Toll-like receptor 9 (TLR9) recognizes DNA fragments in the endosomes. In addition, the binding of DNA fragments in the cytosol activates cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) synthase (cGAS), resulting in the synthesis of the second messenger cyclic GMP-AMP (cGAMP). The binding of cGAMP to stimulator of interferon genes (STING) activates NF-κB and TBK-1 signaling and consequently the production of many inflammatory cytokines including IFNs. Numerous previous studies have demonstrated the role of DNA sensors in self-defense through the recognition of DNA fragments derived from pathogens. Beyond the canonical role of TLR9 and cGAS-STING, this review describes the role of these DNA-sensing mechanism in the inflammatory responses caused by endogenous DNA fragments, and in the pathogenesis of lifestyle-related diseases.