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ID PMID Title PublicationDate abstract
30685069 Reduced levels of Coco in sera of multiple sclerosis patients: A potential role in neuro-r 2019 Feb 15 Demyelination, axonal loss and failure of tissue repair characterize MS lesions. Bone morphogenetic proteins (BMPs) signaling is associated with remyelination failure. Coco is one of the BMP antagonists. We found reduced Coco serum levels in relapsing-remitting MS (RR-MS) and primary progressive MS (PP-MS) patients compared to matched healthy controls (HC) and patients with rheumatoid arthritis. Exposure of P19 cells, in the presence of retinoic acid, BMP-2, or BMP-4 to Coco, at average sera level of MS patients failed to induce neuronal phenotype, in contrast to the average sera level of HC. Coco may be a player in the BMP dysregulation and the tissue repair failure in MS.
30624285 The microbiome in systemic autoimmune disease: mechanistic insights from recent studies. 2019 Mar PURPOSE OF REVIEW: The resident bacterial communities and the host immune system have coevolved for millennia. However, recent changes in modern societies have disrupted this coevolutionary homeostasis and contributed to a rise in immune-mediated conditions. The purpose of this review is to provide an overview of recently elucidated mechanisms of how certain taxa within the bacterial microbiome propagate autoimmunity. RECENT FINDINGS: Interactions between the bacterial microbiome with innate and adaptive immune cells propagate autoreactivity, chronic inflammation, and tissue damage in susceptible hosts. These interactions contribute to autoimmune diseases such as rheumatoid arthritis or systemic lupus erythematosus, which are the focus of this review. Recent findings suggest that autoimmune manifestations in genetically susceptible individuals can arise through cross-reactivity with commensal orthologs of autoantigens or commensal-mediated posttranslational modification of autoantigens. Physiologic responses to gut, oral, or skin commensal bacteria can thus be misdirected toward such autoantigens in susceptible hosts. In addition, recent studies highlight that a breach of the gut barrier and translocation of commensal bacteria to non-gut organs can trigger several autoimmune pathways that can be prevented by commensal vaccination or dietary interventions. SUMMARY: Complex host-microbiota interactions contribute to systemic autoimmunity outside the gut. On a molecular level, posttranslational modification of, and cross-reactivity with, autoantigens represent mechanisms of how the microbiota mediates autoimmunity. On a cellular level, translocation of live gut bacteria across a dysfunctional gut barrier allows for direct interactions with immune and tissue cells, instigating autoimmunity systemically.
30543919 The loss of tolerance to CHI3L1 - A putative role in inflammatory bowel disease? 2019 Feb The incidence of inflammatory bowel disease (IBD) is steadily increasing. IBD is characterized by chronic inflammation of the gastrointestinal tract and is divided into the two main entities Crohn's disease (CD) and ulcerative colitis (UC). Genetic predispositions, environmental factors and a dysregulated immune response are known to be involved at the beginning of IBD. However, their etiopathogenesis is not yet fully understood. Over the last ten years, there has been increasing evidence of the involvement of the member of the 18-glycosylhydrolase family chitinase-3-like protein 1 (CHI3L1) in IBD. CHI3L1 is associated with various diseases such as cancer and chronic inflammatory diseases including rheumatoid arthritis or IBD as well as neurological diseases where it can act as a chemoattractant, mitogen or growth factor. This review will focus on the role of autoimmunity to CHI3L1 in IBD in the context of its expression in inflamed colonic epithelia and interaction with intestinal microbiota. Further, it will provide insights into the interaction of CHI3L1 with different mechanisms of the innate and adaptive immune response in IBD.
30407269 Familial association of attention-deficit hyperactivity disorder with autoimmune diseases 2019 Apr AIMS: In the era of genome-wide association studies, familial risks are used to estimate disease heritability and success in gene identification. We wanted to estimate associations of 42 autoimmune diseases with attention-deficit hyperactivity disorder (ADHD) between individuals and family members. PARTICIPANTS AND METHODS: The availability of a Multigeneration Register in Sweden provides reliable access to family data that covers the last century. An open cohort design of the diseases in individual and family members was obtained through linkage to the Hospital Discharge Register. Standardized incidence ratios were calculated as relative risks for ADHD in family members of affected patients compared with those without affected family members. RESULTS: Among a total of 86 493 patients, 18 153 had a family history of autoimmune diseases. ADHD was associated with 14 autoimmune diseases in the first-degree relatives, including ankylosing spondylitis (standardized incidence ratio:1.13), celiac disease (1.16), Crohn's disease (1.07), diabetes mellitus type 1 (1.19), discoid lupus erythematosus (1.26), glomerular nephritis chronic (1.13), Hashimoto/hypothyroidism (1.11), lupoid hepatitis (1.44), multiple sclerosis (1.11), psoriasis (1.18), Reiter's disease (1.38), rheumatoid arthritis (1.07), Sjögren's syndrome (1.21), and ulcerative colitis (1.05). CONCLUSION: Familial associations with several autoimmune diseases suggest genetic sharing and challenge to gene identification.
30387008 Internet-delivered cognitive behaviour therapy for chronic health conditions: a systematic 2019 Apr This systematic review and meta-analysis aims to evaluate the effectiveness of internet-delivered cognitive behavioural therapy (ICBT) on anxiety and depression among persons with chronic health conditions. A systematic database search was conducted of MEDLINE, CINAHL, PsycInfo, EMBASE, and Cochrane for relevant studies published from 1990 to September 2018. A study was included if the following criteria were met: (1) randomized controlled trial involving an ICBT intervention; (2) participants experienced a chronic health condition; (3) participants ≥ 18 years of age; and (4) effects of ICBT on anxiety and/or depression were reported. The Cochrane Risk of Bias tool was used to assess the risk of bias on the included studies. Pooled analysis was conducted on the primary and condition specific secondary outcomes. Twenty-five studies met inclusion criteria and investigated the following chronic health conditions: tinnitus (n = 6), fibromyalgia (n = 3), pain (n = 7), rheumatoid arthritis (n = 3), cardiovascular disease (n = 2), diabetes (n = 1), cancer (n = 1), heterogeneous chronic disease population (n = 1), and spinal cord injury (n = 1). Pooled analysis demonstrated small effects of ICBT in improving anxiety and depression. Moderate effects of therapist-guided approach were seen for depression and anxiety outcomes; while, self-guided approaches resulted in small effects for depression and moderate effects in anxiety outcomes. ICBT shows promise as an alternative to traditional face-to-face interventions among persons with chronic health conditions. Future research on long-term effects of ICBT for individuals with chronic health conditions is needed.Trial Registration PROSPERO registration number: CRD42018087292.
31364980 Effects of childhood psychological trauma on rheumatic diseases. 2019 Jul OBJECTIVE: The etiology of rheumatic diseases is unclear, but it is thought that environmental factors added to immunogenetic mechanisms in chronic inflammatory diseases play a role. Many inflammatory disorders, autoimmune diseases, and painful conditions have been shown to be associated with the psychological trauma of childhood. The aim of the present study was to investigate childhood psychological trauma that is considered to be one of the environmental factors that initiate inflammation on patients with rheumatic diseases. METHODS: In our study, a total of 440 patients (220 patients who have rheumatic diseases as the case group and 220 patients who have no rheumatic disease as the control group) were examined. The Childhood Trauma Questionnaire-28 (CTQ-28) was administered and was completed by the patients. This was a cross-sectional study design. RESULTS: No statistically significant differences were found between the case and control groups with respect to age, gender, marital status, and educational level. The CTQ-28 scale was found to be significantly higher in patients with rheumatic diseases (ankylosing spondylitis, rheumatoid arthritis, and connective tissue disease) in our study. CONCLUSION: We think that childhood psychiatric traumas are effective in the etiopathogenesis of rheumatic diseases. To make this relationship more understandable, multidisciplinary research and long-term follow-up studies are needed to examine neuroendocrine, genetic, and epidemiological factors.
31312501 A highly sensitive LC-MS/MS method to determine novel Bruton's tyrosine kinase inhibitor s 2019 Jun Spebrutinib (SBT) is a Bruton's tyrosine kinase inhibitor. SBT is currently in phase II and phase I clinical trials for the management of rheumatoid arthritis and chronic lymphocytic leukaemia, respectively. We developed and validated a liquid chromatography tandem mass spectrometry analytical method to quantify SBT and investigate its metabolic stability. SBT and the naquotinib as internal standard were isocratically eluted on a C18 column. The linearity of the developed method is 5-500 ng ml(-1) (r(2) ≥ 0.9999) in the human liver microsomes (HLMs) matrix. Good sensitivity was approved by the very low limit of detection (0.39 ng ml(-1)). Inter- and intra-assay accuracy values of -1.41 to 12.44 and precision values of 0.71% to 4.78%, were obtained. SBT was found to have an in vitro half-life (82.52 min) and intrinsic clearance (8.4 µl min(-1) mg(-1)) as computed following its incubation with HLMs. The latter finding, hypothesize that SBT could be slowly excreted from the body unlike other related tyrosine kinase inhibitors. So, drug plasma level and kidney function should be monitored because of potential bioaccumulation. To the best of our knowledge, this is considered the first analytical method for SBT quantification using LC-MS/MS with application to metabolic stability evaluation.
31078323 The association of pain locus of control with pain outcomes among older adults. 2020 Sep Our primary objective was to 1) determine the prevalence of pain locus of control (LOC) subscales in a population of older adults with pain conditions, and 2) estimate their associated protective effects on pain outcomes. A mailed survey was sent to a stratified sample of older adults age≥65 with diagnosed back pain, osteoarthritis and/or rheumatoid arthritis. Multivariate logistic regression modeling was used to determine the relative protective associations of positive resources, including LOC, resilience and social networks, on pain outcomes. Among respondents (N = 3,824), 31% were identified as internal; 34% as powerful others; and 35% as chance. In adjusted models, internal was associated with outcomes of lower pain severity, reduced chronic opioid use and increased physical functionality. Powerful others was partially protective; chance was associated with the poorest outcomes. Multidimensional pain programs should incorporate the enhancement of positive resources, including LOC, to maximize the effectiveness of pain management strategies.
31063524 Posttraumatic hip bulging mimicking an abscess in a patient with hip prosthesis: the role 2019 May 2 A 48-yr old female patient, with stage 4 rheumatoid arthritis, who had undergone multiple joint prostheses including four arthroplasties of the left hip, presented for a sudden-onset large bulge on the left thigh, after a minor local injury. Orthopedic examination and radiography excluded fractures. Ultrasonography revealed a large mixed hypo- and hyperechoic collection,with no Doppler signal, but with comet tail artifacts. Repeated cultures from the collection were negative. Fluid analysis revealed increased quantities of titanium and cobalt. The sudden-onset deformity and fluid collection were in favor of a shear lesion (Morel-Lavallée). The new collection communicated with a previously asymptomatic periprosthetic aseptic abscess, mimicking an infection. To our knowledge, Morel-Lavallée shear lesions have not been described in patients with hip prostheses. Their presence may add to the difficulties of ruling out silent infections in such patients. Ultrasonography is a very effective method for the diagnosis and follow-up of collections in this setting.
30988645 Anti-IL-10 antibody in systemic lupus erythematosus. 2019 PURPOSE: IL-10 is a cytokine known to inhibit inflammatory cytokines. To determine its role in the pathogenesis of systemic lupus erythematosus (SLE), the presence of anti-IL-10 antibody is required to be examined. Although antibodies against cytokines are known to be present in SLE, no studies have determined the role of IL-10, particularly in Japanese patients. We assayed anti-IL-10 antibody in SLE and examined the clinical significance. PATIENTS AND METHODS: We performed a retrospective study of 80 Japanese patients with SLE. Sixteen scleroderma patients, 19 rheumatoid arthritis (RA) patients, 23 Behcet's disease patients, and 23 healthy subjects were selected as control groups. Clinical information was abstracted from medical records. Anti-IL-10 antibody level was determined with an ELISA. RESULTS: With the cutoff established as serum absorbance +2 SDs (OD 0.729) in healthy subjects, we defined any sample above this cutoff as anti-IL-10 antibody-positive. Fourteen patients with SLE (17.5%) were found to be anti-IL-10 antibody positive. Absorbance was significantly higher in serum from patients with SLE and RA than in healthy individuals. In SLE, patients with low complement values were significantly more common in the antibody-positive group. Serum IgG levels were significantly higher in the antibody-positive group. In multivariable analysis, high level of serum IgG is associated with anti-IL-10 antibody positive. CONCLUSION: The present study found that anti-IL-10 antibody is present in SLE and related to clinical parameters. These results suggest that the presence of anti-IL-10 antibody was associated with high level of serum IgG, but is not associated with disease activity in patients with SLE.
30921227 Adrenocortical hypofunction with simultaneous primary aldosteronism: A case report. 2019 Mar RATIONALE: Cases of adrenocortical hyperfunction combined with primary aldosteronism have been reported in the literature, and the underlying mechanism involves the secretion of aldosterone and glucocorticoids by a tumor or an adenoma. However, adrenocortical hypofunction and coexisting primary aldosteronism have not been reported until now. Herein, we report a case of adrenocortical hypofunction combined with primary aldosteronism. PATIENT CONCERNS: A 66-year-old Chinese woman with rheumatoid arthritis who had been diagnosed with secondary adrenal insufficiency and was taking prednisone acetate tablets for replacement treatment presented to our department. She also had type 2 diabetes mellitus, osteoporosis, bilateral knee osteoarthritis, and lumbar vertebral compression fracture. She had previously developed tuberculosis, which had been cured. DIAGNOSIS: The cortisol and adrenocorticotropic hormone rhythm indicated cortisol dysfunction in the patient. A 64-slice computed tomography and magnetic resonance imaging both showed bilateral adrenal hyperplasia. A postural stimulation test indicated a high level of aldosteronism and a high aldosterone-to-renin ratio (ARR, supine position: aldosterone 1788.73 pg/mL, ARR 146.62; upright position: aldosterone 2916.21 pg/mL, ARR 92.29). The captopril test showed the aldosterone level decreased by 364.70 pg/mL 1 hour after administration of captopril (from 2153.28 to 1788.58 pg/mL). The decline in aldosterone level was approximately 16.90% (i.e., <30%), and the ARR was still >40. Based on the above-mentioned findings, we diagnosed the patient with adrenocortical hypofunction with primary aldosteronism. INTERVENTIONS: We administered spironolactone 20 mg twice daily and continued the glucocorticoid replacement therapy. OUTCOMES: One week after diagnosis, the patient had an aldosterone level of 2201.16 pg/mL, plasma renin activity of 3.88 ng/mL/h, and an ARR of 56.7 (upright position). Her blood pressure was maintained within the normal range. LESSONS: Although adrenocortical hypofunction with primary aldosteronism is rare, cases of primary aldosteronism complicated with hypercortisolism are occasionally encountered. Hence, whenever possible, we recommend testing both aldosterone and cortisol levels in all patients with adrenal dysfunction.
30918839 Seeking for Correlative Genes and Signaling Pathways With Bone Metastasis From Breast Canc 2019 Background: Bone metastasis frequently occurs in advanced breast cancer patients, and it is one of major causes of breast cancer associated mortality. The aim of the current study is to identify potential genes and related signaling pathways in the pathophysiology of breast cancer bone metastasis. Methods: Three mRNA expression datasets for breast cancer bone metastasis were obtained from Gene Expression Omnibus (GEO) dataset. The differentially expressed genes (DEGs) were obtained. Functional analyses, protein-protein interaction (PPI) network, and transcription factors (TFs)-target genes network was constructed. Real-time PCR using clinical specimens was conducted to justify the results from integrated analysis. Results: A 749 DEGs were obtained. Osteoclast differentiation and rheumatoid arthritis were two significantly enriched signaling pathways for DEGs in the bone metastasis of breast cancer. SMAD7 (degree = 10), TGFBR2 (degree = 9), VIM (degree = 8), FOS (degree = 8), PDGFRB (degree = 7), COL5A1 (degree = 6), ARRB2 (degree = 6), and ITGAV (degree = 6) were high degree genes in the PPI network. ETS1 (degree = 12), SPI1 (degree = 12), FOS (degree = 10), FLI1 (degree = 5), KLF4 (degree = 4), JUNB (degree = 4), NR3C1 (degree = 4) were high degree genes in the TFs-target genes network. Validated by QRT-PCR, the expression levels of IBSP, MMP9, MMP13, TNFAIP6, CD200, DHRS3, ASS1, RIPK4, VIM, and PROM1 were roughly consistent with our integrated analysis. Except PROM1, the other genes had a diagnose value for breast cancer bone metastasis. Conclusions: The identified DEGs and signaling pathways may make contribution for understanding the pathological mechanism of bone metastasis from breast cancer.
30910556 De novo whole transcriptome profiling of Edwardsiella tarda isolated from infected fish (L 2019 Jun 15 Edwardsiella tarda belongs to the genera of Gram negative bacterium mainly associated with edwardsiellosis, the most commonly found infectious fish disease throughout the globe. E. tarda is also a widespread pathogen which cause infections such as cellulitis or gas gangrene and generalized infections in humans. To control the escalating infection of E. trada on various species, it is essential to decoded the mysterious mechanism behind the bacterial infection at transcript level. In this present study, we carry out a de novo E. tarda Whole transcriptome sequencing, isolated from infected fish intestine using SOLiD sequencing platform. RNA-Seq data analysis was performed using various bioinformatics pipelines. Protein-protein interaction study for pathway enrichment and gene ontology study were executed for further investigation. Assembly statistics for E. tarda dataset showed that the number of transcript contigs was 9657 out of which 6749 were GO annotated whereas 1528 were not assigned any GO terms. GO analysis showed that the expressed genes were enhanced with molecular function, cellular component and biological process. A KEGG enrichment study showed that pathway's that are directly linked with immune diseases like Rheumatoid arthritis (0.2%), Tuberculosis (0.3%) Endocytosis (0.6%) was considerably enriched. Protein-protein interaction study showed that most of the expressed proteins were involved in metabolic pathways, flagellar assembly, Propanoate metabolism, Microbial metabolism in diverse environments, Butanoate metabolism and Carbon. The present study provides novel E. tarda transcriptome sequence data, allowing us to identify biologically significant genes and their functional relationship with fish diseases, and will be useful in recognize the reliable therapeutic targets in near feature.
30801238 Association of Resilience and Social Networks with Pain Outcomes Among Older Adults. 2019 Dec Depression, stress, and poor sleep have been associated with increased pain among older adults; positive resources, such as resilience and social networks, may help to buffer the impacts of these negative attributes on pain outcomes. The primary objective was to determine the relative effects of positive resources and negative attributes on pain outcomes among older adults with diagnosed back pain, osteoarthritis, and rheumatoid arthritis. The stratified study sample was identified from older adults ages ≥65 years. Members received a survey assessing positive resources (resilience, social networks), negative attributes (depression, stress, poor sleep), and pain outcomes (severity, interference). Opioid and other medication use was determined from pharmaceutical claims. After weighting to representative distributions of pain conditions and adjusting for survey response bias, multinomial logistic regressions were used to determine the relative associations of positive and negative attributes on pain outcomes. Among survey respondents (N = 4161), prevalence of self-reported pain severity and interference for no/mild, moderate, and severe categories was 61%, 21%, and 18%, and 67%, 16%, and 17%, respectively. In bivariate models, negative attributes of depression, stress, and poor sleep had stronger associations with pain severity and interference than the moderating effects of positive resources of high resilience and diverse social networks. In fully adjusted multivariate models, the strongest associations with moderate and severe pain severity and interference remained depression, stress, and poor sleep. Based on these results, multidimensional pain management strategies should include management of negative attributes along with enhancement of positive resources for effective management of chronic pain.
30531019 Association of GTF2IRD1-GTF2I polymorphisms with neuromyelitis optica spectrum disorders i 2019 Feb Variants at the GTF2I repeat domain containing 1 (GTF2IRD1)-GTF2I locus are associated with primary Sjögren's syndrome, systemic lupus erythematosus, and rheumatoid arthritis. Numerous studies have indicated that this susceptibility locus is shared by multiple autoimmune diseases. However, until now there were no studies of the correlation between GTF2IRD1-GTF2I polymorphisms and neuromyelitis optica spectrum disorders (NMOSD). This case control study assessed this association by recruiting 305 participants with neuromyelitis optica spectrum disorders and 487 healthy controls at the Department of Neurology, from September 2014 to April 2017. Peripheral blood was collected, DNA extracteds and the genetic association between GTF2IRD1-GTF2I polymorphisms and neuromyelitis optica spectrum disorders in the Chinese Han population was analyzed by genotyping. We found that the T allele of rs117026326 was associated with an increased risk of neuromyelitis optica spectrum disorders (odds ratio (OR) = 1.364, 95% confidence interval (CI) 1.019-1.828; P = 0.037). This association persisted after stratification analysis for aquaporin-4 immunoglobulin G antibodies (AQP4-IgG) positivity (OR = 1.397, 95% CI 1.021-1.912; P = 0.036) and stratification according to coexisting autoimmune diseases (OR = 1.446, 95% CI 1.072-1.952; P = 0.015). Furthermore, the CC genotype of rs73366469 was frequent in AQP4-IgG-seropositive patients (OR = 3.15, 95% CI 1.183-8.393, P = 0.022). In conclusion, the T allele of rs117026326 was associated with susceptibility to neuromyelitis optica spectrum disorders, and the CC genotype of rs73366469 conferred susceptibility to AQP4-IgG-seropositivity in Han Chinese patients. The protocol was approved by the Ethics Committee of West China Hospital of Sichuan University, China (approval number: 2016-31) on March 2, 2016.
30513071 Utilization of High-Cost Interventions for Targeted Clinical Conditions During the Early S 2019 Oct This study compared utilization patterns of high-cost services and medications for patients receiving care from Accountable Care Organization (ACO)-participating physicians and those receiving care from non-ACO physicians during the initial phases of ACO development in a commercially insured environment. Patients ≥18 years (≥40 years for chronic obstructive pulmonary disease [COPD]) with prevalent rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, type 2 diabetes, COPD, or chronic low back pain between January 1, 2012, and August 31, 2014 were identified in the HealthCore Integrated Research Database(SM). Patients were assigned to the ACO cohort if their primary treating physician was contracted to the health plan through an ACO agreement. Each clinical condition was stratified for severity of illness. Cohort utilization patterns were compared for the 12-month period following the index encounter. The primary outcome measures show that there was no statistically significant utilization difference between the ACO and non-ACO cohorts for 90% of the 82 comparisons made. It is expected that some measures will achieve significant difference simply because of having this many comparisons, but no clear pattern was identified. This study did not observe statistically significant differences in utilization of high-cost services and medications between ACO and non-ACO cohorts with limited experience in the ACO model. Future analyses with longer study durations, at later stages of ACO development, tracking a more granular level of physician organizational structure, and with designs that integrate clinical and administrative data are essential to better understand the impact of payment innovation strategies using an ACO structure.
35107907 2019 Nov Chronic pain has recently been defined by the ICD-11 as pain that persists or recurs for longer than 3 months. Chronic primary pain is defined as pain in one or more anatomical regions that persists or recurs for longer than 3 months and is associated with significant emotional distress or functional disability. Chronic secondary pain syndromes are linked to other diseases as the underlying cause, where pain becomes a problem in its own right. In practice, the division between acute and chronic pain can be difficult to establish. This is particularly true in children and young people, and the committee felt that the looser (non-temporal) term ‘persistent pain’ is more commonly used in this group. According to the British Medical Association briefing paper chronic pain: supporting safer prescribing of analgesics, chronic pain affects about 13% of adults in the UK, and about 8% of children experience severe pain. NICE has published a summary on the evidence base on medicines optimisation in chronic pain. A NICE guideline on chronic pain: assessment and management is in development. This guideline is intended to be used alongside existing NICE guidance for specific conditions that cause pain, including headaches, low back pain and sciatica, rheumatoid arthritis, osteoarthritis, spondyloarthritis, endometriosis and irritable bowel syndrome. The aim of this review was to find out how effective cannabis-based medicinal products are in managing chronic pain, particularly when conventional treatment options have failed or not been tolerated. The review looked into the safety profile (including complications and contraindications) and examined what individual patient requirements, treatment durations, reviewing and stopping criteria need to be considered when prescribing cannabis-based medicinal products. Chronic pain is common in the UK general population but has a heterogeneous aetiology. A recent epidemiological study found that roughly 43.5%, 28 million people in the UK general population were expected to have “severe and chronic pain that is unresponsive to treatment”. Treatment options vary widely depending on the cause of the pain but their effectiveness and side effects vary widely and there is very significant unmet clinical need in the population group whose pain is not adequately controlled by these conventional options. Some chronic pain patients self treat with cannabis based products purchased as health food supplements or online and there is widespread interest in whether Cannabis Based Medicinal Products (CBMPs) should be prescribed on the NHS. However, it is currently very rare for patients with chronic pain to be treated with CBMPs on the NHS. The CBMPs that are currently on the market could cost several thousand pounds per patient per year, based on publicly available sources for price. This, along with the considerations above meant that the potential resource impact of a positive recommendation in this area could be extremely high. The committee therefore prioritised this question for de novo economic modelling as any positive recommendation would need to be underpinned by robust health economic evaluation.
31854165 Population-based Study of 24 Autoimmune Diseases Carried Out in a Brazilian Microregion. 2019 Dec In Brazil, epidemiological data on autoimmune diseases are scarce due to the lack of a specific policy of attention to this group of diseases. This study aimed to estimate the general and relative prevalence of the diseases presented, as well as to know the sociodemographic profile of the identified cases. This cross-sectional study was conducted with an epidemiological survey of patients with confirmed diagnosis of autoimmune diseases from primary health care in the Aguas Formosas microregion, Minas Gerais, Brazil. We have included all new and old cases found of individuals of both sexes and all ages, including those who died and emigrated during this period. A total of 407 carriers and 24 different autoimmune diseases were identified. The prevalence of autoimmune diseases in this region was 673.6 cases per 100,000 inhabitants [95% confidence interval (CI): 609.8-742.4]. Highest prevalence was identified for Hashimoto's thyroiditis 140.6 cases per 100,000 (95% CI: 112.4-173.9), followed by vitiligo 132.4 cases per 100,000 (95% CI: 105.0-164.8), and rheumatoid arthritis 105.9 cases per 100,000 (95% CI: 81.6-135.3). The sex ratio was higher in females (69%), the most affected age group was over 60 years (30.5%), with greater predominance in the urban area (81.3%). Our data showed the general and relative prevalence of the identified diseases, allowing to know the sociodemographic profile of the identified cases and the epidemiological trend of these morbidities in a low-income Brazilian region.
31830562 Relevance of Nrf2 and heme oxygenase-1 in articular diseases. 2020 Sep Joint conditions pose an important public health problem as they are a leading cause of pain, functional limitation and physical disability. Oxidative stress is related to the pathogenesis of many chronic diseases affecting the joints such as rheumatoid arthritis and osteoarthritis. Cells have developed adaptive protection mechanisms to maintain homeostasis such as nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2) which regulates the transcription of many genes involved in redox balance, detoxification, metabolism and inflammation. Activation of Nrf2 results in the synthesis of heme oxygenase-1 (HO-1) leading to the formation of a number of bioactive metabolites, mainly CO, biliverdin and bilirubin. Ample evidence supports the notion that Nrf2 and HO-1 can confer protection against oxidative stress and inflammatory and immune responses in joint tissues. As a consequence, this pathway may control the activation and metabolism of articular cells to play a regulatory role in joint destruction thus offering new opportunities for better treatments. Further studies are necessary to identify improved strategies to regulate Nrf2 and HO-1 activation in order to enable the development of drugs with therapeutic applications in joint diseases.
31824513 Immunomodulatory Effects of Vitamin D in Pregnancy and Beyond. 2019 In addition to its role in calcium homeostasis and bone formation, a modulatory role of the active form of vitamin D on cells of the immune system, particularly T lymphocytes, has been described. The effects of vitamin D on the production and action of several cytokines has been intensively investigated in recent years. In this connection, deficiency of vitamin D has been associated with several autoimmune diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), antiphospholipid syndrome (APS), Hashimoto Thyroiditis (HT), and multiple sclerosis (MS). In a successful pregnancy, the maternal immune response needs to adapt to accommodate the semiallogeneic fetus. Disturbances in maternal tolerance are implicated in infertility and pregnancy complications such as miscarriages (RM) and preeclampsia (PE). It is well-known that a subset of T lymphocytes, regulatory T cells (Tregs) exhibit potent suppressive activity, and have a crucial role in curtailing the destructive response of the immune system during pregnancy, and preventing autoimmune diseases. Interestingly, vitamin D deficiency is common in pregnant women, despite the widespread use of prenatal vitamins, and adverse pregnancy outcomes such as RM, PE, intrauterine growth restriction have been linked to hypovitaminosis D during pregnancy. Research has shown that autoimmune diseases have a significant prevalence within the female population, and women with autoimmune disorders are at higher risk for adverse pregnancy outcomes. Provocatively, dysregulation of T cells plays a crucial role in the pathogenesis of autoimmunity, and adverse pregnancy outcomes where these pathologies are also associated with vitamin D deficiency. This article reviews the immunomodulatory role of vitamin D in autoimmune diseases and pregnancy. In particular, we will describe the role of vitamin D from conception until delivery, including the health of the offspring. This review highlights an observational study where hypovitaminosis D was correlated with decreased fertility, increased disease activity, placental insufficiency, and preeclampsia in women with APS.