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ID PMID Title PublicationDate abstract
34386321 The influence of the gut microbiota on the bioavailability of oral drugs. 2021 Jul Due to its safety, convenience, low cost and good compliance, oral administration attracts lots of attention. However, the efficacy of many oral drugs is limited to their unsatisfactory bioavailability in the gastrointestinal tract. One of the critical and most overlooked factors is the symbiotic gut microbiota that can modulate the bioavailability of oral drugs by participating in the biotransformation of oral drugs, influencing the drug transport process and altering some gastrointestinal properties. In this review, we summarized the existing research investigating the possible relationship between the gut microbiota and the bioavailability of oral drugs, which may provide great ideas and useful instructions for the design of novel drug delivery systems or the achievement of personalized medicine.
31074577 Arthritis, Sleep Health, and Systemic Inflammation in Older Men. 2020 Jul OBJECTIVE: To examine the associations of prevalent arthritis with systemic inflammation in older men and to test whether sleep health mediates the associations. METHODS: Cross-sectional data came from 2,562 community-dwelling older men (all were age 65 years or older; mean age 76 years) in the Osteoporotic Fractures in Men Study who participated in a sleep ancillary study in 2003-2005. Participants were classified as having osteoarthritis (OA) (24%) or rheumatoid arthritis (RA) (0.7%) based on self-reported diagnoses and medication use. We constructed a composite score of multidimensional sleep health (i.e., perceived sleep quality, sleepiness, frequency of daytime napping, wake after sleep onset, and sleep duration) measured by both self-report and actigraphy. We also created binary indicators of elevated inflammation using C-reactive protein (CRP) (>3 mg/liter) and interleukin-6 (IL-6) (>1.08 pg/ml) levels. Analyses controlled for age, diagnosed sleep disorders, body mass index, smoking status, relevant medication use, and comorbidities. RESULTS: Older men with OA did not have higher risk of elevated CRP or IL-6 levels. However, indirect associations of OA through sleep health were found. OA was associated with poorer sleep health, which was further associated with 16% higher odds of elevated CRP (P < 0.001) and 12% higher odds of elevated IL-6 (P < 0.01) levels after controlling for OA. Older men with RA had higher odds of elevated CRP and IL-6 levels, but the associations were not mediated by sleep health. CONCLUSION: Findings suggest that promoting sleep health may help reduce the risk of systemic inflammation in older men with OA.
33029091 Intake of dietary fibre, red and processed meat and risk of late-onset Chronic Inflammator 2020 Background: Human and animal studies support the involvement of diet in the development of CID -chronic inflammatory diseases such as inflammatory bowel disease, psoriasis, rheumatoid arthritis, psoriatic arthritis, and multiple sclerosis. Objective: This cohort study aimed to investigate the association between intake of fibre, red and processed meat, and occurrence of late-onset CID (50+ years of age) in the DCH: Danish Diet, Cancer and Health cohort. We hypothesised that risk of late-onset CID would be lower among those with high intake of fibre and/or low intake of meat compared to individuals with low fibre and/or high meat intake. Methods: The DCH recruited 56,468 individuals, aged 50-64 years, between 1993 and 1997. At recruitment, diet intake was registered using food frequency questionnaires as well as lifestyle factors in 56,075 persons. Exposure variables were generated as sex-adjusted tertiles of fibre and meat (g/day). Development of CIDs was identified in national registries. Hazard ratios (HR) of late-onset CIDs (adjusted for age, sex, energy intake, alcohol, smoking, education, comorbidity, and civil status) were estimated for all three exposure variables. Results: During follow-up of 1,123,754 years (median (Interquartile range) = 22.2 (20.1-23.1)), 1,758 (3.1%) participants developed at least one CID. The adjusted HRs for developing CID (low fibre 1.04 [0.89-1.22] and medium fibre 1.04 [0.91-1.18] (high fibre as reference), and medium meat 0.96 [0.86-1.09] and high meat 0.94 [0.82-1.07] (low meat as reference)) or the individual diseases were not statistically significant. Conclusion: This large study did not support that a high intake of fibre and/or a low intake of meat had a high impact on the risk of late-onset CID.
33521321 Targeting the JAK/STAT pathway in solid tumors. 2020 Aberrant activation of signal transducer and activator of transcription (STAT) proteins is associated with the development and progression of solid tumors. However, as transcription factors, these proteins are difficult to target directly. In this review, we summarize the role of targeting Janus kinases (JAKs), upstream activators of STATs, as a strategy for decreasing STAT activation in solid tumors. Preclinical studies in solid tumor cell line models show that JAK inhibitors decrease STAT activation, cell proliferation, and cell survival; in in vivo models, they also inhibit tumor growth. JAK inhibitors, particularly the JAK1/2 inhibitor ruxolitinib, sensitize cell lines and murine models to chemotherapy, immunotherapy, and oncolytic viral therapy. Ten JAK inhibitors have been or are actively being tested in clinical trials as monotherapy or in combination with other agents in patients with solid tumors; two of these inhibitors are already Food and Drug Administration (FDA) approved for the treatment of myeloproliferative disorders and rheumatoid arthritis, making them attractive agents for use in patients with solid tumors as they are known to be well-tolerated. Four JAK inhibitors (two of which are FDA approved for other indications) have exhibited promising anti-cancer effects in preclinical studies; however, clinical studies specifically assessing their activity against the JAK/STAT pathway in solid tumors have not yet been conducted. In summary, JAK inhibition is a viable option for targeting the JAK/STAT pathway in solid tumors and merits further testing in clinical trials.
33390944 Moringa oleifera Lam and its Therapeutic Effects in Immune Disorders. 2020 Moringa oleifera Lam., a plant native to tropical forests of India, is characterized by its versatile application as a food additive and supplement therapy. Accumulating evidence shows that Moringa plays a critical role in immune-related diseases. In this review, we cover the history, constituents, edibility, and general medicinal value of Moringa. The effects of Moringa in treating immune disorders are discussed in detail. Moringa can not only eliminate pathogens, including bacteria, fungi, viruses, and parasites, but also inhibit chronic inflammation, such as asthma, ulcerative colitis, and metabolic diseases. Additionally, Moringa can attenuate physical and chemical irritation-induced immune disorders, such as metal intoxication, drug side effects, or even the adverse effect of food additives. Autoimmune diseases, like rheumatoid arthritis, atopic dermatitis, and multiple sclerosis, can also be inhibited by Moringa. Collectively, Moringa, with its multiple immune regulatory bioactivities and few side effects, has a marked potential to treat immune disorders.
33354381 Clinical Observation of COVID-19 in a Patient With an Acquired Humoral Deficiency Secondar 2020 Jan INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic due to the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes worldwide devastation. We describe the course of a patient with COVID-19 in the setting of an acquired humoral deficiency as a result of chemotherapeutic treatment for rheumatologic conditions. CASE REPORT: A 49-year-old Caucasian male presented with non-relieving fever, hypoxemia, and persistent diarrhea after seven days following a positive SARS-CoV-2 polymerase chain reaction (PCR) assay. The patient's past medical history was significant for mixed connective tissue disease, rheumatoid arthritis, and systemic lupus erythematosus treated with methotrexate and rituximab since 2008. He was diagnosed with acquired humoral deficiency in 2017 managed by intravenous immunoglobulin (IVIG) infusion every three weeks. The patient's course of hospitalization was complicated by acute respiratory distress which necessitated intensive unit care and required up to 20 L/min oxygen supplementation via a humidified high flow generator. He was treated with hydroxychloroquine and azithromycin and received an IVIG transfusion. The patient was discharged to home after forty-two days of hospitalization with oxygen supplementation only during ambulation and a complete resolution of diarrhea. DISCUSSION: According to current limited data, patients with immunodeficiency have longer length of hospitalization compared to immunocompetent individuals. Our patient demonstrated a form of immunodeficiency as the result of a chemotherapeutic agent, and his clinical course appeared to be more severe. CONCLUSION: More studies are necessary to shed light on the immunological response to SARS-CoV-2 and its impact on immunocompromised and immunocompetent and individuals. We describe the course of a patient with COVID-19 in the setting of an acquired humoral deficiency.
33315138 6-month SARS-CoV-2 antibody persistency in a Tyrolian COVID-19 cohort. 2021 Apr BACKGROUND: As coronavirus disease 2019 caused by severe acute respiratory syndrome coronavirus 2 evolved only recently, the persistency of the anti-viral antibody response remains to be determined. METHODS: We prospectively followed 29 coronavirus disease 2019 cases, mean age 44 ± 13.2 years. Except for one participant with a pre-existing diagnosis of rheumatoid arthritis, all other participants were previously healthy. We determined anti-viral binding antibodies at 2-10 weeks, 3 months, and 6 months after disease onset as well as neutralizing antibodies at 6 months. Two binding antibody assays were used, targeting the S1 subunit of the spike protein, and the receptor binding domain. RESULTS: All participants fully recovered spontaneously except for one who had persisting hyposmia. Antibodies to the receptor binding domain persisted for 6 months in all cases with a slight increase of titers, whereas antibodies to S1 dropped below the cut-off point in 2 participants and showed a minimal decrease on average, mainly at month 3 of follow-up in males; however, neutralizing antibodies were detected in all samples at 6 months of follow-up. CONCLUSION: There is a stable and persisting antibody response against acute respiratory syndrome coronavirus 2 at 6 months after infection. Neutralizing antibodies confirm virus specificity. As the number of coronavirus disease 2019 convalescent cases is increasing sharply, antibody testing should be implemented to identify immunized individuals. This information can be helpful in various settings of professional and private life.
33238163 Combining miR-23b exposure with mesenchymal stem cell transplantation enhances therapeutic 2021 Jan Bone marrow mesenchymal stem cells (BMSCs) have the immuno-modulatory capacity to ameliorate autoimmune diseases, such as multiple schlerosis (MS), systemic lupus erythematosus and rheumatoid arthritis. However, BMSC-mediated immunosuppression can be challenging to achieve. The efficacy of BMSC transplantation may be augmented by an adjuvant therapy. Here, we demonstrated that treatment of mice with experimental autoimmune encephalomyelitis (EAE), a model of MS, with BMSCs over-expressing microRNA (miR)-23b provided better synergistic and longer-term therapeutic effects than treatment with traditional BMSCs. Over-expression of miR-23b enhanced the ability of BMSCs to inhibit differentiation of Th17 cells and reduced IL-17 secretion. Compared to traditional BMSCs, the miR-23b over-expressing BMSCs (miR23b-BMSCs) exhibited enhanced secretion of tumor growth factor beta 1 (TGF-β(1)), a cytokine that promotes the differentiation of regulatory T (Treg) cells. Pathologically, miR23b-BMSC transplantation delayed EAE progression, apparently by reducing the Th17/Treg cell ratio and inhibiting inflammatory cell infiltration across the blood-brain barrier, and thus slowing spinal cord demyelination. These results may lead to better utility of BMSCs as a treatment for autoimmune diseases.
33155857 Methotrexate-Associated Lymphoproliferative Disorders Mimicking Granulomatosis With Polyan 2020 Nov 6 Methotrexate-associated lymphoproliferative disorders (MTX-LPD) frequently involve the extranodal organs throughout the body. Among the extranodal occurrences of MTX-LPD, pulmonary involvement is most frequent. In contrast, there are only a few reports of MTX-LPD in the nasal cavity or paranasal sinuses. Moreover, there are no previous reports of MTX-LPD mimicking granulomatosis with polyangiitis (GPA) in imaging examinations. We describe a case of a 53-year-old woman with MTX-LPD mimicking GPA in the nasal cavity and lungs. She complained of left nasal obstruction and discharge, general fatigue, and continual fever for 2 months. The patient had been diagnosed with rheumatoid arthritis and received methotrexate (MTX) for over 10 years. Contrast-enhanced computed tomography revealed unenhanced masses in the nasal cavity and multiple masses with cavitary changes in the bilateral lungs, suggesting GPA. However, histological examination of the nasal lesion and a history of MTX treatment indicated a diffuse large B-cell lymphoma type MTX-LPD. Two weeks after MTX withdrawal, prominent improvements in both lesions were observed. Complete regression of the nasal lesion was observed 3 months after discontinuation of MTX. Thus, MTX-LPD may mimic GPA in imaging examinations.
33123397 Posner-Schlossman Syndrome in Common Variable Immunodeficiency. 2020 INTRODUCTION: Posner-Schlossman syndrome (PSS) is a rare glaucomatocyclitic crisis with clinical features including recurrent episodes of unilateral elevated intraocular pressure. Autoimmune and infectious causes have been proposed as potential etiologies of PSS. We report the first case of PSS in the setting of common variable immunodeficiency (CVID). Case Report. A sixty-two-year-old Caucasian female with a medical history of CVID and ulcerative colitis presented to the emergency room with complaints of acute right-sided vision changes. She reported image distortion, blurriness, and loss of central vision. Physical exam was significant for mildly injected right conjunctiva, visual acuity of 20/70 in right eye, and 20/25 in left eye. The right intraocular pressure was measured at 34 mmHg and left at 12 mmHg. The gonioscopy and dilated fundus examination were unremarkable. Cup to disc ratio was within normal limits, and no afferent pupillary defects were recorded. The patient was acutely treated with three rounds of dorzolamide/timolol and 0.2% brimonidine which decreased the right eye intraocular pressure to 24 mmHg. On follow-up exam with an ophthalmologist, anterior uveitis including an elevated pressure of 41 mmHg on the right and 18 mmHg on the left eye was noted and a PSS diagnosis was confirmed. CONCLUSION: PSS remains a rare condition with uncertain etiology and no associated systemic conditions. PSS has been postulated to be linked to autoimmune conditions. CVID is associated with many autoimmune disorders including Sjogren's, rheumatoid arthritis, and colitis. There have been a few reported CVID-associated ocular diseases including granulomatous uveitis and conjunctivitis, chronic anterior uveitis, and birdshot retinopathy. We describe the first case of PSS in a patient with CVID.
32959708 Effects of cigarette smoking and human T-cell leukaemia virus type 1 infection on anti-cit 2021 Jul Objectives: We investigated whether the positivity of anti-citrullinated peptide antibody (ACPA) is associated with cigarette-smoking status and human T-cell leukaemia virus type 1 (HTLV-1) infection in a general population in Nagasaki, Japan, which is an ageing and HTLV-1-endemic area.Method: Baseline data from community-dwelling people in the Nagasaki Islands Study (NaIS) were included in this cross-sectional analysis. ACPA and HTLV-1 were measured in 3887 subjects without a history of treatment for rheumatoid arthritis. A logistic regression analysis was performed to assess the relationship between ACPA positivity and candidates of correlation with ACPA, i.e. the cigarette-smoking status quantified by Brinkman's index (BI) and HTLV-1 positivity.Results: Fifty-one subjects (1.3%) showed ACPA positivity, and 650 subjects (16.6%) were HTLV-1 carriers. In an age- and gender-adjusted logistic regression analysis, the BI [odds ratio (OR) 1.09, 95% confidence interval (CI)1.02-1.14, p = 0.0031] and a BI value > 500 (OR 3.92, 95% CI 1.72-9.22, p = 0.0014) were each significantly associated with ACPA positivity. HTLV-1 positivity did not show any association with ACPA positivity.Conclusion: A significant effect of cigarette-smoking status on ACPA production was revealed, whereas HTLV-1 positivity was not associated with ACPA production in this general population.
32824575 Real-Time Impedance Detection of Intra-Articular Space in a Porcine Model Using a Monopola 2020 Aug 17 Rheumatoid arthritis and osteoarthritis can be treated through specific drug injection into the intra-articular space. Several failures during drug injection attempts with conventional fluoroscopy and ultrasonography in a small area of the intra-articular space have been reported. In this work we present an innovative impedance measurement-based method/algorithm for needle tip positioning to enhance image-guided intra-articular vaccination treatment. A novel algorithm for detecting the intra-articular space in the elbow and knee joints of a live porcine model is reported. An impedance measurement system was developed for biological tissue measurement. The electrical impedance in the intra-articular space was monitored and the needle tip was examined by ultrasonography. The contrast dye was vaccinated and checked using fluoroscopy to confirm that the dye was properly inoculated in the cavity. The electrical impedance was estimated for various needle inclusion profundity levels in saline solution, which were broadly used to evaluate the proposed device for in vivo examinations. Good efficiency was observed in the impedance-based measurements using a monopolar injection needle for intra-articular therapy. To enhance the needle tip positioning for intra-articular therapy, the intended impedance measurement device with a monopolar injection needle can be used as a complement to existing modalities.
32666762 Vitamin D and Autoimmune Thyroid Diseases - a Review. 2020 Jun 30 The essential biological action of vitamin D is regulation of calcium and phosphorus metabolism and preserving bone health. In recent years there have been reports about the extraskeletal actions of vitamin D and its role in the regulation of immune system. Vitamin D supplementation appears to reduce the incidence of cardiovascular diseases, cancer, and infections and be able to reduce all-cause mortality. Deficiency of vitamin D has been found to correlate with the increased incidence of autoimmune diseases, including type 1 diabetes mellitus, rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis. Autoimmune thyroid diseases (AITD), including Graves' disease, Hashimoto's thyroiditis are relatively common autoimmune disorders affecting more than 5% of general population. It has been shown that vitamin D receptors (VDR) and 1-alpha hydroxylase are expressed in papillary thyroid cancer and normal thyroid tissue, suggesting local synthesis of 1,25(OH)2D in the thyroid. While VDR gene polymorphism has been found in much research to be associated with AITDs, very few studies have examined the impact of vitamin D deficiency on the incidence of AITDs in humans with conflicting results. This review focuses on the association between vitamin D and autoimmune thyroid diseases and summarizes the results of vitamin D supplementation studies in patients with AITD.
32664207 Mechanisms behind the Immunoregulatory Dialogue between Mesenchymal Stem Cells and Th17 Ce 2020 Jul 10 Mesenchymal stem cells (MSCs) exhibit potent immunoregulatory abilities by interacting with cells of the adaptive and innate immune system. In vitro, MSCs inhibit the differentiation of T cells into T helper 17 (Th17) cells and repress their proliferation. In vivo, the administration of MSCs to treat various experimental inflammatory and autoimmune diseases, such as rheumatoid arthritis, type 1 diabetes, multiple sclerosis, systemic lupus erythematosus, and bowel disease showed promising therapeutic results. These therapeutic properties mediated by MSCs are associated with an attenuated immune response characterized by a reduced frequency of Th17 cells and the generation of regulatory T cells. In this manuscript, we review how MSC and Th17 cells interact, communicate, and exchange information through different ways such as cell-to-cell contact, secretion of soluble factors, and organelle transfer. Moreover, we discuss the consequences of this dynamic dialogue between MSC and Th17 well described by their phenotypic and functional plasticity.
32640727 Cell-Type Targeted NF-kappaB Inhibition for the Treatment of Inflammatory Diseases. 2020 Jul 6 Deregulated NF-k activation is not only involved in cancer but also contributes to the pathogenesis of chronic inflammatory diseases like rheumatoid arthritis (RA) and multiple sclerosis (MS). Ideally, therapeutic NF-KappaB inhibition should only take place in those cell types that are involved in disease pathogenesis to maintain physiological cell functions in all other cells. In contrast, unselective NF-kappaB inhibition in all cells results in multiple adverse effects, a major hindrance in drug development. Hitherto, various substances exist to inhibit different steps of NF-kappaB signaling. However, powerful tools for cell-type specific NF-kappaB inhibition are not yet established. Here, we review the role of NF-kappaB in inflammatory diseases, current strategies for drug delivery and NF-kappaB inhibition and point out the "sneaking ligand" approach. Sneaking ligand fusion proteins (SLFPs) are recombinant proteins with modular architecture consisting of three domains. The prototype SLC1 binds specifically to the activated endothelium and blocks canonical NF-kappaB activation. In vivo, SLC1 attenuated clinical and histological signs of experimental arthritides. The SLFP architecture allows an easy exchange of binding and effector domains and represents an attractive approach to study disease-relevant biological targets in a broad range of diseases. In vivo, SLFP treatment might increase therapeutic efficacy while minimizing adverse effects.
32598773 [Panniculitis in modern rheumatology]. 2020 Jun 5 AIM: To study clinical and laboratory features of panniculitis (Pn) in modern rheumatology. MATERIALS AND METHODS: The study included 690 patients with Pn (615 women and 75 men, average age 39.410.26) with the prevailing referral diagnosis of Erythema nodosum (59.2%), Pn (27.5%), Rheumatic disease Rd (9%), other diseases (4.4%),who had been on outpatient and/or inpatient treatment for 10 years. All patients were examined according to our diagnostic algorithm: general clinical, immunological and histological examinations, computed tomography of the chest organs, tuberculin tests. RESULTS: Pn with Rd was diagnosed in 140 patients (118 women and 22 men, average age 40.2114.87), average disease duration 31.06 [0.1; 541] months. In most cases (49%) patients had idiopathic lobular Pn which belongs to the group of systematic lesions of connective tissue (M35.6), as well as systemic lupus erythematosus and Behcet disease (13% each), rheumatoid arthritis (8%), dermatomyositis (6.4%), etc. Matching of the referral and final diagnoses was 35% in case of Rd. Among the examined patients prevailed those with a moderate (51.07%) degree of activity of the underlying disease. Within the study group Pn was represented by all forms, but mainly by nodular form (64.02%). Mesenteric form was characteristic only for idiopathic lobular Pn. The main features of Pn associated with Rd were identified. In modern clinical practice the type of Pn and the activity of the underlying disease determine the approaches to treatment.
32314877 External Validation of a Risk Score for Major Toxicity Among Nonsteroidal Anti-Inflammator 2020 May OBJECTIVE: We previously derived and validated a risk score for major nonsteroidal anti-inflammatory drug (NSAID) toxicity over 1 year among NSAID users in a randomized controlled trial. This work was extended to examine the risk score's performance in an external population using real-world data. METHODS: Patients enrolled in the Corrona Rheumatoid Arthritis (RA) Registry were included if they initiated use of an NSAID. We defined the original risk factors previously identified in the risk score for major NSAID toxicity: age; male sex; history of cardiovascular disease, hypertension, and diabetes; tobacco use; statin use; elevated serum creatinine and hematocrit values; and RA. Additionally, we defined the occurrence of major toxicity, including major adverse cardiovascular events, acute kidney injury, significant gastrointestinal events, and mortality. The original risk factors were assessed in Cox regression examining discrimination and calibration. Low (less than 1%), intermediate (1%-4%), and high (more than 4%) risk categories for 1-year risk were applied to the population. RESULTS: A total of 5231 patients from Corrona who had a new NSAID exposure period were included. The original risk score model showed good discrimination (C-index 0.70). Not all of the original variables were statistically significant in real-world data. Using the original risk score weights, 1363 (26.1%) patients had predicted risk of less than 1%, 3571 (68.3%) had predicted risk of 1% to 4%, and 297 (5.7%) had predicted risk of more than 4%. CONCLUSION: The original NSAID major toxicity risk score demonstrated good model fit characteristics in this external real-world cohort. These results suggest that such a risk score is valid in typical practice and could be considered for clinical care.
31919772 Prevalence of polymyalgia rheumatica in a cohort of patients with idiopathic inflammatory 2020 Apr Polymyalgia rheumatica (PMR) is a common rheumatological condition occurring in adults aged over 50 years. The association of PMR with other autoimmune diseases such as rheumatoid arthritis is complex. There is a clear relationship with giant cell arteritis. We sought to determine whether there is any association between PMR and idiopathic inflammatory myopathy (IIM). We undertook a database study of adult patients with a diagnosis of IIM under the care of the Rheumatology Department of the Royal Adelaide Hospital, and retrospectively determined the frequency of PMR in this patient cohort. Patients were considered to have PMR if this had been diagnosed by a physician or if they satisfied all five of the following clinical criteria: (1) bilateral shoulder and/or pelvic girdle aching, (2) morning stiffness exceeding 45 min, (3) age greater than 50 years, (4) duration more than 2 weeks, and (5) evidence of an elevated erythrocyte sedimentation rate or C-reactive protein. Amongst 82 patients with IIM, seven (8.5%) were found to have PMR. There was a disproportionate representation of necrotizing autoimmune myopathy (NAM) in patients with IIM/PMR (5/7) compared with patients with IIM alone (19/75), p = 0.02. There was a high prevalence of antibodies to 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) in patients with IIM/PMR (4/7, 57%) compared with those with IIM alone (9/32, 28%), p = 0.19. The prevalence of PMR in our IIM cohort was much higher than the population prevalence 0.91-1.53% and it appears there is a specific association with NAM and anti-HMGCR antibodies. Further studies are required to confirm these findings and explore mechanisms of shared disease susceptibility.Key Points• Idiopathic inflammatory myositis, in particular, statin-associated necrotizing myositis and anti-HMG co-A reductase antibodies, may have a previously unrecognized association with polymyalgia rheumatica.
31806421 The pathogenesis of systemic lupus erythematosus: Harnessing big data to understand the mo 2020 Jun Systemic lupus erythematosus (SLE) is a chronic, systemic autoimmune disease that causes damage to multiple organ systems. Despite decades of research and available murine models that capture some aspects of the human disease, new treatments for SLE lag behind other autoimmune diseases such as Rheumatoid Arthritis and Crohn's disease. Big data genomic assays have transformed our understanding of SLE by providing important insights into the molecular heterogeneity of this multigenic disease. Gene wide association studies have demonstrated more than 100 risk loci, supporting a model of multiple genetic hits increasing SLE risk in a non-linear fashion, and providing evidence of ancestral diversity in susceptibility loci. Epigenetic studies to determine the role of methylation, acetylation and non-coding RNAs have provided new understanding of the modulation of gene expression in SLE patients and identified new drug targets and biomarkers for SLE. Gene expression profiling has led to a greater understanding of the role of myeloid cells in the pathogenesis of SLE, confirmed roles for T and B cells in SLE, promoted clinical trials based on the prominent interferon signature found in SLE patients, and identified candidate biomarkers and cellular signatures to further drug development and drug repurposing. Gene expression studies are advancing our understanding of the underlying molecular heterogeneity in SLE and providing hope that patient stratification will expedite new therapies based on personal molecular signatures. Although big data analyses present unique interpretation challenges, both computationally and biologically, advances in machine learning applications may facilitate the ability to predict changes in SLE disease activity and optimize therapeutic strategies.
33343711 Short-term rates of radiolucency after primary total shoulder arthroplasty using a cementl 2020 Dec BACKGROUND: Total shoulder arthroplasty has shown good clinical efficacy in treating primary and secondary degenerative conditions of the glenohumeral joint. Glenoid loosening, however, remains the commonest cause of failure. The purpose of this study was to investigate the rate of radiographic periprosthetic lucency associated with the use of an uncemented, pegged, metal-backed polyethylene glenoid component. MATERIALS AND METHODS: A retrospective, single-centre study using the Epoca (Synthes, Paoli, Pennsylvania) metal-backed glenoid component. Operations were performed by two experienced consultant upper limb surgeons. Radiographs were analysed for immediate post-operative component seating and periprosthetic radiolucent lines at predefined regular post-operative intervals. Intra- and inter-observer reliability was assessed to improve validity of results. RESULTS: Mean age and follow-up was 72 (48-91) years and 2.5 years (2-5), respectively. Main indications for total shoulder arthroplasty were primary osteoarthritis, rheumatoid arthritis, revision for failed hemi-arthroplasty and acute fracture. Ninety-six per cent of components were completely seated post-operatively. Fifty-four (95%) of the 57 shoulders had no periprosthetic radiolucent lines at most recent follow-up. Complete post-operative glenoid seating was significantly associated with the absence of later periprosthetic radiolucency (p < 0.01). CONCLUSION: This study reports low early radiolucency rates with the pegged, uncemented, metal-backed polyethylene glenoid prosthesis used. Excellent post-operative glenoid seating is associated with a significantly lower rate of radiolucency. Longer follow-up data are required to confirm these early promising results.Level of evidence: Therapeutic, level IV.