Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
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| 35603172 | Comorbidities in the UK Primary Sjögren's Syndrome Registry. | 2022 | INTRODUCTION: Primary Sjögren's Syndrome (PSS) is a chronic disease characterised by symptoms of oral and ocular dryness, pain, fatigue, anxiety and depression. PSS patients can be subclassified by the pattern of severity of these five key symptoms using the Newcastle Sjögren's Stratification Tool (NSST). Although PSS is often associated with one or more comorbidities, the relationship between comorbidities, polypharmacy, and PSS symptom burden is unclear. Using data from the UK Primary Sjögren's Syndrome Registry (UKPSSR) we describe the landscape of polypharmacy and comorbidities in PSS. METHODS: The UKPSSR is research biobank of clinically well-defined PSS patients where clinical, demographic, comorbidities and concomitant medications data are recorded. Patients were subclassified into the four NSST subgroups: Low Symptom Burden (LSB), High Symptom Burden (HSB), Dryness Dominated Fatigue (DDF) and Pain Dominated Fatigue (PDF). Group analyses of comorbid conditions and polypharmacy scores were performed. Comorbidity and Polypharmacy Scores (CPS) were modelled as a function of age, sex, symptom duration, body mass index (BMI), current immunosuppressant and hydroxychloroquine prescriptions and NSST subgroup. RESULTS: There were marked differences in the number and the nature of comorbidities associated with the NSST subgroups. LSB and DDF patients were characterized by fewer comorbidities and medications. In contrast, HSB and PDF patients were associated with more comorbidities and were more likely to be prescribed multiple medications. Group analysis shows that HSB patients are more closely associated with peripheral vascular disease and infection whereas the PDF patients were associated with cardiovascular disease and gastrointestinal comorbidities. Comorbidity and polypharmacy scores increase with age and BMI regardless of symptom subgroup and symptom duration. In addition, the longer the reported symptom duration the higher the associated comorbidities and polypharmacy scores. CONCLUSION: Comorbid conditions are more prevalent in some subgroups of the PSS cohort but increase with age and BMI across the entire cohort. It is unclear from these data whether specific comorbid conditions are a consequence of PSS or represent shared aetiology or pathogenetic susceptibility. Regardless, these findings may have implications for disease management and clinical trial design. | |
| 35349768 | Predictors of Influenza Vaccination in Early Rheumatoid Arthritis 2017-2021: Results From | 2022 Mar 29 | OBJECTIVE: Adults with rheumatoid arthritis (RA) are at a higher risk for infections, including influenza and related complications. We identified influenza vaccination coverage in adults newly diagnosed with RA and examined sociodemographic RA characteristics and attitudes associated with vaccination. METHODS: We used data from patients enrolled in the Canadian Early Arthritis Cohort between September 2017 and February 2021. At enrollment, participants reported their vaccination status in the previous year and completed the Beliefs About Medicines Questionnaire (BMQ). Clinical data were obtained from medical records. Logistic regression was used to identify predictors of vaccination in the year after RA diagnosis. RESULTS: The baseline analytic sample of 431 patients were mostly White (80%) women (67%) with a mean age of 56 (SD 14) years. Prediagnosis, influenza vaccine coverage was 38%, increasing to 46% post diagnosis in the longitudinal sample (n = 229). Participants with previous influenza vaccination (odds ratio [OR] 15.33; 95% confidence interval [CI] 6.37-36.90), on biologics or JAKs (OR 5.42; 95% CI 1.72-17.03), and with a higher change in BMQ Necessity-Concerns Differential scores (OR 1.08; 95% CI 1.02-1.15) had greater odds, whereas women (OR 0.32; 95% CI 0.14-0.71), participants with a non-White racial background (OR 0.13; 95% CI 0.04-0.51), and participants currently smoking (OR 0.09; 95% CI 0.02-0.37) had lower odds of influenza vaccine coverage. CONCLUSION: Influenza vaccination coverage in patients with early RA remains below national targets in adults living with a chronic condition. Discussing vaccine history and medication attitudes at initial clinic visits with new patients with RA may enhance vaccine acceptance and uptake. | |
| 35641125 | Low dose, add-on prednisolone in patients with rheumatoid arthritis aged 65+: the pragmati | 2022 May 31 | BACKGROUND: Low-dose glucocorticoid (GC) therapy is widely used in rheumatoid arthritis (RA) but the balance of benefit and harm is still unclear. METHODS: The GLORIA (Glucocorticoid LOw-dose in RheumatoId Arthritis) pragmatic double-blind randomised trial compared 2 years of prednisolone, 5 mg/day, to placebo in patients aged 65+ with active RA. We allowed all cotreatments except long-term open label GC and minimised exclusion criteria, tailored to seniors. Benefit outcomes included disease activity (disease activity score; DAS28, coprimary) and joint damage (Sharp/van der Heijde, secondary). The other coprimary outcome was harm, expressed as the proportion of patients with ≥1 adverse event (AE) of special interest. Such events comprised serious events, GC-specific events and those causing study discontinuation. Longitudinal models analysed the data, with one-sided testing and 95% confidence limits (95% CL). RESULTS: We randomised 451 patients with established RA and mean 2.1 comorbidities, age 72, disease duration 11 years and DAS28 4.5. 79% were on disease-modifying treatment, including 14% on biologics. 63% prednisolone versus 61% placebo patients completed the trial. Discontinuations were for AE (both, 14%), active disease (3 vs 4%) and for other (including covid pandemic-related disease) reasons (19 vs 21%); mean time in study was 19 months. Disease activity was 0.37 points lower on prednisolone (95% CL 0.23, p<0.0001); joint damage progression was 1.7 points lower (95% CL 0.7, p=0.003). 60% versus 49% of patients experienced the harm outcome, adjusted relative risk 1.24 (95% CL 1.04, p=0.02), with the largest contrast in (mostly non-severe) infections. Other GC-specific events were rare. CONCLUSION: Add-on low-dose prednisolone has beneficial long-term effects in senior patients with established RA, with a trade-off of 24% increase in patients with mostly non-severe AE; this suggests a favourable balance of benefit and harm. TRIAL REGISTRATION NUMBER: NCT02585258. | |
| 35583917 | Genetic liability to rheumatoid arthritis in relation to coronary artery disease and strok | 2022 May 18 | OBJECTIVES: To assess the causality of the associations of rheumatoid arthritis (RA) with coronary artery disease (CAD) and stroke using Mendelian randomization approach. METHODS: Independent single nucleotide polymorphisms strongly associated with RA (n=70) were selected as instrumental variables from a genome-wide association meta-analysis including 14,361 RA cases and 43,923 controls of European ancestry. Summary-level data for CAD, all stroke, any ischemic stroke and its subtypes, intracerebral hemorrhage, and subarachnoid hemorrhage were obtained from meta-analyses of genetic studies, international genetic consortia, the UK Biobank, and the FinnGen consortium. We obtained summary-level data for common cardiovascular risk factors and related inflammatory biomarkers to assess possible mechanisms. RESULTS: Genetic liability to RA was associated with an increased risk of CAD and intracerebral hemorrhage. For one unit increase in log odds of RA, the combined odds ratios were 1.02 (95% confidence interval, 1.01, 1.03; p=0.003) for CAD and 1.05 (95% confidence interval, 1.02, 1.08; p=0.001) for intracerebral hemorrhage. Genetic liability to RA was associated increased levels of tumor necrosis factor and C-reactive protein (CRP). The association for CAD attenuated after adjustment for genetically predicted CRP levels. There were no associations of genetic liability to RA with the other studied outcomes. CONCLUSION: This study found that genetic liability to RA was associated with increased risk of CAD and intracerebral hemorrhage and that the association for CAD might be mediated by CRP. The heightened cardiovascular risk should be actively monitored and managed in RA patients, and this may include damping systemic inflammation. | |
| 35649604 | Making space for patients' preferences in precision medicine: a qualitative study explorin | 2022 Jun 1 | OBJECTIVE: Precision medicine in rheumatoid arthritis (RA) creates new opportunities to involve patients in early identification of accurate indicators of health trajectories. The aim of this study was to explore patient perspectives on patient-centredness in precision medicine for RA treatment. DESIGN: Semistructured interviews were conducted to explore patients' perspectives on a new personalised approach to RA treatment. The interview guide was developed together with patient research partners and health care professionals. SETTING: An invitation to the interviews was sent through a mobile application. The interviews were one-on-one, using an interview guide with open-ended questions. Interviews were conducted digitally (October 2020-February 2021) via Zoom or telephone, depending on each participant's preferences. PARTICIPANTS: Patients with RA (N=12) were purposively recruited. Patients were eligible if they had an RA diagnosis, were aged 18-80 years, and understood and expressed themselves in Swedish. Participants and researchers did not know each other prior to the interviews. RESULTS: Participants expressed desires and needs for patients to have an active role in precision medicine by making shared treatment decisions together with a healthcare professional. In order for that to work, patients need information on potential treatment options, an ability to express their preferences, an individual treatment plan and identification of personal treatment goals. Patients also identified two requirements of healthcare professional in precision medicine: a safe environment to express personal matters and two-way communication with healthcare professionals. CONCLUSION: Communication between patients and healthcare professionals needs to be more focused on patients' individual treatment preferences and expressed needs, in order to increase patient-centredness in treatment decisions, so shared decision-making can become a reality. More research is needed to design multifaceted implementation strategies to support patients and healthcare professionals to increase patient-centredness throughout treatment personalisation. | |
| 35643956 | Tofacitinib and risk of malignancy: results from the Safety of TofAcitinib in Routine care | 2022 May 29 | INTRODUCTION: Results from "ORAL Surveillance" safety trial have indicated an increased risk of malignancy with tofacitinib when compared with tumor necrosis factor inhibitors (TNFI). We further examined this safety concern in rheumatoid arthritis (RA) patients in the real-world setting. METHODS: Using U.S. insurance claims data from Optum Clinformatics (2012-2020), IBM MarketScan (2012-2018), and Medicare (parts A, B, D, 2012-2017), we created two cohorts of RA patients initiating treatment with tofacitinib or TNFI. The first cohort, "Real-world evidence (RWE)" included patients from routine care. The second cohort, "RCT-duplicate cohort", emulated the inclusion and exclusion criteria of the ORAL surveillance trial to assess comparability of our results with the trial. Cox proportional hazards models with propensity score fine-stratification weighting were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for risk of any malignancy (excluding non-melanoma skin cancer). Database-specific estimates were meta-analyzed using fixed effects models with inverse-variance weighting. RESULTS: The RWE cohort included 83,295 patients of whom 10,504 (12.6%) initiated tofacitinib. The pooled weighted HR (95% CI) for the primary any malignancy outcome associated with tofacitinib compared with TNFI was 1.01 (0.83, 1.22) in the RWE cohort and 1.17 (0.85, 1.62) in the RCT-duplicate cohort (versus ORAL Surveillance trial, 1.48 [1.04, 2.09]). DISCUSSION: We did not find evidence for an increased risk of malignancy with tofacitinib, in comparison with TNFI, in RA patients treated in the real-world setting. However, our results cannot rule out a possibility of an increase in risk that may accrue with a longer treatment duration. | |
| 35221217 | Double Versus Triple Arthrodesis Fusion Rates: A Systematic Review. | 2022 Jan 19 | Hindfoot arthrodesis is often required for end-staged deformities, such as posterior tibial tendon dysfunction, osteoarthritis, or rheumatoid arthritis. Although the need for hindfoot arthrodesis is generally accepted in severe deformities, there is a debate whether a double or triple arthrodesis should be performed. The aim of our systematic review is to review the fusion rates and mean time to fusion in double and triple arthrodesis. A total of 184 articles were identified using the keyword search through the database of articles published from 2005 to 2017. After review by 3 physicians, a total of 13 articles met the eligibility criteria. The reason for double or triple arthrodesis within the studies were posterior tibial tendon dysfunction, tarsal coalition, degenerative joint disease, osteoarthritis, rheumatoid arthritis, Charcot Marie Tooth, Multiple Sclerosis, Polio, neuromuscular disorder, cerebral palsy, acrodystrophic neuropathy, clubfoot, post-traumatic, and seronegative arthropathy (spondyloarthritis). Within these 13 studies, there were a total of 343 (6-95) subjects extremities operated on. The overall fusion rate for double arthrodesis was 91.75% (289/315) compared to 92.86% (26/28) triple arthrodesis fusion rate, p value .8370. The mean time to fusion for double arthrodesis was 17.96 ± 7.96 weeks compared to 16.70 ± 8.18 weeks for triple arthrodesis, p value = .8133. There are risks associated with triple arthrodesis including increased surgical times, lateral wound complications, residual deformity, surgical costs and peri-articular arthritis. Given the benefits of double arthrodesis over triple arthrodesis and the nearly equivalent fusion rates and time to fusion, double arthrodesis is an effective alternative to triple arthrodesis. The authors of this systematic review recommend double arthrodesis as the hindfoot fusion procedure of choice. | |
| 35405657 | Case Report: Histoplasma Hepatitis Presenting as Common Bile Duct Obstruction. | 2022 Apr 11 | Histoplasma capsulatum is the most common endemic mycosis in the United States and can cause disseminated histoplasmosis in immunocompromised patients.1 Although hepatic involvement is common with histoplasmosis, it can be challenging to diagnose. We report a case of a 50-year-old woman receiving adalimumab for rheumatoid arthritis who presented with right upper quadrant pain, fever, jaundice, and dyspnea. The initial working diagnosis was biliary obstruction with potential COVID-19 infection. Endoscopic retrograde cholangiopancreatography suggested Mirizzi syndrome, but successful sphincterotomy failed to improve jaundice over subsequent days. Bronchoscopy and liver biopsy were performed, with the first revealing budding yeast and the later growing H. capsulatum. The patient improved with the initiation of itraconazole therapy. | |
| 34284475 | Hypertrophic Pachymeningitis Demonstrated by Whole-Body 67Ga Scintigraphy. | 2022 Feb 1 | Hypertrophic pachymeningitis is a rare inflammatory process characterized by thickening of the dura mater that can be idiopathic or secondary to a variety of conditions such as ANCA-related vasculitis, IgG4-related disease, Sjögren syndrome, rheumatoid arthritis, sarcoidosis, and infections. It can cause various neurological alterations such as headache, cranial nerve disorder, cerebellar disorder, sensory impairment, and weakness. Brain MRI is useful for imaging diagnosis of hypertrophic pachymeningitis, showing focal thickening and enhancement of the dura mater. Here we report 4 cases of idiopathic hypertrophic pachymeningitis where 67Ga clearly accumulated in the dura mater. | |
| 31869185 | Sternoclavicular Joint Infection. | 2022 Jan | The sternoclavicular joint is a saddle-shaped diarthrodial joint that joins the upper extremity appendicular skeleton to the axial skeleton. The large medial clavicle articulates with the superomedial manubrium and costal cartilage of the first rib, forming a joint with very little bony stability. Within the joint is an intra-articular disc ligament composed of dense fibrous cartilage that provides structural support and prevents medial displacement of the clavicle. The surrounding robust costoclavicular ligament and capsule offers an added layer of support. The primary restraints to anterior and posterior translation of the joint are the anterior and posterior sternoclavicular ligaments. Despite these restrictions, the sternoclavicular joint is actually very mobile and moves more than 30 degrees in the axial and coronal planes while having more than 45 degrees of rotation. Functionally, it is quite similar to other amphiarthroses, such as the sacroiliac joint or pubic symphysis. Blood supply to the joint comes from the articular branches of the suprascapular and internal thoracic arteries. The nerve to the subclavius muscle and the medial suprascapular nerves provide innervation to the sternoclavicular joint. Septic arthritis of the sternoclavicular joint is rare and represents less than 1% of all bone and joint infections. A sternoclavicular joint infection is, in the majority of cases, associated with other systemic illnesses and/or general poor health status. Common concurrent issues include diabetes, intravenous drug use, immunosuppression, and rheumatoid arthritis. While rare, prompt diagnosis and treatment are essential to prevent spread into the posteriorly located great vessels, mediastinum, and pleural space. | |
| 35145344 | Perception of Biosimilar Biologics and Non-Medical Prescription Switching among Rheumatolo | 2022 Jan | BACKGROUND: The aim of this study was to evaluate rheumatologists' perceptions of biosimilar biologics and Non-Medical Switching (NMS). METHODS: A cross-sectional survey was conducted among registered members of the Saudi Society for Rheumatology. The questionnaire focused on biosimilars and NMS. Logistic regression was performed to ascertain the effect of demographics and practice characteristics on the use of biosimilars and NMS. RESULTS: Out of 249 SSR members, 143 completed the survey, generating a response rate of 57.4%. Of those (59.44%) were men with a mean (±SD) age and years of practice of 42.3 ± 9.13 and 10.3 ± 8.9, respectively. Rheumatologists managing adult patients (81.82%) and Ministry of Health practice (43.36 %) were the majority of respondents. Previous experience in prescribing a biosimilar was reported by 43 (30.07%) participants, with a higher probability among women (p = 0.015). A total of 26 (18.18%) participants had performed NMS on eligible patients. Adequate knowledge on biosimilars was reported by 69 (48.25%) participants. The adequacy of evidence to grant biosimilar approval for the studied indication and extrapolation to treat other conditions was reported by 88 (61.5%) and 69 (48.3%), respectively. The concept of totality-of-the-evidence was well understood by 37.1%. Biosimilars had been previously used by 43 (30.07) participants in their practice. NMS had been attempted by 26 (18.18), while 86 (60.1%) participants believed that NMS might harm patients. CONCLUSION: There is a clear knowledge gap about the biosimilar approval process among adult and pediatric rheumatologists who took part in the survey. In addition, a large number of participants reported having negative opinions about NMS. There is a need to organize SSR-led educational activities, and develop national guidelines regarding biosimilars and NMS. | |
| 35652244 | Combined conventional synthetic disease modifying therapy vs infliximab for rheumatoid art | 2022 Jun 2 | Observational studies are often considered unreliable for evaluating relative treatment effectiveness, but it has been suggested that following target trial protocols could reduce bias. Using observational data from rheumatoid arthritis (RA) patients in the Swedish Rheumatology Quality Register (SRQ), between 2006 and 2020, we emulated the protocol of the Swedish Farmacotherapy trial (SWEFOT) and compared the results. SWEFOT was a pragmatic trial nested in SRQ, between 2002 and 2005, where methotrexate insufficient responders were randomized to receive additional infliximab or sulfasalazine + hydroxychloroquine. RA patients initiating infliximab (N=313) or sulfasalazine + hydroxychloroquine (N=196) after methotrexate were identified in SRQ and the Prescribed Drugs Register, mimicking the SWEFOT eligibility criteria. The primary outcome was the proportion of EULAR (European Alliance of Associations for Rheumatology) good responders at nine months, classifying patients who discontinued treatment as "non-responders". Through sensitivity analyses, we assessed the impact of relaxing eligibility criteria. The observed proportions reaching EULAR good response were close to those reported in SWEFOT: 39% (vs. 39% in SWEFOT) for infliximab and 28% (vs. 25%) for sulfasalazine + hydroxychloroquine. The crude observed response ratio was 1.39 (95% CI: 1.04 to 1.86), increasing to 1.48 (0.98 to 2.24) after confounding adjustment, compared to 1.59 (1.10 to 2.30) in SWEFOT. Results remained close to SWEFOT when relaxing eligibility criteria until allowing prior DMARD use which reduced the observed difference between treatments. By applying a pre-specified trial emulation protocol to observational clinical registry data, we could replicate the results of SWEFOT, favouring infliximab over sulfasalazine + hydroxychloroquine combination therapy at nine months. | |
| 35559601 | Antiviral Use and Health Care Use Among US Patients With Rheumatoid Arthritis and Influenz | 2022 May 12 | OBJECTIVE: Patients with rheumatoid arthritis (RA) are vulnerable to severe complications of influenza. We assessed whether health care resource use (HRU) and costs differed between patients with RA and influenza who received antiviral medication compared with matched patients with RA and influenza not receiving antiviral therapy. METHODS: This was a retrospective US health insurance claims analysis over three influenza seasons (each October to April) in 2016-2019. Adults with RA and a subsequent diagnosis of influenza were included. Treated patients (receiving antiviral influenza treatment within 2 days of diagnosis) and untreated patients were propensity score matched using baseline covariates. HRU and costs were assessed for inpatient, emergency department (ED), and outpatient visits and compared between cohorts using χ(2) tests and t tests. RESULTS: After matching, 2638 treated and 1319 untreated patients were included. For treated versus untreated patients, the mean number of all-cause outpatient visits was 0.96 versus 1.21 during 14 days of follow-up (P < 0.001) and 1.94 versus 2.24 over 28 days (P = 0.001), respectively. Over 28 days, the mean number of all-cause ED visits was lower among treated (0.23) than untreated (0.30) patients (P = 0.042). The mean number of respiratory-related outpatient visits was significantly lower for treated versus untreated patients, and mean costs for these visits were $17.89 versus $35.27 over 14 days (P < 0.001) and $28.92 versus $48.77 over 28 days (P < 0.001) for treated versus untreated patients, respectively. CONCLUSION: Our findings demonstrate that prompt antiviral treatment after influenza diagnosis may reduce HRU and costs in patients with RA. | |
| 35428724 | Extraarticular Manifestations and Comorbidities in Patients With Rheumatoid Arthritis. | 2022 Apr 15 | We read with great interest the article by Gunderson et al, which reported the multimorbidity burden in rheumatoid arthritis (RA).(1) We appreciate that the authors estimated comorbidities in RA with a novel perspective, thus giving us a chance to further clarify the RA patient complexity. We would like, however, to discuss some key points. | |
| 35105706 | Impaired Humoral Immunogenicity of SARS-CoV-2 Vaccination in Patients With Rheumatoid Arth | 2022 Feb 1 | Humoral immunogenicity of SARS-CoV-2 vaccination in rheumatoid arthritis (RA) seems impaired depending on the underlying immunosuppressive agents, especially with rituximab (RTX), glucocorticoids, and abatacept (ABA), but data are still scarce.(1-9) Identifying an impairment could lead to treatment adaptation or a vaccine booster dose to improve vaccine response. | |
| 34999265 | Cervical Myelopathy Due to Idiopathic Retro-odontoid Pseudotumor. | 2022 Apr | OBJECTIVE: A retro-odontoid pseudotumor (ROP) is commonly associated with atlantoaxial instability or rheumatoid arthritis. However, ROP in the absence of atlantoaxial instability or rheumatoid arthritis, which is termed idiopathic ROP (IROP), is a rare condition. The pathomechanisms and optimal treatment strategies for IROP remain controversial. The aim of the present study was to evaluate the radiographic and clinical characteristics of IROP patients and to assess the efficiency of atlantoaxial/occipitocervical fusion on IROP regression. METHODS: Data from 5 patients diagnosed with IROP were retrospectively reviewed. Posterior atlantoaxial or occipitocervical fixation and fusion were performed in 4 patients and C1 posterior arch resection alone in 1 patient. The patients' features, surgical procedures, and complications were recorded. The retro-odontoid soft tissue thickness was measured on preoperative and postoperative magnetic resonance imaging to evaluate IROP regression. RESULTS: The mean follow-up time was 37 months. ROP regression was achieved in patients who received atlantoaxial/occipitocervical fusion, but not for the patient with C1 posterior resection alone. There were no observed neurovascular complications associated with surgery. CONCLUSIONS: IROP was related to a restricted range of motion of the subaxial spine. Upper cervical fixation is an optional treatment that produces IROP regression over time. By contrast, direct removal of the IROP is unnecessary. | |
| 34916160 | Replication of epidemiological associations of carpal tunnel syndrome in a UK population-b | 2022 Mar | INTRODUCTION: Several phenotypic factors are associated in the literature with an increased risk of carpal tunnel syndrome (CTS). Along with female sex and older age, certain systemic diseases show an association with CTS, with varying degrees of evidence. METHODS: This study was performed using the UK Biobank resource - a cohort study of over 500,000 participants who have allowed linkage of phenotypic data with their medical records. We calculated the prevalence of CTS and a sex-specific prevalence ratio and compared the body mass index (BMI) between cases and controls. We performed a series of nested case-control studies to compute odds ratios for the association between CTS and three systemic diseases. RESULTS: There were 12,312 CTS cases within the curated UK Biobank dataset of 401,656 (3.1% prevalence), and the female:male ratio was 1.95:1. CTS cases had, on average, a BMI > 2.0Â kg/m(2) greater than controls. Odds ratios for the association with CTS for three systemic diseases were 2.31 (95% CI 2.17-2.46) for diabetes, 2.70 (95% CI 2.44-2.99) for rheumatoid arthritis, and 1.47 (95% CI 1.38-1.57) for hypothyroidism. Adjusted for BMI, these odds ratios fell to 1.75 (95% CI 1.65-1.86), 2.43 (95% CI 2.20-2.69), and 1.35 (95% CI 1.26-1.43), respectively. DISCUSSION: We harnessed the size and power of UK Biobank to provide robust replication of evidence for the associations between CTS and female sex, raised BMI, and three systemic diseases, which are only mediated in part by raised BMI. | |
| 30725771 | Chloroquine And Hydroxychloroquine Toxicity. | 2022 Jan | Chloroquine (CQ) is used to prevent and treat malaria and amebiasis, while hydroxychloroquine (HCQ), a less toxic metabolite of chloroquine, is used to treat rheumatic diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA) and Sjogren's syndrome. While generally considered safe, several adverse effects of HCQ and CQ have been reported, gastrointestinal discomfort being the most common. Allergic reactions rarely occur. Even rarer adverse effects include cardiomyopathy, cardiac conduction defects, neuromyotoxicity, cytopenias, and skin hyperpigmentation.  Of all adverse effects of HCQ and CQ, ocular adverse effects are clinically most relevant, and will be the focus of this article. Both medications can cause corneal deposits, posterior subcapsular lens opacity, ciliary body dysfunction, and most important, irregularity in the macular pigmentation in the early phase, a ring of macular pigment dropout in the advanced stage, and peripheral bone spicule formation, vascular attenuation, and optic disc pallor in the end-stage. Ocular symptoms of retinopathy include blurred and partial loss of central vision, side vision, and in the later stage, night vision. Symptoms of corneal deposits include haloes and glare. Clinical research has resulted in precise screening protocols and safe dosing guidelines to prevent ocular toxicity and detect retinal damage at an early stage. | |
| 35154249 | Human Immune System Diseasome Networks and Female Oviductal Microenvironment: New Horizons | 2021 | Human hypofertility and infertility are two worldwide conditions experiencing nowadays an alarming increase due to a complex ensemble of events. The immune system has been suggested as one of the responsible for some of the etiopathogenic mechanisms involved in these conditions. To shed some light into the strong correlation between the reproductive and immune system, as can be inferred by the several and valuable manuscripts published to date, here we built a network using a useful bioinformatic tool (DisGeNET), in which the key genes involved in the sperm-oviduct interaction were linked. This constitutes an important event related with Human fertility since this interaction, and specially the spermatozoa, represents a not-self entity immunotolerated by the female. As a result, we discovered that some proteins involved in the sperm-oviduct interaction are implicated in several immune system diseases while, at the same time, some immune system diseases could interfere by using different pathways with the reproduction process. The data presented here could be of great importance to understand the involvement of the immune system in fertility reduction in Humans, setting the basis for potential immune therapeutic tools in the near future. | |
| 34887338 | Visualizing T-Cell Responses: The T-Cell PET Imaging Toolbox. | 2022 Feb | T lymphocytes are key mediators of the adaptive immune response. Inappropriate or imbalanced T-cell responses are underlying factors in cancer progression, allergy, and other immune disorders. Monitoring the spatiotemporal dynamics of T cells and their functional status has the potential to provide unique biologic insights into health and disease. Noninvasive PET imaging represents an ideal whole-body modality for achieving this goal. With the appropriate PET imaging probes, T-cell dynamics can be monitored in vivo with high specificity and sensitivity. Herein, we provide a comprehensive overview of the applications of this state-of-the-art T-cell PET imaging toolbox and the potential it has to improve the clinical management of cancer immunotherapy and T-cell-driven diseases. We also discuss future directions and prospects for clinical translation. |