Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
33197284 Prognosis after acute exacerbation in patients with interstitial lung disease other than i 2021 Mar BACKGROUND: Acute exacerbation (AE) is recognized as a life-threatening condition with acute respiratory worsening in idiopathic pulmonary fibrosis (IPF). AE also occurs in fibrotic interstitial lung disease (ILD) other than IPF, including other types of idiopathic interstitial pneumonias (IIPs), ILD associated with collagen vascular disease (CVD-ILD), and chronic hypersensitivity pneumonia (CHP). However, the clinical impact after AE in those patients is still unclear. METHODS: A retrospective review of 174 consecutive first-episodes with AE of ILD in our institution from 2002 to 2016 was performed. AE was defined according to the revised definition and diagnostic criteria proposed by an international working group in 2016. Clinical characteristics, 90-day survival, and the requirement of long-term oxygen therapy (LTOT) after AE were evaluated in each underlying ILD. RESULTS: There were 102 patients with AE of IPF (AE-IPF) and 72 with AE of ILD other than IPF, including non-IPF IIPs (n = 29) and secondary ILD (n = 43) [CVD-ILD (n = 39), CHP (n = 4)]. In CVD-ILD, rheumatoid arthritis (n = 17) was most common. The 90-day mortality after AE was 57% in IPF, 29% in non-IPF IIPs, and 33% in secondary ILD. After AE, ILD other than IPF had a significantly better survival rate than IPF (P < 0.001). Among survivors, the rates of patients requiring LTOT after AE were 63% in IPF, 35% in non-IPF IIPs, and 46% in secondary ILD, respectively. CONCLUSIONS: AE of ILD other than IPF might have a better prognosis than AE-IPF, but both are fatal conditions that cause chronic respiratory failure.
33177600 Using static method to measure tolmetin solubility at different pressures and temperatures 2020 Nov 11 Tolmetin is a non-steroidal anti-inflammatory drug being used to decrease the level of hormones which are the reasons for pain, swelling, tiredness, and stiffness for osteoarthritis and rheumatoid arthritis cases. We evaluated its solubility in supercritical carbon dioxide (SC-CO(2)) with the aim of drug nanonization, considering temperature and pressure variations between 120 and 400 bar and 308-338 K, in the experiments. In this way, a PVT solubility cell based on static solubility approach coupled with a simple gravimetric procedure was utilized to evaluate the solubility of tolmetin. The solubility values between 5.00 × 10(-5) and 2.59 × 10(-3) mol fraction were obtained for tolmetin depending on the pressure and temperature of the cell. The measured data demonstrated a direct correlation between pressure and solubility of tolmetin, while the effect of temperature was a dual effect depending on the crossover pressure (160 bar). The calculated solubility data were modeled using several semi-empirical correlations, and the fitting parameters were calculated using the experimental data via appropriate optimization method. The correlated solubility data revealed that the KJ model was the most accurate one with an average absolute relative deviation percent (AARD%) of 6.9. Moreover, the carried out self-consistency analysis utilizing these correlations illustrated great potential of these models to extrapolate the solubility of tolmetin beyond the measured conditions.
33144895 Identification of Differential Intestinal Mucosa Transcriptomic Biomarkers for Ulcerative 2020 BACKGROUND: Ulcerative colitis (UC) is a complicated disease caused by the interaction between genetic and environmental factors that affect mucosal homeostasis and triggers inappropriate immune response. The purpose of the study was to identify significant biomarkers with potential therapeutic targets and the underlying mechanisms. METHODS: The gene expression profiles of GSE48958, GSE73661, and GSE59071 are from the GEO database. Differentially expressed genes (DEGs) were screened by the GEO2R tool. Next, the Database for Annotation, Visualization and Integrated Discovery (DAVID) was applied to analyze gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. Then, protein-protein interaction (PPI) was visualized by Cytoscape with Search Tool for the Retrieval of Interacting Genes (STRING). RESULTS: There were a total of 128 common DEGs genes, including 86 upregulated genes enriched in extracellular space, regulation of inflammatory response, chemokine-mediated signaling pathway, response to lipopolysaccharide, and cell proliferation, while 42 downregulated genes enriched in the integral component of the membrane, the integral component of the plasma membrane, apical plasma membrane, symporter activity, and chloride channel activity. The KEGG pathway analysis results demonstrated that DEGs were particularly enriched in cytokine-cytokine receptor interaction, TNF signaling pathway, chemokine signaling pathway, pertussis, and rheumatoid arthritis. 18 central modules of the PPI networks were selected with Cytotype MCODE. Furthermore, 18 genes were found to significantly enrich in the extracellular space, inflammatory response, chemokine-mediated signaling pathway, TNF signaling pathway, regulation of cell proliferation, and immune response via reanalysis of DAVID. CONCLUSION: The study identified DEGs, key target genes, functional pathways, and pathway analysis of UC, which may provide potential molecular targets and diagnostic biomarkers for UC.
33109610 MMP activation-associated aminopeptidase N reveals a bivalent 14-3-3 binding motif. 2020 Dec 25 Aminopeptidase N (APN, CD13) is a transmembrane ectopeptidase involved in many crucial cellular functions. Besides its role as a peptidase, APN also mediates signal transduction and is involved in the activation of matrix metalloproteinases (MMPs). MMPs function in tissue remodeling within the extracellular space and are therefore involved in many human diseases, such as fibrosis, rheumatoid arthritis, tumor angiogenesis, and metastasis, as well as viral infections. However, the exact mechanism that leads to APN-driven MMP activation is unclear. It was previously shown that extracellular 14-3-3 adapter proteins bind to APN and thereby induce the transcription of MMPs. As a first step, we sought to identify potential 14-3-3-binding sites in the APN sequence. We constructed a set of phosphorylated peptides derived from APN to probe for interactions. We identified and characterized a canonical 14-3-3-binding site (site 1) within the flexible, structurally unresolved N-terminal APN region using direct binding fluorescence polarization assays and thermodynamic analysis. In addition, we identified a secondary, noncanonical binding site (site 2), which enhances the binding affinity in combination with site 1 by many orders of magnitude. Finally, we solved crystal structures of 14-3-3σ bound to mono- and bis-phosphorylated APN-derived peptides, which revealed atomic details of the binding mode of mono- and bivalent 14-3-3 interactions. Therefore, our findings shed some light on the first steps of APN-mediated MMP activation and open the field for further investigation of this important signaling pathway.
33055468 Efficient Prophylactic Management of HBV Reactivation by an Information Technology Encodin 2020 Objective We started an information technology (IT) system that encodes the medical treatment status of hepatitis B virrus (HBV) with a 9-digit number, automatically checks for inappropriate situations occurring due to immunosuppression and chemotherapy that do not comply with the flowchart of the hepatitis B countermeasure guideline, and promotes correct HBV medical treatment in our hospital. We conducted a prospective study of HBV reactivation using this system. Methods Among 21,607 cases that were managed using this system, 1,206 patients who were HBs antigen-negative, HBc antibody- and/or HBs antibody-positive and in whom HBV DNA quantification was performed two times or more were examined for the occurrence of HBV reactivation. The study population included: malignant lymphoma patients using rituximab (n=40), patients with malignant tumors using anticancer agents (n=546), patients treated with steroids (n=274), rheumatoid arthritis (RA) patients (n=144), patients using immunosuppressants/biologics (n=26), and patients undergoing hepatitis C direct acting antiviral (DAA) treatment (n=176). Results HBV reactivation was observed in 27 cases undergoing treatment with the following agents: rituximab (n=6), anticancer agents (n=8), steroids (n=10), anti-RA agents (n=1), and hepatitis C DAA (n=2). Among the 40 patients who were using rituximab, 6 (18.2%) showed a high rate of reactivation. In 10 in which HBV reactivation occurred at a median of 10 (range, 4-32) months after steroid administration, 6 occurred after the 7th month, and 1 patient showed HBs antigen positivity and severe hepatitis. Conclusion Continuing of the operation of an automatic check system using coded medical information to check for the reactivation enabled this prospective study of HBV reactivation. Careful attention should be paid to patients using steroids, as well as malignant lymphoma patients who are treated with rituximab. The results of the present study suggest that the present IT encoding system would be useful for preventing HBV reactivation.
33033263 Pyoderma gangrenosum. 2020 Oct 8 Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis that presents with rapidly developing, painful skin ulcers hallmarked by undermined borders and peripheral erythema. Epidemiological studies indicate that the average age of PG onset is in the mid-40s, with an incidence of a few cases per million person-years. PG is often associated with a variety of other immune-mediated diseases, most commonly inflammatory bowel disease and rheumatoid arthritis. The cause of PG is not well understood, but PG is generally considered an autoinflammatory disorder. Studies have focused on the role of T cells, especially at the wound margin; these cells may support the destructive autoinflammatory response by the innate immune system. PG is difficult to diagnose as several differential diagnoses are possible; in addition to clinical examination, laboratory tests of biopsied wound tissue are required for an accurate diagnosis, and new validated diagnostic criteria will facilitate the process. Treatment of PG typically starts with fast-acting immunosuppressive drugs (corticosteroids and/or cyclosporine) to reduce inflammation followed by the addition of more slowly acting immunosuppressive drugs with superior adverse event profiles, including biologics (in particular, anti-tumour necrosis factor (TNF) agents). Appropriate wound care is also essential. Future research should focus on PG-specific outcome measures and PG quality-of-life studies.
33009534 Effect of Sedentary Time on the Risk of Orthopaedic Problems in People Aged 50 Years and O 2020 OBJECTIVE: Many people experience orthopaedic problems (OPPs), such as knee joint pain, hip joint pain, low back pain, and knee stiffness in their lifetimes. OPPs can impair lower extremity function, cause depression, and worsen quality of life. The aim of this study was to investigate the association between sedentary time (SDT) and OPPs. DESIGN: Retrospective cross-sectional study. SETTING: This study used data from the 2014-2015 Korea National Health and Nutrition Examination Survey. Survey participants with previous or current osteoarthritis or rheumatoid arthritis, as diagnosed by a doctor, were excluded. OPPs were defined as knee joint pain, hip joint pain, low back pain, and knee stiffness. The cut-off value for SDT was 7.5 hours/day. The study population comprised 3,671 people (1,856 men and 1,815 women), all of whom were ≥50 years-old. Multiple logistic regression analyses were performed. RESULTS: A total of 328 men (17.7%) and 519 women (28.6%) had OPPs. Men with SDTs ≥7.5 hours had a greater risk of OPPs than did men with SDTs <7.5 hours (odds ratio [OR], 1.45; 95% confidence interval [CI], 1.08-1.93). A pink-collar job, physical inactivity during leisure time, and passive (e.g. riding in a car or train) versus active (e.g. walking or riding a bicycle) transportation predicted OPPs in men with SDTs ≥7.5 hours. SDT was a risk factor for knee joint pain in men (OR, 1.80; 95% CI, 1.11-2.92) and hip joint pain in women (OR, 2.05; 95% CI, 1.35-3.11). CONCLUSIONS: In men, prolonged SDT is a risk factor for OPPs. More physical activity programmes should be launched at the community level for people ≥50 years-old to reduce the occurrence of OPPs.
32973764 Multifactorial Design of a Supramolecular Peptide Anti-IL-17 Vaccine Toward the Treatment 2020 Current treatments for chronic immune-mediated diseases such as psoriasis, rheumatoid arthritis, or Crohn's disease commonly rely on cytokine neutralization using monoclonal antibodies; however, such approaches have drawbacks. Frequent repeated dosing can lead to the formation of anti-drug antibodies and patient compliance issues, and it is difficult to identify a single antibody that is broadly efficacious across diverse patient populations. As an alternative to monoclonal antibody therapy, anti-cytokine immunization is a potential means for long-term therapeutic control of chronic inflammatory diseases. Here we report a supramolecular peptide-based approach for raising antibodies against IL-17 and demonstrate its efficacy in a murine model of psoriasis. B-cell epitopes from IL-17 were co-assembled with the universal T-cell epitope PADRE using the Q11 self-assembling peptide nanofiber system. These materials, with or without adjuvants, raised antibody responses against IL-17. Exploiting the modularity of the system, multifactorial experimental designs were used to select formulations maximizing titer and avidity. In a mouse model of psoriasis induced by imiquimod, unadjuvanted nanofibers had therapeutic efficacy, which could be enhanced with alum adjuvant but reversed with CpG adjuvant. Measurements of antibody subclass induced by adjuvanted and unadjuvanted formulations revealed strong correlations between therapeutic efficacy and titers of IgG1 (improved efficacy) or IgG2b (worsened efficacy). These findings have important implications for the development of anti-cytokine active immunotherapies and suggest that immune phenotype is an important metric for eliciting therapeutic anti-cytokine antibody responses.
32867459 [Lung cancer combined with connective tissue disease-related interstitial lung disease: CT 2020 Aug 23 Objective: To investigate the CT features and dynamic changes of new developed lung cancer in patients with connective tissue disease-related interstitial lung disease (CTD-ILD). Methods: A series of chest CT images of 58 CTD-ILD patients during follow-up were collected. The CT features of interstitial lung disease, the initial appearance time of lung cancer, the time of diagnosis of lung cancer, the morphological characteristics (location, shape, size) of lung cancer lesions and the dynamic changes of CT features were analyzed. Results: Among 58 patients, rheumatoid arthritis was the most common (31 cases). Chest CT images showed coexistence of two or more interstitial CT signs. During the follow-up, a total of 59 lung cancer lesions were found. The median time of lung cancer lesion occurred was 289 days. The median delay in diagnosis was 43 days. There were 44 cases of non-small cell lung cancer (including 23 cases of squamous cell carcinoma and 19 cases of adenocarcinoma), 12 cases of small cell lung cancer. Forty-three (72.9%) lesions were located in the lower lobes and 41 (69.5%) lesions were located in the area of pulmonary interstitial fibrosis. According to CT morphological characteristics of lung cancer, nodular type (37 cases), inflammatory consolidation (12 cases) and intra-honeycomb type (10 cases) were identified. Conclusions: The chest CT features of patients with CTD-ILD are complex. New developed lung cancer is easily missed or misdiagnosed in the early stage. Pay attention to the special CT characteristics of CTD-ILD with lung cancer is helpful for early diagnosis.
32831877 A Review of the Botany, Traditional Use, Phytochemistry, Analytical Methods, Pharmacologic 2020 Angelicae Pubescentis Radix (AP), as a traditional Chinese medicine (TCM), has been used for thousands of years in China. In this paper, the botany, traditional use, phytochemistry, analytical methods, quality control, pharmacological effects, and toxicity of AP were reviewed. It can provide a reference for the further research and lay a foundation for the rational clinical application of AP. The relevant information on AP was collected from scientific databases (such as Baidu Scholar, CNKI, Google Scholar, PubMed, Science Direct, Web of Science, and SciFinder Scholar), Chinese herbal classics, Chinese Pharmacopoeia, PhD and MSc dissertations, and so on. The components which have been isolated and identified in AP include coumarins, volatile oils, organic acids, terpenes, polysaccharides, flavonoids, sterols, and trace elements. Most of them were analyzed by HPLC and GC. A pharmacological study shows that the AP has extensive pharmacological effects, including anti-inflammatory, antirheumatism, sedative and hypnotic, neuroprotection, antioxidation, antitumor, and allergy, and it is widely used in the treatment of the rheumatoid arthritis, knee osteoarthritis, lumbar disc, ankylosing spondylitis, headaches, stroke hemiplegia, Alzheimer's, and arrhythmia. AP is a valuable natural medicinal plant. So far, significant advances have been made in phytochemistry and pharmacology. Some traditional uses have been demonstrated by modern pharmacology. However, the chemical components and pharmacological effects of AP are complex and varied, and there are different standards for the evaluation of its quality and efficacy. The mechanism of action, the structure-activity relationship among the components, and the potential synergistic and antagonistic effects remain to be studied. At the same time, there are few studies on the specific compounds related to its pharmacodynamics. In order to better develop and utilize AP, we should establish a more reasonable, reliable, and accurate quality control standard and focus on the study of bioactive constituents and the demonstration of their mechanism of action.
32778166 Intra-operative fractures in primary total knee arthroplasty - a systematic review. 2020 Aug 10 BACKGROUND: One of the rare complications of primary total knee arthroplasty is intra-operative fracture. Intra-operative fracture during revision knee arthroplasty has been well-documented but there is limited literature on fractures occurring during primary knee arthroplasty. We conducted a systematic review of the literature to compare and contrast the various studies to clearly define the predisposing factors, incidence, and characteristics of the fracture itself and to arrive at a consensus on the management and prevention of intra-operative fractures during primary knee arthroplasty. METHODS: The PubMed/Medline, Cochrane, Scopus and Embase databases were searched using keywords "intra-operative fracture", "distal femoral fracture", "tibial fracture", "patella fracture" and "primary total knee arthroplasty". A total of 158 articles were retrieved and after further filtration and exclusion processing, 10 articles that evaluated intra-operative fractures in primary total knee arthroplasty were included for the review. RESULTS: The reported incidence of intra-operative fractures varied from 0.2% to 4.4%. A higher incidence in female patients with a male to female ratio of 0.4 was reported. Posterior stabilized (PS) total knee arthroplasty was associated with higher risk of intra-operative femoral fractures by many authors in this review. Timing of occurrence and location of the intra-operative fractures can vary widely, with femoral fractures occurring more commonly during bone preparation, trialing and impaction of the final implant and tibial fractures occurring during preparation for the tibial keel and impaction of the tibial component. CONCLUSIONS: Intra-operative fractures during primary total knee arthroplasty are rare with higher risk associated with osteoporosis, rheumatoid arthritis, advanced age, female gender, chronic steroid use, metabolic bone disorders, PS type of femoral implant and difficult surgical exposure of the knee joint due to severe deformities. A plethora of management options have been utilized according to surgeon preference. Standard principles of fracture fixation and arthroplasty principles should be followed to achieve stable internal fixation and any unstable fracture site should be bypassed with the utilization of stemmed components. Satisfactory radiographic and functional outcome can be expected with appropriate treatment.
32759996 Monitoring and long-term management of giant cell arteritis and polymyalgia rheumatica. 2020 Sep Giant cell arteritis (GCA) is the most common type of primary vasculitis in Western countries. Polymyalgia rheumatica (PMR) is the second most common inflammatory rheumatic disease of the elderly after rheumatoid arthritis. Glucocorticoids are the cornerstone of treatment for GCA and PMR, which are interrelated diseases. Glucocorticoids are effective, but adverse effects occur in a high proportion of patients. Careful use of glucocorticoids and the application of preventive strategies can minimize these adverse effects. Possible long-term complications of GCA include aneurysm and stenosis of vessels, even in patients with apparently clinically inactive disease; acute blindness is rare during glucocorticoid treatment. In PMR, whether subclinical chronic inflammation can lead to long-term damage is less clear. Management of both GCA and PMR is hampered by the lack of universally accepted definitions of remission and other disease states, such as low disease activity or vessel damage without active disease. In this Review, we outline current evidence on the monitoring and long-term management of patients with GCA and PMR, including the tapering of treatment.
32735149 Survival at 11 to 21 years for 779 Metasul® metal-on-metal total hip arthroplasties. 2020 Jan BACKGROUND: Total hip arthroplasties (THAs) bearing is one of the most important factors for hip replacement because THA survival depends on it. Metal-on-metal (MoM) bearing has lower wear than metal-on-polyethylene but lot of aseptic loosening decrease utilization. We analyze the survival rate of 28 mm Metasul® bearings after a mean follow-up of 12.9 years. METHODS: The main objective of this study was to evaluate the survival of the MoM. We evaluate 779 consecutive THAs performed between January 1995 and December 2005 for primary osteoarthritis, congenital dysplasia classified Crowe I, or rheumatoid arthritis. Survival rate was calculated by the Kaplan-Meir method. The association between survival and age, gender, body mass index (BMI), and surface coating was investigated with a proportional odds model. The clinical assessment included Oxford score. RESULTS: Six hundred fifty-two THAs were reviewed. Sixty-two revisions (9.5%) were performed including 34 aseptic loosening and 11 deep infections. The survival for prosthesis with any reason at 20 years was 87% (confidence interval (CI) 83-90.2) for aseptic loosening at 20 years was 90.1% (CI 87-93.8). There was no association with age, BMI, and surface coating. Gender was significant with lower aseptic loosening for men, hazard ratio = 0.45, p value = 0.035. Oxford score was 57 ± 6.7 (19-60). CONCLUSION: The survival rate of Metasul was well and seems to be like our clinical finding. However, radiographic aseptic loosening without surgery is not included in the survival rate. The Oxford score was very good with a lot of patients with asymptomatic hip. LEVEL OF EVIDENCE: Level IV/Retrospective study.
32662879 Media supplementation for targeted manipulation of monoclonal antibody galactosylation and 2020 Nov Monoclonal antibodies are critically important biologics as the largest class of molecules used to treat cancers, rheumatoid arthritis, and other chronic diseases. Antibody glycosylation is a critical quality attribute that has ramifications for patient safety and physiological efficacy-one that can be modified by such factors as media formulation and process conditions during production. Using a design-of-experiments approach, we examined the effect of 2-F-peracetyl fucose (2FP), uridine, and galactose on cell growth and metabolism, titer, and gene expression of key glycosylation-related proteins, and report how the glycoform distribution changed from Days 4 to 7 in a batch process used for IgG1 production from Chinese hamster ovary cells. We observed major glycosylation changes upon supplement addition, where the addition of 2FP decreased antibody fucosylation by up to 48%, galactose addition increased galactosylation by up to 21%, and uridine addition decreased fucosylation and increased galactosylation by 6% and 2%, respectively. Despite having major effects on glycosylation, neither galactose nor 2FP significantly affected cell culture growth, metabolism, or titer. Uridine improved peak cell densities by 23% but also reduced titer by ∼30%. The supplements caused significant changes in gene expression by Day 4 of the cultures where 2FP addition significantly reduced fucosyltransferase 8 and nucleotide sugar transporter gene expression (by ∼2-fold), and uridine addition significantly increased expression of UDP-GlcNAcT (SLC35A3) and B4GALT1-6 genes (by 1.5-3-fold). These gene expression data alongside glycosylation, metabolic, and growth data improve our understanding of the cellular mechanisms affected by media supplementation and suggest approaches for modifying antibody glycosylation in antibody production processes.
32487376 Monoterpenes-containing PEGylated transfersomes for enhancing joint cavity drug delivery e 2020 Aug The synovial tissues are natural sites of drug delivery for the treatment of rheumatoid arthritis. Our previous study showed that mixed monoterpenes edge-activated PEGylated transfersomes (MMPTs) could significantly enhance the percutaneous absorption of sinomenine (SIN), an anti-inflammation drug. The aim of this study was to investigate the potential of MMPTs for delivery of SIN to the synovial tissues in joint cavities. To this end, conventional liposomes (LPSs) were used as a reference. Transmission electron microscope, constant pressure extrusion method, and differential scanning calorimetry (DSC) were used for physicochemical characterization of the formulations. Confocal laser scanning microscopy (CLSM) and double-sited microdialysis coupled with LC-MS/MS were exploited to study the distribution of MMPTs in different skin layers and pharmacokinetics of SIN in the blood and the joint cavities. The results showed that mixed monoterpenes could significantly enhance the elasticity of MMPTs, evidenced by a decrease in the main transition temperature (T(m)) and transition enthalpy (△H). CLSM analyses demonstrated that MMPTs were distributed in deep layers of the skin, indicating that MMPTs might transport SIN through the skin. In contrast, LPSs were confined in the stratum corneum, which deterred SIN from penetrating through the skin. The results from double-sited microdialysis pharmacokinetics showed that in the joint cavities the steady state concentration (C(ss)) and AUC(0→t) of SIN from MMPTs were 2.1-fold and 2.5-fold of those from LPSs, respectively. In contrast, in the blood the C(ss) and AUC(0→t) of SIN from MMPTs were about 1/3 of those from LPSs. This study suggested that MMPTs could enhance the delivery of SIN to the joint cavities. A combination of CLSM and double-sited microdialysis could give an insight into the mechanism of transdermal and local drug delivery.
32197291 Atopic Disease and Anemia in Korean Patients: Cross-Sectional Study with Propensity Score 2020 Mar 18 Atopic disease is associated with chronic inflammation, and anemia has been reported in patients with inflammatory disorders such as rheumatoid arthritis, chronic obstructive pulmonary disease, and irritable bowel disease. The objective of this study was to determine whether atopic disease is associated with an increased risk of anemia. A cross-sectional study with propensity score weighting was conducted using a health insurance review agency claims dataset comprised of randomized patients who used the Korean national health system at least once in 2016. The association between atopic disease (asthma, atopic dermatitis, allergic rhinitis) and anemia (iron deficiency anemia (IDA) and/or anemia of inflammation (AI)) was examined. A total of 1,468,033 patients were included in this study. The IDA/AI prevalence was 3.1% (45,681 patients). After propensity score weighting, there were 46,958 and 45,681 patients in the non-anemic and anemic groups, respectively. The prevalence of IDA/AI in patients with atopic dermatitis, allergic rhinitis, or asthma had an odds ratio (OR) of 1.40 (95% confidence interval (CI), 1.33-1.48; p < 0.001), 1.17 (95% CI, 1.14-1.21; p < 0.001), and 1.32 (95% CI, 1.28-1.36; p < 0.001), respectively. In addition, the prevalence of IDA increased with higher numbers of atopic diseases. In conclusion, the prevalence of IDA/AI was higher in patients with atopic disease, even after adjusting for demographic characteristics and other risk factors. Further study is needed to distinguish between IDA and AI and to enhance understanding of the etiology of anemia in patients with inflammatory conditions.
32139268 Conventional cementless total hip arthroplasty in patients with dwarfism with height less 2021 Jan BACKGROUND: Orthopedic complications can cause issues and severe disability in patients with dwarfism. Thus, these individuals frequently undergo total hip arthroplasty to mitigate decline in daily functioning. Although studies have reported on the difficulties of orthopedic surgery in patients with dwarfism, many do not clearly define dwarfism and have a short follow-up period. We aimed to retrospectively investigate the clinical and radiographic results of total hip arthroplasty for patients with dwarfism. METHODS: A total of 68 hips of 49 patients with height <140 cm and at least 10-year follow-up periods were enrolled. All patients had conventional cementless implants. All hips were evaluated using the Japanese Orthopaedic Association hip score. RESULTS: The main hip disease etiologies were primary hip osteoarthritis (58%) and secondary osteoarthritis due to developmental dysplasia (31%). Rheumatoid arthritis, rapidly destructive coxarthrosis, spondyloepiphyseal dysplasia, childhood infection, and femoral head aseptic necrosis were also causative pathologies. Hip scores significantly improved from 44 to 82 out of 100. Overall implant-associated survival rate after 10 years was 94.1%. Cup loosening was observed in 2 hips, and subsidence >5 mm was observed in 9 hips. Presence of Crowe IV in hips was a significant risk factor for total hip arthroplasty in patients with dwarfism (p < 0.05); leg lengthening had a weak but significant correlation (r = 0.253, p < 0.05). CONCLUSIONS: Total hip arthroplasty using conventional cementless implants for patients with dwarfism shows good clinical and radiological outcomes and has a relatively low perioperative risk.
31855154 Intravenous ferric carboxymaltose is effective and safe in patients with inflammatory rheu 2020 May BACKGROUND: The aim of this study was to evaluate the efficacy and safety of ferric carboxymaltose in rheumatic patients with iron deficiency anaemia. MATERIALS AND METHODS: The study retrospectively evaluated a cohort of 34 patients with iron deficiency anaemia affected by inflammatory rheumatic diseases that are refractory or intolerant to oral iron therapy. They were treated with ferric carboxymaltose for a total of 56 cycles of treatment. The primary end point was to evaluate the increase of haemoglobin after ferric carboxymaltose treatment. The secondary end point was safety, including the occurrence of disease flare. RESULTS: Median age of the cohort was 60 years (range 31-91 years), with a male/female ratio of 4/30. Nine (26.5%) were affected by rheumatoid arthritis, 10 (29.4%) by spondyloarthritis, and 15 (44.1%) by other autoimmune connective tissue diseases. Median time from diagnosis was 7 years (IQR 2-12). At time of treatment (T(0)), median haemoglobin was 9.3 g/dL (IQR 8.2-10.3), transferrin saturation 6.2% (IQR 3.8-9.8), and ferritin 8.5 ng/mL (IQR 6.0-12.8). Median ferric carboxymaltose dose was 1,000 mg. At 6 weeks from T(0), median haemoglobin was 12.3 g/dL (IQR 11.6-13.3), with a mean increase of 3.0 g/dL (p<0.01). Twelve (35.3%) patients needed re-treatment with ferric carboxymaltose for recurrence of iron deficiency anaemia. Four (4.3%) patients developed mild grade side effects. One suspected flare reaction has been observed. DISCUSSION: In patients affected by inflammatory rheumatic diseases, ferric carboxymaltose is safe and effective in correcting iron deficiency anaemia.
31762210 Peripheral neuropathies in rheumatic diseases: More diverse and frequent than expected. A 2020 Feb BACKGROUND/OBJECTIVE: Peripheral neuropathies (PN) are heterogeneous nerve disorders; frequently rheumatic patients have neuropathic symptoms. In some rheumatic diseases (RD) PN are secondary to nerve compression while others are related to metabolic abnormalities, inflammation or vasculitis. Our aim was to explore the frequency of neuropathic symptoms with three neuropathy questionnaires (NQ) and nerve conduction studies (NCS) in RD. METHODS: This is a cross-sectional study in patients with any RD attending for the first time to a rheumatology outpatient clinic. We included all patients who accepted to participate and who answered three NQ and received a physical evaluation. Twenty patients were randomly selected to perform NCS and 10 healthy subjects were included as controls. The topographic diagnoses were: mononeuropathy, multiplex mononeuropathy, and/or polyneuropathy. STATISTICAL ANALYSIS: descriptive statistics (mean, median, standard deviation, interquartile range and frequency, odds ratios and Pearson correlation test). RESULTS: One hundred patients and 10 healthy subjects were included. Sixty-nine were female, mean age 40.6 ± 15.7 years. Rheumatic diagnoses were: systemic lupus erythematosus (26%), rheumatoid arthritis (16%), gout (14%), and osteoarthritis (11%). Fifty-two patients had neuropathic signs during physical examination and 67% had positive questionnaires with variable scores among several RD. Abnormal NCS was reported in 14 patients (70%): 6 (42.8%) median nerve mononeuropathies, 4 (28.5%) multiplex mononeuropathies and 4 (28.5%) polyneuropathies. None of the healthy subjects had neuropathy (NQ, physical evaluation, or NCS). Risk of being NCS positive is higher when the patients were NQ positive. CONCLUSION: PN has variable distribution and high frequency in patients with RD; NQ+ increases the risk of presenting NCS+ for PN.
31755098 CD28 and CD57 define four populations with distinct phenotypic properties within human CD8 2020 Mar After repeated antigen exposure, both memory and terminally differentiated cells can be generated within CD8(+) T cells. Although, during their differentiation, activated CD8(+) T cells may first lose CD28, and CD28(-) cells may eventually express CD57 as a subsequent step, a population of CD28(+) CD57(+) (DP) CD8(+) T cells can be identified in the peripheral blood. How this population is distinct from CD28(-) CD57(-) (DN) CD8(+) T cells, and from the better characterized non-activated/early-activated CD28(+) CD57(-) and senescent-like CD28(-) CD57(+) CD8(+) T cell subsets is currently unknown. Here, RNA expression of the four CD8(+) T cell subsets isolated from human PBMCs was analyzed using microarrays. DN cells were more similar to "early" highly differentiated cells, with decreased TNF and IFN-γ production, impaired DNA damage response and apoptosis. Conversely, increased apoptosis and expression of cytokines, co-inhibitory, and chemokine receptors were found in DP cells. Higher levels of DP CD8(+) T cells were observed 7 days after Hepatitis B vaccination, and decreased levels of DP cells were found in rheumatoid arthritis patients. More DP and DN CD8(+) T cells were present in the bone marrow, in comparison with PBMCs. In summary, our results indicate that DP and DN cells are distinct CD8(+) T cell subsets displaying defined properties.