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ID PMID Title PublicationDate abstract
32373130 Amelogenin Downregulates Interferon Gamma-Induced Major Histocompatibility Complex Class I 2020 Enamel matrix derivatives (EMDs)-based periodontal tissue regenerative therapy is known to promote healing with minimal inflammatory response after periodontal surgery, i. e., it promotes wound healing with reduced pain and swelling. It has also been reported that macrophages stimulated with amelogenin, a major component of EMD, produce various anti-inflammatory cytokines and growth factors. We previously found that stimulation of monocytes with murine recombinant M180 (rM180) amelogenin suppresses major histocompatibility complex class II (MHC II) gene expression using microarray analysis. However, the detailed molecular mechanisms for this process remain unclear. In the present study, we demonstrated that rM180 amelogenin selectively downmodulates the interferon gamma (IFNγ)-induced cell surface expression of MHC II molecules in macrophages and this mechanism mediated by rM180 appeared to be widely conserved across species. Furthermore, rM180 accumulated in the nucleus of macrophages at 15 min after stimulation and inhibited the protein expression of class II transactivator (CIITA) which controls the transcription of MHC II by IFNγ. In addition, reduced MHC II expression on macrophages pretreated with rM180 impaired the expression of T cell activation markers CD25 and CD69, T cell proliferation ability, and IL-2 production by allogenic CD4(+) T lymphocytes in mixed lymphocyte reaction assay. The chromatin immunoprecipitation assay showed that IFNγ stimulation increased the acetylation of histone H3 lysine 27, which is important for conversion to euchromatin, as well as the trimethylation of histone H3 lysine 4 levels in the CIITA promoter IV (p-IV) region, but both were suppressed in the group stimulated with IFNγ after rM180 treatment. In conclusion, the present study shows that amelogenin suppresses MHC II expression by altering chromatin structure and inhibiting CIITA p-IV transcription activity, and attenuates subsequent T cell activation. Clinically observed acceleration of wound healing after periodontal surgery by amelogenin may be partially mediated by the mechanism elucidated in this study. In addition, the use of recombinant amelogenin is safe because it is biologically derived protein. Therefore, amelogenin may also be used in future as an immunosuppressant with minimal side effects for organ transplantation or MHC II-linked autoimmune diseases such as type I diabetes, multiple sclerosis, and rheumatoid arthritis, among others.
32173550 Miniplate-Augmented Interlaminar Fusion in C1-C2 Screwing. 2020 Jun OBJECTIVE: The interlaminar fusion combination involving C1-C2 screwing fixation is one of the most effective techniques for atlantoaxial dislocation or subluxation, and the bone graft is usually stabilized by wiring constructs. However, some adverse events were reported during the insertion of sublaminar wiring, such as accidentally damaging the spinal cord or dura. Thus we used the miniplate to stabilize the harvest bone graft on the C1-C2 laminar, which led to a shorter operation time and prevented spinal canal violation. This study investigated the safety and efficacy of the novel surgical technique, namely miniplate-augmented interlaminar fusion. METHODS: We retrospectively reviewed 43 patients who underwent posterior atlantoaxial fusion with the miniplate-augmented iliac crest autograft at our institute. Complications related to surgery were recorded and calculated. After operation, patients were followed up through routine radiography to examine whether the fusion of the atlantoaxial segment was achieved. Success of fusion was defined as follows: 1) the presence of bone bridging between the bone graft and both the atlas and axis; and 2) the absence of movement of the atlantoaxial spinous process on flexion-extension radiography, which meant that the variation of length measured in 2 views, respectively, was <1 mm. The first time when radiography showed successful fusion after surgery was termed as fusion time and was recorded individually. In addition, overall fusion rates and mean fusion times were analyzed. RESULTS: Of 43 patients, long-term follow-up data were available for 31 patients, whereas the remaining 12 patients had dropped out (mean follow-up duration, 24.91 months; range, 6-72 months). Among 31 patients, 22 (70.96%) were women and 9 (29.03%) were men. The mean age was 63.33 years. Regarding the etiology, atlantoaxial dislocations or subluxations were caused due to degeneration, rheumatoid arthritis, odontoid fracture, trauma, and os odontoideum in 14 (45%), 3 (10%), 5 (16%), 8 (26%), and 1 (3%) patient(s), respectively. Successful fusion was achieved in 30 (96.77%) patients, with a mean fusion time of 6.23 months, whereas only 1 (3.23%) patient did not meet the fusion criteria. No complications related to the miniplate occurred. We noted vertebral artery rupture not requiring blood transfusion in 1 patient, aspiration pneumonia in 1 patient, urinary tract infection in 1 patient, anemia requiring transfusion in 1 patient, and leg dysesthesia in 1 patient. No neurologic deficit was found. CONCLUSIONS: Miniplate-augmented interlaminar fusion with C1-C2 screwing resulted in excellent fusion rates with a considerably low probability of complications. Hence this novel technique for bone graft fixation with atlantoaxial screwing has a good efficacy and safety and can serve as an alternative for bone graft fixation during C1-C2 fusion.
32169603 A novel inhibitor of NF-κB-inducing kinase prevents bone loss by inhibiting osteoclastic 2020 Jun Musculoskeletal diseases and disorders, including osteoporosis and rheumatoid arthritis are diseases that threaten a healthy life expectancy, and in order to extend the healthy life expectancy of elderly people, it is important to prevent bone and joint diseases and disorders. We previously reported that alymphoplasia (aly/aly) mice, which have a loss-of-function mutation in the Nik gene involved in the processing of p100 to p52 in the alternative NF-κB pathway, show mild osteopetrosis with a decrease in the osteoclast number, suggesting that the alternative NF-κB pathway is a potential drug target for ameliorating bone diseases. Recently, the novel NF-κB-inducing kinase (NIK)-specific inhibitor compound 33 (Cpd33) was developed, and we examined its effect on osteoclastic bone resorption in vitro and in vivo. Cpd33 inhibited the receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis accompanied by a decrease in the expression of nfatc1, dc-stamp, and cathepsin K, markers of osteoclast differentiation, without affecting the cell viability, in a dose-dependent manner. Cdp33 specifically suppressed the RANKL-induced processing of p100 to p52 but not the phosphorylation of p65 or the degradation or resynthesis of IκBα in osteoclast precursors. Cpd33 also suppressed the bone-resorbing activity in mature osteoclasts. Furthermore, Cdp33 treatment prevented bone loss by suppressing the osteoclast formation without affecting the osteoblastic bone formation in ovariectomized mice. Taken together, NIK inhibitors may be a new option for patients with a reduced response to conventional pharmacotherapy or who have serious side effects.
32083550 Performance of the 2019 European League Against Rheumatism/American College of Rheumatolog 2020 Nov OBJECTIVES: To evaluate the performance of the 2019 European League against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria for systemic lupus erythematosus (SLE) in Asian patients. METHODS: We conducted an electronic medical chart review of patients with SLE and defined rheumatic diseases. Classification criteria of the 1997 ACR, 2012 Systemic Lupus International Collaborating Clinics (SLICC), and 2019 EULAR/ACR were examined based on sensitivity, specificity, positive predictive value, negative predicted value, and accuracy using clinical diagnosis as the gold standard. RESULTS: A total of 335 SLE patients and 337 non-SLE patients were analysed. Non-SLE patients included rheumatoid arthritis (RA) (n=92), anti-phospholipid syndrome (APS) (n=57), mixed connective tissue disease (n=52), systemic sclerosis (n=43), primary Sjögren's syndrome (SS) (n=39), undifferentiated connective tissue disease (n=28), RA with secondary SS (n=24), dermatomyositis (n=1), and spondyloarthropathy (n=1). The sensitivity was 97.6% (95% confidence interval (CI): 0.954-0.989) for the 2019 EULAR/ACR criteria, 98.5% (95% CI: 0.966-0.995) for the 2012 SLICC criteria and 95.5% (95% CI: 0.927-0.975) for the 1997 ACR criteria. The specificity was 91.4% (95% CI: 0.879-0.942) for the 2019 EULAR/ACR criteria, 92.6% (95% CI: 0.892-0.951) for the 2012 SLICC criteria 93.8% (95% CI: 0.906-0.961) for the 1997 ACR criteria. CONCLUSIONS: The 2019 EULAR/ACR criteria for SLE had comparable performance to the 2012 SLICC criteria regarding diagnostic sensitivity and specificity in Korean population of SLE and other rheumatic diseases. However, the new criteria could not reach higher specificity than the 2012 SLICC criteria.
32064621 Mannuronic Acid in Low-Risk and Intermediate-1-Risk Myelodysplastic Syndromes. 2020 Jul The discovery of hematologic improvement and bone marrow modification by the drug β-D mannuronic acid (M2000) during treatment of rheumatoid arthritis in phase 1/2/3 clinical trials prompted us to design a new trial to target hematologic deficits in myelodysplastic syndromes (MDS). In this open-label, randomized phase 2 clinical trial, the potential effect and tolerability of drug M2000 was assessed in patients with low- and intermediate-1-risk MDS. The primary efficacy end point was hematologic improvement after 12 weeks of β-D-mannuronic acid therapy. Among 34 enrolled patients, half received their conventional therapy plus β-D-mannuronic acid, and the other half received only conventional drugs. In the conventional + β-D mannuronic acid treatment group, hematologic improvement and development of transfusion independence and/or reduction in transfusion requirements were seen in 12 patients (92.3%) and 1 patient (7.7%), respectively. Moreover, 5 patients (38.5%), 2 patients (15.4%), and 1 patient (7.7%) in the β-D-mannuronic acid-treated group showed hematologic improvement of the major parameters of erythroid, neutrophil, and platelet responses, respectively, based on the International Working Group criteria), whereas in the conventional treatment group as control, no hematologic improvements including erythroid, neutrophil, and platelet response was seen. In this trial, the addition of β-D mannuronic acid to conventional treatment showed promising results in MDS patients with low and intermediate-1 risk with effects on hematologic improvements without significant adverse effect.
32062772 Advances in the Diagnosis and Treatment of Large Granular Lymphocytic Leukemia. 2020 Apr PURPOSE OF REVIEW: The past decade in LGL leukemia research has seen increased pairing of clinical data with molecular markers, shedding new insights on LGL leukemia pathogenesis and heterogeneity. This review summarizes the current standard of care of LGL leukemia, updates from clinical trials, and our congruent improved understanding of LGL pathogenesis. RECENT FINDINGS: Various clinical reports have identified associations between stem, bone marrow, and solid organ transplants and incidence of LGL leukemia. There is also a potential for underdiagnosis of LGL leukemia within the rheumatoid arthritis patient population, emphasizing our need for continued study. Preliminary results from the BNZ-1 clinical trial, which targets IL-15 along with IL-2 and IL-9 signaling pathways, show some evidence of clinical response. With advances in our understanding of LGL pathogenesis from both the bench and the clinic, exciting avenues for investigations lie ahead for LGL leukemia.
32045782 Inhibition of neutrophil elastase prevents neutrophil extracellular trap formation and res 2020 Apr Neutrophil elastase (NE) is a serine protease stored in the azurophilic granules of neutrophils and released into the extracellular milieu during inflammatory response or formation of neutrophil extracellular traps (NETs). Neutrophils release NETs to entrap pathogens by externalizing their cellular contents in a DNA framework decorated with anti-microbials and proteases, including NE. Importantly, excess NETs in tissues are implicated in numerous pathologies, including sepsis, rheumatoid arthritis, vasculitis, and cancer. However, it remains unknown how to effectively prevent NET formation. Here, we show that NE plays a major role during NET formation and that inhibition of NE is a promising approach for decreasing NET-mediated tissue injury. NE promoted NET formation by human neutrophils. Whereas sivelestat, a small molecule inhibitor of NE, inhibited the formation of NETs in vitro , administration of free sivelestat did not have any efficacy in a murine model of lipopolysaccharide-induced endotoxic shock. To improve the efficacy of sivelestat in vivo, we have developed a nanoparticle system for delivering sivelestat. We demonstrate that nanoparticle-mediated delivery of sivelestat effectively inhibited NET formation, decreased the clinical signs of lung injury, reduced NE and other proinflammatory cytokines in serum, and rescued animals against endotoxic shock. Collectively, our data demonstrates that NE signaling can initiate NET formation and that nanoparticle-mediated inhibition of NE improves drug efficacy for preventing NET formation.
31982447 5-aminoisoquinolinone attenuates social behavior deficits and immune abnormalities in the 2020 Feb Autism spectrum disorder (ASD) is diagnosed by core symptoms including impaired social communication and the presence of repetitive and stereotypical behaviors. There is also evidence for immune dysfunction in individuals with ASD, but it is a disease that is still insufficiently controlled by current treatment strategies. The use of 5-aminoisoquinolinone (5-AIQ) ameliorates several immune-mediated symptoms including rheumatoid arthritis and colitis, and has neuroprotective properties; however, its role in ASD is not yet characterized. In this study, we investigated the effect of 5-AIQ on sociability tests, self-grooming, marble burying, and locomotor activities in BTBR T(+) Itpr3tf/J (BTBR) mice, which serve as an ASD animal model. We further investigated the possible molecular mechanism of 5-AIQ administration on CXCR4-, CXCR6-, IFN-γ-, IL-22-, NOS2-, STAT1-, T-bet-, and RORγT-producing CD3(+) T cells isolated from the spleens of treated mice. We also explored its effects on mRNA expression in brain tissue. Our results showed that in BTBR mice, 5-AIQ treatment significantly prevented self-grooming and marble burying behaviors and enhanced social interactions without any adverse effects on locomotor activity/anxiety level. Additionally, 5-AIQ treatment substantially decreased CXCR4-, CXCR6-, IFN-γ-, IL-22-, NOS2-, STAT1-, T-bet-, and RORγT-producing CD3(+) T cells in the spleen. Furthermore, 5-AIQ treatment decreased CXCR4, IFN-γ, IL-22, STAT1, and RORγT mRNA expression levels in brain tissue. Our findings demonstrated that 5-AIQ improved behavioral and immune abnormalities associated with ASD, which supports the hypothesis that 5-AIQ has important therapeutic potential for the treatment of behavioral and neuroimmune dysfunctions in ASD.
31981823 Contribution of astrocytes and macrophage migration inhibitory factor to immune-mediated c 2020 Mar Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine that is produced by many cell types in situations of homeostasis or disease. One of its functions is to act as a proinflammatory molecule. In humans, several studies have shown that MIF levels become elevated in the serum, urine, cerebrospinal fluid and tissues of patients with chronic inflammatory diseases (systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, sepsis, atheromas, diabetes and cancer). In dogs, distemper is a viral infectious condition that may lead to demyelination and inflammation in the central nervous system (CNS). In addition to the action of the virus, the inflammatory process may give rise to lesions in the white matter. Therefore, the objectives of the present study were to evaluate the role of MIF in the encephalitis that the canine distemper virus causes and to compare this with immunodetection of major histocompatibility complex-II (MHC-II), CD3 T lymphocytes, MMP-9 and glial fibrillary acidic protein (GFAP; astrocytes) in demyelinated areas of the encephalon, in order to ascertain whether these findings might be related to the severity of the encephalic lesions. To this end, a retrospective study on archived paraffinized blocks was conducted, in which 21 encephala from dogs that had been naturally infected with the canine distemper virus (infected group) and five from dogs that had been free from systemic or CNS-affecting diseases (control group) were used. In the immunohistochemical analysis on the samples, the degree of marking by GFAP, MHC-II, MMP-9 and MIF was greater in the demyelinated areas and in the adjacent neuropil, and this was seen particularly in astrocytes. Detection of CD3 was limited to perivascular cuffs. In areas of liquefactive necrosis, Gitter cells were positive for MMP-9, MIF and MHC-II. Hence, it was concluded that activated astrocytes influenced the afflux of T lymphocytes to the encephalon (encephalitis). In the more advanced phases, activated phagocytes in the areas of liquefactive necrosis (Gitter cells) continued to produce inflammatory mediators even after the astrocytes in these localities had died, thereby worsening the encephalic lesions. Distemper virus-activated astrocytes and microglia produce MIF that results in proinflammatory stimulus on glial cells and brain-infiltrating leukocytes. Therefore, the effect of the inflammatory response is potentiated on the neuropil, resulting in neurological clinical signs.
31838159 Interstitial pneumonia with autoimmune features: A single center prospective follow-up stu 2020 Feb BACKGROUND AND OBJECTIVE: Recently the term "interstitial pneumonia with autoimmune features" (IPAF) has been proposed to identify patients with interstitial lung disease and autoimmune characteristics, not fulfilling the criteria for specific connective tissue diseases (CTD). Only few data are available about the clinical and serological features of IPAF patients, their survival and the possible evolution in a CTD. The aims of the study were to investigate the demographic and clinico-serologic features of patients with IPAF, their relationship to survival, and the possible evolution in a definite CTD. PATIENTS AND METHODS: Fifty-two patients were consecutively enrolled and prospectively followed for 45 ± 31.6 months. Data about disease onset, serological, clinical and therapeutic features, pulmonary function tests and high-resolution computed tomography were periodically repeated. The survival of patients with IPAF was compared with that of 104 patients with idiopathic pulmonary fibrosis (IPF). RESULTS: The clinical domain for IPAF was satisfied in 44 patients, serological domain in 49 and the morphological domain in 29 patients. During the follow-up, a definite CTD was diagnosed in 7 patients, in particular Sjogren's syndrome in 4 patients, rheumatoid arthritis in 2, and polymyositis in the last. The estimated 5-year survival of IPAF patients 69.5 ± 7.8%, significantly higher than survival observed in IPF patients, and the baseline value of FVC and DLCO were the only factors associated to death. CONCLUSIONS: IPAF seems to a distinct entity, with a low tendency to evolve in a definite CTD. Nevertheless, further studies are needed to better define the clinical evolution and the outcome of IPAF.
31810604 Molecular hydrogen suppresses superoxide generation in the mitochondrial complex I and red 2020 Feb 19 Molecular hydrogen (H(2)) is recognized as a medical gas applicable to numerous diseases including neurodegenerative diseases, metabolic disorders, and rheumatoid arthritis. Although the efficacy of H(2) is reportedly attributed to its scavenging capability against the hydroxyl radical, the mechanisms underlying its therapeutic efficacy are not fully understood. Herein, we estimated the role of H(2) in the energy converting system of the mitochondria, the source of reactive oxygen species. To investigate the effects of H(2) on mitochondrial function, direction of electron flow, superoxide generation, and mitochondrial membrane potential were investigated. Forward electron transport (FET) or reverse electron transport (RET) was assessed by monitoring the decrease or increase of β-nicotinamide adenine dinucleotide hydrate (NADH, - or +, μM, respectively) in the presence of β-nicotinamide adenine dinucleotide (NAD(+)) and/or succinate in the isolated mitochondria. H(2)O(2) converted from superoxide by superoxide dismutase (SOD) was measured to estimate electron leakage in the mitochondria. The effects of H(2) on mitochondrial membrane potential were observed by staining cells with the fluorescence probe, teramethylrhodamine ethyl ester (TMRE). Despite the absence of succinate, a distinct RET was observed (from +0.0313 ± 0.0106 μM to +1.20 ± 0.302 μM) by adding 25 μM H(2). In the presence of 5 μM NADH, RET by succinate inverted to FET from +1.62 ± 0.358 μM to -1.83 ± 0.191 μM, accompanied by a suppression of superoxide generated predominantly from complex I by 51.1%. H(2) solely reduced mitochondrial membrane potential of the cultured cells by 11.3% as assessed by TMRE. The direction of electron flow was altered by H(2) depending on the NAD(+)/NADH ratio, accompanied by suppression of superoxide generation H(2) could suppress superoxide generation in complex I in vitro and reduce membrane potential in vivo. H(2) may also neutralize semiquinone radicals to reduce superoxide produced in complex III. H(2) may function as a rectifier of the electron flow affecting the mitochondrial membrane potential to suppress oxidative damage in mitochondria.
31676403 Investigation of the preliminary mechanism of action for the acute anti-inflammatory activ 2020 Feb 10 ETHNOPHARMACOLOGICAL RELEVANCE: In folkloric medicine the dried rhizome of the Jamaican sarsaparilla (Smilax ornate Lem.), is given as a decoction to treat chronic rheumatism and rheumatoid arthritis. This particular claim has been scientifically validated; however, the mechanism for its anti-inflammatory activity is still unknown and hence, it forms the reason for this investigation. OBJECTIVE: The objective of this study is to investigate the mechanism of the anti-inflammatory activity of the methanol extract of Smilax ornate Lem. METHOD: The methanol extract was prepared using the soxhlet apparatus. The preliminary mechanism of action was investigated using models of oedema induced by histamine, bradykinin and prostaglandin E(2). RESULTS: For the histamine-induced oedema model, the methanol extract (400 mg/kg) reduced the oedema formation, however, it was not significant (P > 0.05). For the bradykinin-induced oedema model, the methanol extract (400 mg/kg) exhibited significant (P < 0.05) anti-inflammatory activity when compared with that of the control (saline) group, with an onset on 60 min and a duration of 2 h. For the prostaglandin-induced oedema model, the methanol extract (400 mg/kg) exhibited significant (P < 0.05) anti-inflammatory activity when compared with that of its control group, with an onset on 120 min and a duration of 1.5 h. CONCLUSION: The methanol extract of Smilax ornata Lem. produced significant anti-inflammatory activity in the bradykinin-induced and prostaglandin-induced oedema models. It is possible that the mechanism by which it acts is by reducing the concentration or blocking the action of these mediators.
31735133 Pembrolizumab- and/or pazopanib-induced remitting seronegative symmetrical synovitis with 2020 Jul INTRODUCTION: Immune checkpoint inhibitors and angiogenesis inhibitors are novel treatment options for renal cell carcinoma and widely used in clinical practice. They are related with adverse events that occur as a consequence of immune system activation and inhibition of angiogenesis. Herein, we report a rare case of inflammatory arthritis seen in a patient treated with an anti Programmed cell death-1 pembrolizumab and an anti-vascular endothelial growth factor pazopanib. CASE REPORT: A 60-year-old Caucasian male presented to our clinic with inflammatory arthritis with pitting edema. He had been started on pembrolizumab therapy for metastatic renal cell carcinoma after enrolling in the KEYNOTE-679 study. After six cycles of treatment with pembrolizumab, metastasis had been determined in the lung. Then, the patient's therapy was changed to pazopanib. While the patient was on pazopanib treatment, he noticed a gradual swelling of both hands. Rheumatoid factor, anti-nuclear antibody and anti-cyclic citrullinated peptide were negative. Joint ultrasonography revealed acute tenosynovitis and soft tissue swelling with pitting edema, and a diagnosis of remitting seronegative symmetrical synovitis with pitting edema was made. Management and outcome: He was started on 10 mg prednisolone daily. His symptoms dramatically responded to corticosteroid. He continued to take pazopanib. Then, the patient was discharged with 10 mg prednisolone daily. DISCUSSION: Pembrolizumab- and/or pazopanib-induced remitting seronegative symmetrical synovitis with pitting edema can be among the rare rheumatic immune-related adverse events that clinicians may encounter as the immune check point inhibitors and anti-VEGF use increases. Corticosteroid therapy can relieve symptoms and cessation of therapy may not be necessary.
32813281 Mobile technologies to support healthcare provider to healthcare provider communication an 2020 Aug 18 BACKGROUND: The widespread use of mobile technologies can potentially expand the use of telemedicine approaches to facilitate communication between healthcare providers, this might increase access to specialist advice and improve patient health outcomes. OBJECTIVES: To assess the effects of mobile technologies versus usual care for supporting communication and consultations between healthcare providers on healthcare providers' performance, acceptability and satisfaction, healthcare use, patient health outcomes, acceptability and satisfaction, costs, and technical difficulties. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase and three other databases from 1 January 2000 to 22 July 2019. We searched clinical trials registries, checked references of relevant systematic reviews and included studies, and contacted topic experts. SELECTION CRITERIA: Randomised trials comparing mobile technologies to support healthcare provider to healthcare provider communication and consultations compared with usual care. DATA COLLECTION AND ANALYSIS: We followed standard methodological procedures expected by Cochrane and EPOC. We used the GRADE approach to assess the certainty of the evidence. MAIN RESULTS: We included 19 trials (5766 participants when reported), most were conducted in high-income countries. The most frequently used mobile technology was a mobile phone, often accompanied by training if it was used to transfer digital images. Trials recruited participants with different conditions, and interventions varied in delivery, components, and frequency of contact. We judged most trials to have high risk of performance bias, and approximately half had a high risk of detection, attrition, and reporting biases. Two studies reported data on technical problems, reporting few difficulties. Mobile technologies used by primary care providers to consult with hospital specialists We assessed the certainty of evidence for this group of trials as moderate to low. Mobile technologies: - probably make little or no difference to primary care providers following guidelines for people with chronic kidney disease (CKD; 1 trial, 47 general practices, 3004 participants); - probably reduce the time between presentation and management of individuals with skin conditions, people with symptoms requiring an ultrasound, or being referred for an appointment with a specialist after attending primary care (4 trials, 656 participants); - may reduce referrals and clinic visits among people with some skin conditions, and increase the likelihood of receiving retinopathy screening among people with diabetes, or an ultrasound in those referred with symptoms (9 trials, 4810 participants when reported); - probably make little or no difference to patient-reported quality of life and health-related quality of life (2 trials, 622 participants) or to clinician-assessed clinical recovery (2 trials, 769 participants) among individuals with skin conditions; - may make little or no difference to healthcare provider (2 trials, 378 participants) or participant acceptability and satisfaction (4 trials, 972 participants) when primary care providers consult with dermatologists; - may make little or no difference for total or expected costs per participant for adults with some skin conditions or CKD (6 trials, 5423 participants). Mobile technologies used by emergency physicians to consult with hospital specialists about people attending the emergency department We assessed the certainty of evidence for this group of trials as moderate. Mobile technologies: - probably slightly reduce the consultation time between emergency physicians and hospital specialists (median difference -12 minutes, 95% CI -19 to -7; 1 trial, 345 participants); - probably reduce participants' length of stay in the emergency department by a few minutes (median difference -30 minutes, 95% CI -37 to -25; 1 trial, 345 participants). We did not identify trials that reported on providers' adherence, participants' health status and well-being, healthcare provider and participant acceptability and satisfaction, or costs. Mobile technologies used by community health workers or home-care workers to consult with clinic staff We assessed the certainty of evidence for this group of trials as moderate to low. Mobile technologies: - probably make little or no difference in the number of outpatient clinic and community nurse consultations for participants with diabetes or older individuals treated with home enteral nutrition (2 trials, 370 participants) or hospitalisation of older individuals treated with home enteral nutrition (1 trial, 188 participants); - may lead to little or no difference in mortality among people living with HIV (RR 0.82, 95% CI 0.55 to 1.22) or diabetes (RR 0.94, 95% CI 0.28 to 3.12) (2 trials, 1152 participants); - may make little or no difference to participants' disease activity or health-related quality of life in participants with rheumatoid arthritis (1 trial, 85 participants); - probably make little or no difference for participant acceptability and satisfaction for participants with diabetes and participants with rheumatoid arthritis (2 trials, 178 participants). We did not identify any trials that reported on providers' adherence, time between presentation and management, healthcare provider acceptability and satisfaction, or costs. AUTHORS' CONCLUSIONS: Our confidence in the effect estimates is limited. Interventions including a mobile technology component to support healthcare provider to healthcare provider communication and management of care may reduce the time between presentation and management of the health condition when primary care providers or emergency physicians use them to consult with specialists, and may increase the likelihood of receiving a clinical examination among participants with diabetes and those who required an ultrasound. They may decrease the number of people attending primary care who are referred to secondary or tertiary care in some conditions, such as some skin conditions and CKD. There was little evidence of effects on participants' health status and well-being, satisfaction, or costs.
31708547 Thrombotic Thrombocytopenic Purpura Treated with Rituximab Associated with Primary Sjögre 2020 Mar 1 A 47-year-old man was admitted to our hospital because of thrombocytopenia and consciousness disturbance. As his laboratory data showed undetectable activity of a disintegrin-like and metalloproteinase with thrombospondin type 1 motifs 13 (ADAMTS13) and the presence of ADAMTS13 inhibitor, he was diagnosed with acquired thrombotic thrombocytopenic purpura (TTP). Asymptomatic primary Sjögren's syndrome (SS) and primary hypothyroidism were incidentally diagnosed on screening. After initial plasma exchange therapy and pulse corticosteroid therapy, the patient received rituximab therapy for refractory TTP with "inhibitor boosting" and recovered. TTP secondary to primary SS is rare but can trigger refractory TTP. Treatment with rituximab, which is considered "inhibitor boosting," should be considered when re-exacerbation occurs.
31856039 Enhancing stability by penetrating the apophysis of greater trochanter or the posterior ne 2020 Sep We modified the traditional titanium elastic nail (TEN) technique to increase stability, by involving the apophysis of the greater trochanter (GT) and the femoral neck cortex. We report the clinical/radiological outcomes after at least 5 years of follow-up. We prospectively included 17 children aged 5-12 years diagnosed with subtrochanteric femoral fractures between January 2004 and December 2013. Radiological evaluations of bony union, malunion, and limb-length discrepancies (LLDs) were performed at the final follow-up. Clinical outcomes, as revealed by the Flynn scoring system, and the range of hip motion were also recorded. The mean patient age was 8.4 ± 2.0 years. Twelve patients presented with length-stable fractures and the others with unstable fractures. Bony union was evident at a mean of 4.5 months postoperatively. Radiologically, malunion >5° was evident in three patients, but all angles were <10° at the final follow-up. LLDs >1 cm were evident in five patients, but all were <2 cm at the final follow-up. Thirteen patients showed excellent outcomes and 4 had satisfactory outcomes. Complications were apparent in only two patients; both showed only temporary discomfort caused by prominent nails. The range of hip motion was satisfactory in all cases; no difference compared to the contralateral hip was apparent. Finally, the radiological/clinical outcomes did not differ by the fracture stability or pattern. We penetrated the apophysis of the GT and the femoral neck cortex with TENs to further stabilise subtrochanteric femoral fractures. This was a simple procedure that enhanced patient outcomes. Level of evidence: therapeutic level II.
33455171 Functionalized Carbon Nanotube-Embedded Poly(vinyl alcohol) Microspheres for Efficient Rem 2020 Aug 10 Tumor necrosis factor (TNF)-α has an important role in the pathogenesis of autoimmune and inflammatory diseases such as rheumatoid and septic arthritis. Removal of excess tumor necrosis factor-α (TNF-α) is a promising treatment. In this study, a series of functionalized carbon nanotube-embedded poly(vinyl alcohol) (PVA) nanocomposite adsorbents were prepared for TNF-α removal for the first time. The resulting nanocomposites were characterized by scanning electron microscopy and Raman spectroscopy, which demonstrated that carbon nanotubes were well-dispersed on the surface of PVA macroporous microspheres. Adsorption tests showed that the carboxylated carbon nanotube-embedded composite microspheres (PVA/MWCNTs-COOH) possessed much better adsorption capacity for TNF-α in both simulated serum solution and rat plasma compared to the aminated (PVA/MWCNTs-NH(2)) and raw carbon nanotube-embedded microspheres (PVA/MWCNTs-raw). In addition, the effects on hemolytic activity, the anticoagulant property, and the components of blood were negligible, indicating the excellent blood compatibility of composite beads. Our findings suggest that the carboxylated carbon nanotube-embedded composite microspheres may be potentially useful for the treatment of autoimmune and inflammatory diseases by removing TNF-α from the blood.
32748769 Ferritin, Erythrocyte Sedimentation Rate, and C-Reactive Protein Level in Patients with Ch 2020 Nov Chikungunya virus (CHIKV) is a global emergent arthritogenic alphavirus transmitted by anthropophilic Stegomyia mosquitoes. Chikungunya fever may evolve to chronic arthralgia in 57-80% of infected patients. This study was developed to identify possibly fast, simple low-cost biomarkers to monitor chronic CHIKV-induced articular disease. Between 2017 and 2018, we analyzed clinical data of patients meeting the criteria established by standard protocols to define chronic chikungunya articular disease. Patients were classified according to the disease activity scores, inflammatory biomarkers (erythrocyte sedimentation rate [ESR], ferritin, and C-reactive protein [CRP] serum), positive rheumatoid factor, comorbidities, smoking, and previous use of corticosteroids determined before beginning therapy. Of 106 patients, 98 (92.5%) were women with mean age of 52 ± 13 years, 6.8 ± 4.4 months of illness duration at the first medical appointment, and 6.7 ± 4.5 affected joints. Mean ESR (26 ± 19), CRP (2.6 ± 3.6), and stratified ferritin (144 ± 115) levels were normal according to reference values. There was no significance in comparing the levels of inflammatory biomarkers and the additional variables analyzed in the presence of moderate chronic joint disease in the study population. However, we identified a negative correlation between disease activity measures and duration of disease at the first medical evaluation after initial infection (P < 0.001), corroborating data observed in the literature.
33060303 Soluble Low-density Lipoprotein Receptor-related Protein 1 in Juvenile Idiopathic Arthriti 2021 May OBJECTIVES: This study aimed to expand knowledge about soluble low-density lipoprotein receptor-related protein 1 (sLRP1) in juvenile idiopathic arthritis (JIA) by determining associations of sLRP1 levels in nonsystemic JIA patients with clinical and inflammatory biomarker indicators of disease activity. METHODS: Plasma sLRP1 and 44 inflammation-related biomarkers were measured at enrollment and 6 months later in a cohort of 96 newly diagnosed Canadian patients with nonsystemic JIA. Relationships between sLRP1 levels and indicators of disease activity and biomarker levels were analyzed at both visits. RESULTS: At enrollment, sLRP1 levels correlated negatively with age and active joint counts. Children showed significantly higher levels of sLRP1 than adolescents (mean ranks: 55.4 and 41.9, respectively; P = 0.02). Participants with 4 or fewer active joints, compared to those with 5 or more active joints, had significantly higher sLRP1 levels (mean ranks: 56.2 and 40.7, respectively; P = 0.006). At enrollment, considering the entire cohort, sLRP1 correlated negatively with the number of active joints (r = -0.235, P = 0.017). In the entire cohort, sLRP1 levels at enrollment and 6 months later correlated with 13 and 6 pro- and antiinflammatory biomarkers, respectively. In JIA categories, sLRP1 correlations with inflammatory markers were significant in rheumatoid factor-negative polyarticular JIA, oligoarticular JIA, enthesitis-related arthritis, and psoriatic arthritis at enrollment. Higher sLRP1 levels at enrollment increased the likelihood of absence of active joints 6 months later. CONCLUSION: Plasma sLRP1 levels correlate with clinical and biomarker indicators of short-term improvement in JIA disease activity, supporting sLRP1 as an upstream biomarker of potential utility for assessing JIA disease activity and outcome prediction.
31571337 Preterm birth phenotypes in women with autoimmune rheumatic diseases: a population-based c 2020 Jan OBJECTIVE: To investigate preterm birth (PTB) phenotypes in women with different autoimmune rheumatic diseases in a large population-based cohort. DESIGN: Retrospective cohort study. SETTING: California, USA. POPULATION: All live singleton births in California between 2007 and 2011 were analysed. Patients with autoimmune disease at delivery were identified by International Classification of Diseases, Ninth Revision , Clinical Modification (ICD-9-CM), codes for systemic lupus erythematosus (SLE), systemic sclerosis (SSc), rheumatoid arthritis (RA), polymyositis/dermatomyositis (DM/PM), and juvenile idiopathic arthritis (JIA). METHODS: Maternally linked hospital and birth certificate records of 2 481 516 deliveries were assessed (SLE n = 2272, RA n = 1501, SSc n = 88, JIA n = 187, DM/PM n = 38). Multivariable Poisson regression models estimated the risk ratios (RRs) for different PTB phenotypes (relative to term deliveries) for each autoimmune disease compared with the general obstetric population, adjusting for maternal age, race/ethnicity, body mass index, smoking, education, payer, parity, and prenatal care. MAIN OUTCOME MEASURES: Preterm birth (PTB) was assessed overall (20-36 weeks of gestation) and by subphenotype: preterm prelabour rupture of membranes (PPROM), spontaneous birth, or medically indicated PTB. The risk of PTB overall and for each phenotype was partitioned by gestational age: early (20-31 weeks of gestation) and late (32-36 weeks of gestation). RESULTS: Risks for PTB were elevated for each autoimmune disease evaluated: SLE (RR 3.27, 95% CI 3.01-3.56), RA (RR 2.04, 95% CI 1.79-2.33), SSc (RR 3.74, 95% CI 2.51-5.58), JIA (RR 2.23, 95% CI 1.54-3.23), and DM/PM (RR 5.26, 95% CI 3.12-8.89). These elevated risks were observed for the majority of PTB phenotypes as well. CONCLUSIONS: Women with systemic autoimmune diseases appear to have an elevated risk of various PTB phenotypes. Therefore, preconception counselling and close monitoring during pregnancy is crucial. TWEETABLE ABSTRACT: This study found that women with systemic autoimmune diseases have an elevated risk of preterm birth phenotypes.