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ID PMID Title PublicationDate abstract
31833184 Pharmacokinetics and Safety of a Single Oral Dose of Peficitinib (ASP015K) in Japanese Sub 2020 Aug Peficitinib (ASP015K) is a novel Janus kinase inhibitor developed for the treatment of rheumatoid arthritis (RA). The impact of hepatic impairment on the peficitinib pharmacokinetic (PK) and safety profile was investigated in non-RA subjects (n = 24) in an open-label, parallel-group, multicenter comparative study in Japan. Subjects received a single, clinically relevant, oral dose of a peficitinib 150 mg tablet under fasting conditions. Plasma PK parameters were measured for peficitinib and its metabolites H1 (sulfate and methylated metabolite), H2 (sulfate metabolite), and H4 (methylated metabolite) in subjects with normal hepatic function, mild hepatic impairment, or moderate hepatic impairment. The peficitinib area under the plasma-concentration-time curve from time 0 to infinity (AUC(inf) ) and maximum observed concentration (C(max) ) were not markedly different in subjects with mild hepatic impairment versus normal hepatic function. In subjects with moderate hepatic impairment versus normal hepatic function, the geometric mean ratios for peficitinib AUC(inf) and C(max) , were 1.92 (90% CI: 1.39, 2.66) and 1.82 (90% CI: 1.24, 2.69), respectively. Five treatment-emergent adverse events (TEAEs) were experienced by 3 subjects, 1 in each group. There were no deaths, no serious TEAEs, and no TEAEs leading to withdrawal. In summary, the PK profile was unaltered in subjects with mild hepatic impairment after a single clinically relevant dose of peficitinib, but exposure almost doubled in subjects with moderate hepatic impairment. Peficitinib dose reduction may be considered in RA patients with moderate hepatic impairment.
31713882 A botanical drug composed of three herbal materials attenuates the sensorimotor gating def 2020 Jan OBJECTIVES: A botanical drug derived from the ethanolic extract composed of Clematis chinensis Osbeck (Ranunculaceae), Trichosanthes kirilowii Maximowicz (Cucurbitaceae) and Prunella vulgaris Linné (Lamiaceae) has been used to ameliorate rheumatoid arthritis as an ethical drug in Korea. In our study, we investigated the effect of this herbal complex extract (HCE) on schizophrenia-like behaviours induced by MK-801. METHODS: HCE (30, 100 or 300 mg/kg, p.o) was orally administered to male ICR mice to a schizophrenia-like animal model induced by MK-801. We conducted an acoustic startle response task, an open-field task, a novel object recognition task and a social novelty preference task. KEY FINDINGS: We found that a single administration of HCE (100 or 300 mg/kg) ameliorated MK-801-induced abnormal behaviours including sensorimotor gating deficits and social or object recognition memory deficits. In addition, MK-801-induced increases in phosphorylated Akt and GSK-3β expression levels in the prefrontal cortex were reversed by HCE (30, 100 or 300 mg/kg). CONCLUSIONS: These results imply that HCE ameliorates MK-801-induced dysfunctions in prepulse inhibition, social interactions and cognitive function, partly by regulating the Akt and GSK-3β signalling pathways.
31645276 Osteonecrosis and osteomyelitis of the jaw associated with tumour necrosis factor-alpha (T 2020 Jan Tumour necrosis factor-α (TNF-α) inhibitors are increasingly being used as immunomodulators to manage inflammatory conditions such as rheumatoid arthritis and Crohn's disease. Reported serious side effects include an increased incidence of lymphoma and greater susceptibility to infections such as tuberculosis. The aim of this systematic review was to find out whether there is an associated risk of medication-related osteonecrosis of the jaw (MRONJ). Three authors independently searched PubMed, MEDLINE, EMBASE, CINAHL and the Cochrane Central Register of Controlled Trials for published reports of oral osteonecrosis (ONJ) or osteomyelitis (OM) in patients who took anti TNF-α drugs and had no history of antiangiogenic agents or antiresorptive treatment. All types of studies on humans treated with TNF-α inhibitors were considered. Only six were eligible for analysis, and all were independently assessed for risk of bias. They included six patients with ONJ or OM that was attributed solely to TNF-α inhibitors. The most common site of ONJ was the posterior mandible (n=5). The mean (SD) duration of anti-TNF-α treatment before the development of bony lesions was 62.5 (47.4) months. Invasive surgery was reported as a precipitating factor in five cases, and the ONJ/OM resolved with conservative management in five. Although all the studies were judged to be at high risk of bias, the limited data suggest that some patients will potentially develop ONJ/OM as a result of treatment with TNF-α inhibitors. Studies of higher quality are now needed to establish the relative risk of MRONJ in patients who take them.
33379351 Pathological Insight into 5-HT(2B) Receptor Activation in Fibrosing Interstitial Lung Dise 2020 Dec 28 Interstitial lung disease (ILD) encompasses a heterogeneous group of more than 200 conditions, of which primarily idiopathic pulmonary fibrosis (IPF), idiopathic nonspecific interstitial pneumonia, hypersensitivity pneumonitis, ILD associated with autoimmune diseases and sarcoidosis may present a progressive fibrosing (PF) phenotype. Despite different aetiology and histopathological patterns, the PF-ILDs have similarities regarding disease mechanisms with self-sustaining fibrosis, which suggests that the diseases may share common pathogenetic pathways. Previous studies show an enhanced activation of serotonergic signaling in pulmonary fibrosis, and the serotonin (5-HT)(2) receptors have been implicated to have important roles in observed profibrotic actions. Our research findings in support by others, demonstrate antifibrotic effects with 5-HT(2B) receptor antagonists, alleviating several key events common for the fibrotic diseases such as myofibroblast differentiation and connective tissue deposition. In this review, we will address the potential role of 5-HT and in particular the 5-HT(2B) receptors in three PF-ILDs: ILD associated with systemic sclerosis (SSc-ILD), ILD associated with rheumatoid arthritis (RA-ILD) and IPF. Highlighting the converging pathways in these diseases discloses the 5-HT(2B) receptor as a potential disease target for PF-ILDs, which today have an urgent unmet need for therapeutic strategies.
33148311 Clinical decision support improves the appropriateness of laboratory test ordering in prim 2020 Nov 4 BACKGROUND: Inappropriate laboratory test ordering poses an important burden for healthcare. Clinical decision support systems (CDSS) have been cited as promising tools to improve laboratory test ordering behavior. The objectives of this study were to evaluate the effects of an intervention that integrated a clinical decision support service into a computerized physician order entry (CPOE) on the appropriateness and volume of laboratory test ordering, and on diagnostic error in primary care. METHODS: This study was a pragmatic, cluster randomized, open-label, controlled clinical trial. SETTING: Two hundred eighty general practitioners (GPs) from 72 primary care practices in Belgium. PATIENTS: Patients aged ≥ 18 years with a laboratory test order for at least one of 17 indications: cardiovascular disease management, hypertension, check-up, chronic kidney disease (CKD), thyroid disease, type 2 diabetes mellitus, fatigue, anemia, liver disease, gout, suspicion of acute coronary syndrome (ACS), suspicion of lung embolism, rheumatoid arthritis, sexually transmitted infections (STI), acute diarrhea, chronic diarrhea, and follow-up of medication. INTERVENTIONS: The CDSS was integrated into a computerized physician order entry (CPOE) in the form of evidence-based order sets that suggested appropriate tests based on the indication provided by the general physician. MEASUREMENTS: The primary outcome of the ELMO study was the proportion of appropriate tests over the total number of ordered tests and inappropriately not-requested tests. Secondary outcomes of the ELMO study included diagnostic error, test volume, and cascade activities. RESULTS: CDSS increased the proportion of appropriate tests by 0.21 (95% CI 0.16-0.26, p < 0.0001) for all tests included in the study. GPs in the CDSS arm ordered 7 (7.15 (95% CI 3.37-10.93, p = 0.0002)) tests fewer per panel. CDSS did not increase diagnostic error. The absolute difference in proportions was a decrease of 0.66% (95% CI 1.4% decrease-0.05% increase) in possible diagnostic error. CONCLUSIONS: A CDSS in the form of order sets, integrated within the CPOE improved appropriateness and decreased volume of laboratory test ordering without increasing diagnostic error. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02950142 , registered on October 25, 2016.
32466389 The Spectrum of Interstitial Lung Disease Associated with Autoimmune Diseases: Data of a 3 2020 May 26 Interstitial lung disease (ILD) may occur in patients with a rheumatic autoimmune disease (AD), increasing their risk of morbidity and mortality. However, little is known about the prevalence of AD in patients diagnosed with an ILD. In this prospective study, we determined the spectrum of ILD associated with AD (AD-ILD) among patients sent for assessment to a single clinic of ILD and lung transplantation from a referral center between May 2016 and December 2019. ILD diagnosis was made by pneumologists based on clinical and radiological findings and pulmonary function test abnormalities. All patients with ILD were also assessed by experienced rheumatologists. During the period of assessment, 338 patients were diagnosed with ILD. Among them, 32.8% fulfilled definitions for an AD. Most cases with AD-ILD had a diagnosis of rheumatoid arthritis (27.0%), systemic sclerosis (26.1%) or anti-synthetase syndrome (17.1%). Interestingly, 18% of the patients with AD-ILD were diagnosed as having an interstitial pneumonia with autoimmune features. Antinuclear antibodies and non-specific interstitial pneumonia were the most frequent positive autoantibodies and radiological pattern found in AD-ILD patients, respectively. In conclusion, our study indicates that a high number of ILD patients have a related AD. Consequently, close collaboration among rheumatologists and pneumologists is needed.
32248767 Incidence and risk factors for stroke following percutaneous coronary intervention. 2020 Oct BACKGROUND: Stroke rates and risk factors may change as percutaneous coronary intervention practice evolves and no data are available comparing stroke incidence after percutaneous coronary intervention to the general population. AIMS: This study aimed to identify the incidence and risk factors for inpatient and subsequent stroke following percutaneous coronary intervention with comparison to age-matched controls. METHODS: Data were prospectively collected from 22,618 patients undergoing percutaneous coronary intervention in the Melbourne Interventional Group registry (2005-2015). The cohort was compared to the North-East Melbourne Stroke Incidence Study population-based cohort (1997-1999) and predefined variables assessed for association with inpatient or outpatient stroke. RESULTS: Inpatient stroke occurred in 0.33% (65.3% ischemic, 28.0% haemorrhagic, and 6.7% cause unknown), while outpatient stroke occurred in 0.55%. Inpatient and outpatient stroke were associated with higher rates of in-hospital major adverse cardiovascular outcomes (p < 0.0001) and mortality (p < 0.0001), as well as 12-month mortality (p < 0.0001). Factors independently associated with inpatient stroke were renal impairment, ST-elevation myocardial infarction, previous stroke, left ventricular ejection fraction 30-45%, and female sex, while those associated with outpatient stroke were previous stroke, chronic lung disease, previous myocardial infarction, rheumatoid arthritis, female sex, and older age. Compared to the age-standardized population-based cohort, stroke rates in the 12 months following discharge were higher for percutaneous coronary intervention patients <65 years old, but lower for percutaneous coronary intervention patients ≥65 years old. CONCLUSIONS: Risk of inpatient stroke following percutaneous coronary intervention appears to be largely associated with clinical status at presentation, while outpatient stroke relates more to age and chronic disease. Compared to the general population, outpatient stroke rates following percutaneous coronary intervention are higher for younger, but not older, patients.
32540999 Cutting Edge: TNF Is Essential for Mycobacteria-Induced MINCLE Expression, Macrophage Acti 2020 Jul 15 TNF blockade is a successful treatment for human autoimmune disorders like rheumatoid arthritis and inflammatory bowel disease yet increases susceptibility to tuberculosis and other infections. The C-type lectin receptors (CLR) MINCLE, MCL, and DECTIN-2 are expressed on myeloid cells and sense mycobacterial cell wall glycolipids. In this study, we show that TNF is sufficient to upregulate MINCLE, MCL, and DECTIN-2 in macrophages. TNF signaling through TNFR1 p55 was required for upregulation of these CLR and for cytokine secretion in macrophages stimulated with the MINCLE ligand trehalose-6,6-dibehenate or infected with Mycobacterium bovis bacillus Calmette-Guérin. The Th17 response to immunization with the MINCLE-dependent adjuvant trehalose-6,6-dibehenate was specifically abrogated in TNF-deficient mice and strongly attenuated by TNF blockade with etanercept. Together, interference with production or signaling of TNF antagonized the expression of DECTIN-2 family CLR, thwarting vaccine responses and possibly increasing infection risk.
31843541 A mutation of cysteine 46 in IKK-β promotes mPGES-1 and caveolin-1 expression to exacerba 2020 Feb IKK-β is indispensable for inflammatory osteolysis, the functional residues of IKK-β are therapeutic drug targets for developing inhibitors to treat multiple diseases now. Thus it remains appealing to find the new residues of IKK-β to influence osteoclasts for alleviating bone loss diseases such as rheumatoid arthritis (RA). By employing IKK-β cysteine 46-A transgenic (IKK-β(C46A)) mice, we found that mutation of cysteine 46 to alanine in IKK-β exacerbated inflammatory bone destruction in vivo, and increased osteoclast differentiation and bone resorption ex vivo and in vitro. Consistent with these, IKK-β kinase activity as well as c-Fos, NFATc1 were up-regulated in bone marrow macrophages (BMMs) from IKK-β(C46A) mice during RANKL-induced osteoclastogenesis. Of interesting, we further identified and demonstrated that the expressions of mPGES-1 and caveolin-1 were heightened in BMMs of IKK-β(C46A) mice compared to those in WT mice in RANKL-induced osteoclastogenesis. Together, it revealed that mutating cysteine 46 in IKK-β could increase caveolin-1 and mPGES-1 expression to facilitate osteoclast differentiation and osteolysis. Cysteine 46 can serve as a novel target in IKK-β for designing inhibitors to treat osteolysis.
31774546 Non-obstetric abdominal surgery during pregnancy and birth outcomes: A Danish registry-bas 2020 Apr INTRODUCTION: Surgery during pregnancy may increase the risk of adverse birth outcomes. In this nationwide registry-based cohort study including women aged 15-54 years with singleton birth or miscarriage, we examined the association between non-obstetric abdominal surgery during pregnancy and the birth outcomes small-for-gestational-age (SGA), preterm birth, and miscarriage. MATERIAL AND METHODS: The study used data on births or miscarriages from the large national Danish registries in 1997-2015. We calculated absolute risks and risk differences for the main outcomes and used Cox regression analysis with non-obstetric abdominal surgery as a time-varying exposure, adjusting for maternal age, year of last menstrual period, major abdominal surgery before pregnancy, maternal smoking status, rheumatoid arthritis, diabetes and inflammatory bowel disease. Our main outcome measures were risks and hazard ratios (HRs) for SGA, very preterm or preterm birth, and miscarriage after gestational week 7 overall, stratified by calendar year, and, for SGA, trimester of pregnancy. Finally, absolute risk of miscarriage stratified by time since surgery. RESULTS: Absolute risks in surgically treated vs untreated were 3.4% vs 2.7% for SGA (adjusted HR 1.3, 95% CI 1.1-1.5), 2.2% vs 0.8% for very preterm birth (adjusted HR 2.8, 95% CI 2.2-3.5), 8.3% vs 4.3% for preterm birth (adjusted HR 2.1, 95% CI 1.9-2.3), and 8.2% vs 6.1% for miscarriage (adjusted HR 3.1, 95% CI 2.7-3.5). For miscarriage, the risk was highest the first week after surgery and levelled out after 2 weeks. CONCLUSIONS: Surgery during pregnancy is associated with an increased risk of SGA, very preterm birth, preterm birth and miscarriage, and the risk of miscarriage is highest the first week after surgery.
31618438 Serum immunoglobulin free light chain levels in systemic autoimmune rheumatic diseases. 2020 Feb Several reports have highlighted the abnormal increments of serum immunoglobulin free light chains (FLCs) in the course of systemic autoimmune rheumatic diseases (SARD), but a comparative analysis among different conditions is still lacking. A strong association between elevated FLC and hepatitis C virus (HCV)-related mixed cryoglobulinaemia (HCVMC) has been well established. Here, we aimed to analyse serum FLC levels in patients with four different SARD in comparison with HCVMC. Using a turbidimetric assay, free κ and λ chains were quantified in sera from 198 SARD patients (37 rheumatoid arthritis, RA; 47 systemic lupus erythematosus, SLE; 52 anti-phospholipid syndrome, APS; 62 primary Sjogren's syndrome, pSS), 62 HCVMC and 50 healthy blood donors (HD). All patient groups showed increased κ levels when compared to HD: 33·5 ± 2·6 mg/l in HCVMC, 26·7 ± 2·3 mg/l in RA, 29·7 ± 1·9 mg/l in SLE, 23·8 ± 1·1 mg/l in APS, 24·2 ± 1·1 mg/l in pSS; 10·1 ± 0·6 mg/l in HD. Free λ levels displayed a significant increase only for HCVMC (20·4 ± 1·4 mg/l) and SLE (18·4 ± 1·0 mg/l) compared to HD (13·6 ± 0·9 mg/l). The increase of κ compared to λ takes into account a κ /λ ratio of 1·6 for all groups. Our results substantially analyse and strengthen the association between FLC and SARD focusing the questions regarding their role in the pathogenesis and diagnosis of human diseases. Unfortunately, the biochemical differences distinguishing normal from pathological FLC have not been identified. Production of different isotypes is probably connected to still-unknown pathways.
32707129 Injection of CD40 DNA vaccine ameliorates the autoimmune pathology of non-obese diabetic m 2020 Oct BACKGROUND: Overexpression of CD40 has been reported in patients with primary Sjögren's syndrome (pSS). The increased CD40 expression promote autoimmune response and enhance inflammation in pSS. The aim of this study is to block CD40-CD154 interaction with CD40 DNA vaccine to slow the disease progression of SS in non-obese diabetic (NOD) mice. METHODS: Female NOD mice were treated with CD40 DNA vaccine, empty vector and normal saline. The salivary flow rate was measured, whereas lymphocytes infiltration in the salivary glands was assessed by histopathology. Expression of CD40 and B220 in salivary were examined by immunohistochemistry. Splenic lymphocyte phenotypes were analyzed by flow cytometry. CD40, IL-1β, TNF-α and IL-6 levels in the salivary glands were detected by PCR. Serum anti-CD40 antibody was measured by ELISA. Serum anti-nuclear antibody (ANA) was monitored by immunofluorescence. RESULTS: NOD mice treated with CD40 DNA vaccine showed higher levels of anti-CD40 antibody compared with the controls. The expression of CD40 in the salivary glands of NOD mice in CD40 DNA vaccine group was decreased. The infiltration of lymphocytes was reduced in the salivary glands and saliva secretion was increased in the treatment group. The expression level of TNF-α and IL-6 in salivary glands were declined. The splenic dendritic cell and plasma cell populations were reduced and the level of ANA was decreased in NOD mice with CD40 DNA vaccine treatment. CONCLUSIONS: CD40 DNA vaccine inhibits the immune response and reduce inflammation in epithelial tissues SS in non-obese diabetic (NOD) mice, suggesting that CD40 DNA vaccine could be a new therapeutic approach in treatment of pSS.
33157952 Recurrent optic neuritis in a patient with Sjogren syndrome and neuromyelitis optica spect 2020 Nov 6 RATIONALE: Neuromyelitis optica spectrum disorder (NMOSD) patients, especially those with anti-aquaporin-4 antibody positivity, a water channel expressed on astrocytes, is often accompanied by autoimmune diseases (ADs) including Sjogren syndrome (SS). Here, we report a case of a young Chinese woman with recurrent optic neuritis who was diagnosed with asymptomatic SS and NMOSD. PATIENT CONCERNS: A 22-year-old Chinese woman suffered from optic neuritis for 3 years. The main manifestation was recurrent loss of vision. The anti-aquaporin-4 antibody was positive in the cerebrospinal fluid, and she was diagnosed with NMOSD. Other laboratory tests revealed positive anti-SSA and anti-SSB antibodies, and labial gland biopsy showed lymphocytic infiltration. She also fulfilled the international criteria for SS. DIAGNOSIS: On the basis of recurrent vision loss and laboratory examination, we defined the patient with SS accompanied by NMOSD. INTERVENTIONS: When the patient first experienced vision loss, the corticosteroid treatment in the external hospital was effective, and her visual acuity improved significantly. However, in several later attacks, such treatment was no longer obviously effective. Considering the patient's condition, she was treated with corticosteroids, cyclophosphamide, and immunoglobulin therapy on admission. OUTCOMES: The patient's visual acuity was increased to the right eye 20/800 and left eye finger counting when she was discharged from the hospital. LESSONS: SS accompanied with NMOSD is common in clinical practice, and always with the positive Anti-AQP4 antibody as a potential biomarker. Patients with SS and NMOSD showed significant neurological symptoms and had a worse prognosis than SS patients with negative anti-AQP4 antibody because of cross-immunity between anti-SSA antibody and anti-AQP4 antibody. Rheumatologists and ophthalmologists should pay attention to this and perform appropriate tests.
33042142 Biomarkers and Diagnostic Testing for Renal Disease in Sjogren's Syndrome. 2020 Primary Sjogren's syndrome (pSS) is an autoimmune disorder in which lymphocytic infiltration leads to lacrimal and salivary glands dysfunction, which results in symptoms of dryness (xerophthalmia and xerostomia). Extraglandular features are common and may affect several organs. Renal involvement has long been known as one of the systemic complications of pSS. The most classical lesion observed in pSS is tubulointerstitial nephritis (TIN) and less frequently membranoproliferative glomerulonephritis (MPGN), which is related to cryoglobulinemia. In some cases, renal biopsy is necessary for the definitive diagnosis of kidney involvement. Patients may present with proximal renal tubular acidosis, distal renal tubular acidosis and chronic kidney disease. Response to treatment is usually favorable. However, occasionally severe and rarely lethal outcomes have been described. Recently, several case series and cross-sectional studies have been published which investigated the factors associated with renal involvement in pSS and the most accurate screening tests for early detection. The presence of xerophthalmia, anti-SSA and rheumatoid factor positivity, low C3 levels and other features have all shown either positive or inverse associations with the development of renal complications. Serum creatinine, alpha-1-microglobulin, cystatin-C have been evaluated as early detection biomarkers with variable accuracy. More advanced techniques may be necessary to confirm proximal and distal renal tubular acidosis, along with nephrogenic diabetes insipidus. The aim of the current paper is to summarize and critically examine these findings in order to provide updated guidance on serum biomarkers and further testing for kidney involvement in pSS.
33175664 A comparative study between the disease characteristics in adult-onset and childhood-onset 2021 Feb INTRODUCTION: Disease features and laboratory abnormalities differ among adult-onset and childhood-onset systemic lupus erythematosus (aSLE and cSLE). Socioeconomic status both independent of, and in combination with, ethnicity influences the disease phenotype and outcome. OBJECTIVE: To compare the various disease features among patients with cSLE and aSLE in a limited monetary income Egyptian cohort attending a large free-of-charge university hospital. Patients and methods: Retrospective analysis of the medical records of 714 SLE patients attending Cairo University Hospitals from January 2000 to December 2019. Of them 602 (400 with aSLE and 202 with cSLE) were enrolled in the study. RESULTS: The mean age of disease onset was 28.27 ± 10.55 among aSLE patients compared to 12.88 ± 4.26 years among cSLE patients. Disease duration was 12.03 ± 5.05 and 4.14 ± 3.18 years in aSLE and cSLE, respectively. Female to male ratio was 15:1 among patients with aSLE, as compared to 2.67:1 among cSLE (<0.001). Arthritis (69%), oral ulcers (48.5%), neuropsychiatric (18.3%) and thrombotic manifestations of antiphospholipid syndrome (12%) were significantly more frequent in aSLE. On the other hand, renal (67.8%), serositis (49.6%), fever (49%), lymphopenia (40.6%), hemolytic anemia (38.6%), and discoid lupus (13.4%) were significantly more frequent in cSLE. Weight loss, malar rash, photosensitivity, thrombocytopenia, leucopenia and lymphadenopathy were not significantly different between the two groups. Hypocomplementemia, proteinuria, urinary sediments, hematuria were significantly more frequent in cSLE. For those patients with renal involvement, who underwent renal biopsy (58.3% in aSLE and 63.5% in cSLE), there was no significant difference with regard to the different histopathological classes. Anti-Smith, anti-cardiolipin antibodies and rheumatoid factor were significantly more frequent among aSLE patients, while anti-La antibodies were more frequent among cSLE patients. CONCLUSION: Arthritis was the most common clinical manifestation over time in aSLE compared to renal involvement in cSLE. Renal disease tends to be more active in cSLE. The differences in disease manifestations between this cohort and other studies can be attributed to the ethnic and socioeconomic disparities.
32870351 Future perspective: high-throughput construction of new ultrasensitive cytokine and virion 2020 Nov Pathogen-host cell interactions play an important role in many human infectious and inflammatory diseases. Several pathogens, including Escherichia coli (E. coli), Mycobacterium tuberculosis (M. tb), and even the recent 2019 novel coronavirus (2019-nCoV), can cause serious breathing and brain disorders, tissue injury and inflammation, leading to high rates of mortality and resulting in great loss to human physical and mental health as well as the global economy. These infectious diseases exploit the microbial and host factors to induce serious inflammatory and immunological symptoms. Thus the development of anti-inflammatory drugs targeting bacterial/viral infection is an urgent need. In previous studies, YojI-IFNAR2, YojI-IL10RA, YojI-NRP1,YojI-SIGLEC7, and YojI-MC4R membrane-protein interactions were found to mediate E. coli invasion of the blood-brain barrier (BBB), which activated the downstream anti-inflammatory proteins NACHT, LRR and PYD domains-containing protein 2(NLRP2), using a proteomic chip conjugated with cell immunofluorescence labeling. However, the studies of pathogen (bacteria/virus)-host cell interactions mediated by membrane protein interactions did not extend their principles to broad biomedical applications such as 2019-nCoV infectious disease therapy. The first part of this feature article presents in-depth analysis of the cross-talk of cellular anti-inflammatory transduction signaling among interferon membrane protein receptor II (IFNAR2), interleukin-10 receptor subunit alpha (IL-10RA), NLRP2 and [Ca(2+)]-dependent phospholipase A2 (PLA2G5), based on experimental results and important published studies, which lays a theoretical foundation for the high-throughput construction of the cytokine and virion solution chip. The paper then moves on to the construction of the novel GPCR recombinant herpes virion chip and virion nano-oscillators for profiling membrane protein functions, which drove the idea of constructing the new recombinant virion and cytokine liquid chips for HTS of leading drugs. Due to the different structural properties of GPCR, IFNAR2, ACE2 and Spike of 2019-nCoV, their ligands will either bind the extracellular domain of IFNAR2/ACE2/Spike or the specific loops of the GPCR on the envelope of the recombinant herpes virions to induce dynamic charge distribution changes that lead to the variable electron transition for detection. Taken together, the combined overview of two of the most innovative and exciting developments in the immunoinflammatory field provides new insight into high-throughput construction of ultrasensitive cytokine and virion liquid chips for HTS of anti-inflammatory drugs or clinical diagnosis and treatment of inflammatory diseases including infectious diseases, acute or chronic inflammation (acute gouty arthritis or rheumatoid arthritis), cardiovascular disease, atheromatosis, diabetes, obesity, tissue injury and tumors. It has significant value in the prevention and treatment of these serious and painful diseases. Graphical abstract.
33263372 Rheumatologic manifestations of Hepatitis C Virus. 2021 Apr INTRODUCTION: Hepatitis C Virus (HCV) is a well-known worldwide infection, responsible for hepatic and extrahepatic complications. Among extrahepatic manifestation, the rheumatologic are the most common ones. With the arrival of Direct Antiviral Agents (DAA), the treatment and the clinical perspective have rapidly changed, permitting to achieve a sustained virological response (SVR) and preventing complications of chronic infection. EVIDENCE ACQUISITION: We performed on PubMed a literature search for the articles published by using the search terms "HCV infection," "HCV syndrome," "HCV-related rheumatologic disorders," "cryoglobulinemia," "cryoglobulinemic vasculitis" and "mixed cryoglobulinemia." EVIDENCE SYNTHESIS: Mixed cryoglobulinemia (MC) is the prototype of HCV-associated rheumatologic disorder. HCV-related MC is typically considered by physicians as a human model disease to linking infection with autoimmune diseases. Chronic HCV infection can lead to a multistep process from a simple serological alteration (presence of circulating serum cryoglobulins) to frank systemic vasculitis (cryoglobulinemic vasculitis [CV]) and ultimately to overt malignant B lymphoproliferation (such as non-Hodgkin lymphoma [NHL]). Antiviral therapy is indicated to eradicate the HCV infection and to prevent the complications of chronic infection. Immunosuppressive therapy is reserved in case of organ threatening manifestations of CV. In this review, we discuss the main clinical presentation, diagnostic approach and treatment of rheumatologic manifestations of HCV infection. CONCLUSIONS: Chronic HCV infection is responsible for complex clinical condition, ranging from hepatic to extra-hepatic disorders. Cryoglobulins are the result of this prolonged immune system stimulation, caused by tropism of HCV for B-lymphocyte.
32532904 Neonatal lupus erythematosus presenting with rash, thrombocytopenia compounded by cytomega 2020 Jun 11 Neonatal lupus erythematosus (NLE) should be considered when a newborn develops atrioventricular heart block along with the presence of autoantibodies to Sjogren's syndrome autoantigens in the maternal serum. NLE can also present with features such as cutaneous lesions, hepatic dysfunction or haematological abnormalities. Differential diagnosis usually includes congenital infections as there is a significant overlap of symptoms with NLE. We report a case of NLE who had multiorgan involvement with macular erythematous skin lesions present at birth, and on investigation was found to have cytomegalovirus (CMV) infection. The diagnostic dilemma was whether to consider this infection as symptomatic or just colonisation. In the infant described, the absence of end organ damage specific to CMV infection (hearing loss, intracranial calcifications, retinitis, brain involvement) made a diagnosis of symptomatic CMV unlikely.
32251116 Autogenous Bone Graft With Kirschner Wire Fixation Could Be a Reliable Treatment Option fo 2020 Sep BACKGROUND: Scaphoid nonunion in adolescents is rare, and most treatments include prolonged immobilization and screw fixation. Many studies have shown that Kirschner wires (K-wires) show comparable outcomes in screw fixation in adult scaphoid nonunion. However, few studies have reported K-wire fixation results in the treatment of adolescent scaphoid nonunion. The purpose of this study was to evaluate the clinical and radiologic results after bone graft and K-wire fixation for scaphoid nonunion in adolescents. METHODS: We retrospectively reviewed 12 adolescent patients, mean age 15.4 (12 to 17) years, who underwent surgical treatment of scaphoid nonunion. Autogenous bone grafts with K-wire fixation were performed for all patients. Radiologic results, including bone union and degenerative changes, were evaluated with serial radiographs. Clinical results, including range of motion, grip strength, and a visual analogue scale for pain, were assessed. RESULTS: All patients received <3 years of postoperative follow-up assessments. Stable bony union was achieved in all patients. Radiologic bony unions were identified at an average of 11.4 weeks postoperatively (range, 9 to 15 wk). The mean active range of motion of the injured wrist at 3 years postoperatively was 215 degrees (range, 185 to 230 degrees). None of the patients were treated for wrist pain or needed medication during follow-up. Three patients experienced intermittent pain (visual analogue scale 1) after heavy work. The grip strength was reduced compared with the uninjured hand (31.8 and 32.8 kg, respectively), but there was no statistically significant difference (P=0.19). All patients had the K-wire removed at 12 weeks postoperatively. There was no degenerative change in the scaphoid at the final follow-up radiograph. CONCLUSION: Autogenous bone graft with K-wire fixation could be a reliable treatment option of scaphoid nonunion in adolescents. LEVEL OF EVIDENCE: Level IV-retrospective case series.
32243378 Effects of body weight support and gait velocity via antigravity treadmill on cardiovascul 2020 Apr To investigate the effects of body weight support (BWS) and gait velocity on cardiovascular responses during walking on an antigravity treadmill early after unilateral and bilateral total knee arthroplasty (TKA).This study was a cross-sectional study design. Fifty patients (7 males and 43 females; average age, 72.0 ± 5.1 years) at 4 weeks after unilateral (n = 25) and bilateral (n = 25) primary TKA were enrolled in the study. Subjects walked on an antigravity treadmill at speeds of 2.5 km/hour and 3.5 km/hour with 3 levels (50%, 25%, and 0%) of BWS. Cardiovascular responses were monitored by measuring oxygen consumption (VO2), heart rate (HR), systolic and diastolic blood pressure (SBP/DBP), the respiratory exchange ratio (RER), and rate pressure product (RPP). Borg rating of perceived exertion (RPE) and a visual analog scale (VAS) of knee pain were recorded immediately after each trial.There were no significant differences in cardiovascular responses between the unilateral and bilateral TKA groups. In the repeated measures Analysis of Variance, VO2 levels, HR, RPP, RPE, RER, and VAS were significantly increased in proportion to 3 levels (50%, 25%, and 0%) of BWS for unilateral and bilateral TKA groups, respectively. Meanwhile, SBP and DBP were unaffected by differences in BWS. At 3.5 km/hour, VO2, RPE, and RER values were statistically greater than those at 2.5 km/hour under the same BWS conditions.We found that the reduction in the metabolic demand of activity, coupled with positive pressure on the lower extremities, reduced VO2 and HR values as BWS increased.Cardiovascular responses vary according to BWS and gait velocity during antigravity treadmill walking. BWS rather than gait velocity had the greatest effect on cardiovascular responses and knee pain.