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ID PMID Title PublicationDate abstract
31245048 Arthropathy of Down syndrome: an under-diagnosed inflammatory joint disease that warrants 2019 There is an increased incidence and prevalence of arthropathy in children with Down syndrome. However, it is rarely reported or recognised at onset, and remains under-diagnosed. Children with arthropathy of Down syndrome (A-DS) are presenting with significant joint damage and disability at diagnosis. OBJECTIVE: To identify undiagnosed cases of A-DS and document time to diagnosis. Also to describe clinical, laboratory and radiological features of A-DS at diagnosis. METHODOLOGY: Children with Down syndrome (DS) (0-21 years) were invited to attend a musculoskeletal screening clinic. A second physician at a further clinic confirmed suspected cases of A-DS. Investigations and treatment were instigated as per normal clinical practice for Juvenile idiopathic arthritis (JIA). Data on a convenience sample of 21 newly diagnosed children with JIA was collected to create a comparison group. RESULTS: Over an 18-month period, 503 children with DS were screened for arthritis and 18 new cases diagnosed. In total, 33 children were identified with A-DS (combining cases attending pre-dating commencement of the study and those referred to our centre during the study period). This suggests prevalence of A-DS is 20/1000. A significant delay in diagnosis of A-DS was observed. The majority of children presented with polyarticular-rheumatoid factor-negative arthritis, with predominance in the small joints of the hands and wrists. Erosive changes were reported on X-ray in a significantly greater proportion (42%) of children with A-DS than JIA (14%). MRI was used to confirm diagnosis in four cases. CONCLUSION: Children with DS are at increased risk of arthritis. Future research to accurately define disease pathogenesis and identify a biomarker of disease would be of benefit.
31818901 Neuro-Sweet disease in a Japanese woman with Sjögren's syndrome. 2019 Dec 8 Sweet disease (SD) is a multisystem inflammatory disorder characterised by fever, cutaneous erythematous plaques and aseptic neutrophilic infiltration of various organs. Neuro-Sweet disease (NSD) is a known rare central nervous system complication of SD. We describe a case of a 39-year-old Japanese woman who was diagnosed as NSD associated with Sjögren's syndrome. She was successfully treated with systemic corticosteroid therapy.
31426902 Clinical efficacy of low-dose rituximab on hematological abnormalities in patients with co 2019 Oct OBJECTIVE: To evaluate the efficacy and safety of low-dose rituximab in the treatment of hematologic abnormalities in patients with connective tissue disease. MATERIALS AND METHODS: A total of 13 patients with connective tissue disease who did not respond to prednisolone and multiple immunosuppressive agents, or their disease recurred after treatment, were given 100 mg of rituximab only combined with prednisolone once a week for 4 weeks. Then, the therapeutic effects and adverse reactions were respectively observed in the 13 patients. RESULTS: Rituximab showed good and rapid efficacy in the treatment of refractory thrombocytopenia and autoimmune hemolytic anemia caused by systemic lupus erythematosus, Sjögren's syndrome, and mixed connective tissue disease. Only 1 patient had urinary tract infection. During 24-month follow-up, disease recurred in 7 patients who still responded to azathioprine/Tripterygium wilfordii. CONCLUSION: Low-dose rituximab has good efficacy and safety in the treatment of hematologic abnormalities in patients with connective tissue disease.
30187679 Is sonoelastography a helpful method of evaluation to diagnose Sjögren's syndrome? 2019 Feb OBJECTIVE: A new sonoelastography technique - virtual touch tissue quantification of acoustic radiation force impulses (ARFI) - offers a promising method for measuring tissue rigidity. The aim of this study was to assess the usefulness of ARFI for diagnosing Sjögren's syndrome (SS). METHODS: This transversal prospective study included 41 patients with SS according to American-European Consensus Group (AECG) criteria, and a control group without symptoms. All subjects underwent ARFI high-resolution ultrasound assessment of the parotid glands (PG) and submandibular glands (SMG). RESULTS: In patients with SS, parotid gland shear wave velocity (SWV) was 2.08 m/s ± 0.55, significantly higher than in control subjects (1.2 m/s ± 0.17) (P = 0.0001); submandibular gland SWV was higher in SS patients (2.12 m/s ± 0.44) than control subjects (1.56 m/s ± 0.16) (P = 0.001). CONCLUSIONS: Acoustic radiation force impulses sonoelastography can assist diagnosis of SS, and is a non-invasive and fast method of detecting pathological changes to the parotid and submandibular glands.
31731809 Plasma Metabolic Profiling Analysis of Gout Party on Acute Gout Arthritis Rats Based on UH 2019 Nov 15 Gout Party is a Chinese medicine prescription composed of Aconiti Lateralis Radix Praeparaia, Aconiti Radix Cocta, Cremastrae Pseudobulbus Pleiones Pseudobulbus, Smilacis Glabrae Rhizoma, Rehmanniae Radix, and Glycyrrhizae Radix et Rhizoma, which can relieve joint pain caused by gouty arthritis (GA) and rheumatoid, and has a therapeutic effect on acute gouty arthritis (AGA). However, little information is available on the molecular biological basis and therapeutic mechanism of Gout Party for the treatment of AGA. AGA model was established by injecting sodium urate, and colchicine served as a positive control drug. We established a metabolomic method based on ultra-high-performance liquid chromatography-tandem quadrupole/time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) to analyze the plasma samples of model group rats and blank group rats. Multiple statistical analyses, including principal component analysis (PCA) and partial least square discrimination analysis (PLS-DA), were used to examine metabolite profile changes in plasma samples. Finally, we identified 2-ketobutyric acid, 3-hexenedioic acid, but-2-enoic acid, and so on; 22 endogenous metabolites associated with AGA. After successful molding, we found that 2-ketobutyric acid, 3-hexenedioic acid, but-2-enoic acid, argininic acid, galactonic acid, lactic acid, equol 4'-O-glucuronide, deoxycholic acid glycine conjugate, glycocholic acid, sphinganine 1-phosphate, LPE (0:0/20:3), LPE (0:0/16:0), LPC (15:0) decreased significantly (p < 0.05 or p < 0.01), alanine, erythrulose, 3-dehydrocarnitine, m-methylhippuric acid, 3-hydroxyoctanoic acid, p-cresol sulfate, estriol 3-sulfate 16-glucuronide, 10-hydroxy-9-(phosphonooxy)octadecenoate, docosahexaenoic acid increased significantly (p < 0.05 or p < 0.01). After Gout Party treatment, 14 biomarkers had a tendency to normal conditions. These above biomarkers were mainly involved in fatty acid metabolism, bile acid metabolism, amino acid metabolism, and energy metabolism pathways. These results suggested that Gout Party exerted therapeutic effects of treating AGA by improving energy metabolism disorder and amino acid metabolism dysfunction, and attenuating fatty acid metabolism abnormal and inflammation. The results of this experiment provided a reference for revealing the metabolic mechanism produced by Gout Party in the treatment of AGA, but the subsequent studies need to be further improved and supported by relevant cell experiments and clinical experiments.
31299380 Macrophage activation syndrome in neonates born to mothers with adult-onset Still's diseas 2019 Oct Overproduction of interleukin (IL)-18 is closely related to the pathogenesis of adult-onset Still's disease (AOSD) and the development of macrophage activation syndrome (MAS), a life-threating complication of AOSD. We reported three cases of MAS occurring in infants born to mothers with AOSD. The infants developed MAS at age 13 and 8 days and at birth. Serum IL-18 levels were extremely elevated in all infants (147,000 pg/mL; 378,000 pg/mL; 95,000 pg/mL) as well as in their mothers (58,500 pg/mL; 367,000 pg/mL; 84,000 pg/mL). Physicians should be aware that infants born to mothers with AOSD are at a risk of developing MAS. Serum IL-18 levels in mothers with AOSD and their infants should be monitored.
31277158 Refractory Sjögren's syndrome myelopathy successfully treated with subcutaneous tocilizum 2019 Jul RATIONALE: It is known that 5% to 34% of Sjögren's syndrome (SS) cases are complicated by neuropathy in the form of myelitis. Although SS myelopathy (SSM) is often treated with glucocorticoid (GC) and immunosuppressants such as cyclophosphamide (CY), a therapeutic strategy for SSM has not been established. PATIENT CONCERNS: A 65-year-old female was admitted with weakness and thermal hypoalgesia in the lower limbs. Four months before this admission, she showed weakness in her lower limbs and thermal hypoalgesia of bilateral upper and lower limbs. Magnetic resonance imaging (MRI) revealed that the cause of her neurological symptoms was cervical myelitis. She was diagnosed with SS because she tested positive for the ophthalmic test (Schirmer's test and fluorescent test) and for the anti-SS-A antibodies. Therefore, myelitis was thought to be a complication of SS. She was treated with GC and CY. Both neurological symptoms and MRI findings temporarily improved, and the GC dose was gradually decreased. One month before this admission, her neurological symptoms and MRI findings were exacerbated. Upon relapse of SSM, serum amyloid A protein (SAA) level was markedly elevated. DIAGNOSES: Based on MRI findings, the diagnosis was SSM relapse. INTERVENTIONS: Treatment by subcutaneous tocilizumab (TCZ) 162 mg every two weeks was introduced. OUTCOMES: After introducing TCZ, her neurological symptoms and MRI findings gradually improved. SAA levels remained low. At eight months after the introduction of TCZ, the GC dose has been decreased and so far, the myelitis has not relapsed. LESSONS: This case report is the first report suggesting the effectiveness of TCZ for refractory SSM. Subcutaneous TCZ might be an effective therapeutic option for treating refractory SSM when SAA levels are elevated.
31287410 The levels of CXCL12 and its receptor, CXCR4, as a biomarker of disease activity and cutan 2019 Nov OBJECTIVES: This study evaluated the SDF-1/CXCL12 and soluble CXCR4 (sCXCR4) levels, and investigated their clinical relevance in adult-onset Still's disease (AOSD). METHODS: Forty-two AOSD patients and 30 healthy controls (HC) were enrolled for serum sampling. Expression levels of CXCL12 and CXCR4 in skin biopsy materials of 40 AOSD patients, 10 patients with eczema, or 10 psoriasis, and 10 HC skin were evaluated with immunohistochemistry. RESULTS: The serum CXCL12 levels in patients with AOSD (2,452±1,531 pg/mL) were higher than those in HC (1,708±1,322 pg/mL, p=0.017). The serum sCXCR4 levels in patients with AOSD (14,449±16,627 pg/mL) were higher than those in HC (3,046±2,554 pg/mL, p<0.001). Serum CXCL12 levels correlated positively with counts of leukocytes and neutrophils, erythrocyte sedimentation rate, ferritin, and C-reactive protein (CRP). Serum sCXCR4 levels correlated positively with systemic scores, platelet counts, and CRP levels. The serum levels of CXCL12 and sCXCR4 were decreased significantly in the patients with AOSD followed after resolution of disease activity. On immunohistochemical stain, the mean percentage of CXCR4-positive inflammatory cells was 51.4±27.5% and that of CXCL12-positive inflammatory cells was 16.7±13.3% in AOSD patients. CXCR4 was more frequently expressed in inflammatory cells from AOSD patients than in those with eczema or psoriasis and HC skin. CONCLUSIONS: These results provide that sCXCR4 could be a clinical biomarker of evaluation for disease activity in AOSD, and show that CXCR4/CXCL12 may influence the inflammatory condition and skin manifestations of AOSD.
31154343 Methotrexate-induced iatrogenic immunodeficiency-associated lymphoproliferative disorder c 2019 May 31 Hypercalcaemia is a rare but potentially life-threatening consequence of malignancies. Solid cancers, such as lymphomas, increase serum calcium primarily through parathyroid hormone-related protein or ectopic production of 1alpha-hydroxylase. We present a case of 56-year-old woman with Sjogren's syndrome and psoriasis in the setting of chronic methotrexate (MTX) use who developed worsening hypercalcaemia and symptoms suggestive of lymphoma. Pathology results diagnosed her with MTX-induced iatrogenic immunodeficiency-associated lymphoproliferative disorder (LPD). This case reminds clinicians that chronic MTX use is associated with LPDs and can ultimately lead to hypercalcaemia. The patient's MTX and other immunosuppressive medications were stopped, and her calcium corrected with fluids and calcitonin. At her 8-month follow-up postdischarge, the patient was asymptomatic with normal laboratory results and in partial clinical remission.
31006413 Dry surgical field minor salivary gland harvest using a chalazion clamp for sicca syndrome 2019 May BACKGROUND: Sjögren's syndrome is a rheumatological condition. Diagnosing Sjögren's syndrome can be challenging given the overlapping nature of clinical presentations. Currently, minor salivary gland biopsy is considered the definitive test for diagnosing Sjögren's syndrome. Various surgical techniques have been described, targeting biopsy of minor salivary glands from the lower lip. Identification of minor salivary glands is often difficult because of bleeding. One common complication of minor salivary gland biopsy is lip paraesthesia from iatrogenic sensory nerve injury. OBJECTIVES: To describe a minor salivary gland biopsy technique in a bloodless operative field using a chalazion ophthalmic clamp under local anaesthesia, and to report our clinical outcomes. METHODS: A prospective study was performed on patients who underwent minor salivary gland biopsy using a chalazion ophthalmic clamp between July 2017 and April 2018. RESULTS: The study included 23 patients. The histopathological reports positively identified minor salivary glands for all patients. In nine cases, the histological findings were positive for Sjögren's syndrome. No lip paraesthesia complications were reported post-operatively. CONCLUSION: This technique facilitates a superior yield, ensures adequate sampling of appropriate glands for histopathological analysis, and minimises the complications associated with traditional techniques.
30120806 Predictive value of ultrasound scoring in relation to clinical and histological parameters 2019 Jan BACKGROUND: Salivary gland dysfunction is one of the main clinical features of Sjögren's syndrome (SS), manifested by xerostomia with subsequent complications and well-established effects on the person's quality of life. OBJECTIVES: To determine firstly whether selected tests of salivary gland function and structure, unstimulated whole salivary flow rate (UWSFR), parotid flow rate (PFR), clinical oral dryness score (CODS) and ultrasound score (USS), can discriminate SS from non-SS sicca patients and secondly whether these tests can differentiate between patients in different subgroups of SS. METHOD: Unstimulated whole salivary flow rate, PFR, CODS and USS were determined in 244 patients comprised of SS patients (n = 118), SS patients at higher risk of lymphoma (n = 30) or with lymphoma (n = 26), and non-SS sicca disease controls (n = 70). RESULTS: All assessments showed a significant difference between the overall SS group and the disease control group, attributed mainly to the lymphoma subgroups of SS (p < 0.0001 for all parameters). There was a significant correlation (Spearman r = 0.7, p value <0.0001) and 87.3% agreement between USS and the histology focus scores of 119 patients. CONCLUSION: The results suggest that salivary gland tests including USS can aid in differentiating between SS and non-SS dry mouth, especially the subgroups of SS with lymphoma or at higher risk of developing lymphoma.
30407165 Tuberculin test conversion in patients with chronic inflammatory arthritis receiving biolo 2019 Jan OBJECTIVE: The blockade of inflammatory mediators produced by biological therapies is associated with an increased risk of opportunistic infections, as for example Mycobacterium tuberculosis (MT). Given the endemic situation of tuberculosis (TB) in some countries and immunosuppression/anergy of patients with chronic inflammatory arthritis, we wonder whether it is necessary to monitor the MT infection after starting the biological treatment. To evaluate the frequency of the tuberculin skin test (TST) conversion and its association with an active TB infection and other disease variables. METHODS: Patients with rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), and spondyloarthritis (SpA) receiving treatment with anti-TNF, tocilizumab, and/or abatacept agents were included into the study. Patients had to have a negative TST (<5 mm) at the baseline, and a second TST was performed 2-22 months after the initiation of biologic therapy. The TST conversion was considered as a variation ≥5 mm between the two TSTs performed within an interval between 2 months and 2 years. RESULTS: A total of 85 patients were included into the study, and 78.8% were women, with a median schooling duration of 12 years. A total of 74.1% of patients had RA, 16.5% psoriatic arthritis, and 4.7% AIJ and ankylosing spondylitis. Regarding treatment, 75.3% received anti-TNF therapy (31.8% etanercept, 21.2% adalimumab, 17.6% infliximab, 3.5% golimumab, and 1.2% certolizumab), 15.3% tocilizumab, and 9.4% abatacept. Eight patients (9.4%) developed a TST conversion. The shift was more frequent in men (62.5%) than in women (37.5%) (p=0.009), and in those with a prolonged disease duration (X 226±109 vs X130±105 [p=0.017]). This association remained after adjusting for other variables. All patients who developed a TST conversion received prophylactic isoniazid, and only one patient with other risk factors developed active TB. CONCLUSION: The frequency of a TST conversion in patients with chronic inflammatory arthritis was low and was associated with male gender and longer disease duration.
31682893 Pill or needle? Determinants of the preference for long-acting injection over oral treatme 2020 Mar 2 Although long-acting injection (LAI) is presented as first line treatment option for patients with psychosis, negative attitudes toward this galenic negatively impact the selection of this treatment option. However, these negative attitudes may not be confined to patients but also observed in the general population. A web-based study on 1807 participants was conducted during which participants imagined that they had a particular chronic illness based on clinical vignettes (mental illnesses: schizophrenia, depression; somatic illnesses: multiple sclerosis, rheumatoid arthritis). The frequency of relapse and the intensity of symptoms were experimentally manipulated in the vignettes. Participants rated their subjective distress associated with each vignette, their belief in the effectiveness of treatment, and their treatment preference regarding medication. We examined under which conditions LAI was preferred over pills. Statistical analyses were performed using Bayesian methods. Results showed that participants preferred LAI over pills in 40.5% to 50.8% of cases. LAI was more preferred for illnesses with low frequency of relapse, low subjective distress, and for somatic than for mental illnesses. The perceived advantage for LAI over pills and the belief about the better efficiency of LAI were the main factors that drove the preference for LAI. Keeping in mind some advantages of LAI, the public negative representations of injections might partially influence patients' prejudices against LAI. These attitudes should be named and discussed with the patients when LAI seems to represent a relevant therapeutic option.
31181327 P2X7 receptor: A potential therapeutic target for autoimmune diseases. 2019 Aug P2X7 receptor (P2X7R), a distinct ligand-gated ion channel, is a member of purinergic type 2 receptor family with ubiquitous expression in human body. Previous studies have revealed a pivotal role of P2X7R in innate and adaptive immunity. Once activated, it will meditate some vital cascaded responses including the assembly of nucleotide-binding domain (NOD) like receptor protein 3 (NLRP3) inflammasome, non-classical secretion of IL-1β, modulation of cytokine-independent pathways in inflammation such as P2X7R- transglutaminase-2 (TG2) and P2X7R-cathepsin pathway, activation and regulation of T cells, etc. In fact, above responses have been identified to be involved in the development of autoimmunity, specifically, the NLRP3 inflammasome could promote inflammation in massive autoimmune diseases and TG2, as well as cathepsin may contribute to joint destruction and degeneration in inflammatory arthritis. Recently, numerous evidences further suggested the significance of P2X7R in the pathogenesis of autoimmune diseases, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), inflammatory bowel disease (IBD), multiple sclerosis (MS), etc. In this review, we will succinctly discuss the biological characteristics and summarize the recent progress of the involvement of P2X7R in the development and pathogenesis of autoimmune diseases, as well as its clinical implications and therapeutic potential.
30674715 A recombinant human IgG1 Fc multimer designed to mimic the active fraction of IVIG in auto 2019 Jan 24 The antiinflammatory effects of i.v. Ig (IVIG) in the treatment of autoimmune disease are due, in part, to the Fc fragments of Ig aggregates. In order to capitalize on the known antiinflammatory and tolerogenic properties of Ig Fc aggregates, we created a recombinant human IgG1 Fc multimer, GL-2045. In vitro, GL-2045 demonstrated high-avidity binding to Fc receptors, blocked the binding of circulating immune complexes from patients with rheumatoid arthritis to human Fcγ receptors (FcγRs), and inhibited antibody-mediated phagocytosis at log order-lower concentrations than IVIG. In vivo, administration of GL-2045 conferred partial protection against antibody-mediated platelet loss in a murine immune thrombocytopenic purpura (ITP) model. GL-2045 also suppressed disease activity in a therapeutic model of murine collagen-induced arthritis (CIA), which was associated with reduced circulating levels of IL-6. Furthermore, GL-2045 administration to nonhuman primates (NHPs) transiently increased systemic levels of the antiinflammatory cytokines IL-10 and IL-1RA, reduced the proinflammatory cytokine IL-8, and decreased surface expression of CD14 and HLA-DR on monocytes. These findings demonstrate the immunomodulatory properties of GL-2045 and suggest that it has potential as a treatment for autoimmune and inflammatory diseases, as a recombinant alternative to IVIG.
30618353 Patient attitudes about non-medical switching to biosimilars: results from an online patie 2019 Apr OBJECTIVE: To evaluate patient attitudes regarding non-medical switching (NMS) to biosimilars among patients with autoimmune disease currently receiving a biologic. METHODS: An online survey was conducted among patients meeting the following criteria: ≥18 years of age; residing in the US; diagnosis of rheumatoid arthritis, Crohn's disease, ulcerative colitis, psoriasis or psoriatic arthritis; currently taking a biologic; and consenting to participate. Patients answered questions about their attitudes and experiences related to NMS. Descriptive statistics were used to summarize responses. RESULTS: A total of 1696 patients completed the 20-min survey. Eighty-five per cent of patients were concerned that biosimilars wouldn't treat their disease as well; 85% didn't want to switch to a biosimilar if their current biologic was helping their disease; and 83% were concerned that switching may cause more side-effects. Twenty per cent of patients had previously received notification about a potential NMS to another biologic (that was not a biosimilar) from their insurance company. Of these, 79% took at least one action to avoid the NMS and 45% ultimately switched. Of these patients (n = 150), 67% indicated that their previous biologic worked well for them and 70% didn't want to switch to another biologic. Most patients who switched (67%) did so to avoid paying a higher cost. More than half (56%) went without therapy for administrative reasons during the period of transition from the old biologic to the other treatment. CONCLUSIONS: Patients reported multiple concerns about NMS that might impact treatment outcomes, and many of the patients who non-medically switched in this survey missed treatments. Future studies should be conducted on patient expectations and experiences with NMS to understand the impact on healthcare delivery, treatment persistency, and patient outcomes. The patient perspective and experience should be considered by decision-makers when developing coverage policies for biosimilar medications and associated communication strategies.
31555262 Systematic Review of Safety and Efficacy of Rituximab in Treating Immune-Mediated Disorder 2019 Background: During the past years biologic agents (also termed biologicals or biologics) have become a crucial treatment option in immunological diseases. Numerous articles have been published on biologicals, which complicates the decision making process on the use of the most appropriate biologic for a given immune-mediated disease. This systematic review is the first of a series of articles assessing the safety and efficacy of B cell-targeting biologics for the treatment of immune-mediated diseases. Objective: To evaluate rituximab's safety and efficacy for the treatment of immune-mediated disorders compared to placebo, conventional treatment, or other biologics. Methods: The PRISMA checklist guided the reporting of the data. We searched the PubMed database between 4 October 2016 and 26 July 2018 concentrating on immune-mediated disorders. Results: The literature search identified 19,665 articles. After screening titles and abstracts against the inclusion and exclusion criteria and assessing full texts, 105 articles were finally included in a narrative synthesis. Conclusions: Rituximab is both safe and effective for the treatment of acquired angioedema with C1-inhibitor deficiency, ANCA-associated vasculitis, autoimmune hemolytic anemia, Behçet's disease, bullous pemphigoid, Castleman's disease, cryoglobulinemia, Goodpasture's disease, IgG4-related disease, immune thrombocytopenia, juvenile idiopathic arthritis, relapsing-remitting multiple sclerosis, myasthenia gravis, nephrotic syndrome, neuromyelitis optica, pemphigus, rheumatoid arthritis, spondyloarthropathy, and systemic sclerosis. Conversely, rituximab failed to show an effect for antiphospholipid syndrome, autoimmune hepatitis, IgA nephropathy, inflammatory myositis, primary-progressive multiple sclerosis, systemic lupus erythematosus, and ulcerative colitis. Finally, mixed results were reported for membranous nephropathy, primary Sjögren's syndrome and Graves' disease, therefore warranting better quality trials with larger patient numbers.
31089365 Design and Construction of a Novel Humanized Single-Chain Variable-Fragment Antibody Again 2019 Winter The pro-inflammatory cytokine, TNF-α, which plays a major role in the development and persistence of diseases such as Crohn's disease, psoriasis, psoriatic arthritis, and rheumatoid arthritis, is the basis for the use of anti-TNF-α therapies. The neutralization of TNF-α or blockage of its binding to the corresponding receptor has mainly served as a therapeutic strategy against some inflammatory diseases. This study aimed to investigate the production of a humanized single chain antibody (scFv) against TNF-α. Therefore, a murine monoclonal antibody, D2 mAb, was selected for humanizing by the complementarity determining region (CDR)-grafting method. Briefly, the replacement of the CDRs from D2 mAb with the specific human single chain scaffold led to the production of a novel humanized single chain fragment variable mAb against human TNF-α (hD2). The subsequent cloning of hD2 into a suitable expression vector, pGEX-6P-1, resulted in the expression of a 52-kDa GST-fusion protein in E. coli, mostly in the form of inclusion bodies. The solubilization and refolding of GST-hD2 inclusion bodies was achieved with the addition of 4 M urea and subsequent dialysis to recover the fusion protein in soluble form. Then the soluble GST-hD2 was purified by affinity chromatography through immobilized glutathione. The GST pull-down experiment showed a positive interaction between GST-hD2 and TNF-α protein. Moreover, the results of an MTT assay showed that the purified GST-hD2 has TNF-α neutralizing activity (Kd of 1.03 nM) and hence hD2 has the potential to be developed into a therapeutic agent. However, more investigation is needed to elucidate the potential of in-vivo TNF-α neutralizing activity of hD2 in comparison to other anti-TNF-α antibodies.
31343702 Is Virtual Reality Effective in Orthopedic Rehabilitation? A Systematic Review and Meta-An 2019 Oct 28 BACKGROUND: Virtual reality (VR) is an interactive technology that allows customized treatment and may help in delivering effective person-centered rehabilitation. PURPOSE: The purpose of this review was to systematically review and critically appraise the controlled clinical trials that investigated VR effectiveness in orthopedic rehabilitation. DATA SOURCES: Pubmed, CINAHL, Embase, PEDro, REHABDATA, and Sage publications were searched up to September 2018. In addition, manual searching and snowballing using Scopus and Web of Science were done. STUDY SELECTION: Two reviewers screened studies for eligibility first by title and abstract and then full text. DATA EXTRACTION: Articles were categorized into general or region-specific (upper limbs, lower limbs, and spine) orthopedic disorders. Study quality was assessed using the Evaluation Guidelines for Rating the Quality of an Intervention Study scoring. Meta-analysis quantified VR effectiveness, compared with no treatment, in back pain. DATA SYNTHESIS: Nineteen studies were included in the quality assessment. The majority of the studies were of moderate quality. Fourteen studies showed that VR did not differ compared with exercises. Compared with the no-treatment control, 5 studies favored VR and 3 other studies showed no differences. For low back pain, the meta-analysis revealed no significant difference between VR and no-treatment control (n = 116; standardized mean difference = -0.21; 95% confidence interval = -0.58 to 0.15). LIMITATIONS: Limitations included heterogeneity in interventions and the outcome measures of reviewed studies. Only articles in English were included. CONCLUSION: The evidence of VR effectiveness is promising in chronic neck pain and shoulder impingement syndrome. VR and exercises have similar effects in rheumatoid arthritis, knee arthritis, ankle instability, and post-anterior cruciate reconstruction. For fibromyalgia and back pain, as well as after knee arthroplasty, the evidence of VR effectiveness compared with exercise is absent or inconclusive.
30562564 Cytokine-targeted therapy for the management of solid organ transplant recipients. 2019 Mar INTRODUCTION: The number of solid organ transplants completed annually continues to trend upwards each year. Despite this, maintenance immunosuppression available on the market has remained relatively stagnant. Standard triple immunosuppression, composed typically of tacrolimus, mycophenolate, and steroids, lead to many side effects that limit the use of these medications. Tacrolimus, specifically, causes nephrotoxicity that can lead to renal dysfunction requiring a kidney transplant down the road. Alternative therapies for the management of immunosuppression need to be identified to try to mitigate these adverse effects. BODY: Cytokines are responsible for facilitating T cell differentiation and lead to the activation of inflammatory mediators that can contribute to graft damage and ultimately rejection. IL-4, IL-6, IL-12/23, and IL-15 are attractive targets for medications to try to ameliorate graft rejection. Various cytokine-targeted medications are currently available on the market for the treatment of inflammatory and autoimmune conditions such as rheumatoid arthritis, psoriatic arthritis, Crohn's, and multiple sclerosis. CONCLUSION: This article reviews cytokine involvement in alloimmunity and the potential role cytokine-targeted therapy may play in prevention of allograft rejection in solid organ transplant recipients.