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ID PMID Title PublicationDate abstract
32986386 Management of Glenohumeral Joint Osteoarthritis. 2020 Oct 1 The Management of Glenohumeral Joint Osteoarthritis Evidence-Based Clinical Practice Guideline is based on a systematic review of published studies for the treatment of glenohumeral joint osteoarthritis. The purpose of this clinical practice guideline is to address the management of patients with glenohumeral joint osteoarthritis. It is not intended to address the management of glenohumeral joint arthritis from etiologies other than osteoarthritis (ie, rheumatoid arthritis, inflammatory arthritis, posttraumatic arthritis, osteonecrosis, rotator cuff tear arthroplasty, capsulorrhaphy arthroplasty, and postinfections arthroplasty) This guideline contains 13 recommendations to assist all qualified and appropriately trained healthcare professionals involved in the management of glenohumeral joint osteoarthritis. In addition, the work group highlighted the need for better research for implant survivorship of total shoulder arthroplasty, the efficacy of physical therapy and other nonsurgical treatment modalities, the use of advanced imaging modalities and software and their impact on clinical and functional outcomes, complication rates or implant survivorship, and the need for high-quality studies demonstrating improved clinical outcomes and/or implant survivorship for the use of reverse shoulder arthroplasty as opposed to anatomic shoulder arthroplasty in challenging situations.
32512384 RGS12 Is a Novel Critical NF-κB Activator in Inflammatory Arthritis. 2020 Jun 26 Rheumatoid arthritis (RA) is the most common inflammatory disease, which currently lacks effective treatment. Here, we discovered that the Regulator of G Protein Signaling 12 (RGS12) plays a key role in regulating inflammation. Transcriptional and protein analysis revealed that RGS12 was upregulated in human and mouse RA macrophages. Deletion of RGS12 in myeloid lineage or globally inhibits the development of collagen-induced arthritis including joint swelling and bone destruction. Mechanistically, RGS12 associates with NF-κB(p65) to activate its phosphorylation and nuclear translocation through PTB domain, and NF-κB(p65) regulates RGS12 expression in a transcriptional manner. The nuclear translocation ability of NF-κB(p65) and RGS12 can both be enhanced by cyclooxygenase-2 (COX2). Furthermore, ablation of RGS12 via RNA interference significantly blocks the inflammatory process in vivo and in vitro. These results demonstrate that RGS12 plays a critical role in the pathogenesis of inflammatory arthritis.
32607391 Parameters matter: modulating cytokines using nerve stimulation. 2020 The vagus nerve-based inflammatory reflex regulates inflammation and cytokine release. Recent successful clinical trials using implantable bioelectronic devices to modulate the inflammatory reflex in patients with rheumatoid arthritis and inflammatory bowel disease have demonstrated the efficacy of targeting neural circuits as an efficient alternative to drug treatments. However, the optimal vagus nerve stimulation parameters to achieve efficacious symptomatic relief for inflammation are still unknown. In this issue of Bioelectronic Medicine, Tsaava et al. tested whether altering these electrical stimulation parameters would change circulating cytokine levels in healthy mice. They found that specific combinations of parameters produced significant increases in serum TNF while other parameters selectively lowered serum TNF levels, as compared to sham stimulated mice. These results have considerable implications for determining the optimal stimulation parameters to better treat common conditions and diseases that involve immune regulation.
32116534 The Lateral Hypothalamus: An Uncharted Territory for Processing Peripheral Neurogenic Infl 2020 The roles of the hypothalamus and particularly the lateral hypothalamus (LH) in the regulation of inflammation and pain have been widely studied. The LH consists of a parasympathetic area that has connections with all the major parts of the brain. It controls the autonomic nervous system (ANS), regulates feeding behavior and wakeful cycles, and is a part of the reward system. In addition, it contains different types of neurons, most importantly the orexin neurons. These neurons, though few in number, perform critical functions such as inhibiting pain transmission and interfering with the reward system, feeding behavior and the hypothalamic pituitary axis (HPA). Recent evidence has identified a new role for orexin neurons in the modulation of pain transmission associated with several inflammatory diseases, including rheumatoid arthritis and ulcerative colitis. Here, we review recent findings on the various physiological functions of the LH with special emphasis on the orexin/receptor system and its role in mediating inflammatory pain.
33100674 Therapeutic status of hydroxychloroquine in COVID-19: A review. 2020 Aug Hydroxychloroquine (HCQ), a 4-aminoquinoline, is used worldwide mainly for its role in management of malaria and rheumatoid arthritis. In the present pandemic of coronavirus disease (COVID)-2019, the drug is being repurposed, based on its in vitro evidence of efficacy against coronavirus. There has been a lot of information, for and against the drug, and this review is an effort to bring forth the evidence and current understanding regarding role of HCQ in COVID-19. Clinical studies, case reports, and in vitro studies have generated conflicting results. There are concerns for use of HCQ because of the variable results and the known adverse effects like QT prolongation and hypoglycemia. In the current scenario, recommendations from Indian Council of Medical Research for use of HCQ in the prophylaxis of COVID-19 are being followed.
32661663 Chemokines and Bone. 2020 Chemokines are a family of small proteins, subdivided by their conserved cysteine residues and common structural features. Chemokines interact with their cognate G-protein-coupled receptors to elicit downstream signals that result in cell migration, proliferation, and survival. This review presents evidence for how the various CXC and CC subfamily chemokines influence bone hemostasis by acting on osteoclasts, osteoblasts, and progenitor cells. Also discussed are the ways in which chemokines contribute to bone loss as a result of inflammatory diseases such as rheumatoid arthritis, HIV infection, and periodontal infection. Both positive and negative effects of chemokines on bone formation and bone loss are presented. In addition, the role of chemokines in altering the bone microenvironment through effects on angiogenesis and tumor invasion is discussed. Very few therapeutic agents that influence bone formation by targeting chemokines or chemokine receptors are available, although a few are currently being evaluated.
33122493 Anatomic Repair and Reconstruction of Radial Sagittal Band Ruptures. 2020 Oct 28 Two cases of traumatic sagittal band rupture causing extensor tendon subluxation are reported. A case of subacute rupture is repaired and a new surgical technique for reconstruction of a chronic rupture is described. Extensor tendon subluxation at the metacarpophalangeal joint is a rare occurrence in patients not affected by rheumatoid arthritis. The majority of cases involve the disruption of the radial sagittal band with consequent ulnar subluxation of the extensor tendon. The technique of sagittal band reconstruction described involves harvesting a distally based ulnar-sided strip of the extensor digitorum communis tendon, passing it transversely through the radial component of the tendon, and then looping it deep to the deep transverse metacarpal ligament. From here the tendon is then sutured back onto the central tendon, creating a delta-shaped graft. This technique reconstructs the normal anatomy of the sagittal band and has been found to eliminate the subluxation of the tendon and its associated pain.
32743525 Involvement of long noncoding RNAs in the pathogenesis of autoimmune diseases. 2020 Autoimmune diseases are a group of heterogeneous disorders characterized by damage to various organs caused by abnormal innate and adaptive immune responses. The pathogenesis of autoimmune diseases is extremely complicated and has not yet been fully elucidated. Long noncoding RNAs (lncRNAs), which are defined as transcripts containing more than 200 nucleotides with no protein-coding capacity, are emerging as important regulators of gene expression via epigenetic modification, transcriptional regulation and posttranscriptional regulation. Accumulating evidence has demonstrated that lncRNAs play a key role in the regulation of immunological functions and autoimmunity. In this review, we discuss various molecular mechanisms by which lncRNAs regulate gene expression and recent findings regarding the involvement of lncRNAs in many human autoimmune diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), idiopathic inflammatory myopathy (IIM), systemic sclerosis (SSc) and Sjögren's syndrome (pSS).
32699719 Systemic Lupus Erythematosus Presenting as Alopecia Areata. 2020 Jun 20 Alopecia areata is an inflammatory, non-scarring hair loss associated with autoimmune conditions. It is more commonly seen with thyroid disorders and vitiligo, but alopecia areata has also been linked to diabetes, psoriasis, rheumatoid arthritis, and systemic lupus erythematosus. Indeed, individuals with alopecia areata have an increased risk of developing systemic lupus erythematosus. A 36-year-old woman presented with hair loss characteristic of alopecia areata. After intralesional injections with triamcinolone acetonide, the areas of hair loss exhibited near complete hair regrowth. Laboratory examination and additional history were suggestive of systemic lupus erythematosus. She was referred to a rheumatologist who confirmed the diagnosis. Awareness of the comorbidities associated with alopecia areata can uncover other autoimmune conditions, such as thyroid disorders and systemic lupus erythematosus. The diagnosis of a new-onset alopecia areata may prompt a deeper investigation of potentially associated conditions.
32348521 Serological testing in small vessel vasculitis. 2020 May 1 Serological analysis has a central role in the diagnostic work-up of patients with suspected small vessel vasculitis, both for establishing a specific diagnosis and for the monitoring of response to therapy. Autoantibodies can be detected in all forms of primary small vessel vasculitis as well as in the most common forms of secondary vasculitis. For primary vasculitis the most important serological test is for ANCA. ANCA can be found in 75-95% of patients with pauci-immune small vessel vasculitis leading to this subgroup of vasculitides being named ANCA associated vasculitis. ANCA levels often follow this disease course, but the value of serial ANCA testing is controversial. Other important autoantibodies in primary small vessel vasculitis are anti-glomerular basement membrane antibodies, anti-C1q, anti-galactose deficient IgA and cryoglobulins. A wide variety of systemic inflammatory diseases and infections can be complicated by small vessel vasculitis and detected by serological testing. Important examples are SLE, rheumatoid arthritis, Hepatitis C and HIV.
32148994 Leflunomide-Induced Hidradenitis Suppurativa. 2020 Hidradenitis suppurativa is an inflammatory disease of the pilosebaceous unit with a chronic intermittent course and a devastating effect on quality of life. Rare reports of drug-induced hidradenitis suppurativa exist. We report on 2 women on follow-up for rheumatoid arthritis, who presented hidradenitis suppurativa after different periods of treatment with leflunomide and who improved few weeks after discontinuation of the medication.
32039259 Increasing mortality rate due to rheumatoid arthritis-related lung diseases in Japan. 2020 Jan The rates of death due to RA-LD among deaths from any type of RA-related cause have been increasing in Japan. A large-scale study is required to explain this trend. http://bit.ly/2Ew8fhW.
32122630 The effect of omega-3 in temporomandibular joint synovial tissues of rats with induced art 2020 Oct This study evaluated the effect of systemic administration of omega-3 on the expression of interleukins IL-1β and IL-10 and tumour necrosis factor alpha (TNF-α) and on the thickness of cartilage in the temporomandibular joint (TMJ) inflammatory model induced by complete Freund's adjuvant (CFA). Thirty-two adult rats were divided equally into four groups: control, CFA (induced arthritis), and induced arthritis animals treated with dexamethasone or omega-3. The TMJs were then removed and assigned to histomorphometric analysis or immunoassay. The Kruskal-Wallis test with Dunn post hoc test was applied to the data; the significance level was set at 5%. IL-1β levels (median; interquartile range) were higher (P<0.0001) in the CFA group (46.4 ng/ml; 39.4-53.3) than in the control group (1.81 ng/ml; 1.5-5.4), but there were no differences between the control, omega-3, and dexamethasone groups. TNF-α levels were also higher (P<0.0001) in the CFA group (122.7 ng/ml; 92.9-284.7) than in the control group (29.1 ng/ml; 23.7-31.3). IL-10 levels were lowest (P<0.0001) in the CFA group (73.5 ng/ml; 52.8-90.5), and no differences were found amongst the other groups. In conclusion, omega-3 successfully reduced the damage in the TMJ of induced arthritis rats. Further investigations are warranted to confirm whether the administration of omega-3 has a comparable effect to glucocorticoids in rheumatoid arthritis patients.
30691947 Radioisotope Synoviorthesis in the Control of Refractory Synovitis in Castilla-La Mancha. 2020 Nov Our hospital is the nuclear medicine referral hospital for radioisotopic synoviorthesis for all of Castilla-La Mancha. OBJECTIVE: To describe the experience in the performance of radioisotopic synoviorthesis for arthritis refractory to other treatments in our hospital. METHODOLOGY: Observational, descriptive and cross-sectional study protocolised through the review of the database of radioisotopic synoviorthesis performed between 2007 and 2017. Previous clinical data were collected (age, sex, pathology, previous treatments, previous infiltration and affected joint), and progress at 6 months after administering the isotope. An Excel database was created for a frequency analysis with SPSS 21. RESULTS: 30 radiosynovitis interventions were performed. The most frequent pathologies in this order were: pigmented villonodular synovitis (40%), rheumatoid arthritis (23.3%), spondyloarthritis (13.3%), osteoarthritis (10%) and nonspecific arthritis (6.7%), followed by systemic lupus erythematosus and gout. After 6 months, 56.7% of the patients improved compared to 36.7% who remained the same. Likewise, none of them presented complications related to the procedure. Six point six percent of the patients were lost to follow-up. DISCUSSION AND CONCLUSIONS: In patients with episodes of recurrent arthritis with associated joint effusion in one or two joints, refractory to systemic treatments, to local infiltrations with corticosteroids and for patients for whom other treatments may be contraindicated, we must consider the possibility of performing an isotope radiosinoviortesis, as it is a simple, safe technique with a success rate of more than 50%.
33131688 Immune checkpoint inhibitors therapies in patients with cancer and preexisting autoimmune 2020 Dec INTRODUCTION: Immune checkpoints inhibitors (ICIs) are associated with frequent immune-related adverse events (irAEs), but patients with preexisting autoimmune disease (PAD) have been excluded from clinical trials, leaving serious gaps in knowledge. OBJECTIVE: To evaluate the safety and efficacy of ICIs in PAD patients and cancer and explore the impact of different PAD types and baseline receiving immunosuppressive therapy. METHODS: Systematic searches were performed of PubMed, EMBASE, and the Cochrane library from inception through August 2019 for observational studies reporting safety and efficacy data among ICI-treated patients with cancer and PAD. RESULTS: 619 ICI-treated patients with PAD in 14 publications were finally identified. In the random-effects meta-analysis, pooled incidence of PAD flares, de novo immune-related adverse events (irAEs) or both of any grade was 60% (95%CI = 52%-68%). Separately, there were 219 and 206 patients experiencing PAD exacerbation and de novo irAEs of any grade, yielding a pooled incidence of 35% (95%CI = 29%-41%) and 33% (95%CI = 24%-42%) respectively. Rheumatoid arthritis was associated with a trend toward higher flare occurrence compared with another individual PADs (RR = 1.25-1.88). A total of 136 patients showed complete or partial response, corresponding to a pooled response rates of 30% (95%CI = 22%-39%). There were no statistical differences between patients with and without immunosuppressive therapy at ICI start regarding flare (RR = 1.08, 95%CI = 0.72-1.62), but a trend toward lower response rates was observed in patients with baseline immunosuppressants (RR = 0.58, 95%CI = 0.26-1.33). CONCLUSIONS: Immune toxicities are frequent in ICI-treated patients with PAD but often mild and manageable without discontinuing therapy. ICI treatment are also effective in PAD patients, but close monitoring and multidisciplinary collaboration should be contemplated, especially for those concomitantly receiving immunosuppressant or having rheumatoid arthritis.
32899806 Metformin: A Potential Therapeutic Tool for Rheumatologists. 2020 Sep 4 Metformin is an oral antihyperglycemic drug widely used to treat type 2 diabetes, acting via indirect activation of 5' Adenosine Monophosphate-activated Protein Kinase (AMPK). Actually, evidence has accumulated of an intriguing anti-inflammatory activity, mainly mediated by AMPK through a variety of mechanisms such as the inhibition of cytokine-stimulated Nuclear Factor-κB (NF-κB) and the downregulation of the Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) signaling pathways. Moreover, AMPK plays an important role in the modulation of T lymphocytes and other pivotal cells of the innate immune system. The current understanding of these AMPK effects provides a strong rationale for metformin repurposing in the management of autoimmune and inflammatory conditions. Several studies demonstrated metformin's beneficial effects on both animal and human rheumatologic diseases, especially on rheumatoid arthritis. Unfortunately, even though data are large and remarkable, they almost exclusively come from experimental investigations with only a few from clinical trials. The lack of support from prospective placebo-controlled trials does not allow metformin to enter the therapeutic repertoire of rheumatologists. However, a large proportion of rheumatologic patients can currently benefit from metformin, such as those with concomitant obesity and type 2 diabetes, two conditions strongly associated with rheumatoid arthritis, osteoarthritis, and gout, as well as those with diabetes secondary to steroid therapy.
32211082 Intra-Articular Hyaluronic Acid for Knee Osteoarthritis: A Postmarket, Open-Label, Long-Te 2020 BACKGROUND: Intra-articular injections of hyaluronic acid-also called viscosupplementation (VS)-is frequently used for the symptomatic treatment of knee osteoarthritis, a painful and debilitating long-term disease, affecting an important fraction of elderly populations. Severity of knee osteoarthritis is generally described by Kellgren-Lawrence (KL) radiological classification. VS has been widely studied in many clinical trials; however, the results are rarely analyzed in detail according to KL grade. METHOD: A large, clinical, open-label study was performed in 2004-2007 on 1177 patients with knee osteoarthritis, each treated with VS consisting of 3 injections of Arthrum H 2% (LCA Pharmaceutical, Chartres, France). The characteristics of the patients at baseline included demographic profile, body mass index, KL grade, and clinical scores for pain and function using the Western Ontario and McMaster Universities index. Follow-up visits were at 3, 6, and 9 months after VS procedure. This large database was entirely reprocessed in 2019 to provide a separate analysis per KL grade, complemented by the assessment of the Outcome Measures in Rheumatoid Arthritis Clinical Trials-Osteoarthritis Research Society International rates (%) of responders to the treatment. The analysis was carried out for both intention-to-treat and per-protocol completer populations. RESULTS: A primary outcome in the intention-to-treat analysis, variations of the Western Ontario and McMaster Universities index pain subscore from inclusion to the end of the study were 19.8, 19.8, 17.8, and 14.2 for KL grade I to KL grade IV patients, respectively, on a 0 to 100 scale. In the per-protocol analysis, under the same conditions, the variations were 20.6, 19.9, 17.1, and 11.7. All results were significant (P < 0.001) and clinically relevant for each KL grade. Significant improvements were also observed for the Western Ontario and McMaster Universities index function subscore and for the other secondary outcomes. The Outcome Measures in Rheumatoid Arthritis Clinical Trials-Osteoarthritis Research Society International responders rate reached 72% to 82% for KL grade I through III patients at Month 6 and Month 9. For KL grade IV patients, the maximum rate reached was 47.7% at Month 6. There was evidence that KL grade is a critical parameter, particularly if KL grade IV is present. Other parameters such as gender, body mass index, and age were not identified as prognostic factors of response to VS based on χ(2) and odds ratio (95% CI) testing. CONCLUSIONS: Detailed analysis by KL grade supports that VS treatment with Arthrum H 2% applies to a large variety of patients with knee osteoarthritis.
33077837 Finding disease modules for cancer and COVID-19 in gene co-expression networks with the Co 2020 Oct 19 Genes are organized in functional modules (or pathways), thus their action and their dysregulation in diseases may be better understood by the identification of the modules most affected by the disease (aka disease modules, or active subnetworks). We describe how an algorithm based on the Core&Peel method is used to detect disease modules in co-expression networks of genes. We first validate Core&Peel for the general task of functional module detection by comparison with 42 methods participating in the Disease Module Identification DREAM challenge. Next, we use four specific disease test cases (colorectal cancer, prostate cancer, asthma, and rheumatoid arthritis), four state-of-the-art algorithms (ModuleDiscoverer, Degas, KeyPathwayMiner, and ClustEx), and several pathway databases to validate the proposed algorithm. Core&Peel is the only method able to find significant associations of the predicted disease module with known validated relevant pathways for all four diseases. Moreover, for the two cancer datasets, Core&Peel detects further eight relevant pathways not discovered by the other methods used in the comparative analysis. Finally, we apply Core&Peel and other methods to explore the transcriptional response of human cells to SARS-CoV-2 infection, finding supporting evidence for drug repositioning efforts at a pre-clinical level.
32265938 Targeting ADAM10 in Cancer and Autoimmunity. 2020 Generating inhibitors for A Disintegrin And Metalloproteinase 10 (ADAM10), a zinc-dependent protease, was heavily invested in by the pharmaceutical industry starting over 20 years ago. There has been much enthusiasm in basic research for these inhibitors, with a multitude of studies generating significant data, yet the clinical trials have not replicated the same results. ADAM10 is ubiquitously expressed and cleaves many important substrates such as Notch, PD-L1, EGFR/HER ligands, ICOS-L, TACI, and the "stress related molecules" MIC-A, MIC-B and ULBPs. This review goes through the most recent pre-clinical data with inhibitors as well as clinical data supporting the use of ADAM10 inhibitor use in cancer and autoimmunity. It additionally addresses how ADAM10 inhibitor therapy can be improved and if inhibitor therapy can be paired with other drug treatments to maximize effectiveness in various disease states. Finally, it examines the ADAM10 substrates that are important to each disease state and if any of these substrates or ADAM10 itself is a potential biomarker for disease.
33306021 Monoarticular synovitis of knee: dealing with the dilemma. 2020 INTRODUCTION: Chronic synovitis involving a single large joint remains a diagnostic dilemma. We present 61 cases of chronic synovitis of the knee, followed prospectively for 2 years. The study focuses on the diagnosis, management, and histopathological correlation. METHODS: We prospectively studied 61 patients with chronic mono-articular synovitis of the knee joint, between July 2016 and September 2017. All patients underwent plain radiographs, magnetic resonance imaging, and arthroscopic examination with synovial biopsy. Further treatment was based on findings of histopathological examination. RESULTS: The average duration of symptoms was 7.72 ± 4.34 months. The mean age at presentation was 29.93 ± 15.56 years. Results of histopathological examination showed chronic nonspecific inflammation in 28 patients (46%), features suggesting tubercular infection in 19 patients (31%), pigmented villonodular synovitis in seven patients (11.5%), rheumatoid arthritis in three (5%) patients, acute inflammation in three (5%) patients and findings suggestive of synovial chondromatosis in one (1.5%) patient. Treatment was based on histopathological results. Intra-articular injections of methylprednisolone (80 mg depot preparation) were given to all patients with nonspecific synovitis and rheumatoid arthritis. Anti-tubercular treatment was started for patients with tubercular synovitis. Complete arthroscopic/open synovectomy followed by radiotherapy was carried out for patients with pigmented villonodular synovitis. Non-steroidal anti-inflammatory drugs are used for patients with acute on chronic inflammation. All patients had symptomatic relief and functional improvement in further follow-up. DISCUSSION: Histopathological reporting remains the mainstay for diagnosis. The various differentials should always be kept in mind when approaching patients with chronic mono-articular synovitis. Specific treatment can be started once the diagnosis is confirmed.