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ID PMID Title PublicationDate abstract
33655792 Severe pulmonary arterial hypertension and massive ascites in a patient with systemic lupu 2021 Mar BACKGROUND: Pulmonary arterial hypertension (PAH), is a rare manifestation of systemic lupus erythematosus (SLE), characterized by pulmonary arterial remodeling leading to right ventricular failure and death. To date, optimal management of SLE-associated PAH should be clarified, especially regarding the respective places of immunosuppressants and PAH vasodilator treatments. CASE REPORT: We report the case of a 48-year-old woman with SLE and secondary Sjogren syndrome, associated with severe PAH and lupus peritonitis with massive ascites, who showed a remarkable response, both for SLE flare and PAH, to a treatment combining immunosuppressants and pulmonary arterial vasodilator treatment. CONCLUSION: This observation highlights the interest of combining immunosuppressive therapy in SLE-PAH, whose modalities in association with PAH treatments should be clarified.
32676245 The Use of Closed Incision Negative Pressure Therapy Immediately After Total Ankle Arthrop 2020 Jun 13 Introduction Total ankle arthroplasty (TAA) has become a common procedure in the treatment of end-stage ankle arthritis. Most prostheses utilize an anterior ankle approach, which has been shown to have incisional complication rates of up to 28%, including dehiscence and infection. Wounds in this area can be catastrophic to patient outcomes. Preventing incisional wounds would significantly benefit the patient. The purpose of this study was to evaluate the effect of closed incision negative pressure therapy (ciNPT) in reducing incisional dehiscence and surgical site infection (SSI) after TAA. Materials and methods A retrospective chart review that was approved by the Institutional Review Board (IRB) was performed on patients undergoing TAA. Inclusion criteria were patients undergoing TAA with an anterior incision and ciNPT placed immediately in the operating room. Comorbidities associated with increased wound complications were recorded. Identification of any incisional dehiscence, infections, or deviations from normal postoperative recovery attributed to the former was also recorded. Results Twenty-eight patients met the inclusion criteria. The average age of the patients at the time of surgery was 68 years. Comorbidities associated with compromised healing were obesity (45%), current or former smoking (45%), diabetes (3.5%), and rheumatoid arthritis (7%). There were no postoperative wound complications (100% incisional healing). No patient required any wound-care intervention or had an SSI. None of the patients had any delay in the normal postoperative course. Conclusion Avoiding wound complications in TAA patients is critical to the success of the procedure. This retrospective case series demonstrated 100% healing with the utilization of the ciNPT in both normal and high-risk patients with decreased healing potential. Our results showed a substantial decrease in wound complications and SSIs compared to historical reports. We recommend ciNPT for all TAA procedures utilizing an anterior incision to decrease the risk for wound complications and SSIs.
32637413 Osteoclast Signal Transduction During Bone Metastasis Formation. 2020 Osteoclasts are myeloid lineage-derived bone-resorbing cells of hematopoietic origin. They differentiate from myeloid precursors through a complex regulation process where the differentiation of preosteoclasts is followed by intercellular fusion to generate large multinucleated cells. Under physiological conditions, osteoclastogenesis is primarily directed by interactions between CSF-1R and macrophage colony-stimulating factor (M-CSF, CSF-1), receptor activator of nuclear factor NF-κB (RANK) and RANK ligand (RANKL), as well as adhesion receptors (e.g., integrins) and their ligands. Osteoclasts play a central role in physiological and pathological bone resorption and are also required for excessive bone loss during osteoporosis, inflammatory bone and joint diseases (such as rheumatoid arthritis) and cancer cell-induced osteolysis. Due to the major role of osteoclasts in these diseases the better understanding of their intracellular signaling pathways can lead to the identification of potential novel therapeutic targets. Non-receptor tyrosine kinases and lipid kinases play major roles in osteoclasts and small-molecule kinase inhibitors are emerging new therapeutics in diseases with pathological bone loss. During the last few years, we and others have shown that certain lipid (such as phosphoinositide 3-kinases PI3Kβ and PI3Kδ) and tyrosine (Src-family and Syk) kinases play a critical role in osteoclast differentiation and function in humans and mice. Some of these signaling pathways shows similarity to immunoreceptor-like receptor signaling and involves important other enzymes (e.g., PLCγ2) and adapter proteins (such as the ITAM-bearing adapters DAP12 and the Fc-receptor γ-chain). Here, we review recently identified osteoclast signaling pathways and their role in osteoclast differentiation and function as well as pathological bone loss associated with osteolytic tumors of the bone. A better understanding of osteoclast signaling may facilitate the design of novel and more efficient therapies for pathological bone resorption and osteolytic skeletal metastasis formation.
33364944 Computational Studies of Hydroxychloroquine and Chloroquine Metabolites as Possible Candid 2020 The coronavirus disease 2019 or COVID-19 pandemic is claiming many lives, impacting the health and livelihoods of billions of people worldwide and causing global economic havoc. As a novel disease with protean manifestations, it has pushed the scientific community into a frenzy to find a cure. The chloroquine class of compounds, used for decades for their antimalarial activity, have been well characterized. Hydroxychloroquine (HCQ), a less toxic metabolite of chloroquine, is used to treat rheumatic diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), and Sjögren's syndrome. Preliminary studies in non-randomized clinical trials point to the possible use of chloroquine and its derivatives in the treatment of coronavirus. However, more robust clinical studies carried out in the United States, Italy, Australia, and China have shown mixed and inconclusive results and indicate the need for additional research. Cardiac, neurological, and retinal toxicity as well as increasing parasite resistance to these drugs is a major hindrance for their use in a world that is already dealing with antimicrobial resistance (AMR). In this context, we chose to study the monoquinoline analogs of 4-aminoquinoline as well as their metabolites which have the same mechanism of action albeit with lower toxicity. All the compounds were extensively studied computationally using docking, cheminformatics, and toxicity prediction tools. Based on the docking scores against ACE (angiotensin-converting enzyme) receptors and the toxicity data computed by employing the chemical analyzer module by ViridisChem(™) Inc., the work reveals significant findings that can help in the process of use of these metabolites against coronavirus.
30927517 Rheumatic Care in Under-Resourced Areas Using the Extension for Community Healthcare Outco 2020 Jun OBJECTIVE: To demonstrate the effectiveness of the Extension for Community Healthcare Outcomes (Project ECHO) in educating primary care clinicians (PCCs) to provide best practice rheumatic care to patients in under-resourced communities in New Mexico. METHODS: Attendee data for weekly teleECHO sessions, lectures, grand rounds, and mini-residency trainings were evaluated from June 2006 to June 2014. Participant feedback was evaluated from January 2009 to December 2014, when the program was approved for continuing medical education (CME) credits. Retrospective review of diagnoses associated with case presentations was conducted from June 2006 to June 2014 to evaluate the types of cases presented. A focus group was conducted with a convenience sample of 8 New Mexico PCCs who participated in ECHO Rheumatology (ECHO Rheum) for 1 year or longer. RESULTS: Over the course of 9 years, ECHO Rheum educated 2,230 clinicians, consisting primarily of physicians (53%) and nurse practitioners (22%). A total of 1,958 CME credits were awarded to those who participated. There were 1,173 cases presented; 85% of the cases reflected the 3 most common diagnoses: rheumatoid arthritis (n = 715), fibromyalgia (n = 241), and systemic lupus erythematosus (n = 54). In addition, ECHO Rheum conducted 15 two-day mini-residencies involving 30 PCCs; 21 of these clinicians subsequently completed the American College of Rheumatology online certification. CONCLUSION: Results from this study demonstrate that participation in ECHO Rheum provides clinicians in under-resourced areas access to best-practice knowledge and training in rheumatology.
33080726 Direct anterior approach or posterior approach in total hip arthroplasty: A direct compara 2020 Oct 16 BACKGROUND: Two familiar surgical methods, posterior approach (PA) and direct anterior approach (DAA), have been extensively utilized in the treatment of total hip arthroplasty (THA) with similar long-term rates of success. The sufficient sample size and a good clinical trial are urgently needed. Considering the above factors, we implemented a retrospective research to compare the prognosis of patients with primary THA receiving the techniques of PA or DAA. METHODS: This is an observational retrospective research that prospectively collected information via several surgeons at a center utilizing the 2 above treatment methods for unilateral primary total hip arthroplasty. A review of primary THA performed with DAA or PA between February 2017 and February 2019 was conducted in our hospital. The inclusion criteria contained the degenerative changes in end-stage of hip owing to the rheumatoid arthritis, inflammatory arthritis, and osteoarthritis, as well as the Crowe I and II dysplasia that did not require the enhancement. The primary endpoint was the Harris hip score. The measures of secondary outcome contained the operation time, length of incision, hospital stay, the complications after operation, as well as patient satisfaction. The Statistical Package for Social Sciences version 20.0 was utilizing for the statistical analysis (IBM Corporation, Armonk, NY). RESULTS: We assumed that the 2 treatment methods possess similar results. TRIAL REGISTRATION: This study protocol was registered in Research Registry (researchregistry6008).
32629865 Synergistic Activation of Toll-Like and NOD Receptors by Complementary Antigens as Facilit 2020 Jun 30 Persistent activation of toll-like receptors (TLR) and nucleotide-binding oligomerization domain-containing proteins (NOD) in the innate immune system is one necessary driver of autoimmune disease (AD), but its mechanism remains obscure. This study compares and contrasts TLR and NOD activation profiles for four AD (autoimmune myocarditis, myasthenia gravis, multiple sclerosis and rheumatoid arthritis) and their animal models. The failure of current AD theories to explain the disparate TLR/NOD profiles in AD is reviewed and a novel model is presented that explains innate immune support of persistent chronic inflammation in terms of unique combinations of complementary AD-specific antigens stimulating synergistic TLRs and/or NODs. The potential explanatory power of the model is explored through testable, novel predictions concerning TLR- and NOD-related AD animal models and therapies.
31599089 Altered Cytotoxicity Profile of CD8+ T Cells in Ankylosing Spondylitis. 2020 Mar OBJECTIVE: Ankylosing spondylitis (AS) is an inflammatory arthritis in which men have a higher risk of developing progressive axial disease than women. Transcriptomic studies have shown reduced expression of cytotoxic cell genes in the blood of AS patients. HLA-B27 contributes the greatest risk for AS, suggesting a role for CD8+ T cells. This study was undertaken to profile AS patient cytotoxic cells with the hypothesis that an alteration in CD8+ T cells might explain the aberrant cytotoxic profile observed in patients. METHODS: Whole blood was examined for GZM and PRF1 gene expression by quantitative polymerase chain reaction. Serum and synovial fluid (SF) were examined for granzyme and perforin 1 expression by bead array, and blood and SF mononuclear cells were examined for granzyme and perforin 1 expression by fluorescence-activated cell sorting (FACS). RESULTS: GZM and PRF1 gene expression were both reduced in AS patients compared to healthy controls, especially in men. Perforin 1, but not granzyme, protein levels were reduced in AS patient serum. Granzymes were elevated in AS SF, but not in rheumatoid arthritis or osteoarthritis SF. FACS revealed a reduction in granzyme-positive and perforin 1-positive lymphocytes, but not an intrinsic defect in CD8+ T cell granzyme or perforin 1 production. CD8+ T cell frequency was reduced in the blood and increased in the SF of AS patients. CONCLUSION: Our findings indicate that AS patients have an altered cytotoxic T cell profile. These data suggest that CD8+ T cells with a cytotoxic phenotype are recruited to the joints, where they exhibit an activated phenotype. Thus, a central role for CD8+ T cells in AS may have been overlooked and deserves further study.
32094142 Using internet search data to explore the global public concerns in ankylosing spondylitis 2021 Feb OBJECTIVE: This study explored the changes of global public interest in internet search of ankylosing spondylitis (AS) based on Google Trends (GT) data, in order to reflect the characteristics of AS itself. METHODS: GT was used to obtain the search popularity scores of the term 'AS' on a global scale, between January 2004 and December 2018, under the 'health' classification. Based on the global search data of AS provided by GT, the cosinor analysis was used to test whether there was seasonality in AS. RESULTS: In general, AS related search volume demonstrated a decreasing trend from January 2004 to December 2014 and then remain stable from January 2015 to December 2018. No obvious seasonal variations were detected in AS related search volume (amplitude=1.54; phase: month=3.9; low point: month=9.9; p>0.025), which peaked in April and bottomed out in October. The top 17 rising topics were adalimumab, spondylolisthesis, Morbus, Vladimir Mikhailovich Bekhterev, autoimmune disease, rheumatoid arthritis, ankylosis, HLA- B27 positive, Crohn's disease, rheumatology, spondylosis, arthritis, uveitis, rheumatism, sacroiliac, psoriatic arthritis and spondylitis. CONCLUSIONS: Globally, there is no significant seasonal variation in GT for AS. The top fast-growing topics related to AS may be beneficial for doctors to provide targeted health education of the disease to patients and their families.
32700187 Using qualitative methods for a conceptual analysis of measures of health status and prese 2020 Nov OBJECTIVES: The inclusion of productivity in economic evaluations is a contentious issue. Methods are currently being developed to assess how it may feasibly be included for specific interventions, such as workplace interventions (WPIs), where productivity is a key outcome. Mapping (also called cross-walking or prediction modelling) may offer a solution. Prior to producing a mapping algorithm, it is recommended that the conceptual validity between 'source' and 'target' measures be understood first. This study aimed to understand the conceptual validity of two existing measures of health status (EQ-5D; SF-6D) and presenteeism to inform the potential for a subsequent mapping algorithm. METHODS: A purposive sample of individuals who were currently working and had either rheumatoid arthritis (RA), ankylosing spondylitis (AS) or psoriatic arthritis (PsA). Individuals were recruited through support groups. Semi-structured telephone interviews were conducted until data saturation (no new emerging themes) was reached. Deductive and inductive framework analysis methods were used to identify key aspects of the conditions (themes) that impact on presenteeism (working at reduced levels of health). RESULTS: Twenty-two (RA = 10; AS = 9; PsA = 3) employed individuals were interviewed. Deductive analysis identified evidence which confirmed the domains included in the EQ-5D and SF-6D capture those key aspects of RA, AS and PsA that increase presenteeism. Inductive analysis identified an additional theme; mental clarity, not captured by the EQ-5D or SF-6D, was also found to have a direct impact on presenteeism. CONCLUSIONS: The results of the study indicate conceptual validity of both health status measures to predict presenteeism. The next step is to develop a mapping algorithm for presenteeism.
31941544 Dose reduction and withdrawal strategy for TNF-inhibitors in psoriatic arthritis and axial 2020 Jan 15 BACKGROUND: Tumour necrosis factor inhibitors (TNFi) are effective in the treatment of patients with spondyloarthritis (SpA), including psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA). However, these drugs come with some disadvantages such as adverse events, practical burden for patients and high costs. Dose optimisation of TNFi after patients have reached low disease activity (LDA) has been shown feasible and safe in rheumatoid arthritis (RA). However, data on TNFi dose optimisation in PsA and axSpA are scarce, especially pragmatic, randomised strategy studies. METHODS: We developed an investigator-driven, pragmatic, open-label, randomised, controlled, non-inferiority trial (DRESS-PS) to compare the effects of a disease activity-guided treat-to-target strategy with or without a tapering attempt in patients with SpA (PsA and axSpA combined), ≥ 16 years of age, who are being treated with TNFi, and have had at least 6 months of low disease activity. The primary outcome is the percentage of patients in LDA after 12 months of follow up. Patients are assessed at baseline, 3, 6, 9, and 12 months of follow up. Bayesian power analyses with a weakened prior based on a similar study performed in RA resulted in a sample size of 95 patients in total. DISCUSSION: More knowledge on disease activity-guided treatment algorithms would contribute to better treatment choices and cost savings and potentially decrease the risk of side effects. In this article we elucidate some of our design choices on TNFi dose optimisation and its clinical and methodological consequences. TRIAL REGISTRATION: Dutch Trial Register, NL6771. Registered on 27 November 2018 (CMO NL66181.091.18, 23 October 2018).
33228011 Connection between the Gut Microbiome, Systemic Inflammation, Gut Permeability and FOXP3 E 2020 Nov 19 The aims of this study were to explore intestinal microbial composition and functionality in primary Sjögren's syndrome (pSS) and to relate these findings to inflammation, permeability and the transcription factor Forkhead box protein P3 (FOXP3) gene expression in peripheral blood. The study included 19 pSS patients and 19 healthy controls matched for age, sex, and body mass index. Fecal bacterial DNA was extracted and analyzed by 16S rRNA sequencing using an Ion S5 platform followed by a bioinformatics analysis using Quantitative Insights into Microbial Ecology (QIIME II) and Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt). Our data suggest that the gut microbiota of pSS patients differs at both the taxonomic and functional levels with respect to healthy controls. The gut microbiota profile of our pSS patients was characterized by a lower diversity and richness and with Bacteroidetes dominating at the phylum level. The pSS patients had less beneficial or commensal butyrate-producing bacteria and a higher proportion of opportunistic pathogens with proinflammatory activity, which may impair intestinal barrier function and therefore contribute to inflammatory processes associated with pSS by increasing the production of proinflammatory cytokines and decreasing the release of the anti-inflammatory cytokine IL-10 and the peripheral FOXP3 mRNA expression, implicated in the development and function of regulatory T cells (Treg) cells. Further studies are needed to better understand the real impact of dysbiosis on the course of pSS and to conceive preventive or therapeutic strategies to counteract microbiome-driven inflammation.
33343903 Sjögren's syndrome with nodular pulmonary amyloidosis. 2021 Jan We report a case of Sjögren's syndrome with nodular pulmonary amyloidosis. Amyloidosis is a heterogeneous group of diseases caused by aggregation of autologous protein and its extracellular deposition as fibrils. Most cases of nodular pulmonary amyloidosis are the result of an underlying disorder such as mucosa-associated lymphoid tissue lymphoma, rheumatoid arthritis, or multiple myeloma. Nodular pulmonary amyloidosis with Sjögren's syndrome is very rare. The clinical outcome of patients with nodular pulmonary amyloidosis is good if the underlying disease can be controlled.
33240849 Anticancer Gold(III) Compounds With Porphyrin or N-heterocyclic Carbene Ligands. 2020 The use of gold in medicine has a long history. Recent clinical applications include anti-inflammatory agents for the treatment of rheumatoid arthritis (chrysotherapy), and is currently being developed as potential anticancer chemotherapeutics. Gold(III), being isoelectronic to platinum(II) as in cisplatin, is of great interest but it is inherently unstable and redox-reactive under physiological conditions. Coordination ligands containing C and/or N donor atom(s) such as porphyrin, pincer-type cyclometalated and/or N-heterocyclic carbene (NHC) can be employed to stabilize gold(III) ion for the preparation of anticancer active compounds. In this review, we described our recent work on the anticancer properties of gold(III) compounds and the identification of molecular targets involved in the mechanisms of action. We also summarized the chemical formulation strategies that have been adopted for the delivery of cytotoxic gold compounds, and for ameliorating the in vivo toxicity.
33415105 Communications Between Bone Marrow Macrophages and Bone Cells in Bone Remodeling. 2020 The mammalian skeleton is a metabolically active organ that continuously undergoes bone remodeling, a process of tightly coupled bone resorption and formation throughout life. Recent studies have expanded our knowledge about the interactions between cells within bone marrow in bone remodeling. Macrophages resident in bone (BMMs) can regulate bone metabolism via secreting numbers of cytokines and exosomes. This review summarizes the current understanding of factors, exosomes, and hormones that involved in the communications between BMMs and other bone cells including mensenchymal stem cells, osteoblasts, osteocytes, and so on. We also discuss the role of BMMs and potential therapeutic approaches targeting BMMs in bone remodeling related diseases such as osteoporosis, osteoarthritis, rheumatoid arthritis, and osteosarcoma.
33139372 Leishmania donovani mucosal leishmaniasis in Malta. 2020 Nov 2 We report a case of a 76-year-old British man living in Malta who presented with a 7-month history of recurrent epistaxis and an enlarging right nasal vestibular lesion. Of note, his medical history included rheumatoid arthritis for which he was on long-term methotrexate. Blood results were unremarkable other than a mild lymphopaenia. Despite the use of various antibiotics and intranasal steroids, the lesion failed to resolve. This was eventually biopsied, and the histological picture was that of mucosal leishmaniasis. Leishmania donovani complex was detected by PCR. The patient was treated with liposomal amphotericin B on alternate days for a total of 20 doses. The lesion was found to have healed well at follow-up and the patient denied any further episodes of epistaxis.
32832028 Stereochemical Differences in Fluorocyclopropyl Amides Enable Tuning of Btk Inhibition and 2020 Aug 13 Bruton's tyrosine kinase (Btk) is thought to play a pathogenic role in chronic immune diseases such as rheumatoid arthritis and lupus. While covalent, irreversible Btk inhibitors are approved for treatment of hematologic malignancies, they are not approved for autoimmune indications. In efforts to develop additional series of reversible Btk inhibitors for chronic immune diseases, we sought to differentiate from our clinical stage inhibitor fenebrutinib using cyclopropyl amide isosteres of the 2-aminopyridyl group to occupy the flat, lipophilic H2 pocket. While drug-like properties were retained-and in some cases improved-a safety liability in the form of hERG inhibition was observed. When a fluorocyclopropyl amide was incorporated, Btk and off-target activity was found to be stereodependent and a lead compound was identified in the form of the (R,R)- stereoisomer.
32385762 Correction to: Serum substance P: an indicator of disease activity and subclinical inflamm 2020 Jul Following publication, it was brought to the authors' attention by Dr. Julia Toscano-Garibay that she did not participate as a reviewer of the final version of this manuscript prior to its submission and publication in Clinical Rheumatology.
32010537 Intellectual Disability in Two Brothers Caused by De Novo Novel Unbalanced Translocation ( 2020 Jan 26 We report here two brothers with an intellectual disability (ID), dysmorphic features, speech delay, and congenital hypotonia, with chromosomal microarray confirmed. However, two different de novo chromosomal aberrations; unbalanced translocations (13;18) (q34,q23) were found in the elder boys and de novo 6q25 deletion in the second boy. The boy with 13q34 microdeletion and 18q23 microduplication suffered from ID, obesity, dysmorphic features, speech delay, and seizure while the one with 6q25 deletion presented with ID and speech delay. Both parents were tested and were normal. The third child had mild hypotonia at infancy, which improved later. Whole-exome sequencing (WES) showed the three boys carried a likely benign variant in MED12, inherited from the healthy, asymptomatic mother. The father suffered from rheumatoid arthritis and was on chemotherapy during the conception of the first two affected boys. This report places emphasis on the use of a chromosomal microarray in patients with ID, even with familial cases, and reports the paternal use of methotrexate.
31996665 Osteopontin in Bone Metabolism and Bone Diseases. 2020 Jan 30 Osteopontin (OPN), a secreted phosphoprotein, is a member of the small integrin-binding ligand N-linked glycoprotein (SIBLING) family of cell matrix proteins and participates in many biological activities. Studies have shown that OPN plays a role in bone metabolism and homeostasis. OPN not only is an important factor in neuron-mediated and endocrine-regulated bone mass, but also is involved in biological activities such as proliferation, migration, and adhesion of several bone-related cells, including bone marrow mesenchymal stem cells, hematopoietic stem cells, osteoclasts, and osteoblasts. OPN has been demonstrated to be closely related to the occurrence and development of many bone-related diseases, such as osteoporosis, rheumatoid arthritis, and osteosarcoma. As expected, the functions of OPN in the bone have become a research hotspot. In this article, we try to decipher the mechanism of OPN-regulated bone metabolism and bone diseases.