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ID PMID Title PublicationDate abstract
32558333 End-stage Ankle Arthritis Treated by Ankle Arthrodesis with Screw Fixation Through the Tra 2020 Aug OBJECTIVE: To evaluate the clinical outcome of ankle arthrodesis with screw fixation through the transfibular approach for end-stage ankle arthritis. METHODS: Data of 22 patients (28 ankles) with end-stage ankle arthritis admitted to the Department of Orthopedics and Surgery of the First Hospital of Jilin University from May 2015 to December 2018 were analyzed retrospectively. The study included 9 men and 13 women, with a mean age of 56.86 ± 11.27 years (range, 37-75 years). The mean duration of the disease was 11.36 ± 12.80 years (range, 3 months-50 years). A total of 16 patients had posttraumatic arthritis, 5 patients had osteoarthritis, and 1 patient had rheumatoid arthritis. There were 12 cases of the left ankle and 16 cases of the right ankle; 16 cases were unilateral and 6 were bilateral. The same surgical procedure was applied to all patients. Collected data included the operation time, intraoperative and postoperative blood loss, hospitalization time, bone union rate, time to bone union, and complications. The American Orthopedic Foot and Ankle Society (AOFAS) ankle hindfoot score and the visual analogue scale (VAS) were used to evaluate the preoperative status and the postoperative outcome at the last follow up. RESULTS: The mean follow-up period was 26.14 ± 10.99 months. The mean operation time was 101.82 ± 33.33 min. The mean blood loss was 116.78 ± 68.86 mL during the procedure and 111.07 ± 52.18 mL after the procedure. The mean hospitalization time was 14.22 ± 5.42 days. Bone union of the ankle joint was achieved in all patients. The mean time to bone union was 14.83 ± 2.14 weeks. There was significant difference in the operation time between the patients undergoing unilateral and bilateral ankle arthrodesis. The AOFAS ankle hindfoot score increased from the preoperative value of 43.46 ± 4.39 points to 80.39 ± 5.37 points at the last follow up. During the same interval, the VAS score improved from 6.14 ± 0.80 points to 1.64 ± 0.73 points. The AOFAS ankle hindfoot score of patients who underwent unilateral ankle arthrodesis improved from the preoperative 43.19 ± 3.95 points to 81.75 ± 5.23 points at the last follow up, and the VAS score improved from 6.19 ± 0.83 points to 1.69 ± 0.70 points. The AOFAS ankle hindfoot score of patients undergoing bilateral ankle arthrodesis improved from the preoperative value of 43.83 ± 5.08 points to 78.67 ± 5.05 points at the last follow up, while the VAS score improved from 6.08 ± 0.82 points to 1.58 ± 0.79 points. There was significant difference in the maximum walking distance and walking on any surface between the patients undergoing unilateral and bilateral ankle arthrodesis. One patient developed superficial peroneal nerve palsy, which resolved within 1 year after the operation. In another patient, healing of the incision skin was delayed. During the follow-up period, none of the patients developed an infection of the incision or local skin necrosis; screw loosening, withdrawal, or breakage did not occur in any patient. CONCLUSION: The ankle arthrodesis with screw fixation through the transfibular approach provides satisfactory clinical outcomes for end-stage ankle arthritis.
32427547 Comparison of infection-related hospitalization risk and costs in tumor necrosis factor in 2020 Sep Background: Evidence on the cost and risk of infection-related hospitalizations associated with targeted disease-modifying anti-rheumatic drugs (tDMARDs) in patients with RA previously treated with a tumor necrosis factor inhibitor (TNFi) is limited. This study compared the risk and cost of infection-related hospitalizations in commercially insured TNFi-experienced RA patients receiving abatacept, TNFi, or another non-TNFi.Methods: A retrospective observational study was conducted using 2 large insurance claims databases (1 January 2009-30 June 2017). Adult TNFi-experienced RA patients initiating a subsequent tDMARD (initiation date of tDMARD = index date) with 12 months of continuous enrollment pre-index date, and who had ≥1 inpatient or ≥2 outpatient medical RA claims on 2 different dates were included. Abatacept was compared to TNFis (adalimumab, certolizumab pegol, etanercept, golimumab, and infliximab) and other non-TNFis (tocilizumab, rituximab, and tofacitinib). Cox proportional hazards models estimated the adjusted risk for infection-related hospitalization; costs were calculated on a per-member-per-month (PMPM) and per-patient-per-month (PPPM) basis using generalized linear models.Results: More patients in the abatacept cohort had an infection-related hospitalization at baseline (4.5%) vs TNFis (2.0%, p < .0001) and other non-TNFis (3.6%, p = .2619). However, during follow-up abatacept patients had fewer infection-related hospitalizations (abatacept: 2.8%, TNFi: 3.7% and other non-TNFis: 5.2%; p < .05). Regression results indicated that compared to patients on abatacept, patients receiving a TNFi [HR: 1.6 (95% CI: 1.1, 2.2)] and other non-TNFis [HR: 1.9 (95% CI: 1.3, 2.8)] had a significantly higher risk of infection-related hospitalization. Abatacept PMPM costs were lowest ($0.25 vs $0.39 and $0.43 for TNFi and other non-TNFi respectively). Mean PPPM (95% CI) cost in the follow-up was lower for abatacept compared to TNFi ($73 vs. $115; p = .042), and other non-TNFi ($73 vs. $125; p = .039).Conclusions: There were significantly lower infection-related hospitalizations and associated costs in TNF-experienced RA patients treated with abatacept than TNFis and other non-TNFis.
32653654 Comparison of paediatric and adult classification criteria in juvenile idiopathic arthriti 2021 Jan OBJECTIVES: To determine the characteristics of juvenile idiopathic arthritis (JIA) patients seen during the transition period in order to compare paediatric classification criteria with those for adults. METHODS: Patients with JIA according to the ILAR classification and who had a consultation at transition between 2010 and 2017 were included in a retrospective bi-centre (Lyon, Lausanne) study. JIA classification criteria were compared to ACR/EULAR 2010 criteria for rheumatoid arthritis (RA), Yamaguchi criteria for adult-onset Still's disease (AOSD), ASAS criteria for spondyloarthritis and CASPAR criteria for psoriatic arthritis. RESULTS: One hundred and thirty patients were included: 13.9% with systemic JIA, 22.3% with polyarticular JIA, 22.3% with oligoarticular JIA, 34.6% with enthesitis-related arthritis (ERA) and 6.9% with psoriatic arthritis; 13.1% had suffered from uveitis; 14.5% of patients had erosions or carpitis, mainly those with psoriatic arthritis, polyarticular or systemic JIA; 37.5% of patients with ERA displayed radiological sacroiliitis. When comparing paediatric JIA criteria with adult classifications, we found that: 66.6% of patients with systemic JIA fulfilled the criteria for AOSD, 87.5% of rheumatoid factor-positive polyarticular JIA and 9.5% of rheumatoid factor-negative polyarticular JIA met the criteria for RA, and 34.5% of oligoarticular JIA fulfilled the criteria for spondyloarthritis. Finally, 77.7% of patients with ERA met the criteria for spondyloarthritis, and 100% of patients with psoriatic arthritis JIA met the criteria for psoriatic arthritis. CONCLUSION: Oligoarticular JIA and rheumatoid factor-negative polyarticular JIA seem to be paediatric entities, whereas the other types of JIA tended to meet the respective adult classification criteria.
31948479 Improvement of symptoms in clinically suspect arthralgia and resolution of subclinical joi 2020 Jan 16 INTRODUCTION: Arthralgia and MRI-detected subclinical inflammation can precede the development of clinically evident rheumatoid arthritis (RA). However, part of the patients presenting with clinically suspect arthralgia (CSA) do not progress to RA. In these 'non-progressors', we aimed to study the frequencies of spontaneous improvement of arthralgia and its relation with the course of subclinical inflammation. METHODS: Between April 2012 and April 2015, 241 patients were considered at risk for RA based on the clinical presentation and included in the CSA cohort. One hundred fifty-two patients with complete data on clinical follow-up did not develop clinical arthritis, of which 98 underwent serial 1.5T MRI scans (wrist, MCP2-5, and MTP1-5 joints) at baseline and after 2 years. MRI scans were scored for synovitis, tenosynovitis, and bone marrow oedema (summed: MRI inflammation score). MRI scores were compared to scores of symptom-free persons. RESULTS: After a 2-year follow-up, 33% of the 'non-progressors' had complete resolution of symptoms; 67% had no symptom resolution and were diagnosed as persistent CSA (44%), osteoarthritis (10%), and tendinomuscular complaints (13%). With symptom-free controls as a reference, patients without resolution did not have increased MRI scores at any time point. However, patients achieving resolution of symptoms had increased MRI inflammation scores at baseline (4.0 vs. 2.6, p = 0.037), but not after 2 years (3.0 vs. 2.6; p = 0.57), and during follow-up, their MRI inflammation score decreased significantly (p = 0.036). CONCLUSIONS: A subgroup of CSA patients that did not progress to RA had spontaneous improvement of symptoms and resolution of subclinical joint inflammation. This time relationship suggests that symptoms and inflammation were causally related in these patients. Further research is needed to identify the mechanisms underlying the resolution of inflammation.
32265195 Prognosis and causes of death of patients with acute exacerbation of fibrosing interstitia 2020 Apr BACKGROUND: The aim of this study was to compare the clinical characteristics, causes of death and factors impacting on the prognosis of patients with idiopathic pulmonary fibrosis (IPF) and other fibrosing interstitial lung disease (FILD) with a history of acute exacerbation (AE) of IPF or FILD. METHODS: Retrospective data of hospital treatment periods caused by AE-IPF and AE-FILD were collected from medical records. Clinical features and survival data of IPF and non-IPF cases were evaluated and compared. The underlying and immediate causes of death were gathered from death certificates. RESULTS: A total of 128 patients fulfilled the criteria for inclusion. IPF (n=79/62%), rheumatoid arthritis-associated interstitial lung disease (RA-ILD; n=17/14%) and asbestosis (n=11/8.6%) were the most common FILD subgroups in the study. The median survival after hospitalisation in AE-IPF was 2.6 months compared with 21 months in other AE-FILDs (p<0.001). The survival difference was not explained by age, gender or pulmonary function test results at the time of hospitalisation. Patients with non-specific interstitial pneumonia and RA-ILD had the most favourable prognosis. ILD was the most common underlying cause of death in both patients with IPF and with other FILD accounting for 87% and 78% of deaths, respectively. CONCLUSIONS: We detected a significantly longer survival in AE of patients with non-IPF compared with that of AE-IPFs. The prognosis of patients was affected by the underlying lung disease since pulmonary fibrosis was the underlying cause of death in the majority of all patients with FILD having experienced an AE.
32162152 Drug retention of secondary biologics or JAK inhibitors after tocilizumab or abatacept fai 2020 Sep OBJECTIVES: The aim of this multicenter, retrospective study was to clarify the retention of secondary biological disease-modifying antirheumatic drugs (bDMARDs) or Janus kinase inhibitors (JAKi) in patients with rheumatoid arthritis (RA) who were primarily treated by tocilizumab (TCZ) or abatacept (ABT) as first bDMARDs. METHOD: Patients who were treated by either TCZ (n = 145) or ABT (n = 76) and then switched to either tumor necrosis factor inhibitors (TNFi), TCZ, ABT, or JAKi (including only cases switched from TCZ) from 2001 to 2019 (female 81.0%, age 59.5 years, disease duration 8.8 years; rheumatoid factor positivity 75.4%; Disease Activity Score in 28 joints using C-reactive protein 3.7; concomitant prednisolone (PSL) dose 6.0 mg/day (51.8%) and methotrexate (MTX) dose 8.0 mg/week (56.1%); 81.9% discontinued first bDMARDs due to lack of effectiveness) were included. Drug retention and discontinuation reasons were estimated at 24 months using the Kaplan-Meier method and adjusted for potential confounders by Cox proportional hazards modeling. RESULTS: Drug retentions for each of the reasons for discontinuation were as follows: lack of effectiveness in TCZ-switched group (TNFi (59.5%), ABT (82.2%), and JAKi (84.3%); TNFi vs. ABT; P = 0.009) and ABT-switched group (TNFi (79.6%) and TCZ (92.6%); P = 0.053). Overall retention excluding non-toxic reasons and remission for discontinuation were TNFi (49.9%), ABT (72.7%), and JAKi (72.6%) (TNFi vs. ABT; P = 0.017) in the TCZ-switched group and TNFi (69.6%) and TCZ (72.4%) (P = 0.44) in the ABT-switched group. CONCLUSIONS: Switching to ABT in TCZ-treated patients led to higher retention as compared with TNFi. Switching to TCZ in ABT-treated patients tended to lead to higher retention due to effectiveness, although total retention was similar as compared with TNFi. Key Point • This is the first retrospective, multi-center study aimed to clarify the retention rates of secondary bDMARDs or JAKi in patients with RA who were primarily being treated by TCZ or ABT as the first bDMARDs.
31512538 Increased plasticity of non-classic Th1 cells toward the Th17 phenotype. 2020 Sep Objectives: To analyze occurrence and plasticity of two recently described distinct subtypes of Th1 cells named classic (CD161-/CCR6-) and non-classic (CD161+/CCR6+) Th1 cells in early rheumatoid arthritis (RA) patients and healthy controls (HCs).Methods: Frequencies of in vivo-generated Th1 cell populations were assessed after cytokine secretion assay for IFNγ/IL-17 and surface staining for CD161/CCR6. Viable Th1 cells (IFNγ+IL-17-) were sorted into classic Th1 (CD161-CCR6-) and non-classic Th1 (CD161+CCR6+) cells, trans-differentiated under different Th cell-inducing conditions, and assessed for plastic changes by analyzing the Th cell-associated cytokine and transcription factor profiles.Results: Ex vivo frequencies of classic (CD161-CCR6-) and non-classic (CD161+CCR6+) Th1 cells as well as related Th1 cell subpopulations CD161+CCR6- and CD161-/CCR6+ did not differ significantly between RA and HCs. However, trans-differentiation of ex vivo non-classic (CD161+CCR6+) and CD161-/CCR6+ Th1 cells resulted in a substantial shift toward Th17 and Th1/Th17 phenotypes, particularly under Th17-inducing conditions. In contrast, classic (CD161-/CCR6-) and CD161+CCR6- Th1 cells showed higher plasticity towards IL-4-producing cells, most of them shifting to a Th1/Th2 phenotype.Conclusion: Whereas non-classic (CD161+/CCR6+) and CD161-CCR6+ Th1 cells demonstrated an increased plasticity towards IL-17- phenotypes, classic Th1 and CD161+CCR6- Th1 cells showed more plasticity towards IL-4-producing phenotypes.
33180998 Increased sympathetic and haemodynamic responses to exercise and muscle metaboreflex activ 2021 Feb KEY POINTS: Rheumatoid arthritis (RA) patients present exacerbated blood pressure responses to exercise, but little is known regarding the underlying mechanisms involved.  This study assessed autonomic and haemodynamic responses to exercise and to the isolated activation of muscle metaboreflex in post-menopausal women with RA.  Participants with RA showed augmented pressor and sympathetic responses to exercise and to the activation of muscle metaboreflex. These responses were associated with multiple pro- and anti-inflammatory cytokines and with pain.  The results of the present study support the suggestion that an abnormal reflex control of circulation is an important mechanism underlying the exacerbated cardiovascular response to exercise and increased cardiovascular risk in RA. ABSTRACT: Studies have reported abnormal cardiovascular responses to exercise in rheumatoid arthritis (RA) patients, but little is known regarding the underlying mechanisms involved. This study assessed haemodynamic and sympathetic responses to exercise and to the isolated activation of muscle metaboreflex in women diagnosed with RA. Thirty-three post-menopausal women diagnosed with RA and 10 matched controls (CON) participated in this study. Mean arterial pressure (MAP), heart rate (HR) and muscle sympathetic nerve activity (MSNA frequency and incidence) were measured during a protocol of isometric knee extension exercise (3 min, 30% of maximal voluntary contraction), followed by post-exercise ischaemia (PEI). Participants with RA showed greater increases in MAP and MSNA during exercise and PEI than CON (ΔMAP(exercise)  = 16 ± 11 vs. 9 ± 6 mmHg, P = 0.03; ΔMAP(PEI)  = 15 ± 10 vs. 5 ± 5 mmHg, P = 0.001; ΔMSNA(exercise)  = 17 ± 14 vs. 7 ± 9 bursts min(-1) , P = 0.04; ΔMSNA(PEI)  = 14 ± 10 vs. 6 ± 4 bursts min(-1) , P = 0.04). Autonomic responses to exercise showed significant (P < 0.05) association with pro- (i.e. IFN-γ, IL-8, MCP-1 and TNFα) and anti-inflammatory (i.e. IL-1ra and IL-10) cytokines and with pain. In conclusion, post-menopausal women with RA showed augmented pressor and sympathetic responses to exercise and to the activation of muscle metaboreflex. These findings provide mechanistic insights that may explain the abnormal cardiovascular responses to exercise in RA.
32881056 Long non-coding RNA XIST binding to let-7c-5p contributes to rheumatoid arthritis through 2020 Nov BACKGROUND: Rheumatoid arthritis (RA), a chronic autoimmune disease, affects around 1% population worldwide, with the life quality of patients severely reduced. In this study, it is intended to explore the role of long non-coding RNA X-inactive specific transcript (lncRNA XIST) in RA and the underlying mechanisms associated with let-7c-5p and signal transducer and activator of transcription 3 (STAT3). METHODS: LncRNA XIST, let-7c-5p, and STAT3 expressions were determined in RA and normal cartilage tissues, and their relationship was analyzed in osteoblasts. The regulatory effects of lncRNA XIST in RA were investigated when XIST expression was upregulated or downregulated in osteoblasts. TNF-α, IL-2, IL-6, alkaline phosphatase (ALP), osteocalcin, TGF-β1, and IGF1 were measured in vivo in RA rats. RESULTS: LncRNA XIST and STAT3 were expressed at high levels and let-7c-5p expressed at a low level in RA cartilage tissues. LncRNA XIST silencing or let-7c-5p enhancement led to decreased levels of TNF-α, IL-2, and IL-6, suggestive of suppressed inflammatory response, and increased levels of ALP, osteocalcin, TGF-β1, and IGF-1 as well as reduced damage in cartilage tissues. CONCLUSION: LncRNA XIST downregulation could promote proliferation and differentiation of osteoblasts in RA, serving as a future therapeutic target for RA.
32016224 Improving the anti-inflammatory efficacy of dexamethasone in the treatment of rheumatoid a 2020 Mar 4 Rheumatoid arthritis (RA) is an autoimmune disease that causes chronic inflammation of the joints of the body. Although liposomes are a promising drug delivery vehicle, there is still a challenge of using conventional liposomes for the treatment of RA due to their short circulation time and physicochemical instability in blood vessels. Here, we report the formation of polymerized stealth liposomes composed of 1,2-bis(10,12-tricosadiynoyl)-sn-glycero-3-phosphocholine (DC8,9PC) and 1,2-distearoyl-sn-glycero-3-phospho-ethanolamine-poly(ethyleneglycol) (DSPE-PEG2000) with a thin-film hydration method, in which DC8,9PC molecules are cross-linked in the bilayer of the liposomes by UV irradiation and the PEG chains present at the surface of the liposomes provide a stealth layer. We demonstrate that the polymerized stealth liposomes are stable and show long circulation time in blood vessels. They can be internalized by cells without significant toxicity. After being injected into arthritic rats, the polymerized stealth liposomes with loaded dexamethasone (Dex) show long blood circulation time and accumulate preferentially in inflamed joints, consequently suppressing the level of proinflammatory cytokines (TNF-α and IL-1β) in joint tissues, reducing the swelling of inflamed joints and alleviating the progression of RA. We believe that polymerized stealth liposomes can be used as a promising drug delivery vehicle for various therapeutic applications.
33360228 Systemic sclerosis overlap and non-overlap syndromes share clinical characteristics but di 2021 Feb OBJECTIVES: To screen for concomitant autoimmune disease in patients with systemic sclerosis (overlap SSc) and to describe their clinical characteristics and prognosis. METHODS: This was a two-center retrospective observational study. Patients diagnosed with SSc according to the 2013 ACR-EULAR scleroderma classification criteria were screened for concomitant rheumatoid arthritis (RA), Sjögren syndrome (SgS) and systemic lupus erythematosus (SLE). Patient characteristics were retrieved from the medical records and were compared to those of a non-overlap SSc cohort. RESULTS: Among the 534 SSc patients studied, thirty-four (6.4%) were identified as having overlap SSc. There were 21 (3.9%) patients with RA, 14 (2.6%) with SgS and 4 (0.7%) with SLE (5 patients had 2 AISD) . The disease phenotype of overlap SSc was similar to that of non-overlap SSc in terms of cutaneous phenotype, prevalence of pulmonary arterial hypertension, interstitial lung disease, digital ulcers and mortality. Using a multivariate Cox model, age (HR = 1.04, 95% CI [1.02-1.07]), the modified Rodnan skin score (HR = 1.08 per point, 95% CI [1.05-1.11]), and the presence of concomitant SgS (HR = 3.79, 95% CI [1.38-10.40]) were significantly associated with mortality. Overlap SSc were more likely to receive corticosteroids (85.3% vs. 45%, p < 0.001), immunosuppressive drugs (82.4% vs. 49.2%, p < 0.001) and biologics (52.9% vs. 3.8%, p < ZZ0.001). CONCLUSIONS: While overlap and non-overlap SSc shared common characteristics, patients with SgS/SSc had a higher risk of mortality, and those with RA/SSc received more corticosteroids, methotrexate and biologics. Screening for an associated AISD should be promoted since their co-occurrence with SSc may affect prognosis and treatments.
32562070 A complex COVID-19 case with rheumatoid arthritis treated with tocilizumab. 2020 Sep Recurrences of COVID-19 were observed in a patient with long-term usage of hydroxychloroquine, leflunomide, and glucocorticoids due to her 30-year history of rheumatoid arthritis (RA). Tocilizumab was applied and intended to target both COVID-19 and RA. However, disease of this patient aggravated after usage of tocilizumab. After the discussion of a multiple disciplinary team (MDT) including rheumatologists, antimicrobial treatments were applied to target the potential opportunistic infections (Pneumocystis jirovecii and Aspergillus fumigatus), which were authenticated several days later via high throughput sequencing. As an important cytokine in immune responses, IL-6 can be a double-edged sword: interference in the IL-6-IL-6 receptor signaling may save patients from cytokine release storm (CRS), but can also weaken the anti-infectious immunity, particularly in rheumatic patients, who may have received a long-term treatment with immunosuppressive/modulatory agents. Thus, we suggest careful considerations before and close monitoring in the administration of tocilizumab in rheumatic patients with COVID-19. Besides tocilizumab, several disease-modifying antirheumatic drugs (DMARDs) can also be applied in the treatment of COVID-19. Therefore, we also reviewed and discussed the application of these DMARDs in COVID-19 condition.
31959364 [Mucopolysaccharidosis: A review]. 2020 Mar Mucopolysaccharidosis are lysosomal storage diseases, secondary to the accumulation of mucopolysaccharides. Type 1 mucopolysaccharidosis is the most common form and affects between 0.69 and 1.66 newborns per 100,000. The severity of mucopolysaccharidosis is variable with lethal forms in utero and attenuated forms diagnosed in adults. The most common symptoms are short stature, facial dysmorphism, chronic articular pains that can mimic chronic inflammatory rheumatism, axial and peripheral bone involvement, hepatosplenomegaly and an early carpal tunnel. Depending on the type of mucopolysaccharidosis, corneal, cerebral or cardiac involvements are possible. Screening is based on the analysis of urinary glycosaminoglycans. The deficient enzyme assay and the gene analysis confirm the diagnosis. Mucopolysaccharidosis recognition is important for patient management and family screening. In addition, specific enzyme replacement therapy exists for certain types of mucopolysaccharidosis. Role of clinician is important to evoke and diagnose mucopolysaccharidosis.
32676896 Renal pathological analysis using galactose-deficient IgA1-specific monoclonal antibody is 2021 Feb In several cases with IgA nephropathy (IgAN), differential diagnosis is difficult due to the complication with other systemic diseases which can induce secondary IgAN. Recently, we demonstrated that immunostaining with galactose-deficient IgA1-specific monoclonal antibody (KM55 mAb) specifically showed positive in primary IgAN cases. Here, we report four cases which we could make definitive diagnosis by immunohistological analysis using KM55 mAb. The underlying systemic diseases are rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), hepatitis C (HCV) and Crohn's disease (CD). Renal pathological findings in the four cases revealed mesangial proliferative glomerulonephritis with IgA and C3 deposits. Immunostaining with KM55 mAb was positive for three cases complicated with RA, SLE and CD, respectively. Thus, these three cases were diagnosed as primary IgAN and treated with tonsillectomy and steroid pulse therapy. These three cases finally achieved clinical remission. On the other hand, the case with HCV showed negative for KM55. Finally, we diagnosed as HCV-related nephropathy and successfully treated by antiviral agents. These cases suggested KM55 mAb is a strong tool to differentiate primary IgAN from secondary IgAN.
31948469 Composite Epstein-Barr virus-positive mucosa-associated lymphoid tissue lymphoma and Epste 2020 Jan 17 BACKGROUND: Epstein-Barr virus is associated with many human hematopoietic neoplasms; however, Epstein-Barr virus-positive mucosa-associated lymphoid tissue lymphoma is extremely rare. In routine clinical practice, detection of mucosa-associated lymphoid tissue lymphoma and diffuse large B-cell lymphoma in a tissue sample presumes a clonal relation between these neoplasms and that diffuse large B-cell lymphoma developed by transformation of the mucosa-associated lymphoid tissue lymphoma. However, evidence to support this presumption is sparse and controversial. Assessment of the clonal relationship of the lymphoid components of a composite lymphoma is important for understanding its pathogenesis and correct diagnosis. CASE PRESENTATION: We present an unusual case of composite lymphoma (Epstein-Barr virus-positive mucosa-associated lymphoid tissue lymphoma/Epstein-Barr virus-negative diffuse large B-cell lymphoma) in the parotid salivary gland of a 62-year-old Caucasian woman with Sjögren's syndrome and rheumatoid arthritis. Simultaneous occurrence of mucosa-associated lymphoid tissue lymphoma and diffuse large B-cell lymphoma in the parotid salivary gland led us to initially assume a clonal relationship between diffuse large B-cell lymphoma and mucosa-associated lymphoid tissue lymphoma. Epstein-Barr virus was detected by in situ hybridization and polymerase chain reaction in the mucosa-associated lymphoid tissue lymphoma, but not in diffuse large B-cell lymphoma, suggesting that these lymphomas were not clonally related. Fragment analysis of frame region 3 polymerase chain reaction products from microdissected mucosa-associated lymphoid tissue lymphoma and diffuse large B-cell lymphoma components revealed different clonal pattern rearrangements of the immunoglobulin heavy chain gene. CONCLUSIONS: Our patient's case highlights the importance of assessing the clonal relationships of the lymphoid components of a composite lymphoma and Epstein-Barr virus screening in mucosa-associated lymphoid tissue lymphoma in patients with autoimmune disease.
32322981 Adalimumab-induced myasthenia gravis: case-based review. 2020 Nov Myasthenia gravis (MG) is an autoimmune disease characterised by the presence of acetylcholine receptor antibodies and by blocking the transmission of the signal in the neuromuscular junction causing muscle weakness. It can be associated with several autoimmune diseases and certain drugs, between them Etanercept an anti-tumour necrosis factor (TNF) agent. A 42-year-old woman with rheumatoid arthritis (RA) refractory to methotrexate, was treated with adalimumab (ADA), a human monoclonal antibody against the TNF, in a dosage scheme of 40 mg every 14 days subcutaneously. The patient responded well to ADA therapy with sustained remission for 18 months when she developed blurred vision and eyelid ptosis of the left eye. The diagnosis of ocular MG was made. ADA has been discontinued and she started a treatment with pyridostigmine showing an excellent response and complete remission within a 2-month period. This is the first report making an association of ADA and ocular MG. Thus, rheumatologists dealing with patients treated with TNF inhibitors should be aware of the possible development of neurological adverse events, among them MG.
33626115 The presence of effusions between the volar plate of the proximal interphalangeal joint an 2021 May 20 AIM: In clinical practice, an anechoic signal was often exhibited between the volar plate (VP) of the proximal interphalan-geal joint (PIPJ) (PIPJVP) and the flexor digitorum tendon (FDT) on ultrasound, which suggests the presence of effusions (PIPJVP-FDT effusions). The purpose of this study was to investigate the prevalence of PIPJVP-FDT effusions and to explore the possible mechanism preliminarily. MATERIAL AND METHODS: A single-center, cross sectional study in hand osteoarthritis (HOA) patients, rheumatoid arthritis (RA) patients and healthy controls was conducted. Ultrasound examination was per-formed by the same real-time scanner with 18-MHz linear array transducer. Bilateral interphalangeal joints (IPJs) of the thumb, 2ed, 3rd, 4th and 5th PIPJs were examined. The PIPJVP-FDT effusions was defined as an anechoic signal between the PIPJVP and FDT in two perpendicular ultrasound planes. RESULTS: In total, 200 patients with HOA, 78 patients with RA and 101 healthy controls were eligible for the study. 37.6% of healthy controls and 35.0% of HOA patients showed PIPJVP-FDT effusions, while only 11.5% of RA patients had PIPJVP-FDT effusions (p<0.001). The 2ed, 3rdand 4th PIPJs showed more PIPJVP-FDT effusions, while the IPJs of the thumbs and 5th PIPJs showed less PIPJVP-FDT effusions (p<0.05). Furthermore, the prevalence of PIPJVP-FDT effusions in different age groups were similar in HOA patients and healthy controls. CONCLUSION: To the best of our knowledge, this paper is the first to demonstrate that the presence of PIPJVP-FDT effusions is a very common phenomenon in HOA patients and healthy individuals, and may be unrelated to inflammation, degeneration and age.
31907973 Expression patterns of CD28 and CTLA-4 in early, chronic, and untreated rheumatoid arthrit 2020 May BACKGROUND: T-cell activation pathways have been proposed as trigger mechanisms in the pathogenesis of rheumatoid arthritis (RA). CD28 and CTLA-4 play major roles in regulating the stimulatory and inhibitory co-signals in T cells. OBJECTIVE: To analyze the association between soluble and surface expression of CD28 and CTLA-4 with the clinical parameters of RA patients. METHODS: A total of 35 RA patients classified as early RA (n = 14), chronic RA (n = 14), and untreated RA (n = 7), as well as 7 age- and sex-matched control subjects (CS) were included. Surface expression of CD28 and CTLA-4 on T cells was evaluated by flow cytometry. Soluble levels of CD28 (sCD28), CTLA-4 (sCTLA-4), and anti-CCP antibodies were measured by ELISA. RESULTS: A significant lower percentage of CD8 + T cells positive to CD28 (CS = 64.9% vs RA = 42.7%, P = .04), and diminished surface expression of CD28 (CS: MFI = 122.9 vs RA: MFI = 33.1, P = .006), were found in chronic RA patients compared to CS. Higher sCD28 were observed in early RA patients compared with chronic RA patients (P < .05). sCTLA-4 was found increased in untreated RA patients compared to early RA patients (P < .05). sCD28 concentration correlated with anti-CCP levels (rho = -0.12; P = .032). The soluble and surface expressions of CTLA-4 were not associated with RA clinical parameters. CONCLUSIONS: In RA, the percentage of CD8 + CD28+ T cells decreases and expresses fewer membrane CD28 than CS. sCD28 levels are lower in chronic RA and are associated negatively with anti-CCP levels. sCTLA 4 levels are lower in early RA patients than in untreated RA patients.
31648940 Association between HTLV-1 infection and adverse health outcomes: a systematic review and 2020 Jan BACKGROUND: Human T-cell lymphotropic virus type 1 (HTLV-1) is a human retrovirus that causes a lifelong infection. Several diseases, including an aggressive form of leukaemia, have been designated as associated with HTLV-1, whereby having HTLV-1 is a necessary condition for diagnosis. Beyond these diseases, there is uncertainty about other health effects of HTLV-1. We aimed to synthesise evidence from epidemiological studies on associations between health outcomes and HTLV-1. METHODS: For this systematic review and meta-analysis, we searched Embase, MEDLINE, MEDLINE In-Process, and Global Health for publications from their inception to July, 2018. We included cohort, case-control, and controlled cross-sectional studies that compared mortality or morbidity between people with and without HTLV-1. We excluded studies of psychiatric conditions, of symptoms or clinical findings only, of people who had undergone blood transfusion or organ transplant, and of population groups defined by a behavioural characteristic putting them at increased risk of co-infection with another virus. We extracted the risk estimates (relative risks [RRs] or odds ratios [ORs]) that reflected the greatest degree of control for potential confounders. We did a random-effects meta-analysis for groups of effect estimates where case ascertainment methods, age groups, and confounders were similar, presenting pooled estimates with 95% CIs and prediction intervals. FINDINGS: Of the 3318 identified studies, 39 met the inclusion criteria, examining 42 clinical conditions between them. The adjusted risk of death due to any cause was higher in people with HTLV-1 when compared with HTLV-1-negative counterparts (RR 1·57, 95% CI 1·37-1·80). From meta-analysis, HTLV-1 was associated with increased odds of seborrheic dermatitis (OR 3·95, 95% CI 1·99-7·81), Sjogren's syndrome (3·25, 1·85-5·70), and, inversely, with lower relative risk of gastric cancer (RR 0·45, 0·28-0·71). There were a further 14 diseases with significant associations or substantially elevated risk with HTLV-1 from single studies (eczema [children]; bronchiectasis, bronchitis and bronchiolitis [analysed together]; asthma [males]; fibromyalgia; rheumatoid arthritis; arthritis; tuberculosis; kidney and bladder infections; dermatophytosis; community acquired pneumonia; strongyloides hyperinfection syndrome; liver cancer; lymphoma other than adult T-cell leukaemia-lymphoma; and cervical cancer). INTERPRETATION: There is a broad range of diseases studied in association with HTLV-1. However, the elevated risk for death among people with HTLV-1 is not explained by available studies of morbidity. Many of the diseases shown to be associated with HTLV-1 are not fatal, and those that are (eg, leukaemia) occur too rarely to account for the observed mortality effect. There are substantial research gaps in relation to HTLV-1 and cardiovascular, cerebrovascular, and metabolic disease. The burden of disease associated with the virus might be broader than generally recognised. FUNDING: Commonwealth Department of Health, Australia.
31907007 Therapeutic drug monitoring of infliximab compared to standard clinical treatment with inf 2020 Jan 6 BACKGROUND: Infliximab (INX) and other tumour necrosis factor inhibitors (TNFi) have revolutionised the treatment of several immune mediated inflammatory diseases. Still, many patients do not respond sufficiently to therapy or lose efficacy over time. The large interindividual variation in serum drug concentrations on standard doses and the development of anti-drug antibodies are thought to be major reasons for treatment failures. Therapeutic drug monitoring (TDM), an individualised treatment strategy based on systematic assessments of serum drug concentrations, has been proposed as a clinical tool to optimise efficacy of INX treatment. TDM seems reasonable both from a clinical and an economical point of view, but the effectiveness of this treatment strategy has not yet been demonstrated in randomised clinical trials. The NORwegian DRUg Monitoring study (NOR-DRUM) aims to assess the effectiveness of TDM, both with regard to the achievement of remission in patients starting INX treatment (part A) as well as to maintain disease control in patients on INX treatment (part B). METHODS: The NOR-DRUM study is a randomised, open, controlled, parallel-group, comparative, multi-centre, national, superiority, phase IV study with two separate parts, NOR-DRUM A and NOR-DRUM B. Patients with rheumatoid arthritis, psoriatic arthritis, spondyloarthritis, ulcerative colitis, Crohn's disease and psoriasis are included. In both study parts participants are randomised 1:1 to either TDM of infliximab (intervention group) or to standard treatment with infliximab without knowledge of drug levels or ADAb status (control group). NOR-DRUM A will include 400 patients starting INX therapy. The primary outcome is remission at 30 weeks. In NOR-DRUM B, 450 patients on maintenance treatment with INX will be included. The primary endpoint is occurrence of disease worsening during the 52-week study period. DISCUSSION: As the first trial to assess the effectiveness, safety and cost-effectiveness of TDM in patients receiving TNFi for a range of immune mediated inflammatory diseases, we hope that the NOR-DRUM study will contribute to the advancement of evidence based personalised treatment with biological medicines. TRIAL REGISTRATION: Clinicaltrials.gov, NCT03074656. Registered on 090317.