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ID PMID Title PublicationDate abstract
29531790 Improving the peer review skills of young rheumatologists and researchers in rheumatology: 2018 Although peer review plays a central role in the maintenance of high standards in scientific research, training of reviewing skills is not included in the common education programmes. The Emerging EULAR (European League Against Rheumatism) Network (EMEUNET) developed a programme to address this unmet need. The EMEUNET Peer Review Mentoring Program for Rheumatology Journals promotes a systematic training of reviewing skills by engaging mentees in a 'real world' peer review experience supervised by experienced mentors with support from rheumatology journals. This viewpoint provides an overview of this initiative and its outcomes, and discusses its potential limitations. Over 4 years, 18 mentors and 86 mentees have participated. Among the 33 participants who have completed the programme, 13 (39.3%) have become independent reviewers for Annals of the Rheumatic Diseases after the training. This programme has been recently evaluated by a survey and qualitative interviews, revealing a high interest in this initiative. The main strengths (involvement of a top journal and learning opportunities) and weaknesses of the programme (limited number of places and insufficient dissemination) were identified. Overall, this programme represents an innovative and successful approach to peer review training. Continuous evaluation and improvement are key to its functioning. The EMEUNET Peer Review Mentoring Program may be used as a reference for peer review training in areas outside rheumatology.
28967053 Multifaceted aseptic protocol decreases surgical site infections following hip arthroplast 2018 Mar INTRODUCTION: We investigate the effectiveness of a comprehensive aseptic protocol in reducing surgical site infection (SSI) after hip arthroplasty in a single medical centre with a high prevalence of methicillin-resistant Staphylococcus aureus (MRSA). METHODS: A prospectively collected database of all patients undergoing hip arthroplasty in a single centre between 2005 and 2011 was reviewed for SSI using Centers for Disease Control (CDC) criteria and AAOS guidelines. All patients were administered an aseptic protocol consisting of: preoperative 2% mupirocin nasal ointment and 0.4% chlorhexidine surgical-site wipes; modified instrument care; perioperative prophylactic vancomycin and cefazolin; and surgical-site skin preparation with chlorhexidine, alcohol and iodophor. We compare our protocol hip arthroplasty SSI rate to our institutional historical control and to contemporary literature. RESULTS: Among 774 patients, 69% were ASA>2, 45% had BMI≥30 and 10.3% had rheumatoid arthritis. We found an overall 0.39% infection rate; significantly lower than our institutional historical control (0.39% vs. 2.60%, p<0.001, OR 0.15, NNT 200) and significantly lower than 6 published reports (p<0.001-0.022, OR 0.16-0.22). Compared to these cohorts, significantly more of our patients were ASA>2, had BMI≥30 or had rheumatoid arthritis. Patients with 3 or more identifiable risk factors were at an increased risk of SSI compared to those with 2 or fewer risk factors. CONCLUSIONS: Our aseptic protocol decreases SSI in a high-risk population undergoing hip arthroplasty in a medical centre and community with a high prevalence of MRSA.
29745886 Primary myelofibrosis but not autoimmune myelofibrosis accompanied by Sjögren's syndrome 2018 May Bone marrow fibrosis has been found to be associated with autoimmune disorders, and autoimmune myelofibrosis (AIMF) has been defined. Primary myelofibrosis (PMF), a clonal myeloproliferative disorder, should be distinguished from AIMF which has a good response to steroids, as the former has a high mortality and very bad response to conventional treatment. This case report describes a rare case of PMF accompanied with Sjögren's syndrome (SJS) and primary biliary cirrhosis (PBC), in a patient with trisomy 8 mosaic. Careful clinical assessment, gene mutation screening, and bone marrow evaluation can lead to an accurate diagnosis.
29753087 Effects of salazosulfapyridine on the profile of cell surface proteins, revealed by biotin 2019 Jan OBJECTIVE: We investigated effects of salazosulfapyridine (SASP) on the protein profile of cell surface (CS)-proteins of SW982, a human synovial sarcoma cell line, using biotinylation of CS-proteins and 2-dimensional fluorescence difference gel electrophoresis (2D-DIGE). METHODS: SW982 cells were treated with SASP and its metabolites, sulfapyridine (SP) and 5-aminosalicylic acid (5ASA). Then the cells were treated with a membrane-impermeable biotinylating reagent. Biotinylated CS-proteins were isolated using NeutrAvidin-bound beads. CS-proteins affected by the drugs were detected by 2D-DIGE and subjected to mass spectrometry. RESULTS: By the 2D-DIGE analysis, in total 576 spots were detected, 29 out of which showed more than ±1.5-fold different intensity in the SASP-, SP-, and 5ASA-treated cells, compared to non-treated cells (p < 0.05). Interestingly, 7 out of the 29 spots changed their intensity only by SASP and 17 spots changed their intensity only by SP. We identified 9 protein from 15 out of the 29 spots, most of which were evidenced to exist on the cell surface by flow cytometry. CONCLUSION: We found novel effects of SASP and its metabolites on SW982 cells by the combination of biotinylation of cell surface proteins and 2D-DIGE analysis. These data would help understanding of anti-rheumatic actions of SASP. Furthermore, the combination would be a useful method for the analysis of CS-proteins in various conditions.
29175662 Comorbidities in relation to fatality of first myocardial infarction. 2018 Jan INTRODUCTION: Present knowledge concerning potential associations between comorbidities and the fatality of a first myocardial infarction (MI) is limited. AIM: To identify comorbidities in 45-70-year-old individuals who suffered a first MI and died within 7 days in Stockholm County from 1992-1994. In addition, to assess how each of the comorbidities identified, as well as the number of hospitalizations during the 10-year period prior to the MI, was associated with MI fatality. METHODS: The data collected on our inception cohort of 1984 first MI, of which 524 were fatal within 7 days, were primarily self-reported, proxy-reported by questionnaire and/or extracted from comprehensive national registers. Comorbidities among fatal cases with a prevalence >2% were identified. Risk ratios (with 95% confidence intervals) for the association of MI fatality with number of prior hospitalizations and specific comorbidities were calculated using binomial regression with log link. A structured review of autopsy reports on fatal cases was performed in order to identify additional indicators of comorbidities. RESULTS: After adjusting for sex, age and disposable income, the number of previous hospitalizations was associated with 7-day MI fatality. Of the comorbidities identified as prevalent in fatal cases, the following were associated with 7-day fatality in crude analysis: epilepsy, heart failure, stroke, alcoholism, cancer, renal diseases, asthma, psychiatric diseases, diabetes, and rheumatoid arthritis. Indicators of comorbidities identified from autopsy data included a silent MI, severe atherosclerosis of the abdominal aorta, and hepatic steatosis. Adjustments for sex and age (although not possible for epilepsy and alcoholism), did not substantially alter results. CONCLUSIONS: Our current findings indicate that in connection with a first MI, particular attention should be paid to those with repeated prior hospitalizations and/or epilepsy, heart failure, stroke, alcoholism, cancer, renal diseases, asthma, psychiatric diseases, diabetes and rheumatoid arthritis.
30464411 Comparative pharmacokinetics of an adalimumab biosimilar SB5 administered via autoinjector 2018 PURPOSE: The objective of this study was to demonstrate comparable pharmacokinetic (PK), safety, and tolerability parameters of the adalimumab biosimilar SB5 administered via autoinjector (AI) pen or prefilled syringe (PFS). PATIENTS AND METHODS: In this phase 1, randomized, open-label, single-dose, parallel-group study, healthy subjects aged 18-55 years were randomized 1:1 to a single dose of 40 mg SB5 delivered subcutaneously via AI or PFS. PK parameters, safety, and tolerability were assessed for 57 days post-dose. The primary endpoint was area under the curve (AUC) of the concentration-time curve from zero to infinity (AUC(inf)) and from zero to last quantifiable concentration (AUC(last)) and maximum serum concentration (C(max)). Equivalence was determined using predefined margins of 0.80-1.25 for the 90% CI for the ratio of SB5 AI to SB5 PFS. RESULTS: Ninety-five subjects were randomized to each group. Mean serum concentration-time profiles were superimposable between groups. Mean values for AUC(inf), AUC(last), and C(max) were similar between the SB5 AI and SB5 PFS groups. For the primary endpoints, the 90% CIs for the ratio of geometric least squares means for SB5 AI to SB5 PFS ranged between 0.9503 and 1.2240, which were all within the equivalence margin of 0.80-1.25. Incidence of treatment-emergent adverse events and injection site reactions was similar between groups. CONCLUSION: In healthy subjects receiving a single dose of SB5 via AI or PFS, PK parameters and corresponding 90% CIs were within the predefined margins, showing bioequivalence between the two delivery methods. Safety and tolerability assessments were also similar between groups. CLINICALTRIALSGOV IDENTIFIER: NCT02326233. EUDRACT NUMBER: 2014-005178-12.
30288187 Losartan, but not Enalapril and Valsartan, Inhibits the Expression of IFN-γ, IL-6, IL-17F 2018 BACKGROUND: Rheumatoid Arthritis (RA) is a chronic and inflammatory disease that affects about 1% of the world's population. Almost 70% of RA patients have a cardiovascular disease such as Systemic Arterial Hypertension (SAH). Inflammatory cytokines are clearly involved in the pathogenesis of RA and correlated with SAH. OBJECTIVE: It is necessary to understand whether the antihypertensive drugs have a dual effect as immunomodulators and which one is the best choice for RA SAH patients. METHODS: Peripheral Blood Mononuclear Cells (PBMCs) from 16 RA patients were purified and stimulated or not stimulated with anti-CD3 and anti-CD28 mAB and were treated with Enalapril, Losartan and Valsartan at 100μM. Patients were evaluated for clinical and laboratory variables including measures of disease activity by Clinical Disease Activity Index (CDAI) and Disease Activity Score (DAS28). Cytokines were quantified by ELISA sandwich. RESULTS: Losartan was able to reduce levels of IFN-γ (p = 0.0181), IL-6 (p = 0.0056), IL-17F (0.0046) and IL-22 (p = 0.0234) in RA patients. In addition, patients in remission and mild score (DAS28<3.2 and CDAI<10) had a better response to treatment. On the other hand, patients in moderate and severe activity had poor response to Losartan in cytokine inhibition. CONCLUSION: PBMCs from RA patients are responsive in inhibiting proinflammatory cytokines using Losartan better than Enalapril and Valsartan and it could be a better antihypertensive choice for patients with RA and systemic arterial hypertension treatment.
30268770 The role of flavonoids in autoimmune diseases: Therapeutic updates. 2019 Feb Flavonoids are natural polyphenolic compounds which are included in a panoply of drugs and used to treat and/or manage human ailments such as metabolic, cardiovascular, neurological disorders and cancer. Thus, the purpose of this review is to emphasize the importance of flavonoids for the treatment of autoimmune diseases and put into the limelight of the scientific community several health-promoting effects of flavonoids which could be beneficial for the development of novel drugs from natural products. Despite available reviews on flavonoids targeting various disease conditions, a comprehensive review of flavonoids for autoimmune diseases is still lacking. To the best of our knowledge, this is the first attempt to review the potential of flavonoids for autoimmune diseases. The structure-activity relationship of flavonoids in this review revealed that the rearrangement and introduction of other functional groups into the basic skeleton of flavonoids might lead to the development of new drugs which will be helpful in relieving the painful symptoms of various autoimmune diseases.
30185359 A study on characteristics of rheumatoid arthritis patients achieving remission in depress 2018 Jul OBJECTIVE: To investigate the relationship between baseline factors and depression remission after a 6-month biological disease-modifying antirheumatic drugs (bDMARDs) treatment in rheumatoid arthritis (RA) patients. METHODS: The study was conducted in 152 RA patients treated with bDMARDs. The following patient's characteristics were studied: gender, age, disease duration, baseline prednisolone dosage, and serum matrix metalloproteinase3 (MMP3) levels. For assessment, we used the simple disease activity index (SDAI) for RA disease activity, Health Assessment Questionnaire Disability Index (HAQ-DI) for activities of daily living (ADL), Short Form-36 for nonspecific health-related quality of life (QOL), and Hamilton Depression Rating Scale (HAM-D) scores for the depression status. Depressed remission was clarified using HAM-D ≤7 after 6 months of treatment. The patients were divided into two groups according to the presence or absence of depression, and a retrospective study was conducted. RESULTS: Based on binominal logistic analyses, RA patients' with depression remission (n=124) compared to those without depression remission (n=28) had a younger age (p=0.0045, odd ratio: 0.94, 95% confidence interval [CI]:0.8-0.98), female sex (p=0.021, odd ratio:0.21, 95% CI:0.054-0.79), and lower HAM-D scores (p=0.0073, odd ratio:0.85, 95% CI:0.76-0.96) CONCLUSION: It was proposed that RA patients who are females, younger in age, and have lower depressed scores at baseline can achieve a depression remission status with the bDMARDs treatment.
28941123 Renal involvement in primary Sjögren's syndrome: A retrospective study of 103 biopsy-prov 2018 Jan AIM: To retrospectively investigate the features of renal involvements in patients with primary Sjögren's syndrome (pSS) with biopsy results. METHODS: A total of 2096 pSS inpatients at Peking Union Medical College Hospital in China from 2005 to 2015 were identified. Patients with biopsy-proven renal involvement (SS-renal) and matched controls (SS-only) were recruited. The clinical and pathologic features as well as treatments and outcomes were systematically analyzed. RESULTS: One hundred and three pSS nephritis (inpatients had biopsy-proven renal involvement. Tubulointerstitial 53, 51.5%) was the prominent pathologic pattern with glomerulonephritis (GN) present in 50 (48.5%) of the renal lesions. The patterns of GN lesions included membranous nephropathy (37, 35.9%), mesangial proliferative glomerulonephritis (six, 5.8%) or immunoglobulin A nephropathy (three, 2.9%), minimal change disease (four, 3.9%) and focal segmental glomerulosclerosis (three, 2.9%). Compared to SS-only patients, SS-renal patients had fewer dry eyes and positive objective xerostomia (P < 0.05). They presented with a significantly lower incidence of interstitial lung disease (ILD), leukocytopenia and elevated immunoglobulin G levels (P < 0.05). They received a larger initial dosage of corticosteroid and had a higher mortality rate (P < 0.05). CONCLUSION: This Chinese SS-renal population with biopsy results has diverse pathologic patterns and distinct clinical features. They are characterized with prominent renal-associated and mild SS-associated features. They received more vigorous treatment but had poorer prognosis.
30532571 Budget impact analysis of sarilumab for the treatment of rheumatoid arthritis in patients 2018 OBJECTIVE: To estimate the 5-year budget impact (BI) on a US health plan of introducing sarilumab - a human immunoglobulin G1 anti-IL-6 receptor α monoclonal antibody - as combination treatment with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or monotherapy in patients with moderate-to-severe rheumatoid arthritis (RA). METHODS: BI analysis was conducted from a commercial payer perspective. Treatment-eligible populations included adult patients with moderate-to-severe RA and inadequate response (IR) to csDMARDs or tumor necrosis factor (TNF)-α inhibitors-IR. All licensed biologic treatments recommended by the American College of Rheumatology guidelines were included. RESULTS: For a hypothetical plan of one million members, 409 csDMARD-IR and 345 TNF-IR patients were annually eligible for combination therapy and 226 csDMARD and TNF-IR patients for monotherapy with sarilumab. Based on 2018 US direct treatment costs, the introduction of sarilumab was estimated to save $526,424, $322,637 and $264,306 over 5 years for csDMARD-IR combination therapy patients, TNF-IR combination therapy patients, and csDMARD-IR/TNF-IR monotherapy patients, respectively. As sarilumab absorbed a greater market share over the horizon, annual savings increased from years 1 to 5, $28,610 (-0.14%) to $194,646 (-0.83%) in csDMARD-IR, $16,986 (-0.11%) to $120,893 (-0.67%) in TNF-IR, and $14,256 (-0.13%) to $98,040 (-0.79%) in monotherapy. One-way sensitivity analyses revealed that the model was most sensitive to variations in sarilumab adherence. CONCLUSION: Total cost savings of introducing sarilumab to a health-care plan accrued from years 1 to 5, attributable to the lower treatment cost, stable dosing paradigm, and price parity for the two available doses (150 and 200 mg every 2 weeks) compared with alternative biologic DMARDs that have substantial variability in dose titration/schedules.
29909689 Intra-articular Injections in the Treatment of Symptoms from Ankle Arthritis: A Systematic 2018 Oct BACKGROUND: Intra-articular (IA) injections are commonly used to treat knee arthritis pain; however, whether their efficacy generalizes to ankle arthritis remains debatable. We aimed to evaluate the evidence for IA therapies in the management of this patient population. METHODS: We performed a literature search for observational and randomized controlled trials (RCTs). Treatments included corticosteroids (CS), hyaluronic acid (HA), platelet-rich plasma (PRP), and mesenchymal stem cells (MSC). We extracted study details, patient demographics, treatment characteristics, efficacy outcomes, and safety. When feasible, data from RCTs were meta-analyzed using a random-effects model and 95% confidence intervals (CIs) were calculated. A P value <.05 was considered statistically significant. RESULTS: We identified 27 studies (1085 patients). Ankle OA, rheumatoid arthritis (RA), and hemophilic arthropathy populations were examined. The majority of studies were observational (20 studies); the only RCTs were those evaluating HA. Case series demonstrated favorable results in terms of symptomatic relief with CS, HA, PRP, and MSC injections; however, the effects of CS may only be short term and the evidence on MSCs was limited to 1 study with 6 ankle OA patients. Pooled results (3 RCTs, 109 patients) suggested significantly improved Ankle Osteoarthritis Scale scores with HA over saline at 6 months, with a mean difference of 12.47 points (95% CI 1.18-23.77, P = .03). CONCLUSION: Evidence from small trials favors HA and PRP injections for the treatment of pain associated with ankle osteoarthritis. However, the relative efficacy of all injectable therapies is far from definitive and warrants further high-quality comparative trials. LEVEL OF EVIDENCE: Level III, systematic review.
29301941 The role of microRNAs in glucocorticoid action. 2018 Feb 9 Glucocorticoids (GCs) are steroids with profound anti-inflammatory and immunomodulatory activities. Synthetic GCs are widely used for managing chronic inflammatory and autoimmune conditions, as immunosuppressants in transplantation, and as anti-tumor agents in certain hematological cancers. However, prolonged GC exposure can cause adverse effects. A detailed understanding of GCs' mechanisms of action may enable harnessing of their desirable actions while minimizing harmful effects. Here, we review the impact on the GC biology of microRNAs, small non-coding RNAs that post-transcriptionally regulate gene expression. Emerging evidence indicates that microRNAs modulate GC production by the adrenal glands and the cells' responses to GCs. Furthermore, GCs influence cell proliferation, survival, and function at least in part by regulating microRNA expression. We propose that the beneficial effects of GCs may be enhanced through combination with reagents targeting specific microRNAs.
29479475 Long-term persistence of TNF-inhibitor treatment in patients with psoriatic arthritis. Dat 2018 BACKGROUND: Long-term effectiveness of tumour necrosis factor alpha inhibitors (TNFi) has mainly been explored in patients with rheumatoid arthritis (RA) and the data available on patients with psoriatic arthritis (PsA) includes limited follow-up. OBJECTIVE: Investigate long-term effectiveness of first TNFi in a PsA population by describing treatment persistence, identify factors associated with 5-year persistence and further investigate comparative long-term effectiveness of subsequent TNFi treatments through persistence to treatment. METHODS: Patients with a rheumatologist diagnosis of PsA receiving their first TNFi registered in the British Society for Rheumatology Biologics Register (BSRBR) (2002-2006) were included. Treatment at different time points was described and factors associated with 5-year treatment persistence were identified by logistic regression. Kaplan-Meier analysis was used to assess factors associated with persistence to first TNFi and subsequent TNFi treatments. RESULTS: At 5 years, 46.7% of patients were still on their initial TNFi treatment. Better 5 -year persistence was associated with male gender, use of etanercept or adalimumab rather than infliximab and absence of baseline comorbidity. Five-year persistence estimates (95% CI) of first, second and third TNFi were 53% (49% to 57%), 60% (43% to 57%) and 48% (36% to 59%), respectively. CONCLUSION: We found good long-term persistence of TNFi in this PsA population both for the first and subsequent TNFi treatments. The relationship between persistence and relevant clinical factors was not strong and demonstrates the difficulties in predicting outcome of TNFi treatment in PsA.
29470778 Guselkumab for the Treatment of Psoriasis. 2018 Apr Psoriasis is a common, chronic, immune-mediated, inflammatory skin disease with systemic involvement and significant impact on patients' quality of life. Several biologic treatments have been developed in recent decades, such as tumor necrosis factor (TNF)-α inhibitors, a non-selective interleukin (IL)-23 inhibitor (ustekinumab, which also inhibits IL-12), and-most recently-IL-17 inhibitors. Guselkumab is a novel biological therapy that selectively targets IL-23 and is the first-in-class selective IL-23 inhibitor approved to treat moderate-to-severe plaque psoriasis. These inhibitors are expected to have some advantages over the highly effective IL-17 inhibitors, as they do not worsen inflammatory bowel disease and are not involved in the development of candida infections. Additionally, selective inhibition of IL-23 may have additional benefits over ustekinumab as the IL-12-dependent cascades remain functional. These benefits include a decrease in IL-17A-producing T cells in the skin and the promotion of an anti-inflammatory effect through production of interferon-γ and IL-10. In terms of efficacy, guselkumab showed promising results in the treatment of psoriasis and psoriatic arthritis, although it did not show significant clinical improvement in rheumatoid arthritis. Studies in other inflammatory diseases and Crohn's disease are expected to begin soon. Overall, guselkumab was well tolerated; the most common adverse event was nasopharyngitis. Head-to-head studies comparing IL-23 inhibitors with agents in different classes, namely IL-17 inhibitors, will be crucial to establish the true role of these agents in psoriasis treatment.
30976734 Pyrolytic carbon humeral head in hemi-shoulder arthroplasty: preliminary results at 2-year 2019 Mar BACKGROUND: In patients with osteoarthritis (OA) and an intact rotator cuff, hemi-shoulder arthroplasty (HSA) can be a viable option as it offers the advantage of keeping the native glenoid intact. However, glenoid erosion has frequently been reported. The aim of this study was to report preliminary clinical results of HSA with a new pyrolytic carbon (pyrocarbon) humeral head. METHODS: This prospective multicenter study included a continuous series of 65 patients who underwent pyrocarbon HSA in 5 centers. RESULTS: At the time of analysis, 1 patient was lost to follow-up, 3 patients underwent revision, and 61 patients were evaluated at a mean follow-up of 25.9 ± 3.3 months. The mean age at index surgery was 57.9 ± 13.3 years. The indications were primary glenohumeral OA in 37 patients, osteonecrosis in 11, secondary OA in 11, and rheumatoid arthritis in 2. The mean Constant score increased from 31.0 ± 15.8 points at baseline to 74.6 ± 17 points at last follow-up. Radiographic analyses showed that 86% of glenoids remained unchanged whereas 14% evolved slightly. CONCLUSIONS: Pyrocarbon HSA grants improvement in pain and function in patients with primary OA or secondary OA after instability but at a lower level in patients with post-traumatic sequelae (secondary OA or osteonecrosis). These preliminary clinical and radiologic results are encouraging, although they need to be confirmed by longer-term follow-up observations.
29667926 Proximal tibia stress fracture with Osteoarthritis of knee - Radiological and functional a 2018 INTRODUCTION: Proximal tibia stress fractures with knee osteoarthritis pose a challenging situation. We evaluated the radiological and functional outcome of one-stage total knee arthroplasty (TKA) and long stem for patients with varied grades of knee arthritis and proximal tibia stress fractures.  Methods: We analysed 20 patients from April 2012 to March 2017 with proximal tibia stress fractures associated with knee osteoarthritis of varied grades. Out of 20 patients, five were acute fresh fractures. The mean age was 64 years (range, 52-78) which includes three men and 17 women. Previous surgery in the same limb, rheumatoid arthritis, valgus deformity were excluded. All patients were treated with posterior stabilised TKA with long stem, of which, four patients had screw augmentation for medial tibial bone defect and two patients with malunited fracture at stress fracture site required osteotomy, plating and bone grafting. Two patients had two level stress fracture of tibia in the same leg. RESULTS: The mean follow-up period was 28 (range, 6-60) months. The mean tibiofemoral angle improved from 18.27° varus to 1.8° valgus. The mean knee society score improved from 21.9 (range, -10 to 45) to 82.8 (range, 15-99) [p < 0.05]. The mean Knee Society functional score improved from 15.5 (range, -10 to 40) to 76.8 (range, 10-100) [p < 0.05]. All fractures got united at the last follow-up. One patient had infection and wound dehiscence at six months for which debridement done and had poor functional outcome. CONCLUSION: TKA with long stem gives excellent outcome, irrespective of severity of arthritis associated with stress fracture. By restoring limb alignment and bypassing the fracture site, it facilitates fracture healing. Early detection and prompt intervention is necessary to prevent the progression to recalcitrant non-union or malunion.
30113844 Dual Inhibition of TYK2 and JAK1 for the Treatment of Autoimmune Diseases: Discovery of (( 2018 Oct 11 Cytokine signaling is an important characteristic of autoimmune diseases. Many pro-inflammatory cytokines signal through the Janus kinase (JAK)/Signal transducer and activator of transcription (STAT) pathway. JAK1 is important for the γ-common chain cytokines, interleukin (IL)-6, and type-I interferon (IFN) family, while TYK2 in addition to type-I IFN signaling also plays a role in IL-23 and IL-12 signaling. Intervention with monoclonal antibodies (mAbs) or JAK1 inhibitors has demonstrated efficacy in Phase III psoriasis, psoriatic arthritis, inflammatory bowel disease, and rheumatoid arthritis studies, leading to multiple drug approvals. We hypothesized that a dual JAK1/TYK2 inhibitor will provide additional efficacy, while managing risk by optimizing selectivity against JAK2 driven hematopoietic changes. Our program began with a conformationally constrained piperazinyl-pyrimidine Type 1 ATP site inhibitor, subsequent work led to the discovery of PF-06700841 (compound 23), which is in Phase II clinical development (NCT02969018, NCT02958865, NCT03395184, and NCT02974868).
29846161 Prevalence and spectrum of symptomatic pulmonary involvement in primary Sjögren's syndrom 2018 May OBJECTIVES: The present cross-sectional study aimed to estimate the prevalence of chronic respiratory symptoms in primary Sjögren's syndrome (pSS) and define the clinical, functional and imaging characteristics of symptomatic pulmonary disease in pSS. METHODS: Four hundred and fourteen consecutive pSS patients were interviewed for the presence of chronic respiratory complaints (cough and/or dyspnea). Symptomatic pSS patients without respiratory or other comorbidities underwent further investigation with clinical evaluation and assessment with pulmonary functional testing (PFTs) and chest high resolution CT (hrCT) on inspiratory and expiratory phase. Comparison of clinical and laboratory features between symptomatic and asymptomatic pSS patients was also performed. RESULTS: Prevalence of chronic respiratory symptoms in pSS was estimated at 21.5% (89/414). Symptoms were attributed to underlying comorbidities in approximately one third of cases (30/89). Thirty nine of the remaining 59 patients were finally assessed with PFTs and hrCT. Small airway disease was diagnosed in 20 individuals with an obstructive pattern in PFTs and/or compatible radiological signs. Seven patients were diagnosed with interstitial lung disease, while in the remaining 12 pSS patients, with normal PFTs and hrCT, symptoms were attributed to xerotrachea. Raynaud's phenomenon occurred more frequently in symptomatic than asymptomatic patients (p=0.024). CONCLUSIONS: Approximately one fifth of a large cohort of pSS patients presented chronic respiratory symptoms. Small airway disease was the most commonly recognized pulmonary disorder among symptomatic pSS patients, followed by xerotrachea and interstitial lung disease.
29968329 Interstitial lung disease in non-sicca onset primary Sjögren's syndrome: a large-scale ca 2018 Jul AIM: This study investigated the common initial clinical presentations of primary Sjögren's syndrome (pSS) with interstitial lung disease (ILD) and explored differences between sicca and non-sicca onset pSS-ILD patients. METHOD: A total of 1341 SS patients hospitalized between 2003 and 2012 were retrospectively reviewed. Of them, 102 were analyzed and recruited to examine the differences between non-sicca and sicca onset. RESULTS: Fifty-one percent of pSS-ILD patients presented with non-sicca onset. Although the mean diagnosis time was equal, only 4% of non-sicca onset patients were diagnosed with pSS at onset versus 34% with sicca onset (P = 0.000). Hyperglobulinemia, elevated rheumatoid factor (RF) titer, and anti-SSA and/or anti-SSB presence were less predominant in patients with non-sicca onset (immunoglobulin G, 16 [12-21] vs. 21 [15-28] g/L, P = 0.032; RF, 22 [20-171] vs. 104 [20-237] IU/mL, P = 0.048; anti-SSA and/or anti-SSB presence, 33% vs. 72%, P = 0.000). The usual interstitial pneumonia pattern was more commonly seen in non-sicca onset patients (20.0% vs. 14.3%). The high-resolution computed tomography score was higher (12 [88-15] vs. 8 [5-13], P = 0.070) and predicted total lung capacity and forced vital capacity were lower (87 ± 23% vs. 97 ± 20%, P = 0.050; 88 ± 28% vs. 100 ± 27%, P = 0.089) in non-sicca patients. CONCLUSION: Non-sicca is a common initial manifestation in pSS-ILD. Anti-SSA presence, elevated RF titer and hyperglobulinemia were less predominant, and pulmonary complications were more progressive and severe in non-sicca onset patients than sicca onset patients.