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Objective: Pregnancy may influence the course of inflammatory rheumatic diseases and, conversely, rheumatic and musculoskeletal diseases (RMDs) can affect the outcome of pregnancy. This study aimed to retrospectively analyse the outcome of pregnancy and disease in women with RMDs.Method: Subjects were patients with high-risk pregnancy and connective tissue diseases (CTDs) or inflammatory joint diseases (IJDs) managed at a specialized rheumatology outpatient clinic from 2007 to 2014. Data from conception to 6 months postpartum were collected from medical records and a questionnaire, and analysed regarding clinical symptoms, medications, pregnancy complications, birth outcomes, and infant development. Generalized estimating equations were used to compare the groups (CTD vs IJD).Results: The eligible 66 pregnancies in 57 RMD patients were divided into two groups by RMD type: CTD (n = 48) or IJD (n = 18). The live birth rate was 97% overall. Pregnancy complications (excluding two twin pregnancies) were incurred in 39.1%: miscarriage (n = 2), premature delivery (n = 12), small-for-gestational-age infants (n = 5), and/or pregnancy-related diseases (n = 14). Three children born to women with CTDs had affected development (autism spectrum disorder, congenital heart disease, bronchopulmonary dysplasia). CTD infants had a significantly lower mean gestational age (in weeks) (p = 0.042), weight (p = 0.009), and length (p = 0.016) at birth than IJD infants.Conclusion: Although the live birth rate was high, complications occurred in 39.1% of pregnancies in this cohort. Therefore, interdisciplinary management of pregnant women with RMDs at specialized clinics is strongly recommended. [ABSTRACT FROM AUTHOR]

Copyright of Monatsschrift Kinderheilkunde is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Zeitschrift für Rheumatologie. Supplements is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Zeitschrift für Rheumatologie. Supplements is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objectives: To assess the efficacy and safety of certolizumab pegol (CZP)+dose-optimised methotrexate (MTX) versus placebo (PBO)+dose-optimised MTX in inducing and sustaining clinical remission in DMARD-naïve patients with moderate-to-severe, active, progressive rheumatoid arthritis (RA), with poor prognostic factors over 52 weeks.Methods: DMARD-naïve patients with ≤1 year of active RA were randomised (3:1) in a double-blind manner to CZP (400 mg Weeks 0, 2, 4, then 200 mg Q2W to Week 52)+MTX or PBO+MTX (the mean optimised-MTX dose=21 and 22 mg/week, respectively). Sustained remission (sREM) and sustained low disease activity (sLDA; DAS28(ESR)<2.6 and DAS28(ESR)≤3.2, respectively, at both Weeks 40 and 52) were the primary and secondary endpoints.Results: Patients were randomised to CZP+MTX (n=660) and PBO+MTX (n=219). At Week 52, significantly more patients assigned to CZP+MTX compared with PBO+MTX achieved sREM (28.9% vs 15.0%, p<0.001) and sLDA (43.8% vs 28.6%, p<0.001). Inhibition of radiographic progression and improvements in physical functioning were significantly greater for CZP+MTX versus PBO+MTX (van der Heijde modified total Sharp score (mTSS) mean absolute change from baseline (CFB): 0.2 vs 1.8, p<0.001, rate of mTSS non-progressors: 70.3% vs 49.7%, p<0.001; least squares (LS) mean CFB in Health Assessment Questionnaire-Disability Index (HAQ-DI): -1.00 vs -0.82, p<0.001). Incidence of adverse events (AEs) and serious AEs was similar between treatment groups. Infection was the most frequent AE, with higher incidence for CZP+MTX (71.8/100 patient-years (PY)) versus PBO+MTX (52.7/100 PY); the rate of serious infection was similar between CZP+MTX (3.3/100 PY) and PBO+MTX (3.7/100 PY).Conclusions: CZP+dose-optimised MTX treatment of DMARD-naïve early RA resulted in significantly more patients achieving sREM and sLDA, improved physical function and inhibited structural damage compared with PBO+dose-optimised MTX.Trial Registration Number: NCT01519791. [ABSTRACT FROM AUTHOR]

The initial inflammatory phase of fracture healing is of great importance for the clinical outcome. We aimed to develop a detailed time-dependent analysis of the initial fracture hematoma. We analyzed the composition of immune cell subpopulations by flow cytometry and the concentration of cytokines and chemokines by bioplex in 42 samples from human fractures of long bones <72 h post-trauma. The early human fracture hematoma is characterized by maturation of granulocytes and migration of monocytes/macrophages and hematopoietic stem cells. Both T helper cells and cytotoxic T cells proliferate within the fracture hematoma and/or migrate to the fracture site. Humoral immunity characteristics comprise high concentration of pro-inflammatory cytokines such as IL-6, IL-8, IFNγ and TNFα, but also elevated concentration of anti-inflammatory cytokines, e.g., IL-1 receptor antagonist and IL-10. Furthermore, we found that cells of the fracture hematoma represent a source for key chemokines. Even under the bioenergetically restricted conditions that exist in the initial fracture hematoma, immune cells are not only present, but also survive, mature, function and migrate. They secrete a cytokine/chemokine cocktail that contributes to the onset of regeneration. We hypothesize that this specific microenvironment of the initial fracture hematoma is among the crucial factors that determine fracture healing. [ABSTRACT FROM AUTHOR]

Issues of fertility and pregnancy require special attention in the long-term care of patients with autoimmune diseases (AD), who are candidates for haematopoietic stem cell transplantation (HSCT). In this single-centre observational study, we report fertility status and pregnancy outcomes in 15 patients (11 female and 4 male) after immunoablation with cyclophosphamide, antithymocyte globulin and autologous CD34-selected HSCT for severe, refractory AD. The median follow-up after HSCT was 12 years (range 2-16 years). Impaired fertility was observed in six patients (five females and one male) before HSCT based on sexual hormone measurements. Higher age and cumulative cyclophosphamide dosage before HSCT correlated with fertility impairment. Median serum level of follicle-stimulating hormone (FSH) was significantly higher in female patients at 1 year after HSCT compared to baseline values, but premature ovarian failure developed in only one patient. Four women had five pregnancies and six healthy offsprings during follow-up, and no miscarriages were observed. The mothers were in treatment-free remissions during conception. No peripartal flare of their AD occurred. Although AD patients undergoing HSCT are at risk of developing infertility, pre-HSCT treatment and patients' age seem to have higher impact on long-term fertility status than HSCT itself. HSCT offers the opportunity to conceive during treatment-free remissions with favourable pregnancy outcomes. [ABSTRACT FROM AUTHOR]

Background: Since the publication of the European League Against Rheumatism recommendations for the pharmacological treatment of psoriatic arthritis (PsA) in 2012, new evidence and new therapeutic agents have emerged. The objective was to update these recommendations.Methods: A systematic literature review was performed regarding pharmacological treatment in PsA. Subsequently, recommendations were formulated based on the evidence and the expert opinion of the 34 Task Force members. Levels of evidence and strengths of recommendations were allocated.Results: The updated recommendations comprise 5 overarching principles and 10 recommendations, covering pharmacological therapies for PsA from non-steroidal anti-inflammatory drugs (NSAIDs), to conventional synthetic (csDMARD) and biological (bDMARD) disease-modifying antirheumatic drugs, whatever their mode of action, taking articular and extra-articular manifestations of PsA into account, but focusing on musculoskeletal involvement. The overarching principles address the need for shared decision-making and treatment objectives. The recommendations address csDMARDs as an initial therapy after failure of NSAIDs and local therapy for active disease, followed, if necessary, by a bDMARD or a targeted synthetic DMARD (tsDMARD). The first bDMARD would usually be a tumour necrosis factor (TNF) inhibitor. bDMARDs targeting interleukin (IL)12/23 (ustekinumab) or IL-17 pathways (secukinumab) may be used in patients for whom TNF inhibitors are inappropriate and a tsDMARD such as a phosphodiesterase 4-inhibitor (apremilast) if bDMARDs are inappropriate. If the first bDMARD strategy fails, any other bDMARD or tsDMARD may be used.Conclusions: These recommendations provide stakeholders with an updated consensus on the pharmacological treatment of PsA and strategies to reach optimal outcomes in PsA, based on a combination of evidence and expert opinion. [ABSTRACT FROM AUTHOR]

Background: In rheumatoid arthritis (RA), hand synovitis appears especially in wrist, metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints. In hand osteoarthritis (OA), potential inflammatory changes are mainly present in PIP and distal interphalangeal (DIP) joints. Joint inflammation can be visualised by fluorescence optical imaging (FOI) and musculoskeletal ultrasound (US).Objective: Comparison of the amount and distribution of inflammatory signs in wrist and finger joints of the clinically dominant hand in patients with OA and RA by FOI and gray-scale (GSUS) and power Doppler US (PDUS).Methods: FOI and GSUS/PDUS were performed in 1.170 joints (wrists, MCP, PIP, DIP) in 90 patients (67 RA, 23 OA). Joint inflammation was graded by a semiquantitative score (0-3) for each imaging method.Results: GSUS/PDUS showed wrist and MCP joints mostly affected in RA. DIP joints were graded higher in OA. In FOI, RA and OA featured inflammatory changes in the respective joint groups depending on the phase of fluorescence dye flooding.Conclusions: US and FOI detected inflammation in both RA and OA highlighting the inflammatory component in the course of OA. The different inflammatory patterns and various shapes of fluorescence enhancement in FOI may offer opportunities to distinguish and determine the inflammatory status in both diseases. [ABSTRACT FROM AUTHOR]

The objective of the study was to evaluate the growth-promoting activity of human platelet supernatant on primary chondrocytes in comparison with fetal calf serum (FCS) supplemented cell culture medium. Furthermore, the differentiation potential of platelet supernatant was determined in three-dimensional artificial cartilage tissues of bovine articular chondrocytes. Proliferation of articular and nasal septal chondrocytes was assayed by incorporation of BrdU upon stimulation with ten different batches of human platelet supernatant. On bovine articular chondrocytes, all these batches were at least as growth-promoting as FCS. On nasal septal chondrocytes, nine out of ten batches revealed increased or equivalent mitogenic stimulation compared with medium supplemented with FCS. Three-dimensional culture and subsequent histological analysis of matrix formation were used to determine the differentiation properties of platelet supernatant on articular chondrocytes. Human platelet supernatant failed to induce the deposition of typical cartilage matrix components, whereas differentiation and matrix formation were apparent upon cultivation of articular chondrocytes with FCS. Proliferation assays demonstrated that human platelet supernatant stimulates growth of articular and nasal septal chondrocytes; however, platelet supernatant failed to stimulate articular chondrocytes to redifferentiate in three-dimensional chondrocyte cultures. Therefore platelet lysate may be suitable for chondrocyte expansion, but not for maturation of tissue-engineered cartilage. [ABSTRACT FROM AUTHOR]

Objective To study the relationship of spinal inflammation and fatty degeneration (FD) as detected by MRI and new bone formation seen on conventional radiographs (CRs) in ankylosing spondylitis (AS). Methods CRs at baseline, 2 years and 5 years and spinal MRIs at baseline and 2 years of 73 AS patients treated with infliximab in European AS Infliximab Cohort were available. Relative risks (RR) were calculated with a general linear model after adjustment for within-patient variation. Results In a total of 1466 vertebral edges (VEs) without baseline syndesmophytes, 61 syndesmophytes developed at 5 years, the majority of which (57.4%) had no corresponding detectable MRI lesions at baseline. VEs with both in ammation and FD at baseline had the highest risk (RR 3.3, p=0.009) for syndesmophyte formation at 5 years, followed by VEs that developed new FD or did not resolve FD at 2 years (RR=2.3, p=0.034), while in ammation at baseline with no FD at 2 years had the lowest risk for syndesmophyte formation at 5 years (RR=0.8). Of the VEs with in ammation at baseline, >70% resolved completely, 28.8% turned into FD after 2 years, but only 1 syndesmophyte developed within 5 years. Conclusions Parallel occurrence of in ammation and FD at baseline and development of FD without prior in ammation after 2 years were significantly associated with syndesmophyte formation after 5 years of anti-tumour necrosis factor (TNF) therapy. However, the sequence 'in ammation--FD--new bone formation' was rarely observed, an argument against the TNF-brake hypothesis. Whether an early suppression of in ammation leads to a decrease of the risk for new bone formation remains to be demonstrated. [ABSTRACT FROM AUTHOR]

Copyright of Der Internist is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The objectives of this study are to evaluate a new semi-quantitative (0-5) musculoskeletal ultrasound (US) erosion score in patients with rheumatoid arthritis (RA) and to prove its usefulness in the detection of disease activity and success of therapy. Thirty-eight patients with RA (mean disease duration 10.1 ± 11.9 years) were enrolled. Start or change of therapy (DMARD/biologics) was an inclusion criterion. DAS28, laboratory (ESR and CRP) and US data were evaluated before new therapy initiation and after 1, 3, 6 and 12 months. Thirteen joints of the clinically more affected hand and forefoot (wrist and MCP, PIP, MTP joints 2-5) were analyzed for synovitis in grayscale (GS) and power Doppler (PD) US, tenosynovitis/paratenonitis in GS/PDUS (wrist, MCP level) and for erosions. Erosions were analyzed by a new semi-quantitative score (grade 0, no erosion; grade 1, <1 mm, grade 2, 1 to <2 mm; grade 3, 2 to ≤3 mm; grade 4, >3 mm; grade 5, multiple bone erosions). After 12 months, DAS28 decreased from 4.5 to 3.4 ( p < 0.001), the synovitis score in GSUS from 26.3 to 12.8 ( p = 0.001) and the synovitis score in PDUS from 10.6 to 4.1 ( p < 0.001). The erosion score decreased from 21.5 to 18.1 ( p = 0.046). There were longitudinal significant correlations between the new erosion score and both the DAS28 ( r = 0.368; p = 0.025) and the synovitis score in PDUS ( r = 0.365; p = 0.026) over a 1-year follow-up period. The new erosion score might be a useful tool for the evaluation of erosive changes by US in RA patients. In the course of DMARD and biologic therapy, it was responsive under 1-year follow-up examination. [ABSTRACT FROM AUTHOR]

Objective To assess the value of gray-scale (GS) and power Doppler (PD) ultrasound (US) in detecting inflammatory/destructive changes and for prediction of necessity of re-therapy with rituximab (RTX) in patients with rheumatoid arthritis (RA) over 1 year of followup. Methods GSUS and PDUS were performed to assess synovitis, tenosynovitis, and erosions on the clinically dominant hand and forefoot of 20 patients with RA before and after therapy with RTX. US parameters were compared with clinical (Disease Activity Score in 28 joints, tender/swollen joint counts, and patients' visual analog scale of disease activity) and laboratory parameters (C-reactive protein level and erythrocyte sedimentation rate). Results were compared for patients with and without re-therapy with RTX. Results Significant decreases in clinical and laboratory parameters were observed after 6 and 12 months. US synovitis scores significantly decreased after 6 and 12 months ( P < 0.05 for each). Regarding patients who received re-therapy between 6 and 9 months after the start of therapy (n = 9), a fair therapy response was still detectable before re-therapy. In these patients, PD-positive synovitis was the only parameter that increased up to the 6-month examination. All patients negative for rheumatoid factor and anti-cyclic citrullinated peptide (n = 4) were in the group of patients receiving a second course of treatment. Seropositive patients showed a better response to treatment with less need for re-therapy. Conclusion Response to therapy was measurable by clinical and laboratory parameters as well as by US. Since PDUS was able to detect the onset of disease activity before worsening of clinical symptoms occurred, PDUS is most helpful in evaluating disease activity and making earlier therapy decisions. [ABSTRACT FROM AUTHOR]