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ID PMID Title PublicationDate abstract
25636309 Characterization of Angiogenesis and Lymphangiogenesis in Human Minor Salivary Glands with 2015 May Angiogenesis has been proposed to play a role in the inflammation observed in Sjögren's Syndrome (SS). However, no studies have validated the degree of angiogenesis in salivary glands with SS. Therefore, the goal of this study was to determine the presence and localization of angiogenesis and lymphangiogenesis in salivary glands with SS. We used frozen tissue sections from human minor salivary glands (hMSG) with and without SS in our analyses. To investigate signs of angiogenesis, hMSG tissue lysates were used to detect levels of the pro-angiogenic protein vascular endothelial growth factor (VEGF) by western blot analyses. Additionally, we labeled blood vessels using antibodies specific to platelet endothelial cell adhesion molecule-1 (PECAM-1) and von Willebrand Factor (vWF) to determine blood vessel organization and volume fraction using fluorescence microscopy. Lymphatic vessel organization and volume fraction were determined using antibodies specific to lymphatic vessel endothelial hyaluronan receptor (LYVE-1). Our results suggest that expression levels of VEGF are decreased in hMSG with SS as compared with controls. Interestingly, there were no significant differences in blood or lymphatic vessel organization or volume fraction between hMSG with and without SS, suggesting that angiogenesis and lymphangiogenesis have little impact on the progression of SS.
27896585 Effect of an herbal mixture of Cinnamon Cortex, Persicae Semen, and Natril Sulfas on colla 2016 Nov 17 OBJECTIVE: To investigate the anti-arthritic and anti-inflammatory effects of the mixture of three herbal agents, Cinnamon Cortex, Persica Semen, and Natril Sulfas (CPN), the major ingredients of Taoren Chengqi Decoction (). METHODS: Collagen-induced arthritis (CIA) was induced by immunization with bovine type II collagen on day 1 and 21. DBA/1J mice were orally administered the water extract of CPN (100 and 500 mg/kg) and indomethacin (1 mg/kg) or vehicle (water) 3 times per week for 6 weeks. Arthritic symptoms were recorded on day 29, 31, 33, 36 and 38. On sacrififi ce, serum was obtained for inflammatory markers and anti-collagen antibodies as well as arthritic joints were obtained for histologic analysis. For the evaluation of in vitro anti-inflammatory mechanism of CPN, peritoneal macrophages were isolated from thioglycollate injected C57BL/6 mice and stimulated with lipopolysaccharides (LPS) for 15 min in the presence of CPN extract. Levels of inhibitor of NF-κB α isoform (IκBα), phospho-p38, phospho-C-Jun N-terminal kinases (JNK) and phospho-extracellular signal-regulated kinase 1/2 (ERK1/2) were detected by Western blot. RESULTS: Compared with mice in CIA group, oral administration of CPN signififi cantly reduced the clinical scores (P<0.05), histological analysis revealed the protective effect of CPN on inflamed joints. Serum levels of the pro-inflammatory markers tumor necrosis factor-α, interleukin-6 and prostaglandin E(2), but not anti-collagen antibodies, were significantly reduced (P<0.05). CPN did not affect the activation of p38, JNK and ERK1/2 but inhibited LPS-induced IκBα degradation, a required event prior to the translocation of NF-κB to the nucleus. CONCLUSIONS: The ameliorating effect of CPN on arthritis progression seems to be mediated by its anti-inflammatory effect, without affecting antibody response. As a supplementary agent, CPN could be benefifi cial for treatment of CIA.
28078285 Combination of Salivary Gland Ultrasonography and Virtual Touch Quantification for Diagnos 2016 A total of 136 subjects (51 SS patients, 35 sicca syndrome patients without SS, and 50 healthy volunteers) were enrolled in this study. The mean SWV value for salivary glands of SS patients was statistically higher than that of controls (2.81 ± 0.66 m/s versus 1.85 ± 0.28 m/s for parotid glands and 2.29 ± 0.34 m/s versus 1.82 ± 0.25 m/s for submandibular glands, resp.). Combining SWV values of parotid and submandibular glands gives a sensitivity of 88.2% (95% CI: 76.1-95.6%) and specificity of 96.0% (95% CI: 86.3-99.5%) at the cutoff point of 2.19 m/s, with an AUROC of 0.954 (95% CI: 0.893-0.986). In addition, combining SGUS score and SWV value yields a sensitivity of 98.0% (95% CI: 89.6-100%), specificity of 90.0% (95% CI: 78.2-96.7%), and AUROC of 0.962 (95% CI: 0.904-0.990). Classification tree considering the sequential use of SGUS score and SWV value achieved 92.1% accuracy for diagnosis of SS. Similarly, the ROC curve of combined SGUS scores and SWV values yields an AUROC of 0.954 (95% CI: 0.885-0.987), sensitivity of 97.1% (95% CI: 85.1-99.9%), and specificity of 92.2% (95% CI: 81.1-97.8%) for separating sicca syndrome patients (without SS) from SS patients. Combining SGUS and VTQ provides a promising tool for diagnosis of SS.
26921905 Sjögren's syndrome patients with ectopic germinal centers present with a distinct salivar 2016 Jun OBJECTIVE: Clinical expression of SS shows considerable interpatient heterogeneity. Thus, the aim of this study was to assess whether individual salivary proteomic profiles provide a framework for identification of disease-phenotype-driven biomarker signatures. METHODS: Using a 187-plex capture antibody-based assay, proteomic biomarker profiles from unstimulated whole saliva were generated from a SS-cohort representing six clinically distinct disease phenotypes. Discriminant function analyses identified the most powerful biomarker signatures for correct recapitulation of each patient's status with respect to hyposalivation and histopathological features of salivary gland inflammation. In addition, gene ontology-based network analyses allowed systematic interpretation of the molecular patterns underlying these specific disease features. RESULTS: Presentation of hyposalivation was associated with significant alteration in 22 out of 119 reliably detectable biomarkers. Thereof, a 4-plex signature allowed accurate prediction of salivary gland function for >80% of the cases. With respect to histopathological features, the most distinct profiles were identified in conjunction with ectopic germinal centres. Selected from the 13 analytes relevant here, pregnancy-associated plasma protein A, thrombospondin 1 and peptide YY would recapitulate the presence or absence of tertiary lymphoid organization for 93.8% of the patients. Whereas functional annotation of alterations associated with hyposalivation identified the IL1 system as a dominant pro-inflammatory component, changes observed in context with ectopic lymphoid organization revealed specific shifts in chemotactic profiles and altered regulation of apoptotic processes. CONCLUSION: Multivariate analyses of a patient's salivary proteome could reliably recapitulate specific aspects of SS disease. Accessible and repetitively collectable, such biomarker signatures harbour great potential for patient subclassification and subsequent follow-up.
26162302 Anti-SSA/SSB-negative Sjögren's syndrome shows a lower prevalence of lymphoproliferative 2015 Nov OBJECTIVE: This study aims to compare clinical and laboratory features of patients who, while satisfying the American European Consensus Group (AECG) criteria for primary Sjögren's syndrome (SS), do not present the positivity for anti-Ro/SSA and/or anti-La/SSB, with patients that meet the AECG criteria and are positive for anti-Ro/SSA and/or anti-La/SSB. METHODS: 548 patients were selected based on the following criteria, and exclusion of patients negative for histopathology but positive for anti-Ro/SSA and anti-La/SSB: 1. Fulfilment of the AECG criteria, 2. Performance of minor salivary gland biopsy, 3. Search for anti-Ro/SSA and anti-La/SSB, 4. Absence of hepatitis C virus infection. Univariate and multivariate analyses were performed. RESULTS: Two groups were compared: 342 patients were positive for both the histopathology and for anti-Ro/SSA and/or anti-La/SSB (H-only) and 206 patients were positive for histopathology, but negative for autoantibodies (H+SSA/SSB). The following variables were statistically found to be associated with H+SSA/SSB: younger age at diagnosis (p<0.0001), glandular swelling (p=0.01), purpura (p=0.04), leucopoenia (p=0.0001), lymphoma (p=0.002), low C3 (p=0.04), low C4 (p=0.01), hypergammaglobulinemia (p<0.0001), ANA (p<0.0001), rheumatoid factor (p<0.0001), and serum cryoglobulins (p=0.039). ANA positivity (OR 6.9), hypergammaglobulinemia (OR 5.1), positive rheumatoid factor (OR 2.3), and age at diagnosis (OR 0.97) were also selected by multivariate analyses as associated with H+SSA/SSB. CONCLUSION: Primary SS negative for anti-Ro/SSA and anti-La/SSB antibodies appears to be characterized by a lower risk of lymphoma and by a lower level of B-cell expansion.
26150646 Adult-onset Still's disease in a Nigerian woman. 2015 Jul 6 Adult-onset Still's disease (AOSD) is an uncommon systemic inflammatory disorder of unknown aetiology. Although there have been reports and series elsewhere, there have been very few such reports on black Africans. The rarity of the reporting of this disease has been associated with a low index of suspicion and hence delayed diagnosis in patients suffering from it. We report a case of a 28-year-old woman, a teacher, who had been repeatedly treated for malarial fever over a 2-month period. She was also briefly managed elsewhere for systemic lupus erythematosus due to a persistent fever with associated polyarthralgia, sore throat, rash and high erythrocyte sedimentation rate. On presentation to our facility, she fulfilled the Yamaguchi criteria for AOSD and had a markedly elevated serum ferritin level. She was successfully managed with etanercept and methotrexate. This is the first report of AOSD from Nigeria.
25362659 Etiopathogenic role of surfactant protein d in the clinical and immunological expression o 2015 Jan OBJECTIVE: To analyze the etiopathogenic role of genetic polymorphisms and serum levels of surfactant protein-D (SP-D) in primary Sjögren syndrome (pSS). METHODS: We analyzed 210 consecutive patients with pSS. SFTPD genotyping (M11T polymorphism rs721917) was analyzed by sequence-based typing and serum SP-D by ELISA. RESULTS: Thirty-two patients (15%) had the Thr11/Thr11 genotype, 80 (38%) the Met11/Met11 genotype, and 96 (46%) the Met11/Thr11 genotype; 2 patients could not be genotyped. Patients carrying the Thr11/Thr11 genotype had a higher prevalence of renal involvement (13% vs 1% and 4% in comparison with patients carrying the other genotypes, p = 0.014). Serum SP-D levels were analyzed in 119 patients (mean 733.94 ± 49.88 ng/ml). No significant association was found between serum SP-D levels and the SP-D genotypes. Higher mean values of serum SP-D were observed in patients with severe scintigraphic involvement (851.10 ± 685.69 vs 636.07 ± 315.93 ng/ml, p = 0.038), interstitial pulmonary disease (1053.60 ± 852.03 vs 700.36 ± 479.33 ng/ml, p = 0.029), renal involvement (1880.64 ± 1842.79 vs 716.42 ± 488.01 ng/ml, p = 0.002), leukopenia (899.83 ± 661.71 vs 673.13 ± 465.88 ng/ml, p = 0.038), positive anti-Ro/SS-A (927.26 ± 731.29 vs 642.75 ± 377.23 ng/ml, p = 0.006), and positive anti-La/SS-B (933.28 ± 689.63 vs 650.41 ± 428.14 ng/ml, p = 0.007), while lower mean values of serum SP-D were observed in patients with bronchiectasis (489.49 vs 788.81 ng/ml, p = 0.019). CONCLUSION: In pSS, high SP-D levels were found in patients with severe glandular involvement, hypergammaglobulinemia, leukopenia, extraglandular manifestations, and positive anti-Ro/La antibodies. The specific association between SP-D levels and pulmonary and renal involvements may have pathophysiological implications.
27462914 Efficacy of tocilizumab therapy in Korean patients with adult-onset Still's disease: a mul 2016 Sep OBJECTIVES: To evaluate the efficacy of tocilizumab (TCZ), a monoclonal antibody against the interleukin (IL)-6 receptor, for refractory adult-onset Still's disease (AOSD) in the Korean population. METHODS: This retrospective study included 22 Korean patients with refractory AOSD who were given TCZ at one of seven university hospital-based clinics for rheumatic disease. Patients were subdivided into groups according to disease course: monocyclic, systemic polycyclic, and chronic articular. Modified Pouchot scores, including laboratory and clinical findings, were analysed at 6 months and 12 months. RESULTS: TCZ was given at 4-8 mg/kg every 4-5 weeks (8 mg/kg every 4-5 weeks in 18 patients, 6 mg/kg every 4 weeks in 2, and 4 mg/kg every 4 weeks in 2) for 7.5 months (median, IQR: 4.0-12.3). A good response (measured as a decrease of >2 in the modified Pouchot score) was achieved in 50.0% of patients (11 of 22) at 6 months and in 64.3% (9 of 14) at 12 months. The dose of corticosteroid dose was reduced from 11.5 mg/day (median, IQR: 10.0-21.3) immediately before TCZ therapy to 7.5 mg/day (median, IQR: 5.0-10.0, p=0.002) at 6 months and finally to 6.3 mg/day (median, IQR: 5.0-7.5, p=0.002) at 12 months. Only one patient discontinued TCZ treatment due to facial swelling accompanied by high blood pressure. In all others, adverse events subsided with delayed TCZ therapy, and TCZ therapy was continued successfully without problems. CONCLUSIONS: TCZ was effective for treating Korean AOSD patients who were refractory to conventional therapy or other anti-cytokine biologics, showing a corticosteroid-sparing effect and an acceptable tolerance profile.
27616561 Present and future of biologic drugs in primary Sjögren's syndrome. 2017 Jan Primary Sjögren's (pSS) syndrome is a chronic, autoimmune, and systemic disease characterized by xerostomia, xerophthalmia, muscle pain and fatigue. The disease may be complicated by a systemic involvement, such as a pulmonary fibrosis or the development of lymphoma which severely worsens the prognosis. Actually, there are no recommendations for the management of pSS. However, recent advances in the understanding of its pathogenesis have uncovered some pathways that have potential as therapeutic targets. Areas covered: In this review, the authors present the biologic drugs potentially valuable to the treatment of pSS in light of its physiopathology with a 'bird's eye' view of future prospects. The authors took into account relevant studies published from 2004 to 2016. Expert opinion: Biological treatment in pSS is a promising opportunity to potentially control disease activity and prevent its complication. Currently, inhibition of B-cell and IL-17 pathways seem to be the most promising avenues. New achievements in the knowledge of pSS pathophysiology are necessary in order to try to simultaneously predict the predominant pathogenic pathway, the kind of patients at major risk to develop a more severe disease, and the appropriate biological therapy to use.
25926425 Subclinical articular involvement in primary Sjögren's syndrome assessed by ultrasonograp 2015 OBJECTIVES: To evaluate the subclinical articular involvement in patients with primary Sjögren's syndrome (pSS) using musculoskeletal ultrasound (MSUS), and to correlate the findings with laboratory results and clinical manifestations. METHODS: Forty-eight consecutive patients with pSS were enrolled. The bilateral metacarpophalangeal, proximal interphalangeal, and interphalangeal joints were examined using MSUS, and the synovial hypertrophy and power Doppler signal were recorded for each joint using semi-quantitative scores (0 = normal, 1 = mild change compared with undamaged joint, 2 = moderate change, and 3 = severe change). RESULTS: Mild or moderate synovial hypertrophy was found in 151 (15.7%) and 2 (0.2%) out of 960 hand joints, respectively, and power Doppler signals were present in 19 (2.0%) of the 960 joints. While anti-centromere antibody (ACA) was found in 10 patients (20.8%), none of the patients with MSUS-confirmed synovitis was positive for ACA. No other autoantibodies, laboratory tests, or clinical manifestations correlated with MSUS-confirmed synovitis. CONCLUSION: MSUS is useful for detecting subclinical synovitis in pSS patients. MSUS showed that ACA-positive pSS patients had a low prevalence of synovitis.
25758816 Age-Related Conjunctival Disease in the C57BL/6.NOD-Aec1Aec2 Mouse Model of Sjögren Syndr 2015 Apr PURPOSE: To investigate parameters of ocular surface disease in C57BL/6.NOD-Aec1Aec2 (Aec) mice with aging and their correlation with development of Sjögren syndrome (SS)-like lacrimal gland (LG) disease. METHODS: Aec and C57BL/6 wild-type (B6) female mice were evaluated at 4, 12, and 20 weeks of age. Whole LG and eyes and adnexa were excised for histology and gene expression analysis and evaluated by flow cytometry and immunohistochemistry. Tear volume and goblet cell density was measured. Quantitative PCR evaluated T-cell-related cytokine expression in cornea and conjunctiva. RESULTS: Both strains showed age-related conjunctival goblet cell loss that was more pronounced in the Aec strain and significantly greater than in B6 mice at 12 weeks. This was accompanied by CD4+ T-cell infiltration of the conjunctiva that was greater in Aec strain at 20 weeks. Aec mice had higher levels of IL-17A, IL-17R, IL-1α, IL-1β, and TNF-α in the conjunctiva, and they significantly increase with aging. Aec mice had greater lymphocytic infiltration of the LG and conjunctiva at 20 weeks that consisted of a mixture of CD4+ and CD8+ cells. Flow cytometry showed a significant increase in CD4+ T cells in Aec LG compared to B6 mice. Tear volume was significantly increased in both strains at 20 weeks. CONCLUSIONS: Aec mice developed greater conjunctival goblet cell loss associated with lymphocytic infiltration of the LG and conjunctiva with aging. Increased expression of certain T helper or inflammatory cytokines in these tissues was observed in Aec mice. The conjunctival disease appeared to be due to inflammation and not a decrease in tear volume.
25751774 [Manifestation of rheumatic diseases in the larynx]. 2015 Mar Rheumatic disorders (rheumatoid arthritis, sarcoidosis, systemic lupus erythematosus, Wegener's granulomatosis, relapsing polychondritis) may affect the larynx. The clinical symptoms are often unspecific, leading to delayed diagnosis. Malignant tumours should be considered in differential diagnosis with necessitating biopsy. Treatment may require interdisciplinary approach together with a specialist in internal medicine and rheumatology.
27810512 Increased frequency of the PTPN22W* variant in primary Sjogren's Syndrome: Association wit 2016 Dec Recent data suggest the association of the autoimmune gene variant PTPN22W* with dampened type I Interferon (IFN) responses, seen in a subset of primary Sjogren's Syndrome (pSS) patients. We sought to explore the potential contribution of PTPN22W* in this setting. PTPN22W* was identified in DNA samples derived from 352 pSS patients and 482 healthy controls (HC). Type I IFN score was determined in available peripheral blood cDNA of 164 pSS patients by Real-Time PCR. Increased prevalence of the PTPN22W* variant was detected in pSS patients compared to HC [9.7% vs 5.0%, p-value: 0.02]. Of interest, only the low but not the high type I IFN pSS subgroup displayed higher PTPN22W* rates compared to HC (12.2% vs 5.0%, p-value: 0.03). PTPN22W* risk variant increases susceptibility for pSS, particularly the low type I IFN subset implying the presence of distinct genetic backgrounds among low and high type I IFN autoimmune subgroups.
27200376 The Effect of Autologous Platelet Lysate Eye Drops: An In Vivo Confocal Microscopy Study. 2016 Purpose. To determine the effectiveness of autologous platelet lysate (APL) eye drops in patients with primary Sjögren syndrome (SS) dry eye, refractory to standard therapy, in comparison with patients treated with artificial tears. We focused on the effect of APL on cornea morphology with the in vivo confocal microscopy (IVCM). Methods. Patients were assigned to two groups: group A used autologous platelet lysate QID, and group B used preservative-free artificial tears QID, for 90 days. Ophthalmological assessments included ocular surface disease index (OSDI), best corrected visual acuity (BCVA), Schirmer test, fluorescein score, and breakup time (BUT). A subgroup of patients in group A underwent IVCM: corneal basal epithelium, subbasal nerves, Langerhans cells, anterior stroma activated keratocytes, and reflectivity were evaluated. Results. 60 eyes of 30 patients were enrolled; in group A (n = 20 patients) mean OSDI, fluorescein score, and BUT showed significant improvement compared with group B (n = 10 patients). The IVCM showed a significant increase in basal epithelium cells density and subbasal nerve plexus density and number and a decrease in Langerhans cells density (p < 0.05). Conclusion. APL was found effective in the treatment of SS dry eye. IVCM seems to be a useful tool to visualize cornea morphologic modifications.
26774177 Sicca symptoms are associated with similar fatigue, anxiety, depression, and quality-of-li 2016 Dec OBJECTIVE: To compare quality of life (QoL), depression, anxiety, and fatigue in prospectively included patients with primary Sjögren's syndrome (pSS) or with sicca but no diagnosis of Sjögren's syndrome. METHODS: Patients undergoing a multidisciplinary evaluation at a single university center in Brest, France, for suspected pSS and having sicca symptoms were included prospectively between November 2006 and December 2013. The same standardized investigations were performed in all patients. pSS and sicca not due to pSS diagnoses were based on evaluating physician opinion. Each patient completed three validated questionnaires on QoL (SF-36), fatigue (MFI), depression and anxiety (HADS). RESULTS: Of the 95 included patients, 55 (57.9%) had pSS and 40 (42.1%) had sicca without pSS. Gender distribution, age, disease duration, and sicca symptoms were similar in the two groups. The pSS group had a significantly higher proportion of patients with abnormal objective tests for dryness (Schirmer's test and salivary flow rate). The SF-36, HADS, and MFI scores were similarly altered in the two groups. Anxiety was more common than depression in both groups. The most affected domains were vitality in the SF-36 and general/physical fatigue in the MFI. Extraglandular systemic involvement was not a major determinant of QoL alteration in patients with pSS. CONCLUSIONS: Sicca symptoms are associated with severe alterations in SF-36, HADS, and MFI scores regardless of objective test abnormalities and pSS diagnosis. Anxiety is more common than depression and should be taken into account when managing all patients with sicca symptoms.
25925697 Clinical and laboratory profiles of primary Sjogren's syndrome in a Chinese population: A 2015 May AIM: To assess the clinical and laboratory features of primary Sjogren's syndrome (pSS) in a large teaching hospital in China. METHODS: Three hundred and fifteen pSS patients diagnosed according to American-European Classification Criteria and consecutively admitted to Anhui Provincial Hospital from 1 January 1999 to 30 September 2012 were retrospectively selected in this study. RESULTS: The median age was 46.8 ± 14.4 years (range 13-83 years) and the majority of patients were female (96.5%). The common clinical features at initial presentations were dry mouth (50.2%), dry eyes (31.4%) and joint pain (24.8%); 92.6% of patients had positive anti-SSA antibody and 49.2% patients had positive anti-SSB antibody. One hundred and eighteen patients underwent labial salivary gland biopsy. According to Chisholm grading criteria, grade 3 to 4 was present in 58.5% of the patients. The frequency of interstitial lung disease (ILD) occurred (20.9%) in the patients with systemic extraglandular manifestations. The patients with ILD were frequently associated with positive anti-SSA (P = 0.005) and low levels of C3. The most common impairment of lung function was small airway function abnormalities. Sixty-six pSS patients with ILD (pSS-ILD) were diagnosed with high-resolution computed tomography and treated with corticosteroids and/or immunosuppressants, in which 18 patients had improved pulmonary function. CONCLUSION: Labial salivary gland biopsy and anti-nuclear antibodies spectrum were important to the diagnosis of pSS. The pSS patients had high percentage of ILD, especially small airway function abnormalities. The combination of corticosteroids and immunosuppressants appears to be effective in treatment of pSS patients with ILD.
26955985 Methotrexate-associated EBV-positive vasculitis in the skin: a report of two cases simulat 2016 Jun Rheumatoid vasculitis (RV) is one of the most serious extra-articular complications of rheumatoid arthritis (RA), generally treated with a high dose of immunosuppressive drugs. Recently, we encountered two cases of ulcerative vasculitis in methotrexate (MTX)-prescribed RA patients, which simulated RV; however, Epstein-Barr virus (EBV)-encoded RNA in situ hybridization on their skin biopsies revealed many EBV-positive lymphocytes (over 50 cells/high-power field) within the vessel walls and perivascular stroma, which led us to the diagnosis of EBV-related vasculitis instead of RV. Subsequently, both ulcers regressed after the discontinuation of MTX and no recurrence was noted during the follow-up period. To prevent unnecessary treatment, EBV-positive vasculitis should be added in the differential diagnosis of lymphocytic vasculitis observed in MTX-administered RA patients.
25843554 Complications of systemic juvenile idiopathic arthritis: risk factors and management recom 2015 May Systemic juvenile idiopathic arthritis (SJIA) is an inflammatory condition characterized by fever, lymphadenopathy, arthritis, rash and serositis. Systemic inflammation has been associated with dysregulation of the innate immune system, suggesting that SJIA is an autoinflammatory disorder. IL-1 and IL-6 play a major role in the pathogenesis of SJIA, and treatment with IL-1 and IL-6 inhibitors has shown to be highly effective. However, complications of SJIA, including macrophage activation syndrome, limitations in functional outcome by arthritis and long-term damage from chronic inflammation, continue to be a major issue in SJIA patients' care. Translational research leading to a profound understanding of the cytokine crosstalk in SJIA and the identification of risk factors for SJIA complications will help to improve long-term outcome.
26430590 Distal Junctional Disease after Occipitothoracic Fusion for Rheumatoid Cervical Disorders: 2015 Oct Study Design Retrospective radiographic study. Objective We have performed occipitothoracic (OT) fusion for severe rheumatoid cervical disorders since 1991. In our previous study, we reported that the distal junctional disease occurred in patients with fusion of O-T4 or longer due to increased mechanical stress. The present study further evaluated the association between the distal junctional disease and the cervical spine sagittal alignment. Methods Among 60 consecutive OT fusion cases between 1991 and 2010, 24 patients who underwent O-T5 fusion were enrolled in this study. The patients were grouped based on whether they developed postoperative distal junctional disease (group F) or not (group N). We measured pre- and postoperative O-C2, C2-C7, and O-C7 angles and evaluated the association between these values and the occurrence of distal junctional disease. Results Seven (29%) of 24 patients developed adjacent-level vertebral fractures as distal junctional disease. In group F, the mean pre- and postoperative O-C2, C2-C7, and O-C7 angles were 12.1 and 16.8, 7.2 and 11.2, and 19.4 and 27.9 degrees, respectively. In group N, the mean pre- and postoperative O-C2, C2-C7, and O-C7 angles were 15.9 and 15.0, 4.9 and 5.8, and 21.0 and 20.9 degrees, respectively. There were no significant differences between the two groups. The difference in the O-C7 angle (postoperative angle - preoperative angle) in group F was significantly larger than that in group N (p = 0.04). Conclusion Excessive correction of the O-C7 angle (hyperlordotic alignment) is likely to cause postoperative distal junctional disease following the OT fusion.
27913271 Histone deacetylases (HDAC) in physiological and pathological bone remodelling. 2017 Feb Histone deacetylases (HDACs)(2) play important roles in the epigenetic regulation of gene expression in cells and are emerging therapeutic targets for treating a wide range of diseases. HDAC inhibitors (HDACi)(3) that act on multiple HDAC enzymes have been used clinically to treat a number of solid and hematological malignancies. HDACi are also currently being studied for their efficacy in non-malignant diseases, including pathologic bone loss, but this has necessitated a better understanding of the roles of individual HDAC enzymes, particularly the eleven zinc-containing isozymes. Selective isozyme-specific inhibitors currently being developed against class I HDACs (1, 2, 3 and 8) and class II HDACs (4, 5, 6, 7, 9 and 10) will be valuable tools for elucidating the roles played by individual HDACs in different physiological and pathological settings. Isozyme-specific HDACi promise to have greater efficacy and reduced side effects, as required for treating chronic disease over extended periods of time. This article reviews the current understanding of roles for individual HDAC isozymes and effects of HDACi on bone cells, (osteoblasts, osteoclasts and osteocytes), in relation to bone remodelling in conditions characterised by pathological bone loss, including periodontitis, rheumatoid arthritis and myeloma bone disease.