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ID PMID Title PublicationDate abstract
26324998 Non-proliferating plasma cells detected in the salivary glands and bone marrow of autoimmu 2016 Autoantibody secreting plasma cells (PCs) are essential contributors in the development of autoimmune conditions such as primary Sjögren's syndrome (pSS). Particularly, the long-lived PC subset residing in the bone marrow has shown to continuously produce autoantibodies, whilst remaining unaffected by immunosuppressive treatment. We have previously shown accumulation of potentially long-lived PCs in chronically inflamed salivary glands of pSS patients. In this study, we aimed to characterise the PC compartment in the salivary glands (the target organ for pSS) and bone marrow before the onset of the murine pSS like disease versus advanced diseases progression. Bromodeoxyuridine (BrdU) was incorporated to distinguish the long-lived PCs. Double immunohistochemical staining and immunofluorescence were then conducted on submandibular gland and bone marrow sections from 8- and 40-week-old mice to identify BrdU and CD138. BrdU(+) cells were detected in the submandibular glands of 8-week-old mice, and observed within all focal infiltrates by 40 weeks of age. Most CD138(+) PCs were however BrdU(-) and located predominantly on the periphery of these infiltrates. This observation was verified through immunofluorescence. A comparable staining pattern was observed in the bone marrow of 8- and 40-week-old NOD.B10.H2b mice, where some of the CD138(+) cells also expressed BrdU. Interestingly, megakaryocytes in the bone marrow of NOD.B10.H2b mice were detected in close proximity to CD138(+) cells, illustrating a possible presence of PC survival niches. Our results demonstrate the presence and accumulation of potentially long-lived PCs in NOD.B10.H2b mice as the disease advances.
25277651 Upholding the T cell immune-regulatory function of CD31 inhibits the formation of T/B immu 2015 Jan CD31, a trans-homophilic inhibitory receptor expressed on both T- and B-lymphocytes, drives the mutual detachment of interacting leukocytes. Intriguingly, T cell CD31 molecules relocate to the immunological synapse (IS), where the T and B cells establish a stable interaction. Here, we show that intact CD31 molecules, which are able to drive an inhibitory signal, are concentrated at the periphery of the IS but are excluded from the center of the IS. At this site, were the cells establish the closest contact, the CD31 molecules are cleaved, and most of the extracellular portion of the protein, including the trans-homophilic binding sites, is shed from the cell surface. T cells lacking CD31 trans-homophilic binding sites easily establish stable interactions with B cells; at the opposite, CD31 signaling agonists inhibit T/B IS formation as well as the ensuing helper T cell activation and function. Confocal microscopy and flow cytometry analysis of experimental T/B IS shows that the T cell inhibitory effects of CD31 agonists depend on SHP-2 signaling, which reduces the phosphorylation of ZAP70. The analysis of synovial tissue biopsies from patients affected by rheumatoid arthritis showed that T cell CD31 molecules are excluded from the center of the T/B cell synapses in vivo. Interestingly, the administration of CD31 agonists in vivo significantly attenuated the development of the clinical signs of collagen-induced arthritis in DBA1/J mice. Altogether, our data indicate that the T cell co-inhibitory receptor CD31 prevents the formation of functional T/B immunological synapses and that therapeutic strategies aimed at sustaining CD31 signaling will attenuate the development of autoimmune responses in vivo.
27694530 AT-RvD1 combined with DEX is highly effective in treating TNF-α-mediated disruption of th 2016 Oct Sjögren's syndrome (SS) is an autoimmune disorder characterized by chronic inflammation and destruction of salivary and lacrimal glands leading to dry mouth and dry eyes, respectively. Currently, the etiology of SS is unknown and the current therapies have no permanent benefit; therefore, new approaches are necessary to effectively treat this condition. Resolvins are highly potent endogenous lipid mediators that are synthesized during the resolution of inflammation to restore tissue homeostasis. Previous studies indicate that the resolvin family member, RvD1, binds to the ALX/FPR2 receptor to block inflammatory signals caused by tumor necrosis factor-alpha (TNF-α) in the salivary epithelium. More recently, the corticosteroid, dexamethasone (DEX), was shown to be effective in reducing salivary gland inflammation. However, DEX, as with other corticosteroids, elicits adverse secondary effects that could be ameliorated when used in smaller doses. Therefore, we investigated whether the more stable aspirin-triggered (AT) epimer, AT-RvD1, combined with reduced doses of DEX is effective in treating TNF-α-mediated disruption of polarized rat parotid gland (Par-C10) epithelial cell clusters. Our results indicate that AT-RvD1 and DEX individually reduced TNF-α-mediated alteration in the salivary epithelium (i.e, maintained cell cluster formation, increased lumen size, reduced apoptosis, and preserved cell survival signaling responses) as compared to untreated cells. Furthermore, AT-RvD1 combined with a reduced dose of DEX produced stronger responses (i.e., robust salivary cell cluster formation, larger lumen sizes, further reduced apoptosis, and sustained survival signaling responses) as compared to those observed with individual treatments. These studies demonstrate that AT-RvD1 combined with DEX is highly effective in treating TNF-α-mediated disruption of salivary gland epithelium.
27815440 Identification of Novel CD4+ T Cell Subsets in the Target Tissue of Sjögren's Syndrome an 2016 Nov 15 Despite being one of the most common rheumatologic diseases, there is still no disease-modifying drug for primary Sjögren's syndrome (pSS). Advancing our knowledge of the target tissue has been limited by the low dimensionality of histology techniques and the small size of human salivary gland biopsies. In this study, we took advantage of a molecularly validated mouse model of pSS to characterize tissue-infiltrating CD4(+) T cells and their regulation by the lymphotoxin/LIGHT signaling axis. Novel cell subsets were identified by combining highly dimensional flow and mass cytometry with transcriptomic analyses. Pharmacologic modulation of the LTβR signaling pathway was achieved by treating mice with LTβR-Ig, a therapeutic intervention currently being tested in pSS patients (Baminercept trial NCT01552681). Using these approaches, we identified two novel CD4(+) T cell subsets characterized by high levels of PD1: Prdm1(+) effector regulatory T cells expressing immunoregulatory factors, such as Il10, Areg, Fgl2, and Itgb8, and Il21(+) effector conventional T cells expressing a pathogenic transcriptional signature. Mirroring these observations in mice, large numbers of CD4(+)PD1(+) T cells were detected in salivary glands from Sjögren's patients but not in normal salivary glands or kidney biopsies from lupus nephritis patients. Unexpectedly, LTβR-Ig selectively halted the recruitment of PD1(-) naive, but not PD1(+), effector T cells to the target tissue, leaving the cells with pathogenic potential unaffected. Altogether, this study revealed new cellular players in pSS pathogenesis, their transcriptional signatures, and differential dependency on the lymphotoxin/LIGHT signaling axis that help to interpret the negative results of the Baminercept trial and will guide future therapeutic interventions.
25740829 Treatment with belimumab restores B cell subsets and their expression of B cell activating 2015 Aug OBJECTIVE: The aim of this study was to investigate the biological effects of belimumab on B cells in the first phase II open-label trial with belimumab in patients with primary SS (pSS) (BELISS). METHODS: Peripheral blood B cell subsets and their B cell activating factor-receptor (BAFF-R) expression were analysed by multicolour flow cytometry in 10 pSS patients either before or after 24 and 52 weeks of therapy with belimumab. Serum BAFF levels were analysed by ELISA. RESULTS: At baseline, pSS patients showed a significant increase in circulating B cells compared with healthy donors matched for age and sex, with a predominant expansion of transitional and naive B cell subsets. pSS patients also showed higher serum BAFF levels and lower B cell BAFF-R expression. Therapy with belimumab in pSS patients induced a significant reduction in transitional and naive B cell subsets to levels similar to those observed in healthy donors. Furthermore, belimumab normalized BAFF-R expression in all B subsets comprised within the memory compartment. The restoration of B cell frequency and subset composition in response to belimumab was also associated with a decrease in serum levels of Ig, RF, ANAs, and with an increase in the C4 complement fraction. All of these belimumab-mediated effects were observed after 24 weeks of therapy and maintained until the end of the therapeutic protocol. CONCLUSION: Taken together, our findings show that targeting BAFF with belimumab is successful in normalizing B cell frequency, phenotype and functions in pSS. TRIAL REGISTRATION: clinicaltrials.gov; https://clinicaltrials.gov/; NCT01008982.
27271701 Association between primary Sjögren's syndrome and pregnancy complications: a systematic 2016 Aug Systemic autoimmune disorders may interfere with normal reproductive function resulting in negative outcome of pregnancy. Primary Sjögren's syndrome (pSS) is a common rheumatic disease that mostly affects females. There are many reports that this condition may increase risk of pregnancy complications and fetal loss. However, data regarding these adverse outcomes are scarce and inconclusive. We performed a systematic review and meta-analysis of available articles that assess the association between pSS and adverse pregnancy outcome. We comprehensively searched the databases of MEDLINE and EMBASE from their dates of inception to March 2016 and reviewed papers with validity criteria. A random-effects model was used to evaluate pregnancy complications in patients with pSS and healthy controls. From 20 full-text articles, 7 studies involving 544 patients and 1586 pregnancies were included in the meta-analysis. Fetal complications included spontaneous abortion, stillbirth, neonatal deaths, and intrauterine growth retardation. Compared with healthy pregnancy, patients with pSS had significantly higher chance of neonatal deaths (pooled odds ratio (OR) = 1.77, 95 % confidence interval (CI) 1.28 to 1.46, p = 0.01). However, there were no significant associations between pSS and premature birth (OR = 2.10, 95 % CI 0.59-7.46, p = 0.25), spontaneous abortion (OR = 1.46, 95 % CI 0.72-2.93, p = 0.29), artificial abortion (OR = 1.12, 95 % CI 0.52-2.61, p = 0.71), or stillbirth (OR = 1.05, 95 % CI 0.38-2.97, p = 0.92). There is an increased risk of fetal loss in pregnant patients with pSS. The presented evidence further supports multidisciplinary care for these patients to prevent complications during pregnancy.
26598428 Diagnostic contribution of quantitative analysis of salivary scintigraphy in patients with 2016 May AIM: The evaluation of the salivary scintigraphy is part of the classification criteria of Sjögren's syndrome (SS). The aim of the study was to determine a method of quantitative evaluation of this technique with easy application and high diagnostic accuracy. MATERIAL AND METHODS: A review was carried out on a total of 111 patients with clinical suspicion of SS, referred to our department over the last 4 years (94 women, range 14-82 years). Thirty-minute dynamic studies were performed after injection of (99m)Tc-pertechnetate, with secretory stimulus at 15 minutes. After drawing regions of interest in both parotids, submandibular glands, and in the background, quantitative parameters were determined. These included the ejection fraction, uptake ratio at 15 min, and the percentage uptake (PC). Based on the definitive diagnosis, the subjects were classified into patients with SS, with sicca syndrome, and healthy subjects. RESULTS: Significant differences were found between the SS group and healthy subjects in the 3 quantitative parameters for the 4 glands. Significant differences in the PC parameter were observed between the group with sicca syndrome and healthy subjects. ROC analysis showed that the best differentiation parameter for the 3 groups was the PC in both parotid and submandibular glands. CONCLUSIONS: The quantitative analysis of salivary scintigraphy has proved to be a useful method and easy to apply in daily practice to differentiate patients with SS from healthy subjects, with the PC, both in parotid and submandibular glands, being the parameter with highest diagnostic accuracy.
26053983 Intraductal infusion of steroids in patients with Sjögren syndrome to treat painful saliv 2015 Jun Painful salivary swelling in patients with Sjögren syndrome presents the clinician with a difficult-to-manage condition, and treatment options are limited. We report 2 cases that demonstrate the utility of a clinic-based intraductal corticosteroid infusion for the treatment of painful salivary swelling associated with Sjögren syndrome. Steroid infusion is a cost-effective, simple-to-perform, well-tolerated gland-sparing procedure that may yield good clinical results in selected patients.
25286988 Increased prevalence of MEFV exon 10 variants in Japanese patients with adult-onset Still' 2015 Mar Autoinflammatory diseases include a large spectrum of monogenic diseases, e.g. familial Mediterranean fever (FMF), as well as complex genetic trait diseases, e.g. adult-onset Still's disease (AOSD). In populations where FMF is common, an increased MEFV mutation rate is found in patients with rheumatic diseases. The aim of this study was to examine MEFV mutations in Japanese patients with AOSD. Genomic DNA was isolated from 49 AOSD patients and 105 healthy controls, and exons 1, 2, 3 and 10 of the MEFV gene genotyped by direct sequencing. MEFV mutation frequencies in AOSD patients were compared with controls. We found no significant difference in overall allele frequencies of MEFV variants between AOSD patients and controls. However, MEFV exon 10 variants (M694I and G632S) were significantly higher in AOSD patients than controls (6.1 versus 0%). In addition, there was no significant difference between MEFV variant carriers and non-carriers with clinical manifestations, but the monocyclic clinical course of the AOSD disease phenotype was observed less frequently in patients without MEFV variants. AOSD patients had significantly higher frequencies of MEFV exon 10 mutations, suggesting that low-frequency variants of MEFV gene may be one of the susceptibility factors of AOSD.
26482060 Swallowing Disorders in Sjögren's Syndrome: Prevalence, Risk Factors, and Effects on Qual 2016 Feb This epidemiological investigation examined the prevalence, risk factors, and quality-of-life effects of swallowing disorders in Sjögren's syndrome (SS). One hundred and one individuals with primary or secondary SS (94 females, 7 males; mean age 59.4, SD = 14.1) were interviewed regarding the presence, nature, and impact of swallowing disorders and symptoms. Associations among swallowing disorders and symptoms, select medical and social history factors, SS disease severity, and the M.D. Anderson Dysphagia Inventory (MDADI) and Short Form 36 Health Survey (SF-36) were examined. The prevalence of a current self-reported swallowing disorder was 64.4 %. SS disease severity was the strongest predictor of swallowing disorders, including significant associations with the following swallow symptoms: taking smaller bites, thick mucus in the throat, difficulty placing food in the mouth, and wheezing while eating (p < .05). Additional swallowing disorder risk factors included the presence of a self-reported voice disorder, esophageal reflux, current exposure to secondary tobacco smoke, frequent neck or throat tension, frequent throat clearing, chronic post-nasal drip, and stomach or duodenal ulcers. Swallowing disorders did not differ on the basis of primary or secondary SS. Swallowing disorders and specific swallowing symptoms were uniquely associated with reduced quality of life. Among those with swallowing disorders, 42 % sought treatment, with approximately half reporting improvement. Patient-perceived swallowing disorders are relatively common in SS and increase with disease severity. Specific swallowing symptoms uniquely and significantly reduce swallow and health-related quality of life, indicating the need for increased identification and management of dysphagia in this population.
26445930 Low-intensity pulsed ultrasound rescues insufficient salivary secretion in autoimmune sial 2015 Oct 7 INTRODUCTION: Low-intensity pulsed ultrasound (LIPUS) has been known to promote bone healing by nonthermal effects. In recent studies, LIPUS has been shown to reduce inflammation in injured soft tissues. Xerostomia is one of the most common symptoms in Sjögren syndrome (SS). It is caused by a decrease in the quantity or quality of saliva. The successful treatment of xerostomia is still difficult to achieve and often unsatisfactory. The aim of this study is to clarify the therapeutic effects of LIPUS on xerostomia in SS. METHODS: Human salivary gland acinar (NS-SV-AC) and ductal (NS-SV-DC) cells were cultured with or without tumor necrosis factor-α (TNF-α; 10 ng/ml) before LIPUS or sham exposure. The pulsed ultrasound signal was transmitted at a frequency of 1.5 MHz or 3 MHz with a spatial average intensity of 30 mW/cm(2) and a pulse rate of 20 %. Cell number, net fluid secretion rate, and expression of aquaporin 5 (AQP5) and TNF-α were subsequently analyzed. Inhibitory effects of LIPUS on the nuclear factor κB (NF-κB) pathway were determined by Western blot analysis. The effectiveness of LIPUS in recovering salivary secretion was also examined in a MRL/MpJ/lpr/lpr (MRL/lpr) mouse model of SS with autoimmune sialadenitis. RESULTS: TNF-α stimulation of NS-SV-AC and NS-SV-DC cells resulted in a significant decrease in cell number and net fluid secretion rate (p < 0.01), whereas LIPUS treatment abolished them (p < 0.05). The expression changes of AQP5 and TNF-α were also inhibited in LIPUS treatment by blocking the NF-κB pathway. Furthermore, we found that mRNA expression of A20, a negative feedback regulator, was significantly increased by LIPUS treatment after TNF-α or interleukin 1β stimulation (NS-SV-AC, p < 0.01; NS-SV-DC, p < 0.05). In vivo LIPUS exposure to MRL/lpr mice exhibited a significant increase in both salivary flow and AQP5 expression by reducing inflammation in salivary glands (p < 0.01). CONCLUSIONS: These results suggest that LIPUS upregulates expression of AQP5 and inhibits TNF-α production. Thus, LIPUS may restore secretion by inflamed salivary glands. It may synergistically activate negative feedback of NF-κB signaling in response to inflammatory stimulation. Collectively, LIPUS might be a new strategic therapy for xerostomia in autoimmune sialadenitis with SS.
27283334 Long-term outcome in juvenile-onset mixed connective tissue disease: a nationwide Norwegia 2017 Jan OBJECTIVES: To describe the characteristics, outcome and predictive factors of juvenile mixed connective tissue disease (JMCTD) in a nationwide cohort of patients. METHODS: We examined 55 patients with JMCTD after a mean disease duration of 16.2 years (SD 10.0). Patients were registered according to Kasukawa's criteria. Remission criteria were defined according to those for juvenile idiopathic arthritis, plus absence of cytopenia, myositis, progressive sclerodactyly, lung and oesophageal manifestations. Organ damage was assessed with the Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) Damage Index and the Juvenile Arthritis Damage Index (JADI). Medical records were reviewed for early predictors for outcome, which were assessed by multivariate logistic regression analyses. RESULTS: Three patients developed systemic lupus erythematosus (SLE). Fifty-two patients had continuous JMCTD; the most common manifestations were: Raynaud (100%), arthritis (94%), puffy hands (77%) and pulmonary manifestations (58%). SLE-like, systemic sclerosis (SSc)-like and polymyositis (PM)-like findings were found in 98%, 77% and 48%, respectively. Over time, SLE-like and PM-like manifestations decreased, and SSc-like findings increased. At follow-up, 35 patients (67%) had active disease and 17 (33%) were in remission. In 34 patients (65%), SLICC or JADI≥1 assessments indicated organ damage. Active disease was associated with higher anti-ribonucleoprotein antibody titres at follow-up and positive rheumatoid factor (RF) at diagnosis and follow-up. CONCLUSIONS: Most patients with JMCTD had active disease and organ damage after a mean follow-up of 16.2 years. Active disease was associated with higher anti-ribonucleoprotein antibody levels and positive RF. The presence of RF at diagnosis predicted persistent disease activity.
27039478 Implant Treatment in Patients with Sjogren's Syndrome: A Review of the Literature and Two 2016 Mar Implant rehabilitation in patients with Sjogren's Syndrome is reported to offer an improvementin the quality of life, but the scientific evidence on implant survival in patients with Sjogren's Syndrome is scarce. The paper presents a review of the literature on the performance of dental implants in patients with Sjogren's Syndrome and two case reports of patients with Sjogren's Syndrome treated successfully with dental implants. Two female patients suffering from Sjogren's Syndrome were rehabilitated with implant-supported prostheses. After eighteen months and two years respectively, the patients were satisfied with function and aesthetics; restorations were comfortable, stable radiographic bone levels were noted and xerostomia was not reported to affect the function anymore.
26206346 Ultrasonography of major salivary glands: a highly specific tool for distinguishing primar 2015 Dec OBJECTIVES: Recently, convincing data have been published on the value of salivary gland ultrasonography (SGUS) in differentiating primary SS from non-immune-mediated sicca syndrome. Limited data are available regarding the diagnostic accuracy of SGUS in distinguishing SS from other rheumatic diseases. The purpose of this study was to assess the usefulness of SGUS in distinguishing patients with SS from those with xerostomia and/or xerophthalmia and a diagnosis of stable UCTD. METHODS: This cross-sectional study consecutively enrolled 150 patients either diagnosed with SS (as established by the American-European Consensus Group criteria) or affected by UCTD but not SS. Parotid and submandibular glands on both sides were assessed for size, parenchymal echogenicity and inhomogeneity by means of SGUS, which was performed by a radiologist blinded to the diagnosis. Echostructural alterations of the salivary glands were graded from 0 to 3 (cut-off >2). RESULTS: This study included 109 patients: 55 with SS and 54 with UCTD. Patients with SS showed a higher SGUS score in comparison with those with UCTD [mean 2.2 (s.d. 1.8) vs 0.2 (s.d. 0.5), P < 0.0001]. The SGUS cut-off >2 showed a sensitivity of 65%, a specificity of 96%, a positive predictive value of 95% and a negative predictive value of 73% for SS diagnosis. A significant correlation was also found between the SGUS score and the minor salivary gland biopsy/focus score (r = 0.484, P < 0.0001). CONCLUSION: This study confirmed the good sensitivity and the high specificity of SGUS in differentiating SS from other CTDs.
27571340 Eczema as an adverse effect of anti-TNFα therapy in psoriasis and other Th1-mediated dise 2017 May INTRODUCTION: There have been rare reports of eczema occurring as an adverse effect of anti-tumor necrosis factor-alpha (TNFα) therapy. METHODS: A literature search was conducted on PubMed for articles describing new onset or worsening of preexisting eczema during anti-TNFα therapy for the treatment of various inflammatory diseases. RESULTS: Eczema as an adverse effect of anti-TNFα therapy may occur in approximately 5-20% of patients with various Th1-mediated inflammatory diseases such as psoriasis, inflammatory arthritis and inflammatory bowel disease. Personal history of atopy appears to increase this risk. Out of the anti-TNFα agents indicated for the treatment of moderate-to-severe psoriasis, infliximab may be more strongly associated with development or exacerbation of preexisting eczema. DISCUSSION: Inhibitors of key mediators in the Th1 pathway such as TNFα are successful therapeutic targets for the treatment of various inflammatory conditions such as psoriasis, psoriatic arthritis, rheumatoid arthritis and inflammatory bowel disease. Blocking the Th1 pathway may create an imbalance favoring increased activity of the opposing Th2 pathway implicated in inflammatory conditions such as eczema. Further research is needed to better understand the role of the Th1/Th2 balance in various inflammatory diseases and how the immunologic environment is affected by immunotherapies.
26548380 Efficacy, Tolerability, and Safety of Cannabinoid Treatments in the Rheumatic Diseases: A 2016 May OBJECTIVE: To assess the efficacy, tolerability, and safety of cannabinoids (phyto- and syntheto-) in the management of rheumatic diseases. METHODS: Multiple databases, including Medline, Embase, and CENTRAL, were searched. Randomized controlled trials with outcomes of pain, sleep, quality of life, tolerability (dropouts due to adverse events), and safety (serious adverse events), with comparison of cannabinoids with any type of control, were included. Study methodology quality was evaluated with the Cochrane risk of bias tool. RESULTS: In 4 short-term studies comprising 203 patients (58 with rheumatoid arthritis, 71 with fibromyalgia, and 74 with osteoarthritis [OA]), cannabinoids had a statistically significant effect on pain in 2, sleep in 2, and improved quality of life in 1, with the OA study prematurely terminated due to futility. The risk of bias was high for all 3 completed studies. Dizziness, cognitive problems, and drowsiness, as well as nausea, were reported for almost half of the patients. No serious adverse events were reported for cannabinoids during the study duration. No studies of herbal cannabis were identified. CONCLUSION: Extremely small sample sizes, short study duration, heterogeneity of rheumatic conditions and products, and absence of studies of herbal cannabis allow for only limited conclusions for the effects of cannabinoids in rheumatic conditions. Pain relief and effect on sleep may have some potential therapeutic benefit, but with considerable mild to moderate adverse events. There is currently insufficient evidence to recommend cannabinoid treatments for management of rheumatic diseases pending further study.
26248759 Ankle Arthrodesis Using the Ilizarov Technique in Difficult Situations - a Prospective Stu 2015 Mar BACKGROUND: Although various operative techniques are available for ankle arthrodesis, it is not rare to see orthopaedic surgeons facing difficult situations with ankles that cannot be reliably treated by any conventional methods other than the Ilizarov technique. This study was conducted to measure the outcome in such patients using the Ilizarov Ring fixator. MATERIAL AND METHODS: Sixteen patients (average age 47.5 years) had primary or revision unilateral ankle arthrodesis using the Ilizarov technique. Among the 16 patients the pathology included severe difficult posttraumatic arthritis with diabetes mellitus (n=7), failed arthrodesis with internal fixation (n=4), difficult post-septic arthritis (n=3) and 1 case each of rheumatoid arthritis and post-polio residual palsy with instability. The primary outcome was bony union and ankle alignment. The clinical results were further evaluated according to the American Orthopaedic Foot and Ankle Society scoring (AOFAS) System at 6 months and yearly till final follow-up. RESULTS: All ankles achieved arthrodesis at an average of 14 weeks (range 12-18 weeks). The average duration of follow-up was 5.7 years (range 4- 10 years). No major complication was seen except for 5 cases of superficial pin track infections, wound dehiscence in 1 patient and chronic discharging sinus in 1 patient. The average AOFAS score improved from an average of 35.25 (range 20- 44) points pre-operatively to an average of 78.37 (range 72-89) points at final follow-up. CONCLUSION: Ankle arthrodesis using Ilizarov technique shows a high fusion rate with no major complications and operative failures even in difficult and complicated situations.
26142537 First experience with single-source dual-energy computed tomography in six patients with a 2015 Nov OBJECTIVES: Dual-energy computed tomography (DECT) is an emerging imaging technique for examining patients with suspected gout. Single-source dual-energy CT (S-DECT) is a new way of obtaining DECT information on conventional CT scanners rather than using special dual-source CT systems. METHODS: We tested the feasibility of S-DECT (320-row CT; Aquilion ONE, Toshiba Medical Systems, Otawara, Japan) in 6 patients (5 men, 1 woman; mean age 61.3, range 48 to 69 years) with acute arthralgia and suspected gout, and compared the S-DECT findings with the results of joint aspiration. RESULTS: Three patients had a diagnosis of gouty arthritis with negatively birefringent crystals in synovial fluid, in addition to gouty tophi in S-DECT. Three patients had no detectable crystals by polarization microscopy and no tophi on DECT. Their final diagnoses were rheumatoid arthritis, activated osteoarthritis, and septic arthritis in one case each. CONCLUSION: This initial experience suggests that S-DECT might be a valuable alternative to dual-source CT. Hence, more patients may benefit from its additional diagnostic abilities in the future.
27688083 Leptin and leptin receptors in salivary glands of primary Sjögren's syndrome. 2016 Nov BACKGROUND: The role of leptin in primary Sjögren's syndrome (SS) pathogenesis is unknown. The aim of this study was to investigate the expression of leptin and leptin receptor (LEPR) in minor salivary glands in patients with SS. MATERIALS AND METHODS: The expression of leptin and LEPR in minor salivary gland specimens obtained from patients with primary SS (n=50) and control subjects (n=50) were examined using immunohistochemical staining. RESULTS: Acinar cells, epithelial cells and adipocytes in salivary glands can express leptin and LEPR. It was observed that there was intense staining in the focal lymphocytic infiltration areas in SS patients. The intensity of leptin and LEPR staining under microscopy (400×) were graded semiquantitatively as negative, mild, moderate or strongly positive, and scored as 1, 2 or 3, respectively. The expression levels of leptin and LEPR in patients with primary SS were not higher than in controls. There was no significant difference in degrees of leptin and LEPR staining, staining intensity, and immunoreactive scores between groups. The expression of leptin and LEPR were not correlated with autoantibodies such as RF, ANA, anti-Ro, and/or anti-La positivity. CONCLUSIONS: These findings indicate that leptin and its receptors do not play an important role in primary SS pathophysiology.
26426623 Efficacy of Anakinra in Refractory Adult-Onset Still's Disease: Multicenter Study of 41 Pa 2015 Sep Adult-onset Still's disease (AOSD) is often refractory to standard therapy. Anakinra (ANK), an interleukin-1 receptor antagonist, has demonstrated efficacy in single cases and small series of AOSD. We assessed the efficacy of ANK in a series of AOSD patients. Multicenter retrospective open-label study. ANK was used due to lack of efficacy to standard synthetic immunosuppressive drugs and in some cases also to at least 1 biologic agent. Forty-one patients (26 women/15 men) were recruited. They had a mean age of 34.4 ± 14 years and a median [interquartile range (IQR)] AOSD duration of 3.5 [2-6] years before ANK onset. At that time the most common clinical features were joint manifestations 87.8%, fever 78%, and cutaneous rash 58.5%. ANK yielded rapid and maintained clinical and laboratory improvement. After 1 year of therapy, the frequency of joint and cutaneous manifestations had decreased to 41.5% and to 7.3% respectively, fever from 78% to 14.6%, anemia from 56.1% to 9.8%, and lymphadenopathy from 26.8% to 4.9%. A dramatic improvement of laboratory parameters was also achieved. The median [IQR] prednisone dose was also reduced from 20 [11.3-47.5] mg/day at ANK onset to 5 [0-10] at 12 months. After a median [IQR] follow-up of 16 [5-50] months, the most important side effects were cutaneous manifestations (n = 8), mild leukopenia (n = 3), myopathy (n = 1), and infections (n = 5). ANK is associated with rapid and maintained clinical and laboratory improvement, even in nonresponders to other biologic agents. However, joint manifestations are more refractory than the systemic manifestations.