The aim of the study was to evaluate the clinical and genetic predictors of AA amyloidosis in patients with familial Mediterranean fever (FMF). We retrospectively studied 170 Armenian patients who were admitted to the two tertiary centers in 2003-2014. The diagnosis of amyloidosis that was suspected clinically (new proteinuria or nephrotic syndrome) was confirmed histologically. Screening for MEFV gene mutations was performed in 70 patients. The most common genotype was M694V/M694V (in 36 % of patients). Biopsy-proven AA amyloidosis was found in 102 (60 %) of 170 patients. AA amyloidosis was diagnosed in 17 (68 %) of 25 patients with homozygous M694V mutation, 17 (53 %) of 32 patients with heterozygous M694V allele and 4 (31 %) of 13 patients with other MEFV gene mutations. The M694V homozygosity and heterozygosity were associated with increased risk of AA amyloidosis, but this association did not reach statistical significance (odds ratio 2.43; 95 % CI 0.87-6.76, and 3.33; 0.91-12.1, respectively). Male gender, early onset of disease, severity of FMF, frequent attacks, peritonitis, pleuritis and erysipelas-like erythema also did not predict AA amyloidosis development. Recurrent arthritis was the only clinical finding that was significantly associated with AA amyloidosis (odds ratio 2.28; 95 % CI 1.17-4.42). Involvement of the joint synovial membrane, that is capable of active serum amyloid A production, is the main predictor of renal amyloidosis in FMF.

Hintergrund: Ziel dieser Studie war es herauszufinden, ob das mit Cochlea-Implantaten erreichbare Tonhö henunterscheidungsvermö gen vom Ort der Stimulation (apikal, medial, basal) und von der Stimulationsrate abhä ngt. Dabei wurde auch der Einfluss der Lage der Messfrequenz innerhalb der Teilbä nder (Bandmitte oder Ü berlappungsbereich zweier benachbarter Bä nder) untersucht. Verglichen wurden zwei Sprachkodierungsstrategien, nä mlich die Stimulationsstrategie CISþ, basierend auf der Continuous Interleaved Sampling-Strategie (CIS), und die Feinstruktur-Strategie (FS), welche im tieffrequenten Bereich zusä tzliche Details der zeitlichen Struktur des Eingangssignals reprä sentiert. Weiters wurde untersucht, ob signifikante Unterschiede in der Tonhö henwahrnehmung feststellbar sind, wenn pro Kanal entweder mit 1818 Pulsen pro Sekunde (pps) oder mit 3030 pps stimuliert wird.Material und Methoden: Die Hö rversuche wurden mit sieben postlingual ertaubten Erwachsenen durchgefü hrt. Alle Testpersonen waren erfahrene Benü tzer der MED-EL COMBI 40þ-und PULSAR CI 100 -Implantate. Nach der Anpassung der patientenspezifischen Parameter wurde mit den Testpersonen ein Lautstä rkenabgleich durchgefü hrt. Dabei wurden die generierten Sinustö ne mit gleichmä ßigen Frequenzschritten auf gleichen Lautstä rkeeindruck eingestellt. Das Ergebnis dieses Lautstä rkenabgleichs ist in die verwendete Alternative Forced Choice(AFC)-Testsoftware eingeflossen, mit der auch die differentielle Tonhö henWahrnehmbarkeitsschwelle gemessen wurde. Tonhö henunterscheidbarkeitsschwellen -auch als "Just Noticeable Differences (JNDs) in pitch" bezeichnet -wurden mit Hilfe eines mittels MATLAB entwickelten Softwareprogramms gemessen. Dieses Softwareprogramm bestimmt Unterscheidbarkeitsschwellen mittels einer "Two-Interval Two Alternative Forced-Choice(2I-2AFC)"-Prozedur unter Verwendung einer "Three-down one-up"-Regel zur Abschä tzung des 79,4-%-Punktes auf der psychometrischen Funktion.Ergebnisse: Die Mittelwerte der differenziellen Wahrnehmbarkeitsschwelle lagen bei Verwendung der Filtermittenfrequenz als Basisfrequenz und den apikalen Kanä len bei der FS-Strategie zwischen 5 % und 8 %, bei CISþ zwischen 7 % und 32 % und zeigten somit signifikante Unterschiede. Bei der Ü berlappungsfrequenz lagen die JNDs mit der FS-Strategie zwischen 5 % und 9 %, mit CISþ zwischen 6 % und 9 %. Bei den apikalen Kanä len zeigte sich außerdem, dass eine hö here Stimulationsrate zu deutlich besseren Ergebnissen bei der Tonhö henunterscheidung fü hrte, ebenso wie bei den medialen Kanä len bei Filtermittenfrequenz. Hinsichtlich der Strategien ergaben sich nur bei hö herer Stimulationsrate signifikante Unterschiede. Die JNDs lagen mit der FS-Strategie zwischen 3 % und 5 %, mit CISþ zwischen 4 % und 7 %. Bei den basalen Kanä len konnte durch die Anordnung der Feinstruktur-Kanä le nur der Einfluss der Stimulationsrate bei CISþ untersucht werden. Hierbei ergaben sich keine signifikanten Unterschiede, die JNDs lagen unabhä ngig von der Stimulationsrate zwischen 6 % und 9 %.Schluss...

Background:Chronic anticoagulation with vitamin K antagonists (VKA) is the standard treatment to prevent thrombotic events in antiphospholipid syndrome (APS). But in recent years treatment schemes began to include rivaroxaban. Use of direct oral anticoagulants (DOAC) is an attractive and often preferred alternative to VKAs in other medical settings owing to greater ease of use, fewer food and drug interactions, and lower bleeding risks [1].However, according to last guidelines, rivaroxaban should not be used in patients with triple aPL positivity due to the high risk of recurrent events [2].Objectives:1.To determine the risk of recurrent thrombosis in single or double positive APS patients treated with rivaroxaban.2.Find out possible association between presence of particular antiphospholipid antibodies or high level of lupus anticoagulant (LA) and type of vascular events.Methods:33 patients with confirmed APS (25 female (75.8%), 8 male (24.2%), mean age 43.2±11.6 years) were included in the study. 17 (51.5%) of investigated patients had primary APS, in remaining 16 (48.5%) APS was included in the framework of SLE. 18 (54.5%) patients were treated with warfarin 2.5-7.5 mg/daily, 15 (45.5%) patients - with rivaroxaban 20mg/daily for a follow-up period of 12 months. The data is introduced as odds ratios (OR) with 95% confidence interval (CI). The results were considered significant when p <0.05.Results:At baseline 21 (63.6%) patients had history of arterial thrombosis, 10 (30.3%) - venous thrombosis, 17 (51.5%) - pregnancy loss. According to results of serum immunology check, 29 (87.9%) patients were anticardiolipin antibody (ACA) positive, 9 (27.3%) - LA positive, 19 (57.6%) - anti-ß2-glycoprotein antibodies (anti-ß2-gp) positive; 20 (60.6%) patients were double positive (12 (36.4%) of them had positive ACA and anti-ß2-gp, 6 (18.2%) - ACA and LA, and 2 (6.1%) - anti-ß2-gp and LA), 4 (12.1%) patients were triple positive.No association between vascular event and/or pregnancy loss in patients with single positive ACA was found. We have found positive association between arterial thrombosis and single positive anti-ß2-gp (OR /CI 95%/ = 5.0 /2.08 – 23.06/, p< 0.05), positive association between positive LA and venous thrombosis (OR /CI 95%/ = 10 /1.7-57.7/, p< 0.05), strong positive association between positive LA and thromboembolism of pulmonary artery (OR /CI 95%/ = 46.0 /4.0-525.1/, p< 0.001), negative association between positive LA and pregnancy loss (OR /CI 95%/ =0.06 /0.03 – 0.1/, p< 0.01).Risk of thrombosis and/or pregnancy loss was not significantly increased in double positive patients, but triple positive patients had increased risk of venous thrombosis (OR /CI 95%/ =9.4 /3.2 – 105.8/, p<0.04).Recurrent thrombosis was detected in 16 patients: 2 patients (12.5%) were on warfarin, 14 (87.5%) - on rivaroxaban (10 (71.4%) arterial thrombosis, 4 (28.6%) venous thrombosis).No association between warfarin 2.5-7.5 mg/daily and occurrence of recurrent thrombosis was detected. An association between use of warfarin and increased risk of bleeding was found, but the risk was not significant (OR /CI 95%/ = 7.0 /0.7 – 66/, p= 0.09). Rivaroxaban 20 mg/daily was associated with recurrent thrombosis not only for triple positive patients (p< 0.02), but also in double positive patients (OR /CI 95%/ = 21.3 /1.8 – 251/, p< 0.04).Conclusion:Rivaroxaban does not prevent recurrent thrombosis not only in triple positive patients, but also in single and double positive APS patients. Type of antiphospholipid antibodies can be predictive for the type of further vascular event.References:[1]Vittorio Pengo, Gentian Denas, Giacomo Zoppellaro et al.Rivroxaban vs warfarin in high risk patients with antiphospholipid syndrome, Blood. 2018 Sep 27; 132(13); 1357-1358.[2]EULAR recommendations for the management of antiphospholipid syndrome in adults, Annals of the Rheumatic Diseases/ Volume 78: Issue 10:1296-1304.Disclosure of Interests:None declared

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Background Although glucocorticoids (GC) may effectively be used in the management of many inflammatory conditions, such as asthma, rheumatoid arthritis, inflammatory bowel disease and autoimmune diseases, their use is associated with significant morbidity and mortality. Osteoporosis, with resultant fractures, constitutes one of these morbid complications and is associated with significant pain and disability. According to ACR 2010 Recommendations for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis (GIOP) bisphosphonates should be used as a first-line treatment in these patients. Nevertheless, in some cases of chronic continuous use of GC bisphosphonates remain inefficacious, creating a major requisite for investigation of efficacy of other anti-osteoporotic medications in the treatment of GIOP Objectives To evaluate the efficacy of strontium ranelate after 24 weeks of treatment of GIOP in postmenopausal women with inadequate response to bisphosphonates. Methods 30 female postmenopausal patients (mean age (± SD) 51,87±4,9 years, mean daily dose of prednisone 8,16±2,7 mg, mean duration of GC therapy 12,5±9,07 months, 13 patients (43,3%) had prior history of fragility fractures) with rheumatoid arthritis and confirmed concomitant GIOP, having prior inadequate response to bisphosphonates, were treated with strontium ranelate (2 g/daily) for a follow-up period of 24 weeks. Calcium and vitamin D preparations in standard doses were included in the treatment regimen. Exclusion criteria included congenital bone defects, endocrine diseases, hematological diseases, renal diseases, cardiovascular diseases. Dual-energy x-ray absorptiometry (DXA), vertebral and hip imaging, as well as determination of serum concentration of β-CrossLaps (β-form of C-terminal telopeptide of type I collagen) were performed twice – at baseline and at the end of follow-up period. Routine investigation included accurate collection of disease history, objective examination with determining the disease activity (DAS) and functioning (HAQ-Di and global functional status), CBC, measurement of plasma creatinine level and lipid profile, ECG, echocardiography and other examinations. Results DXA had shown the following results at baseline: mean spine T-score -3,16±0,48, mean hip T-score -3,18±0,52. Serum concentration of β-CrossLaps at baseline made 989,9±506,4 pg/mL. All enrolled patients completed 24 weeks of treatment. Strontium ranelate was well tolerated, no serious adverse events occurred. At the end of study period DXA mean T-scores both spine and hip had shown significantly higher results: -3,0±0,45 (p<0,01) and -3,01±0,53 (p<0,05) respectively. Mean serum concentration of β-CrossLaps after 24 weeks of strontium ranelate treatment was significantly lower than at baseline (874,4±505,6 pg/mL, p<0,05). Conclusions Strontium ranelate may be used for the treatment of GIOP in patients with inadequate response to bisphosphonates. Taking into account the possible negative impact of strontium ranelate on cardiovascular system, s...