Clinical characteristics and disease course before and after SARS-CoV-2 infection in a large cohort of systemic sclerosis patients.

Background/aim: The objective of this study is to evaluate the clinical presentations and adverse outcomes of Coronavirus Disease 2019 (COVID-19) in patients with systemic sclerosis (SSc) and assess the impact of SSc features on the clinical course of COVID-19. Materials and methods: In this multicenter, retrospective study, SSc patients with COVID-19 were included. Clinical features of SSc, along with detailed COVID-19 data, were extracted from medical records and patient interviews. Results: The study included 112 patients (mean age 51.4 ± 12.8 years; 90.2% female). SSc-associated interstitial lung disease (ILD) was evident in 57.1% of the patients. The findings revealed hospitalization in 25.5%, respiratory support in 16.3%, intensive care unit admission in 3.6%, and a mortality rate of 2.7% among SSc patients with COVID-19. Risk factors for respiratory failure, identified through univariate analysis, included ILD (OR: 7.49, 95% CI: 1.63-34.46), ≥1 comorbidity (OR: 4.55, 95% CI: 1.39-14.88), a higher physician global assessment score at the last outpatient visit (OR 2.73, 95% CI: 1.22-6.10), and the use of mycophenolate at the time of infection (OR: 5.16, 95 %CI: 1.79-14.99). Notably, ≥1 comorbidity emerged as the sole significant predictor of the need for respiratory support in COVID-19 (OR: 5.78, 95% CI: 1.14-29.23). In the early post-COVID-19 period, 17% of patients reported the progression of the Raynaud phenomenon, and 10.6% developed new digital ulcers. Furthermore, progression or new onset of dyspnea and cough were detected in 28.3% and 11.4% of patients, respectively. Conclusion: This study suggests a potential association between adverse outcomes of COVID-19 and SSc-related ILD, severe disease activity, and the use of mycophenolate. Additionally, it highlights that having comorbidities is an independent risk factor for the need for respiratory support in COVID-19 cases.

Association between oxygen delivery and digital ulcers in systemic sclerosis.

OBJECTIVE: Tissue hypoxia due to microvasculopathy is the main cause of digital ulcers (DUs) in systemic sclerosis (SSc). Reduced oxygen delivery (DO2) to the tissues may also contribute to the development of DU. This study was conducted to investigate the association between DO2 and DUs in patients with SSc. METHODS: In all, 111 patients and 30 healthy controls were enrolled. DO2 was calculated by using the formula; DO2 = Cardiac output × arterial oxygen saturation (SpO2) × serum haemoglobin level × 1.39 × 10. Both right index finger SpO2 measurements (index-SpO2) and highest value of SpO2 (maximum SpO2) obtained among the fingers of the subjects were used for the calculations and DO2 results were adjusted both for weight and body surface area (BSA). RESULTS: Mean DO2 was lower in SSc patients as compared to controls in all 4 different calculations but the difference was only statistically significant when using index-SpO2 and adjusting for BSA (498 mL/min/m2 vs 549 mL/min/m2, p = 0.03). There was a strong positive correlation between cardiac output and DO2 calculated by using the index-SpO2 (r = 0.903; p < 0.001). Of the SSc patients, 46 (41.4 %) had DUs within the last 12 months. Patients with DUs had higher mean mRSS, lover mean FVC and more frequently diffuse disease, interstitial lung disease, anti-SCL70 antibody positivity (p < 0.05 for all). No difference was observed in DO2 among DU positive or DU negative groups by any calculation (p > 0.05 for all). CONCLUSIONS: DO2 in SSc patients seems to be lower than healthy controls. However, DO2 is similar between the patients with and without DUs. Our results suggest that the contribution of DO2 is negligible to the development of DU and support the major role of microvasculopathy in SSc patients with DUs.

Treatment of systemic sclerosis-associated digital ulcers: recommendations of the Turkish Society for Rheumatology.

OBJECTIVES: Digital ulcers (DUs) are associated with a significant burden in systemic sclerosis (SSc) by leading to severe pain, physical disability, and reduced quality of life. This effort aimed to develop recommendations of the Turkish Society for Rheumatology (TRD) on the management of DUs associated with SSc. METHODS: In the first meeting held in December 2020 with the participation of a task force consisting of 23 rheumatologists the scope of the recommendations and research questions were determined. A systematic literature review was conducted by 5 fellows and results were presented to the task force during the second meeting. The Oxford system was used to determine the level of evidence. The preliminary recommendations were discussed, modified, and voted by the task force and then by members of TRD via e-mail invitation allowing personalised access to a web-based questionnaire [SurveyMonkey®]. RESULTS: A total of 23 recommendations under 7 main headings were formulated covering non-pharmacological measures for the prevention of DUs and pharmacological treatments including vasodilators, anti-aggregants, antibiotics, wound care, pain control, and interventions including sympathectomy, botulinum toxin, and surgery. Risk factors, poor prognostic factors, prevention of DU and adverse effects of medical treatments were reported as 4 overarching principles. CONCLUSIONS: These evidence-based recommendations for the management of SSc-associated DUs were developed to provide a useful guide to all physicians who are involved in the care of patients with SSc, as well as to point out unmet needs in this field.

Does decision tree analysis predict oral ulcer activity-related factors in patients with Behçet's syndrome?

OBJECTIVES: The study aimed to identify the interactions among treatment protocols and oral ulcer activity related factors in patients with Behçet's syndrome (BS) using the Classification and Regression Tree (CART) algorithm. METHODS: In this cross-sectional study, 979 patients with BS were included from16 centres in Turkey, Jordan, Brazil and the United Kingdom. In the CART algorithm, activities of oral ulcer (active vs. inactive), genital ulcer (active vs. inactive), cutaneous involvement (active vs. inactive), musculoskeletal involvement (active vs. inactive), gender (male vs. female), disease severity (mucocutaneous and musculoskeletal involvement vs. major organ involvement), smoking habits (current smoker vs. non-smoker), tooth brushing habits (irregular vs. regular), were input variables. The treatment protocols regarding immunosuppressive (IS) or non-IS medications were the target variable used to split from parent nodes to purer child nodes in the study. RESULTS: In mucocutaneous and musculoskeletal involvement (n=538), the ratio of IS use was higher in patients with irregular toothbrushing (ITB) habits (27.1%) than in patients with regular toothbrushing (RTB) habits (14.2%) in oral ulcer activity. In major organ involvement (n=441), male patients with ITB habits were more likely treated with IS medications compared to those with RTB habits (91.6% vs. 77.6%, respectively). CONCLUSIONS: Male BS patients on IS who have major organ involvement and oral ulcer activity with mucocutaneous and musculoskeletal involvement have irregular toothbrushing habits. Improved oral hygiene practices should be considered to be an integral part for implementing patient empowerment strategies for BS.

Pulmonary hypertension in Behçet's disease: echocardiographic screening and multidisciplinary approach.

BACKGROUND: Little is known about the prevalence and causes of pulmonary hypertension (PH) in Behçet's disease (BD). This study was conducted to determine the prevalence and causes of PH in BD. METHODS: In this descriptive study, we screened 154 patients with BD for PH using transthoracic echocardiography between February 2017 and October 2017. An estimated systolic pulmonary arterial pressure (sPAP ≥ 40 mmHg) was used as the cutoff value to define PH. Patients with BD were categorized into 5 groups according to organ involvement including mucocutaneous/ articular, ocular, vascular, gastrointestinal, and neurologic involvement. Additional laboratory and imaging results were obtained from hospital file records to determine the causes of PH. RESULTS: PH was detected in 17 (11%) patients. Nine (52.9%) of these patients had group II PH (due to left heart disease), 4 (23.5%) had IV PH (due to pulmonary arterial involvement), and 1 had III PH (due to chronic obstructive lung disease). The frequency of PH was higher in BD patients with vascular involvement than those without (52.9% vs 28.5%; p = 0.04). Among 10 patients with pulmonary artery involvement (PAI) 4 (40%) had PH. Although the vascular BD group had the highest rate of PH, we observed no statistically significant difference in the frequency of PH between the predefined BD subgroups. DISCUSSION: : PH is not rare in patients with BD. The majority of BD patients with PH are in group II or IV PH. Patients with vascularinvolvement carry a higher risk for the development of PH. Monitoring BD patients with PAI should be considered for the development of group IV PH.

The impact of antiphospholipid antibodies in Takayasu arteritis.

BACKGROUND: The significance of antiphospholipid antibodies (aPL) is controversial in Takayasu arteritis (TA). This study was conducted to explore the frequency of aPL and their association with disease-related complications in TA. METHODS: : This cross-sectional study was conducted to investigate the presence of anti-cardiolipin (aCL), anti-beta 2 glycoprotein- 1(aß2G1) antibodies, and lupus anticoagulant (LA) in TA patients. TA patients admitted to the Department of Rheumatology of Hacettepe University Faculty of Medicine between December 2015 and September 2016 who fulfilled the American College of Rheumatology (ACR) classification criteria for TA were consecutively enrolled in the study. Patients were grouped according to aPL positivity and compared in terms of disease manifestations, type of vascular involvement at diagnosis, and vascular complications/interventions attributable to TA. RESULTS: Fifty-three TA (49 female) patients were enrolled in the study. We detected 9 (16.9%) patients with IgM and/or IgG aß2G1 and/or LA positivity. There were no patients with positive aCL. All aß2G1 titers were low. There were no differences in terms of symptoms, signs, type of vascular involvement, the number of patients with disease-related complications or vascular interventions/surgery between aPL (+) and aPL(-) groups (p > 0.05 for all). The number of patients with thrombotic lesions was similar between the groups (p > 0.05). There were no patients with a history of venous thrombosis or on anticoagulant treatment in the aPL(+) group. Only 1 patient with IgM aß2G1 (+) had a history of pregnancy loss. DISCUSSION: Our results indicate that aPL positivity is not rare in TA. On the other hand, all aPL titers were low and no differences were found in the frequency of disease-related complications between aPL(+) and aPL(-) patient groups. Only TA patients with atypical manifestations with high suspicion of aPL-related complications should be considered to be investigated for aPL.

Is the impact of biologic agents in enteropathic spondylitis different from other spondylitis? Real life data from the HUR-BIO Registry.

OBJECTIVES: To compare enteropathic spondylitis (ES) with psoriatic spondylitis (PS) and ankylosing spondylitis (AS), in patients on biological disease-modifying anti-rheumatic drug (bDMARD) treatment. METHODS: Patients who were enrolled in the HUR-BIO registry were included. ES patients were considered as the main study group; AS and PS patients were included as the control groups. ES was defined as patients with inflammatory bowel disease (IBD) having inflammatory back pain/spine symptoms plus radiological sacroiliitis. RESULTS: Sixty-four ES patients (46.9% female), 128 AS patients (39.1% female), and 92 PS patients (62% female) were analysed. Baseline erythrocyte sedimentation rate (ESR) was significantly higher in the ES group than in the AS group. Both the baseline ESR and C-reactive protein were also higher in the ES group compared with the PS group. Among the first bDMARD use, infliximab use was higher in the ES group than the other groups. There was a marginal significant difference between the SpA subgroups in the retention rates of the first bDMARDs (log-rank, p=0.059). Ulcerative colitis was a significant predictor for switching of bDMARDs in comparison to Crohn's disease. Regarding the treatment responses, no significant differences were relevant for the three groups in terms of 50% improvement of the initial Bath Ankylosing Spondylitis Disease Activity Index score, the Assessment of Spondyloarthritis International Society partial remission score, and 20% improvement of ASAS score. CONCLUSIONS: A large majority of enteropathic spondyloarthritis patients on bDMARD treatment had radiographic sacroiliitis. ES patients had distinctive features that distinguish them from AS and PS patients.

Effects of 3 months of treatment with empagliflozin on left ventricle global longitudinal strain and myocardial mechano-energetic effiency.

PURPOSE: Sodium glucose transporter-2 (SGLT-2) inhibitors are employed in the treatment of cardiovascular diseases such as heart failure and coronary artery disease. In the present study, we aimed to investigate how Empagliflozin in SGLT 2 inhibitors affects cardiac contraction and pump efficiency in patients who have Diabetes Mellitus (DM) without cardiovascular disease. METHODS: The conventional echocardiographic records and biochemical values ​​of 62 patients who had DM without a history of cardiovascular disease were evaluated before using Empagliflozin. The myocardial mechano-energetic (MME) activity and index, and global longitudinal strain (GLS) were also calculated. After 3 months of Empagliflozin use, the tests were repeated and compared with previous data. A p < .05 was considered statistically significant. RESULTS: Left ventricular GLS and MME efficiency were found to be significantly higher after treatment (-17.71 ± 2.12, -19.15 ± .71; p < .001 and 62.14 ± 18.21, 72.24 ± 26.57; p: .019). CONCLUSION: An increase was detected in left ventricular longitudinal strain and MME efficiency after using Empagliflozin for 3 months in patients with DM. This result suggests that Empagliflozin improves left ventricular pump efficiency and contraction.

Pleuroparenchymal fibroelastosis in systemic sclerosis-associated interstitial lung disease.

BACKGROUND: To explore the frequency and clinical associations of radiologic pleuroparenchymal fibroelastosis (PPFE) in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD). METHODS: In this single-center retrospective study, high resolution computed tomography (HRCT) images of 105 patients with SSc-ILD were examined for the presence of PPFE. Demographic, clinical, laboratory, and pulmonary function test (PFT) data of patients with and without PPFE were compared. RESULTS: PPFE was detected in 19 (18.1%) patients ('definite PPFE' in 13 and 'consistent with PPFE' in 6 patients). Patients with PPFE had higher age and longer disease duration than PPFE (-) patients (p < 0.05 for both). Radiologic usual interstitial pneumoniae (UIP) pattern was more frequent (26.3% vs. 4.7%, p = 0.01) and median force vital capacity (FVC) was lower in patients with PPFE (64% vs. 82%, p = 0.005). Spontaneous pneumothorax developed in one patient with PPFE. More deaths occured in PPFE (+) group during follow-up (31% vs. 11%, p = 0.04).

Predictors of persistent inflammation in familial Mediterranean fever and association with damage.

OBJECTIVE: Persistent inflammation is an insidious and less studied feature of FMF. We investigated clinical determinants of persistent inflammation and its associations with individual damage items. METHODS: This is a cross-sectional analysis of 917 FMF patients, who fulfilled the Tel Hashomer criteria and had at least 6 months' follow-up. Patients were stratified based on whether they had persistent inflammation. We used logistic regression analysis to investigate independent predictors of persistent inflammation and the associated individual damage items. RESULTS: One hundred and forty-two (15%) patients had persistent inflammation. Active FMF (54%) was the most prominent reason for the persistent inflammation. Spondylarthritis (16%), other inflammatory arthritis (8%) and IBD (2%) were other frequent reasons. Male gender, history of exertional leg pain, inflammatory comorbidities, M694V homozygosity, colchicine resistance, lower education levels and musculoskeletal attack dominance were found to be the independent predictors of persistent inflammation. Earlier disease onset led to a tendency towards persistent inflammation. Patients with persistent inflammation were more likely to suffer damage. There is an increased risk of developing proteinuria, amyloidosis and renal insufficiency. CONCLUSION: We identified, for the first time, the predictors of persistent inflammation in adult FMF patients and related individual damage items of the Autoinflammatory Disease Damage Index. Persistent inflammation is insidious and one of the chief causes of damage; therefore, especially patients with these predictors should be followed up more closely. If detected, underlying inflammatory comorbidities should be assessed meticulously as early detection and proper treatment strategies may favourably impact the natural history of the disease.

Is Takayasu's arteritis more severe in children?

OBJECTIVES: Takayasu's arteritis (TAK) is a chronic vasculitis, affecting predominantly the aorta and/or its major branches. The aim of this study was to compare the differences between childhood and adult onset TAK. METHODS: We retrospectively evaluated 179 TAK patients followed between August 2005 and July 2019. Demographic characteristics, laboratory features, disease activity, echocardiographic data at diagnosis and treatment regimens in the disease course were compared between the paediatric and adult onset patients. RESULTS: Twenty-five paediatric-onset (<18 years of age at diagnosis) and 154 adult-onset patients (≥18 years of age at diagnosis) were enrolled. The mean age at diagnosis for children and adults were 13.6±4 and 35.6±13, respectively. Paediatric onset TAK patients had more intense inflammation at the time of diagnosis reflected in their clinical findings. Acute phase reactants were high in all paediatric patients and significantly higher in patients with paediatric-onset TAK (p=0.006 and p=0.005, respectively). Abdominal predominant disease was more common in the paediatric group, in contrast, focal disease and aortic arch predominant disease were more common in the adult group. Ascending aortic dilatation, left ventricular hypertrophy and moderate-severe aortic insufficiency were more frequent in echocardiography findings of paediatric onset TAK patients. In comorbidities, hypertension was more common in paediatric TAK patients during follow-up, whereas cerebrovascular disease was more common in adult patients. CONCLUSIONS: Our paediatric onset TAK patients presented with a more severe inflammation and more widespread vascular involvement. Multicentre studies from different geographic areas are needed to verify our observation and understand the underlying causes.

Pulmonary manifestations of antiphospholipid syndrome: a retrospective analysis of 67 patients.

Antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by arterial and/ or venous thrombosis accompanied by persistently elevated levels of antiphospholipid antibodies (aPLs). The aim of this study is to evaluate the pulmonary manifestations of APS and compare the levels of aPLs in patients with and without pulmonary involvement. We retrospectively reviewed the files of patients with the diagnosis of APS between October 2010 and May 2017. Demographic data, clinical, radiological and laboratory findings were recorded. The study included 67 patients (56 female/11 male) with a mean age of 39 ± 13 years. Pulmonary manifestations such as parenchymal and/or vascular involvement were seen in 12 (17.9%) patients. The patients with and without pulmonary manifestations were not significantly different in terms of age (p = 0.46), comorbidities (p = 0.48) and APS duration (p = 0.66). Acute pulmonary thromboembolism (PE) was determined in 11 (16.4%), alveolar hemorrhage in 2 (3%) patients. Four patients with acute PE (36%) developed chronic thromboembolic pulmonary hypertension (CTEPH). One patient developed both CTEPH and diffuse alveolar hemorrhage after acute PE during follow up. Antiphosholipid antibody IgM was highly positive in patients with PE compared to patients without PE (p = 0.005). Other antibodies and lupus anticoagulant were not significantly different in patients with and without PE. None of the patients were deceased due to pulmonary manifestations of APS. PE was the most common pulmonary manifestation of APS. The development of CTEPH was high among APS patients. Patients with APS should be closely followed for the onset of PE and CTEPH.

Appendectomy history is associated with severe disease and colchicine resistance in adult familial Mediterranean fever patients

Background/aim: Peritonitis attacks of Familial Mediterranean Fever (FMF) usually requires emergency medical admissions and it's hard to distinguish a typical abdominal attack from surgical causes of acute abdomen. Therefore, history of abdominal surgery, particularly appendectomy, is very common in patients with FMF. However, history of appendectomy might also give some clues about the course of FMF in the adulthood. This study was to determine whether the history of appendectomy help to anticipate disease course of FMF in the adulthood. Materials and methods: All patients recruited from FMF in Central Anatolia (FiCA) cohort, comprising 971 adult subjects. All patients fulfilled the Tel Hashomer criteria. Demographic data, FMF disease characteristics, co-morbid conditions, past medical history, surgical history and disease complications were meticulously questioned and laboratory features and genotype data (if available) were recruited from patient files. Results: Appendectomy history was evident in 240 (24.7%) subjects. Disease onset was earlier and peritonitis is strikingly more prevalent (97.1% vs. 89.6%, p < 0.001) in appendectomized patients. These patients had reported almost two fold more frequent attacks in the last year compared to appendix intact patients (median 3.5 vs. 2 attacks, p = 0.001) without a difference in frequency of musculoskeletal and skin attacks. Severe disease was more common (10% vs. 5.9%, p = 0.038) due to involvement of more attack sites throughout the life and more frequent attacks. Appendectomy patients had used higher daily doses of colchicine to control disease (1.43 ± 0.6 mg vs. 1.27 ± 0.52 mg, p = 0.002) but colchicine resistance was also more common in these patients, 15% vs. 6.7% respectively, p < 0.001. Conclusion: Appendectomy history is common in FMF patients and associated with frequent serositis attacks in adulthood. These patients require higher colchicine doses with a lower rate of response and more need for Interleukin-1 antagonist therapies.

Phenotypic characterization of Familial Mediterranean Fever patients harboring variants of uncertain significance

Background/aim: Familial Mediterranean Fever (FMF) is the prototype of hereditary autoinflammatory disorders and caused by mutations on the MEFV gene located on the short arm of chromosome 16. Although some MEFV variants are clearly associated with disease phenotype, there are numerous variants with unknown clinical association which are termed as variants of uncertain significance (VUS). Here, we present clinical correlations of VUS in a large cohort of adult FMF patients from three tertiary centers located in Central Anatolia. Materials and methods: All patients were recruited from FMF in Central Anatolia (FiCA) cohort. Demographic (sex, age at disease onset) and clinical features (disease characteristics, attack frequency, mean colchicine dose, colchicine nonresponsiveness, amyloidosis, and persistent inflammation) of patients with VUS were compared with those harboring pathogenic variants. Disease severity and damage were also evaluated using international severity score for FMF (ISSF) and autoinflammatory disease damage index (ADDI), respectively. Results: Among 971 participants included, MEFV gene analysis results were available for 814 patients. Twenty-six (3.2%) patients had single heterozygous VUS and 54 (6.6%) had pathogenic/VUS complex heterozygous variants. Patients with single heterozygous VUS had similar demographic/clinical features, ISSF and ADDI scores compared to those with single heterozygous pathogenic variant (p > 0.05 for all). No difference was observed in the demographic and clinical features of patients with single heterozygous pathogenic mutation and pathogenic/VUS complex heterozygous variant (p > 0.05 for all). ISSF and ADDI scores were lower in pathogenic/VUS complex heterozygous patients than those harboring single pathogenic mutation (p = 0.006 and 0.004, respectively). Conclusion: Our findings suggest that patients with single heterozygous VUS has mild FMF phenotype similar to those with single pathogenic mutation. Pathogenic/VUS complex heterozygosity does not lead to a more severe clinical phenotype than having a single pathogenic variant.

Damage assessment in adult IgA vasculitis. Cross-sectional results of a multicentre cohort.

OBJECTIVES: Immunoglobulin (Ig) A vasculitis affects children more commonly than adults and previous literature lacks any formal damage assessment. Our aim in this study is to investigate the disease course, relapse rates and prognostic factors in adult patients with IgA vasculitis and to evaluate the disease-related damage. METHODS: We assembled a retrospective cohort of adult IgA vasculitis from six tertiary Rheumatology Centres in Turkey. The demographics, clinical characteristics, treatment and outcomes of patients were abstracted from medical records. RESULTS: The study included 130 (male/female: 85/45) patients and the mean age was 42.2±17 years. Cutaneous manifestations and arthritis/arthralgia were the most common clinical manifestations. One hundred thirteen patients (86.9%) were treated with oral glucocorticoids (GC). As additional immunosuppressive (IS) agents, azathioprine was given to 44 (34.9%) and pulse cyclophosphamide to 18 (12.6%) patients. Seventy-nine patients (60%) had follow-up of median 15 (IQR 7-40) months. Twelve (15%) patients relapsed during follow-up. The mean VDI score was 0.4 in the last visit. Nineteen (24.7%) patients had at least one damage item at the end of follow-up. Most frequent damage items were renal 11 (42%), ocular 4 (15%) and cardiovascular 4 (15%). CONCLUSIONS: In this cohort the most frequent damage item was renal and was related to the disease itself. Damage score was higher in patients with more severe disease and treated more aggressively. Our results suggest that more effective treatment options are needed in a subgroup of patients with IgA vasculitis to prevent the damage related with the vasculitis, especially with more severe disease.

Predictors of drug retention and treatment response in axial spondyloarthritis patients treated with certolizumab: real-life results from the HURBIO registry.

OBJECTIVES: To assess the real-life retention rate of certolizumab and factors related to retention of certolizumab. METHODS: We analysed all patients who received at least 1 dose of certolizumab and were registered in the HURBIO database. Patients with at least 1 control visit were included in efficacy analysis. Drug retention rates were calculated using the Kaplan-Meier method and predictors of drug retention was determined by Cox proportional hazard model. Factors predicting BASDAI50 response at first visit were analysed by the logistic regression analysis. Reasons of switching and discontinuation were also determined. RESULTS: A total of 325 (AS (76%), female 55%) patients were recruited. Median follow-up while receiving certolizumab was 13 (4.7-22.7) months. At 1 year, overall certolizumab retention rate was 72.5%. Predictors of poor certolizumab retention were: Current or ex-smoker [HR 1.11 (0.70-1.76), p=0.65], high CRP levels [HR 0.72 (0.45-1.16), p=0.18], biologic-naïve [HR 0.81 (0.49-1.32), p=0.39] and good BASDAI50 response at first control visit [HR 0.54 (0.30-0.96), p=0.04]. Mean duration from starting certolizumab to the first control visit was 3 (3-6) months. Predictors of poor BASDAI50 response: Presence of nr-axSpa [RR 2.12 (1.01-4.51), p=0.05], female gender [RR 2.14 (1.20-3.82), p=0.01] and history of biologic therapy [RR 3.52 (1.95-6.33), p<0.001]. The most common causes of drug switch were primary failure and drug side-effects. CONCLUSIONS: In this study, good BASDAI50 response at first visit seems to be a strong predictor of higher retention of certolizumab in patients with axial spondyloarthritis.

Factors associated with damage in patients with familial Mediterranean fever.

OBJECTIVES: Defining predictors of damage would improve patient care. We applied damage indexes to patients with familial Mediterranean fever (FMF) and identified the predictors of damage. METHODS: This is a cross-sectional analysis of 926 FMF patients, who fulfilled the Tel-Hashomer criteria and had at least six months of follow-up. Patients were stratified according to their damage status (damage vs. no damage) defined with autoinflammatory disease damage index (ADDI) and modified ADDI (excluding musculoskeletal pain). We used logistic regression analysis to investigate independent predictors of damage for both indexes. RESULTS: Mean disease duration was 21.6±11.9 years. 527 patients (57%) had damage according to ADDI. Median ADDI score was 1 (0-11). Most common FMF-related damages were observed in musculoskeletal, reproductive and kidney domains. Female gender, inflammatory comorbidity, colchicine resistance, colchicine nonadherence, musculoskeletal attack dominance, diagnostic delay, follow-up time, and smoking history remained independent predictors of damage according to ADDI score. The rate of patients with damage defined by modified ADDI was only to 23%. M694V/M694V homozygosity, female gender, musculoskeletal attack dominance, colchicine resistance, persistent inflammation, follow up time and family history of amyloidosis were found to be predictors of damage according to modified ADDI score. CONCLUSIONS: Our study is the first to apply comprehensive damage indexes to FMF patients and identified predictors of damage. Factors linked to a severe FMF phenotype, including M694V homozygosity and persistent inflammation, were associated with only modified ADDI. Our findings justify the concerns about musculoskeletal pain and might point to the need for re-evaluation of ADDI for FMF patients.

Familial Mediterranean fever is associated with a wide spectrum of inflammatory disorders: results from a large cohort study.

Familial Mediterranean fever (FMF) is characterized by recurrent short-lived/self-limiting inflammatory attacks. Besides these, a substantial number of patients with FMF present with a variety of other inflammatory diseases; however, this issue has not been systematically studied previously. Hence, we aimed to investigate the frequency of inflammatory comorbid diseases in a large FMF cohort. All patients were recruited from "FMF in Central Anatolia (FiCA) Cohort", comprising 971 (mean age 35.3 ± 12 years, 61.5% female) adult subjects. All patients fulfilled Tel Hashomer criteria. Demographic data, FMF disease characteristics, MEFV gene mutations, and comorbid inflammatory diseases were meticulously questioned, and laboratory features and genotype data were retrieved from hospital records. There were comorbid inflammatory diseases in 205 (21.1%) patients. The most common inflammatory disease was spondyloarthritis (12.9%). Other remarkable inflammatory disorders were psoriasis, immunoglobulin A vasculitis/Henoch-Schönlein purpura, Behçet's disease and inflammatory bowel diseases. Cryptogenic organizing pneumonia is a newly defined entity in our cohort which is seemed to be associated with FMF (0.3%). Number of patients with persistent inflammation was higher in those with comorbid diseases (p < 0.001). Our results suggest that FMF is commonly associated with other inflammatory diseases. Therefore, clinicians should be cautious about comorbid inflammatory diseases in FMF patients, particularly in those with persistent inflammation. Identification of pathogenic pathways linking FMF to these diseases warrants further investigations.

Free Serratus Fascia Flap for Reconstruction of Soft Tissue Defects Involving the Distal Upper and Lower Extremity.

BACKGROUND: Free fascial flaps are widely used for the reconstruction of defects located on the distal extremities as they provide thin yet durable soft tissue coverage. The serratus anterior fascia flap stands out from other fascial flap alternatives as it has optimal anatomical properties that can provide ideal coverage in a wide range of reconstructive challenges. The purpose of this study was to present our experience with the serratus anterior fascia flap in a variety of complex soft tissue defects. METHODS: A retrospective review was conducted on patients who underwent reconstruction with the free serratus anterior fascia flap for complex soft tissue defects involving the distal extremities. RESULTS: Complex soft tissue defects of 13 patients were reconstructed using the free serratus fascia flap. No major postoperative complications such as flap loss, dehiscence, infection, or hematoma were encountered in any of the patients. All of the patients demonstrated durable and harmonious long-term flap coverage that facilitated movement without any signs of scar contractures and tendon adhesions at the site of reconstruction. CONCLUSIONS: The serratus anterior fascia flap demonstrates versatility and stability for the closure of complex distal extremity defects. It creates thin yet durable coverage that facilitates underlying tendon gliding while providing harmony with the natural contours of these anatomic areas and has low donor site morbidity, making it a primary choice in the reconstruction complex soft tissue defects involving the hands and feet.

Geoepidemiology and clinical characteristics of neonatal lupus erythematosus: a systematic literature review of individual patients' data

Background/aim: Neonatal lupus erythematosus (NLE) is an autoimmune syndrome caused by transplacental transmission of maternal autoantibodies, often with devastating consequences. The objective of this systematic literature review was to analyze the demographic data, geoepidemiology, clinical, and serological characteristics associated with NLE. Materials and methods: We performed a systematic literature search of the Pubmed database covering the period from 1976 to August 2015, using the MeSH terms "neonatal lupus" or "congenital heart block". To be included in the study, articles of any type (original articles, case series, and case reports) had to report on infants with NLE on an individualized (i.e. patient-by-patient) basis. Results: A total of198 studies were included in the review, reporting on a total of 755 NLE patients. The most frequently reported clinical manifestations of NLE were congenital heart block (CHB, 65.2%), cutaneous lupus (33.1%), and cytopenias (15.5%). We found differences in NLE characteristics based on study geographical origin, with CHB being much more frequent in patients of European or American descent (49.4% and 35%, respectively), while reports originating from Asia reported a higher prevalence of skin involvement (45.2%). Most CHB cases (72.9%) were diagnosed between the 18th and 26th week of gestation. Conclusions: Phenotypic differences of NLE depending on race and country may reflect true pathophysiologic differences or methodologic discrepancies. While maternal autoimmune disease is not a prerequisite for the development of NLE, the existence of a truly "immunonegative" CHB is questionable.