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Objective Semaphorin 3A (Sema3A) plays a regulatory role in immune responses. The aim of this study was to evaluate Sema3A levels in patients with systemic sclerosis (SSc), especially in major vascular involvements such as digital ulcer (DU), scleroderma renal crisis (SRC), pulmonary arterial hypertension (PAH), and to compare Sema3A level with SSc disease activity. Methods In SSc patients, patients with DU, SRC, or PAH were grouped as major vascular involvements and those without as nonvascular, and Sema3A levels were compared between the groups and with a healthy control group. The Sema3A levels and acute phase reactants in SSc patients, as well as their association with the Valentini disease activity index and modified Rodnan skin score, were evaluated. Results The Sema3A values (mean ± SD) were 57.60 ± 19.81 ng/mL in the control group (n = 31), 44.32 ± 5.87 ng/mL in patients with major vascular involvement SSc (n = 21), and 49.96 ± 14.00 ng/mL in the nonvascular SSc group (n = 35). When all SSc patients were examined as a single group, the mean Sema3A value was significantly lower than controls (P  = .016). The SSc with major vascular involvement group had significantly lower Sema3A levels than SSc with nonmajor vascular involvement group (P  = .04). No correlation was found between Sema3A, acute phase reactants, and disease activity scores. Also, no relationship was observed between Sema3A levels and diffuse (48.36 ± 11.47 ng/mL) or limited (47.43 ± 12.38 ng/mL) SSc types (P  = .775). Conclusion Our study suggests that Sema3A may play a significant role in the pathogenesis of vasculopathy and can be used as a biomarker in SSc patients with vascular complications such as DU and PAH. [ABSTRACT FROM AUTHOR]

Context: Homozygous leptin (LEP) and leptin receptor (LEPR) variants lead to childhood-onset obesity. Objective: To present new cases with LEP and LEPR deficiency, report the long-term follow-up of previously described patients, and to define, based on all reported cases in literature, genotype-phenotype relationships. Methods: Our cohort included 18 patients (LEP = 11, LEPR = 7), 8 of whom had been previously reported. A systematic literature review was conducted in July 2022. Forty-two of 47 studies on LEP/LEPR were selected. Results: Of 10 new cases, 2 novel pathogenic variants were identified in LEP (c.16delC) and LEPR (c.40 + 5G > C). Eleven patients with LEP deficiency received metreleptin, 4 of whom had been treated for over 20 years. One patient developed loss of efficacy associated with neutralizing antibody development. Of 152 patients, including 134 cases from the literature review in addition to our cases, frameshift variants were the most common (48%) in LEP and missense variants (35%) in LEPR. Patients with LEP deficiency were diagnosed at a younger age [3 (9) vs 7 (13) years, P = .02] and had a higher median body mass index (BMI) SD score [3.1 (2) vs 2.8 (1) kg/m², P = 0.02], which was more closely associated with frameshift variants (P = .02). Patients with LEP deficiency were more likely to have hyperinsulinemia (P = .02). Conclusion: Frameshift variants were more common in patients with LEP deficiency whereas missense variants were more common in LEPR deficiency. Patients with LEP deficiency were identified at younger ages, had higher BMI SD scores, and had higher rates of hyperinsulinemia than patients with LEPR deficiency. Eleven patients benefitted from long-term metreleptin, with 1 losing efficacy due to neutralizing antibodies. [ABSTRACT FROM AUTHOR]

Objectives We sought to evaluate the performance of the SLE Risk Probability Index (SLERPI) for identification of SLE in a large cohort of patients with UCTD. Methods The SLERPI was applied in a cohort of patients who met classification criteria for UCTD and did not fulfil any classification criteria for other defined CTD including SLE. Patients with a SLERPI score of >7 were 'diagnosed' as SLE. Patients diagnosed with SLE and those not were compared in terms of disease characteristics and index parameters. Results A total of 422 patients with UCTD were included in the study. Median (interquartile range) SLERPI was 4.25 (2.5) points, while 39 (9.2%) patients had a SLERPI score >7 and were diagnosed as SLE. Patients with younger age (P  = 0.026) and presence of malar rash (P  < 0.0001), mucosal ulcer (P  < 0.0001), alopecia (P  < 0.0001), ANA positivity (P  < 0.0001), low C3 and C4 (P  = 0.002), proteinuria >500 mg/24 h (P  = 0.001), thrombocytopenia (P  = 0.009) or autoimmune haemolytic anaemia (P  < 0.0001) were more likely to fulfil criteria for SLE by the SLERPI. Conclusion SLERPI enabled a significant proportion of patients to be identified as SLE in our UCTD cohort. This new probability index may be useful for early identification of SLE among patients with signs of CTD without fulfilling any definite criteria set. [ABSTRACT FROM AUTHOR]

Objective The aim of this study is to evaluate semaphorin 3A levels in patients with systemic lupus erythematosus (SLE) with and without renal involvement and secondary antiphospholipid antibody syndrome (APS). Methods Patients with SLE were grouped according to the presence of secondary APS or renal involvement. The control group consisted of age-matched, nonsmoking, healthy volunteers. Semaphorin 3A levels were compared among groups. All patients with SLE were regrouped according to the presence of thrombotic events, miscarriages, and proteinuria, and semaphorin 3A levels were investigated. Finally, semaphorin 3A levels of all patients with SLE as a single group were compared to those of the control patients. Results The mean semaphorin 3A values were 16.16 ± 2.84 ng/mL in the control group, 9.05 ± 5.65 ng/mL in patients with SLE without nephritis and APS, 11.28 ± 5.23 ng/mL in the SLE with APS group, and 8.53 ± 5.11 ng/mL in the lupus nephritis group. When all 3 patient groups were examined as a single group, the mean semaphorin 3A value was significantly lower than that of the control group. Semaphorin 3A was reduced in patients with SLE with thromboembolism and/or history of miscarriage. Conclusion Semaphorin 3A levels were lower in all patient groups compared to the control group. Moreover, the reduced semaphorin 3A levels in patients with a history of thromboembolism and/or miscarriage suggest that semaphorin 3A may play an important role in the pathogenesis of vasculopathy. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study is to investigate the outcomes of coronavirus disease 2019 (COVID-19) in our cohort of Behçet's disease (BD) patients and to reveal the rate of BD exacerbations due to COVID-19. Methods: Patients who have been followed with a diagnosis of BD were retrospectively investigated for a positive severe acute respiratory syndrome-coronavirus 2 polymerized chain reaction (PCR) test. Data regarding demographics, clinical features and COVID-19 outcomes were collected from medical records for patients with a positive PCR. PCR-positive patients were reached via phone numbers, and 'Behçet's Disease Current Activity Form' (BDCAF) scores for pre- and post-COVID-19 BD symptoms were calculated. Results: Out of a total 648 BD patients, 59 were detected to have a positive PCR test. Three of the 59 patients (5.0%) were found to be hospitalized, none of them was admitted to the ICU or died. An increasing trend in the frequency of comorbid diseases and older age was observed in hospitalized patients. 32.2% of BD patients suffered from exacerbation of at least one symptom related to BD. Conclusions: We observed no ICU admission or mortality with COVID-19 in our BD patient cohort. A substantial number of patients suffered from exacerbation of BD symptoms. [ABSTRACT FROM AUTHOR]

Objectives Our aim is to understand clinical characteristics, real-life treatment strategies, outcomes of early PsA patients and determine the differences between the inception and established PsA cohorts. Methods PsArt-ID (Psoriatic Arthritis- International Database) is a multicentre registry. From that registry, patients with a diagnosis of PsA up to 6 months were classified as the inception cohort (n ==388). Two periods were identified for the established cohort: Patients with PsA diagnosis within 5–10 years (n  = 328), ≥10 years (n  = 326). Demographic, clinical characteristics, treatment strategies, outcomes were determined for the inception cohort and compared with the established cohorts. Results The mean (s. d.) age of the inception cohort was 44.7 (13.3) and 167/388 (43.0%) of the patients were male. Polyarticular and mono-oligoarticular presentations were comparable in the inception and established cohorts. Axial involvement rate was higher in the cohort of patients with PsA ≥10 years compared with the inception cohort (34.8% vs 27.7%). As well as dactylitis and nail involvement (P = 0.004, P = 0.001 respectively). Both enthesitis, deformity rates were lower in the inception cohort. Overall, 13% of patients in the inception group had a deformity. MTX was the most commonly prescribed treatment for all cohorts with 10.7% of the early PsA patients were given anti-TNF agents after 16 months. Conclusion The real-life experience in PsA patients showed no significant differences in the disease pattern rates except for the axial involvement. The dactylitis, nail involvement rates had increased significantly after 10 years from the diagnosis and the enthesitis, deformity had an increasing trend over time. [ABSTRACT FROM AUTHOR]

Objective. The aim was to assess the characteristics of PsA, find out how well the disease is controlled in real life, demonstrate the treatments and identify the unmet needs. Methods. The PsA registry of Turkey is a multicentre Web-based registry established in 2014 and including 32 rheumatology centres. Detailed data regarding demographics for skin and joint disease, disease activity assessments and treatment choices were collected. Results. One thousand and eighty-one patients (64.7% women) with a mean (S.D.) PSA duration of 5.8 (6.7) years were enrolled. The most frequent type of PsA was polyarticular [437 (40.5%)], followed by oligoarticular [407 (37.7%)] and axial disease [372 (34.4%)]. The mean (S.D.) swollen and tender joint counts were 1.7 (3) and 3.6 (4.8), respectively. Of these patients, 38.6% were on conventional synthetic DMARD monotherapy, 7.1% were on anti-TNF monotherapy, and 22.5% were using anti-TNF plus conventional synthetic DMARD combinations. According to DAS28, 86 (12.4%) patients had high and 105 (15.2%) had moderate disease activity. Low disease activity was achieved in 317 (45.7%) patients, and 185 (26.7%) were in remission. Minimal disease activity data could be calculated in 247 patients, 105 of whom (42.5%) had minimal disease activity. The major differences among sexes were that women were older and had less frequent axial disease, more fatigue, higher HAQ scores and less remission. Conclusion. The PsA registry of Turkey had similarities with previously published registries, supporting its external validity. The finding that women had more fatigue and worse functioning as well as the high percentage of active disease state highlight the unmet need in treatment of PsA. [ABSTRACT FROM AUTHOR]

Dear Editor, The temporal relationship between the onset of skin psoriasis and psoriatic arthritis (PsA) is a long and well-known feature of psoriatic disease. The diagnosis of psoriasis before or after 40 years of age was defined as type 1 psoriasis or type 2 psoriasis, respectively.4 The primary analytical variable was the time elapsed (months) between the diagnosis of skin psoriasis and PsA, with negative times indicating the diagnosis of PsA before psoriasis. Of these patients, 71 (4-4%) were diagnosed with PsA earlier than psoriasis by at least 12 months, 309 (18-9%) were diagnosed with PsA and psoriasis within 12 months, and 1251 (76-7%) were diagnosed with psoriasis at least 12 months earlier than PsA (Table 1). [Extracted from the article]

We examine the distribution of injected energy in three-dimensional, adaptive-grid simulations of the heating of cooling flows. We show that less than 10 per cent of the injected energy goes into bubbles. Consequently, the energy input from the nucleus is underestimated by a factor of order 6 when it is taken to be given by , where P and V are the pressure and volume of the bubble, and γ is the ratio of principal specific heats. [ABSTRACT FROM AUTHOR]

Active galactic nuclei are clearly heating gas in ‘cooling flows’. The effectiveness and spatial distribution of the heating are controversial. We use three-dimensional simulations on adaptive grids to study the impact on a cooling flow of weak, subrelativistic jets. The simulations show cavities and vortex rings as in the observations. The cavities are fast-expanding dynamical objects rather than buoyant bubbles as previously modelled, but shocks still remain extremely hard to detect with X-rays. At late times the cavities turn into overdensities that strongly excite the g modes of a cluster. These modes damp on a long time-scale. Radial mixing is shown to be an important phenomenon, but the jets weaken the metallicity gradient only very near the centre. The central entropy density is modestly increased by the jets. We use a novel algorithm to impose the jets on the simulations. [ABSTRACT FROM AUTHOR]

Three-dimensional hydrodynamical simulations are used to investigate the structural stability of cooling flows that are episodically heated by jets from a central AGN. The radial profile of energy deposition is controlled by (a) the power of the jets, and (b) the pre-outburst density profile. A delay in the ignition of the jets causes more powerful jets to impact on a more centrally concentrated medium. The net effect is a sufficient increase in the central concentration of energy deposition to cause the post-outburst density profile to be less centrally concentrated than that of an identical cluster in which the outburst happened earlier and was weaker. These results suggest that the density profiles of cooling flows oscillate around an attracting profile, thus explaining why cooling flows are observed to have similar density profiles. The possibility is raised that powerful FR II systems are ones in which this feedback mechanism has broken down and a runaway growth of the source parameters has occurred. [ABSTRACT FROM AUTHOR]