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Objective. Data from trials demonstrated that abatacept (ABA) has a good safety and efficacy profile in treating rheumatoid arthritis. We have studied the retention rate of ABA in a real-life cohort of patients with rheumatoid arthritis. Methods. This is a monocentric, retrospective study including patients with rheumatoid arthritis classified by the American College of Rheumatology/European League Against Rheumatism 2010 criteria who started treatment with ABA. The Kaplan-Meier method was applied to evaluate the ABA retention rate. Results. This analysis was conducted on 161 patients [male/female 21/140, median age 65 years, interquartile range (IQR) 18.7, median disease duration 169 months, IQR 144.0]. 111 patients (68.9%) received ABA subcutaneously. ABA was associated with methotrexate in 61.9% of patients and was the first biological disease-modifying antirheumatic drug in 41%. We observed a median ABA survival of 66 months [95% confidence interval (CI) 57.3-74.7], with a retention rate of 88% at 6 months and 50.9% at 5 years. Drug survival was significantly higher in patients treated with ABA subcutaneously and in male patients (p=0.039 and p=0.018, respectively). Adjusted for main confounders, female gender was the main predictor of withdrawal (hazard ratio 5.1, 95% CI 1.2-21.3). Conclusions. Our study shows that better survival is associated with subcutaneous administration and male gender, confirming ABA effectiveness.

Background: Systemic sclerosis (SSc) is an autoimmune disease characterized by vascular and immunity alterations and skin/internal organ fibrosis. Aberrant levels of plasma CXCL4, CXCL4–RNA/DNA complexes, type I IFN (IFN-I) and anti-CXCL4 antibodies characterize SSc. These parameters influence each other: CXCL4–self-DNA/RNA complexes are triggers of IFN-I in plasmacytoid dendritic cells (pDCs), and anti-CXCL4 autoantibodies amplify this effect. Here, we assess the modulation over time of plasma CXCL4 and the related parameters of CXCL4–DNA/RNA complexes, anti-CXCL4 antibodies, IFN-α and TNF-α in an SSc cohort under the synthetic analogue of prostacyclin PGI2 (iloprost) treatment to address contribution of these parameters to pathogenesis and their role as biomarkers. Methods: We analyzed immunological parameters at baseline (T0) and after 3 (T3) and 6 (T6) months in 30 SSc patients. Responders were the patients that lowered their disease activity parameters after six months of treatment. Results: Anti-CXCL4 autoantibodies correlated with both IFN-α and TNF-α levels in SSc plasma. Responders significantly down-regulated serum IFN-α. In seven patients with a shorter disease duration, improvement coincides with a decrease in plasma IFN-α, CXCL4 and TNF-α. Iloprost efficiently blocks pDCs IFN-α production induced by CXCL4–DNA/RNA complexes in vitro. Conclusions: The data suggest a possible role of iloprost as a disease-modifying drug, mainly accompanied by down-regulation of plasma IFN-I levels. Since CXCL4, IFN-I and TNF-α down-modulation was evident and significant in improving SSc patients with a shorter disease duration, these results warrant future investigations on the early use of iloprost to slow SSc progression.

The genus Myrmecina was described basing on males of M. graminicola. Though representing the caste type, males were sufficiently described in only two out of 105 species known in the genus. However, the morphology of the male external genitalia remained undescribed. Re-examining by SEM the male of M. graminicola, we describe and illustrate in detail for the first time the external genitalia, redefining and updating the morphological male diagnosis of the genus. We also analyze the overall morphology, illustrating additional peculiar characters of this species as follows: (i) a very distinctive stipital groove in the dorsolateral stipes; (ii) a developed uncinate-shaped mesoscutellar arm; (iii) the antennal cleaning; and (iv) the absence of meso- and metatibial spurs. This morphological study will be useful as a base for further morphological descriptions of the males in other species of the same genus to support correct taxonomic identifications.

Background and Objectives: In SSc, ILD is a major cause of morbidity and mortality. We aimed to investigate the performance of DLCO (diffusing capacity of lung carbon monoxide) and FVC (forced vital capacity) delta change (Δ) and baseline values in predicting the development of SSc-ILD. Methods: Longitudinal data of DLCO, FVC, and ILD on the HRCT of SSc patients from the EUSTAR database were evaluated at baseline (t0) and after 12 (±4) (t1) and 24 (±4) (t2) months. Results: 474/17805 patients were eligible for the study (403 females); 46 (9.7%) developed ILD at t2. Positivity for anti-topoisomerase antibodies (117 patients) showed an association with ILD development at t2 (p = 0.0031). Neither the mean t0 to t1 change (Δ) of DLCO nor the mean t0 to t1 FVCΔ predicted the appearance of ILD at t2. Investigating the possible role of baseline DLCO and FVC values in predicting ILD appearance after 24 (±4) months, we observed a moderate predictive capability of t0 DLCO < 80%, stronger than that of FVC < 80%. Conclusions: We suggest that an impaired baseline DLCO may be predictive of the appearance of ILD after 2 years of follow-up. This result advances the hypothesis that a reduction in gas exchange may be considered an early sign of lung involvement. However, further rigorous studies are warranted to understand the predictive role of DLCO evaluation in the course of SSc.

Blister beetles (Coleoptera: Meloidae) are currently subdivided into three subfamilies: Eleticinae (a basal group), Nemognathinae, and Meloinae. These are all characterized by the endogenous production of the defensive terpene cantharidin (CA), whereas the two most derived subfamilies show a hypermetamorphic larval development. Here, we provide novel draft genome assemblies of five species sampled across the three blister beetle subfamilies (Iselma pallidipennis, Stenodera caucasica, Zonitis immaculata, Lydus trimaculatus, and Mylabris variabilis) and performed a comparative analysis with other available Meloidae genomes and the closely‐related canthariphilous species (Pyrochroa serraticornis) to disclose adaptations at a molecular level. Our results highlighted the expansion and selection of genes potentially responsible for CA production and metabolism, as well as its mobilization and vesicular compartmentalization. Furthermore, we observed adaptive selection patterns and gain of genes devoted to epigenetic regulation, development, and morphogenesis, possibly related to hypermetamorphosis. We hypothesize that most genetic adaptations occurred to support both CA biosynthesis and hypermetamorphosis, two crucial aspects of Meloidae biology that likely contributed to their evolutionary success. [ABSTRACT FROM AUTHOR]

Background: Systemic sclerosis (SSc) is an autoimmune disease characterized by vascular and immunity alterations and skin/internal organ fibrosis. Aberrant levels of plasma CXCL4, CXCL4–RNA/DNA complexes, type I IFN (IFN-I) and anti-CXCL4 antibodies characterize SSc. These parameters influence each other: CXCL4–self-DNA/RNA complexes are triggers of IFN-I in plasmacytoid dendritic cells (pDCs), and anti-CXCL4 autoantibodies amplify this effect. Here, we assess the modulation over time of plasma CXCL4 and the related parameters of CXCL4–DNA/RNA complexes, anti-CXCL4 antibodies, IFN-α and TNF-α in an SSc cohort under the synthetic analogue of prostacyclin PGI2 (iloprost) treatment to address contribution of these parameters to pathogenesis and their role as biomarkers. Methods: We analyzed immunological parameters at baseline (T0) and after 3 (T3) and 6 (T6) months in 30 SSc patients. Responders were the patients that lowered their disease activity parameters after six months of treatment. Results: Anti-CXCL4 autoantibodies correlated with both IFN-α and TNF-α levels in SSc plasma. Responders significantly down-regulated serum IFN-α. In seven patients with a shorter disease duration, improvement coincides with a decrease in plasma IFN-α, CXCL4 and TNF-α. Iloprost efficiently blocks pDCs IFN-α production induced by CXCL4–DNA/RNA complexes in vitro. Conclusions: The data suggest a possible role of iloprost as a disease-modifying drug, mainly accompanied by down-regulation of plasma IFN-I levels. Since CXCL4, IFN-I and TNF-α down-modulation was evident and significant in improving SSc patients with a shorter disease duration, these results warrant future investigations on the early use of iloprost to slow SSc progression. [ABSTRACT FROM AUTHOR]

The genus Myrmecina was described basing on males of M. graminicola. Though representing the caste type, males were sufficiently described in only two out of 105 species known in the genus. However, the morphology of the male external genitalia remained undescribed. Re‐examining by SEM the male of M. graminicola, we describe and illustrate in detail for the first time the external genitalia, redefining and updating the morphological male diagnosis of the genus. We also analyze the overall morphology, illustrating additional peculiar characters of this species as follows: (i) a very distinctive stipital groove in the dorsolateral stipes; (ii) a developed uncinate‐shaped mesoscutellar arm; (iii) the antennal cleaning; and (iv) the absence of meso‐ and metatibial spurs. This morphological study will be useful as a base for further morphological descriptions of the males in other species of the same genus to support correct taxonomic identifications. [ABSTRACT FROM AUTHOR]

Objective To evaluate differences in nailfold videocapillaroscopy (NVC) findings between SSc patients with and without a diagnosis of pulmonary arterial hypertension (PAH). Methods One hundred and ten SSc patients were enrolled in this cross-sectional, case–control, multicentre study. Patients were divided into cases (SSc-PAH confirmed by right heart catheterization) and controls (SSc-nonPAH with low probability of PAH). NVC patterns (early, active and late) and morphological parameters (microvascular density, non-specific abnormalities, giant capillaries, micro-haemorrhages, avascular areas) were considered using a semiquantitative scoring system. Results SSc-PAH patients showed higher frequencies of late pattern (P  < 0.01), non-specific abnormalities (P  < 0.01), lower capillary density (P  < 0.01), higher avascular areas (P  < 0.01) and a higher mean NVC score (P  < 0.01). Contrarily, the early/active pattern (P  < 0.01) and a higher rate of micro-haemorrhages (P  = 0.04) were more frequent in non-PAH patients. By a multivariate analysis, SSc-PAH patients, compared with non-PAH, had more non-specific abnormalities [27/55, 49.1% vs 10/55, 18.2%; adjusted odd ratio (OR) 16.89; 95% CI: 3.06, 93.16], a lower capillary density (grade 3, 20/55, 36.4% vs 5/55, 9.1%; adjusted OR 38.33; 95% CI: 2.34, 367.80) and avascular areas (18/55, 32.7% vs 10/55, 18.2%; adjusted OR 16.90; 95% CI: 2.64, 44.35). A correlation was found between the mean pulmonary arterial pressure and avascular areas (P  < 0.01), capillary density (P  < 0.01) and non-specific abnormalities (P  < 0.01). A clinical model including the NVC variables may be able to predict a diagnosis of PAH. Conclusion Our results indicate that the distinctive peripheral microcirculatory injury of SSc, i.e. capillary loss and morphological abnormalities, appear more severe and pronounced in patients with SSc-PAH. [ABSTRACT FROM AUTHOR]

Background Lung ultrasound (LUS) is a promising tool for detecting SSc-associated interstitial lung disease (SSc-ILD). Currently, consensus on the best LUS findings and execution technique is lacking. Objectives To compare qualitative and quantitative assessment of B-lines and pleural line (PL) alterations in SSc-ILD with chest CT analysis. Methods During 2021–2022, consecutive SSc patients according to 2013 ACR/EULAR classification criteria underwent pulmonary functional tests (PFTs). On the same day, if a CT was performed over a ± 6 months period, LUS was performed by two certified blinded operators using a 14-scans method. The ≥10 B-lines cut-off proposed by Tardella and the Fairchild's PL criteria fulfilment were selected as qualitative findings. As quantitative assessment, total B-lines number and the quantitative PL score adapted from the semi-quantitative Pinal-Fernande z score were collected. CT scans were evaluated by two thoracic radiologists for ILD presence, with further processing by automated texture analysis software (QCT). Results Twenty-nine SSc patients were enrolled. Both qualitative LUS scores were significantly associated to ILD presence on CT, with Fairchild's PL criteria resulting in slightly more accuracy. Results were confirmed on multivariate analysis. All qualitative and quantitative LUS findings were found to be significantly associated with QCT ILD extension and radiological abnormalities. Mid and basal PL quantitative score correlated with mid and basal QCT ILD extents. Both B-lines and PL alterations differently correlated with PFTs and clinical variables. Conclusion This preliminary study suggests the utility of a comprehensive LUS assessment for SSc-ILD detection compared with CT and QCT. [ABSTRACT FROM AUTHOR]

The false blister beetle tribe Stenostomatini includes only the genus Stenostoma , with four species showing an intriguing distribution: Stenostoma lowei (Madeira), Stenostoma cossyrense (Pantelleria), Stenostoma melitense (Malta and southern Sicily) and Stenostoma rostratum, widely distributed along the Mediterranean and North Atlantic coasts. The evolutionary history leading to this distribution has not been investigated. Here, we explore the phylogeny and evolutionary history of the tribe, adopting an integrative approach that combines morphological and molecular data (mitochondrial COI and nuclear CAD and 28S). Moreover, we propose a new key for species identification and update the knowledge on adult and larval ecology. Finally, we propose the following explanation for the current distribution of the species. The genus originated in the Miocene, with S. lowei belonging to the oldest lineage. The remaining species share a common ancestor, dating to the Messinian Salinity Crisis. Stenostoma melitense and S. cossyrense are well differentiated according to morphology, but not according to molecular analysis. The wide distribution of S. rostratum might be related to its strategy of laying eggs within beached driftwood, where larvae develop, easily transported by the currents. Given that neither morphological nor molecular differentiation was detected between the two subspecies of S. rostratum , we propose the new synonymy Stenostoma rostratum septentrionale Švihla, 2005  =  Stenostoma rostratum (Fabricius, 1787) syn. nov. [ABSTRACT FROM AUTHOR]

The Italian geographic region is characterized by complex and diversified biogeographic patterns and is represented by a high number of endemic species. Endemic species characterized by a limited distribution range should be a primary concern in conservation. This article aimed to investigate the phylogenetic and biogeographic relationships of 2 Italian endemic species of the wingless blister beetle genus Meloe Linnaeus, 1758: Meloe (Eurymeloe) apenninicus and Meloe (E.) baudii. Our inferences, based on morphological characters, 2 mitochondrial (16S and COI) and 2 nuclear (CAD and 28S) markers and the use of 3 species delimitation analyses approaches, pointed out the presence of a new Italian endemic species (M. (E.) digiuliorum sp. n.), here described, and 3 different patterns of phylogenetic and biogeographic affinities. M. digiuliorum is close to the Spanish endemic M. orobates comb. n. , revealing a possible fragmentation of the ancestor range in the Pleistocene (ca. 0.84 Mya) followed by isolation in Italy and Spain. M. apenninicus is the sister species of the European-Anatolian M. rugous and M. cfr. rugosus , and this pattern originated around the Plio-Pleistocene boundary (ca. 2.83 Mya) likely influenced by the climatic fluctuations and the presence of the Alpine barrier. Finally, 2 subspecies were referred to M. baudii : the nominal one, endemic to Italy, and the Turanian-E European M. b. glazunovi stat. n. , disclosing a third more recent (ca. 0.64 Mya) pattern of biogeographic disjunction. [ABSTRACT FROM AUTHOR]

Background and Objectives: In SSc, ILD is a major cause of morbidity and mortality. We aimed to investigate the performance of DLCO (diffusing capacity of lung carbon monoxide) and FVC (forced vital capacity) delta change (Δ) and baseline values in predicting the development of SSc-ILD. Methods: Longitudinal data of DLCO, FVC, and ILD on the HRCT of SSc patients from the EUSTAR database were evaluated at baseline (t0) and after 12 (±4) (t1) and 24 (±4) (t2) months. Results: 474/17805 patients were eligible for the study (403 females); 46 (9.7%) developed ILD at t2. Positivity for anti-topoisomerase antibodies (117 patients) showed an association with ILD development at t2 (p = 0.0031). Neither the mean t0 to t1 change (Δ) of DLCO nor the mean t0 to t1 FVCΔ predicted the appearance of ILD at t2. Investigating the possible role of baseline DLCO and FVC values in predicting ILD appearance after 24 (±4) months, we observed a moderate predictive capability of t0 DLCO < 80%, stronger than that of FVC < 80%. Conclusions: We suggest that an impaired baseline DLCO may be predictive of the appearance of ILD after 2 years of follow-up. This result advances the hypothesis that a reduction in gas exchange may be considered an early sign of lung involvement. However, further rigorous studies are warranted to understand the predictive role of DLCO evaluation in the course of SSc. [ABSTRACT FROM AUTHOR]