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Background: This study aimed to evaluate the effectiveness and drug retention rate of secukinumab (SCK) in axial spondyloarthritis (ax-SpA) within a multicentric real-life cohort. Methods: Data from patients with ax-SpA treated with SCK at five Italian centers were collected retrospectively, excluding those with a diagnosis of Psoriatic Arthritis. Evaluations were conducted at baseline and at 3, 6, 12, 18, and 24 months. Assessments included C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), BASDAI, and ASDAS-CRP. Results: Seventy-one ax-SpA patients (57.7% female, mean age: 53.86 ± 12.67 years) were enrolled. Baseline mean BASDAI was 6.2 ± 1.4 and ASDAS-CRP was 2.9 ± 1.3. Significant improvements in BASDAI and ASDAS-CRP were observed over time, with BASDAI reducing to 3.5 ± 1.9 (p < 0.0001) and ASDAS-CRP to 1.7 ± 0.9 (p < 0.0001) at 24 months. The follow-up duration averaged 20.46 ± 13.46 months. By the end of follow-up, 29.5% of patients discontinued SCK. The two-year retention rate was 72%. Dropout risk was higher in patients with fibromyalgia (HR: 2.896, p = 0.026). No significant retention differences were found based on sex, age, enthesitis, radiographic disease, combination with cDMARDs, SCK dosage, or previous bDMARD exposure. Lower ASDAS-CRP at the study's end was noted in patients without fibromyalgia (1.4 vs. 2.5, p < 0.001). Conclusions: SCK showed rapid and lasting effectiveness for ax-SpA with a favorable retention rate, though fibromyalgia may reduce treatment persistence. [ABSTRACT FROM AUTHOR]

Registry-based observational prospective study aimed at describing the use of biologic drugs in pediatric-onset scleritis. Data were collected at baseline, at 3-, 6-, 12-month follow-up and at last assessment. Scleral inflammation was graded according to Sen classification. Five patients (9 eyes) treated with adalimumab, infliximab, abatacept and secukinumab were included. All patients were previously treated with conventional immunosuppressors and glucocorticoids. Median biologic treatment duration was 28 (IQR = 118) months. At 6-months, scleritis resolved in all eyes. At 12-months, complete disease control was observed in 7/9 eyes (77.8%). The number of relapses 12 months before and after treatment initiation was 17 and 2, respectively. Mean BCVA was 0.83 (range 0.3–1.0) at baseline and 1.0 for all eyes after 12 months. Glucocorticoids had been withdrawn in 4/5 patients. In conclusion, biological agents proved to be effective in pediatric-onset scleritis, allowing a noticeable steroid-sparing effect and preserving visual function and bulbar integrity. [ABSTRACT FROM AUTHOR]

Background: It is reported that treatment with anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) induces hypogonadism both in male patients with ALK‐positive cancer and in murine models. Methods: In this study, three groups, including an experimental group of male patients with ALK‐positive, advanced non–small cell lung cancer (ANSCLC) who were receiving alectinib (cohort A), a control group of female patients with ALK‐positive ANSCLC who were receiving alectinib (cohort B), and a control group of male patients with ALK‐negative ANSCLC (cohort C), prospectively underwent a full hormone assessment for androgen deficiency at 8 weeks after the start of treatment and in case of reported suspected symptoms. Patients with major sexual dysfunctions were referred to an endocrinologist. Results: Ninety‐five patients were consecutively enrolled onto the study. Among sixty‐eight male patients, both median total testosterone levels (2.93 vs. 4.92 ng/ml; p =.0001) and free testosterone levels (0.11 vs. 0.17 pg/ml; p =.0002) were significantly lower in ALK‐positive ANSCLC patients in cohort A compared with ALK‐negative patients in cohort C; conversely, median FSH (10.32 vs. 17.52 mUI/ml; p =.0059) and LH levels (4.72 vs. 7.49 mUI/ml; p =.0131) were significantly higher in cohort C compared to cohort A. Median inhibin B levels were higher in ALK‐positive male patients (74.3 vs. 44.24 pg/ml; p =.0038), but all patients had inhibin B values within the normal range. The percentage of male patients who had positive scores on the Androgen Deficiency in Aging Males (ADAM) questionnaire was 62% in cohort A and 26.8% in cohort C, including eight patients who reported at least one major symptom and were referred to Andrology Unit. No significant differences in the endocrine assessment were reported between cohorts A and B. Conclusions: Symptoms of androgen deficiency should be tracked in male patients with ALK‐positive ANSCLC who are receiving alectinib, and testosterone replacement should be considered, as appropriate. Male patients with ALK‐positive advanced non–small cell lung cancer treated with first‐line alectinib had lower median total testosterone (p =.0001) and free testosterone (p =.0002) levels compared with male patients who had ALK‐negative disease and were receiving other anticancer treatments. Symptoms of hypogonadism were more frequent in ALK‐positive patients compared with ALK‐negative patients (62% vs 26.8% rates of positive score at ADAM questionnaire, respectively), suggesting the need for hormone assessment and referral to an andrologist, as appropriate. [ABSTRACT FROM AUTHOR]

Objective: We aimed to evaluate the clinical usefulness of the systemic score in the prediction of life‐threatening evolution in Still disease. We also aimed to assess the clinical relevance of each component of the systemic score in predicting life‐threatening evolution and to derive patient subsets accordingly. Methods: A multicenter, observational, prospective study was designed including patients included in the Gruppo Italiano Di Ricerca in Reumatologia Clinica e Sperimentale Adult‐Onset Still Disease Study Group and the Autoinflammatory Disease Alliance Network Still Disease Registry. Patients were assessed to see if the variables to derive the systemic score were available. The life‐threatening evolution was defined as mortality, whatever the clinical course, and/or macrophage activation syndrome, a secondary hemophagocytic lymphohistiocytosis associated with a poor prognosis. Results: A total of 597 patients with Still disease were assessed (mean ± SD age 36.6 ± 17.3 years; male 44.4%). The systemic score, assessed as a continuous variable, significantly predicted the life‐threatening evolution (odds ratio [OR] 1.24; 95% confidence interval [CI] 1.07–1.42; P = 0.004). A systemic score ≥7 also significantly predicted the likelihood of a patient experiencing life‐threatening evolution (OR 3.36; 95% CI 1.81–6.25; P < 0.001). Assessing the clinical relevance of each component of the systemic score, liver involvement (OR 1.68; 95% CI 1.48–2.67; P = 0.031) and lung disease (OR 2.12; 95% CI 1.14–4.49; P = 0.042) both significantly predicted life‐threatening evolution. The clinical characteristics of patients with liver involvement and lung disease were derived, highlighting their relevance in multiorgan disease manifestations. Conclusion: The clinical utility of the systemic score was shown in identifying Still disease at a higher risk of life‐threatening evolution in a large cohort. Furthermore, the clinical relevance of liver involvement and lung disease was highlighted. [ABSTRACT FROM AUTHOR]

The term NaTech was coined to describe events where natural hazards trigger technological accidents in industrial facilities. Structural damage to the installations, caused by natural events such as earthquakes or tsunami, may cause loss of containment, which may in turn lead to fires, blasts, or dispersion of toxic gases. Thus, NaTech quantitative risk assessment (QRA) requires a measure of structural risk to provide estimates of future losses and a detailed assessment of the consequences arising from such losses. This paper presents an industrial risk analysis for anchored atmospheric storage tanks subjected to tsunami hazard, by means of a multidisciplinary approach integrating structural analysis and consequence assessment. This is performed for a case study consisting of a waterfront tank farm located at a coastal Italian site. The first part of the analysis requires calculation of the structural failure rate of storage tanks that suffer content release due to damage induced by tsunami inundation, via models of probabilistic hazard for the site of interest and the vulnerability (fragility) of the examined structures. Structural failure rates are evaluated for various numbers of simultaneous waterfront storage tank failures, using tsunami fragility curves for variable tank geometry and filling level. The failure rates and consequence analysis for the tank farm are then used as input parameters for the NaTech QRA, leading to the calculation of risk figures for tsunami hazard. [ABSTRACT FROM AUTHOR]

Process towers, whose purpose includes executing operations of mass transfer such as stripping, distillation, or liquid-liquid extraction, are usually constructed as vertical steel cylindrical pressurised shells, supported on a cylindrical skirt. Seismic risk analysts in an industrial setting, especially in NaTech context, are often faced with the issue that structural vulnerability models are not always available for the various industrial facilities. Process towers, although widespread, are one of those cases. The objective of the study presented in the paper is to simulate the behaviour of such towers when subjected to earthquake-induced ground shaking, with the goal of numerically deriving seismic fragility models. To this end, as a case study, two towers were considered with the same height and internal diameter, but different operating pressures, which determines the thickness of the pressure vessel and, consequently, the configuration of the anchorage system. For each of the two models, multi-stripe dynamic analysis was conducted, using a selection of hazard-consistent ground motion records, on joystick models. The results of the dynamic analyses are presented and their use for the derivation of fragility functions for certain damage states is discussed. This modelling strategy can contribute to streamline the fragility evaluation of such structures, given the variety of geometries which appear in industrial plants. [ABSTRACT FROM AUTHOR]

This article discusses the case of a 44-year-old woman with hyperimmunoglobulinemia D periodic fever syndrome (HIDS) who also developed hidradenitis suppurativa (HS). HIDS is a rare autoinflammatory disorder caused by mutations in the MVK gene, while HS is a chronic skin disease characterized by recurrent nodules, abscesses, and scars. The article suggests that the coexistence of HIDS and HS may provide insights into the molecular pathways underlying autoinflammation and could potentially lead to new therapeutic strategies for both conditions. [Extracted from the article]

PurposeMethodsResultsConclusionThe survey aims to explore the use of existing nomenclature and current clinical and multimodal imaging (MMI) approach in diagnosing white dot syndromes (WDS) among uveitis and retina specialists.The members of the International Uveitis Study Group (IUSG) task force MUV (Multimodal imaging in UVeitis) developed a survey. The questionnaire, created using Qualtrics, consisted of 22 questions. The responses were compared against regions, workplace setting, sub-specialty, and experience of the participants.A total of 432 participants initiated the background section; 343 initiated the investigation section and 263/343 completed the survey (76.7%). The majority (43.7%) reported a specialty/practice focus mostly on uveitis, 32.2% on uveitis and retina, and 20.1% mostly on retina. Specifically, 55.7% were in practice > 10 years post-fellowship and 65.8% worked in academic settings. The term WDS was not universally used in clinical practice, with no significant differences by region, subspecialty, experience, workplace setting or number of WDS patients managed in the prior year (p > 0.01). Nearly 90% of participants reported using MMI to diagnose WDS. More than 70% advocated redefining the nomenclature and classification of WDS based on the primary anatomical location of disease using MMI without significant regional or professional differences (p > 0.01).These results underscore the widespread adoption of MMI among uveitis and retina specialists in the characterization of entities traditionally grouped under the term WDS. Respondents strongly agree that MMI provides a precise distinction between these posterior uveitis, advocating for the overcoming of the clinical term WDS in favor of a patho-anatomic redefinition. [ABSTRACT FROM AUTHOR]

Summary Vacuoles, E1 enzyme, X‐linked, autoinflammatory, somatic (VEXAS) is a haemato‐inflammatory syndrome genetically defined by somatic mutations in the X‐linked UBA1 gene, typically Val/Thr/Leu substitutions at the Met41 hotspot. Clinical manifestations are heterogeneous and refractory to most haemato‐rheumatological treatments. To date, no guidelines exist for the management of VEXAS, and scarce is the evidence on methodology and clinical significance of longitudinal UBA1 clonal burden evaluation upon therapy. Here, we validated a method to quantify UBA1 clonal burden and explored its applicability in patients with VEXAS. Given the different treatment interactions, droplet digital polymerase chain reaction (ddPCR) may allow for informed therapeutic decisions and implementation of personalized strategies. [ABSTRACT FROM AUTHOR]

PurposeMethodsResultsConclusionsThe clinical relevance of human leukocyte antigen (HLA) subtypes such as HLA-B51 on Behçet’s disease (BD)-related uveitis and non-infectious uveitis (NIU) unrelated to BD remains largely unknown.Data were prospectively collected from the International AIDA Network Registry for BD and for NIU. We assessed differences between groups (NIU unrelated to BD and positive for HLA-B51, BD-related uveitis positive for HLA-B51 and BD-related uveitis negative for HLA-B51) in terms of long-term ocular complications, visual acuity (VA) measured by best corrected visual acuity (BCVA), anatomical pattern, occurrence of retinal vasculitis (RV) and macular edema over time.Records of 213 patients (341 eyes) were analyzed. No differences in complications were observed (p = 0.465). With regard to VA, a significant difference was detected in median BCVA (p = 0.046), which was not maintained after Bonferroni correction (p = 0.060). RV was significantly more prevalent in NIU-affected patients who tested positive for HLA-B51, irrespective of the systemic diagnosis of BD (p = 0.025). No differences emerged in the occurrence of macular edema (p = 0.99).Patients with NIU testing positive for HLA-B51 exhibit an increased likelihood of RV throughout disease course, irrespective of a systemic diagnosis of BD. The rate of complications as well as VA are comparable between NIU cases unrelated to BD testing positive for HLA-B51 and uveitis associated with BD. Therefore, it is advisable to perform the HLA-B typing in patients with NIU or retinal vasculitis, even in the absence of typical BD features. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the cardiac involvement in patients with Still's disease with a focus on myocarditis included in the multicenter AIDA (AutoInflammatory Disease Alliance) network Still's disease registry. To exploit the predictive factors for myocarditis in deriving a clinical risk patient profile for this severe manifestation., Methods: A multicenter observational study was built up assessing consecutive patients with Still's disease characterized by the cardiac involvement among those included in the AIDA Network Still's Disease Registry. The cardiac involvement was defined according to the presence of pericarditis, tamponade, myocarditis, and/or aseptic endocarditis., Results: In total, 73 patients with Still's disease and cardiac involvement were assessed (mean age 36.3±19.9 years, 42.5% male sex); out of them, 21.9% were children. The most common cardiac manifestation was the pericarditis in 90.4% of patients, 26.0% presented with myocarditis, and less frequently endocarditis (2.7%) and tamponade (1.4%). Comparing clinical features of patients with myocarditis than others, significantly increased frequencies of skin rash, and pleuritis as well as higher values of systemic score were recognised. Furthermore, an enhanced mortality rate was registered in patients with myocarditis. In regression models, the skin rash and the systemic score independently predicted the myocarditis., Conclusion: The characteristics of patients with Still's disease and cardiac involvement were assessed in the AIDA network. The most common feature was the pericarditis but also a more severe clinical picture was reported in patients with myocarditis. The latter was associated with increased mortality rate and with higher systemic score, identifying patients to be carefully managed.