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Valerio Sansone,1,2 Emanuele Maiorano,1 Alessandro Galluzzo,1 Valerio Pascale1,2 1Department of Orthopaedics, University of Milan, 2Department of Orthopaedics, I.R.C.C.S. Istituto Ortopedico Galeazzi, Milan, Italy Abstract: Calcific tendinopathy (CT) of the shoulder is a common, painful condition characterized by the presence of calcium deposits in the rotator cuff tendons. Current theories indicate that CT may be the result of a cell-mediated process in which, after a stage of calcium deposition, calcifications are spontaneously resorbed. However, in a minority of cases, this self-healing process is somehow disrupted, resulting in symptoms. Recent literature shows an emerging role of biological and genetic factors underlying CT. This new evidence could supplement the classic mechanical theory of rotator cuff tendinopathy complicated by calcium precipitation, and it may also explain why the majority of the therapies currently in use are only able to provide partially satisfactory outcomes. This review aims to summarize the current knowledge about the pathological processes underlying CT of the shoulder and thereby justify the quest for advanced biological treatments of this condition when it becomes symptomatic. Keywords: rotator cuff tendons, calcific tendinopathy, calcific deposits, shoulder, tendinitis, review

This project is a single ongoing case study that focuses on the teaching experiences of two early-career math teachers working in rural schools and the factors that influenced their decision to work in these environments (Yin, 2014). Both teachers are graduates of Clarkson University's STEM Up NY program, a National Science Foundation (NSF)-funded Robert Noyce Teacher Scholarship Program designed to strengthen STEM teaching and to learn in high-need schools. This project is part of a larger, 14-partner Noyce research collaboration focusing on STEM teacher persistence, retention, and recruitment (TPR2) in rural schools. TPR2 addresses the national shortage of STEM teachers in rural communities, which is critical for future student success. This larger project seeks to identify programmatic features of STEM teacher preparation programs that aid in rural STEM teachers' recruitment, retention, and persistence.

Concentration polarization in an electrolyte comprising dissociated ions and a solvent is often modeled using concentrated solution theory developed by Newman. This theory is built upon two differential equations for electrolyte concentration and solvent velocity fields. We characterize the concentration and solvent velocity fields in a polystyrene-block-polyethylene oxide (SEO) block copolymer electrolyte using operando X-ray transmission measurements and X-ray photon correlation spectroscopy, respectively. Using calculations based on the assumption that the SEO chain behaves as a single species, we show that the experimental data are consistent with a cation transference number, t+0, ≈ 0.7. Previously published electrochemical experiments using small polarizations led to the conclusion that t+0 is less than 0.3. The discrepancy indicates that the block copolymer electrolyte cannot be approximated as a three-component system (cation, anion, and a single solvent), and frictional interactions involving the glassy polystyrene cannot be lumped with those involving rubbery poly(ethylene oxide) segments.

Abstract Background Although second-generation antipsychotics (SGAs) have proven to be effective therapeutic options for patients with schizophrenia, there is a notable lack of evidence on patients’ subjective perspectives regarding their well-being, quality of life, and satisfaction with these medications. This study aimed to evaluate the treatment satisfaction and effectiveness of lurasidone on quality of life and functioning in adult patients with schizophrenia in real-world Italian clinical practice. Methods This was a multicentre, national, non-interventional, single-arm, 3-month prospective study. Patients who were naive to lurasidone treatment and whose treating physician had decided to start them on this medication were enrolled and evaluated over a 3-month period. Eligible patients were adults (≥ 18 years of age) with a primary diagnosis of schizophrenia who were being treated with lurasidone (for the first time [i.e., they were lurasidone naive]) as part of routine clinical practice. Efficacy endpoints were changes in patient/caregiver treatment satisfaction (seven-point Likert scale from the Treatment Satisfaction Questionnaire for Medication), patient quality of life and functioning (QLS), investigator-rated global assessment of functioning (CGI-S, IAQ) after 6 weeks and 3 months of lurasidone, and number of relapses and hospitalizations. Results Sixty-one patients were enrolled and 59 completed the study. The median dosage of lurasidone at baseline was 37.00 mg/day. The median duration of titration was 86.0 days (Min 28; Max 115 days); the median number of dosage changes was 1.0. At the end of 3-month observation period, the median dose of lurasidone was 74.00 mg/day. QoL and Functioning Score showed a trend of improvement over time, reaching a mean change from baseline of 9.8 at the end of the study. According to the CGI-S, the percentage of patients who were “markedly or severely ill” showed a continuous decrease from baseline to 3 months, from 62.29% to 8.20%. Patient satisfaction increased over time, with 80.32% of patients reporting that they were somewhat, fairly, or very satisfied (including 63.93% who were completely or very satisfied) at the end of the study. No relapses/hospitalizations for psychiatric reasons were reported. Lurasidone was well tolerated with no safety concerns or discontinuations due to AEs. Conclusions Lurasidone represents a valid option for the treatment of schizophrenia and positively affects subjective well-being, quality of life and satisfaction. Trial registration NCT06527885 retrospectively registered (01/08/2024).

This study explores secondary mathematics teachers' perceptions of the experiences that contributed to their capacities to understand mathematical modeling and to facilitate students' modeling experiences. The retrospective research methods and transformative learning theory frame used in the study honor teachers as adult learners and value their perspectives while providing a way to study the complexity of learning to model and to teach modeling. Data analysis identified triggers and knowledge dilemmas that challenged and prompted teacher learning as well as opportunities to resolve dilemmas through rational discourse and critical reflection. Patterns in teacher-identified meaningful learning experiences reveal a trajectory with strands that address aspects of doing and teaching mathematical modeling: mathematics, social aspects of learning, real-world contexts, student thinking, and curriculum. Results of this study provide a holistic view of learning to do and teach mathematical modeling, complementing studies of designed professional learning interventions that out of necessity target specific parts of the modeling process. The results both support and challenge common teacher education content and practices. The study illustrates the usefulness of retrospective methods to understand teachers as lifelong learners.

This curated collection covers a selection of PRIMUS articles published over a roughly 12-year period that focus on modeling and applications. The collection includes sections on individual projects, courses with a significant modeling component, and modeling and applications in extracurricular settings and throughout the curriculum.

Concentrated solution theory has furthered our understanding of ion transport in electrolytes. This theory can be used to predict salt concentration profiles under an applied current if the transport properties of the electrolyte (conductivity (κ), restricted diffusion coefficient (D), and the cation transference number with respect to the solvent velocity ( t + 0 )), and the thermodynamic factor (T f ) are known. In this work, we provide the first study comparing the predicted salt concentration profiles with measurements based on operando Raman spectroscopy. Concentration polarization is asymmetrical; the increase in salt concentration near the positive electrode is a factor of two greater than the decrease in salt concentration near the negative electrode. We find qualitative agreement between theory and experiment. Further work is needed to resolve the quantitative differences.

Pulmonary sequestration is a rare congenital pulmonary anomaly where a portion of the lung parenchyma is supplied by an anomalous systemic artery, usually originating from the thoracic or abdominal aorta. Traditionally surgical resection and ligation of the aberrant feeding vessel are the gold standard treatments of this disease. Hybrid operations consisting in endovascular arterial embolization and surgical resection is a promising treatment option. We report a case of a 69-years-old man with symptomatic intralobular sequestration successfully treated by hybrid approach.

Gastric volvulus is a rare condition determined by the rotation of one part of stomach around another. Stomach can rotate around its longitudinal or short axis or both. The presentation can be acute, subacute and chronic due to twisting and untwisting andimaging should be performed in the acute phase. MDCT shows high accuracy in thediagnosis and definition of gastric volvulus being the preferred diagnostic test in emergency settings. Gastric volvulus may be associated or determined by pre-existing hiatal hernia and accurate analysis of CT signs may be evaluated on order to differentiate between a stomach in an abnormal position and a volvulus.At CT, a displaced antrum at the same level or cranial to the fundus and a transition point at the pylorus is diagnostic for mesenteroaxial volvulus. We present a case of a 70 years old woman with mesenteroaxial volvulus in hiatal hernia.

Small bowel jejunoileal diverticulosis is an uncommon and usually asymptomatic condition. Complications may occur such as acute diverticulitis including infection or perforation, bleeding, small bowel obstruction and volvulus. Herein we report a case of a 76 years-old woman with acute left side abdominal pain and tenderness. A clinical suspected diagnosis of colonic diverticulitis was formulated. She underwent Ultrasound that revealed a collapsed small bowel loop with a large sac-like out-pouching lesion with mixed content (fluid and pockets of air) associated to hyperechogenicity of perilesional fat. Because of the atypical US findings, the patient underwent abdominopelvic CT that confirmed that the large sac-like out-pouching was a jejunal inflamed diverticulum. The patient underwent emergency surgery. Radiologist should be aware of imaging findings of jejunoileal diverticulitis in order to achieve a prompt diagnosis.

The differential diagnosis between renal arteriovenous malformations (AVM) and cancer may be a challenge, due to the similar clinical and imaging findings. Herein, we report the case of an 80-year-old male patient presenting gross hematuria, initially diagnosed and treated with embolization for a renal AVM. Due to the recurrence of hematuria and rapid progression and changes of the vascular lesion with detection also of an intralesional solid nodule, a radical nephrectomy was performed revealing the presence of a renal cell carcinoma (RCC). Renal cell carcinoma and renal AVM can be difficult to differentiate from one another, for this reason a short-term follow-up should be carried out in patients diagnosed and treated for renal AVM to confirm the resolution of AVM or to assess any changes, such as atypical neovascularization or intralesional renal masses, which may increase the suspect of a hidden renal tumor.

Multiple fractures of the femur, defined for the purposes of this study as the association of three or more non-contiguous fractures on the same bone segment, is an exceedingly rare condition with an unknown incidence in the literature. A limited number of studies, mainly consisting of case reports or small case series, have addressed this topic, and no shared consensus or guidelines exist on what the ideal timing and sequence of multiple fracture fixation is. The present paper reports the clinical case of a 36 years old man who sustained a blunt chest injury, a non-concussive head injury, a displaced intracapsular fracture of the left femur (AO 31B2), a left diaphyseal multifragmentary fracture (AO 32B3), a supradiacondylar fracture of the distal end of the left femur (AO 33C1.1), a Hoffa fracture of the lateral left femoral condyle (AO 33B3.2 f), and a multifragmentary fracture of the left patella with bone loss (AO 34C3) due to a vehicular high-energy trauma. The patient was surgically treated by open reduction and internal fixation according to a proposed algorithm of treatment and reported excellent clinical and radiological outcomes at 32 months follow-up. The primary aim of this study is to describe our experience in the treatment of such complex fractures, by presenting our clinical and radiological results, and to propose a treatment algorithm. The secondary aim is to provide a comprehensive review of the literature on this topic.

In Malawi, tetanus toxoid vaccination (TTV) is recommended in pregnancy, but few studies have assessed the prevalence of infant seroprotection against tetanus. Anti-TT levels from 84 6-week-old infants, born in 2019–2020 to mothers living with HIV (HEU: HIV-exposed-uninfected) infants and to HIV-negative women (HUU: HIV-unexposed-uninfected) infants were determined by ELISA assay. Although 94% of the infants (HEU=94.8%, HUU=92.3%) showed protective levels (>0.1 IU/mL), the mean titers observed (0.51 IU/mL) suggest an incomplete compliance with TT vaccination. The only factor positively correlated to anti-TT IgG levels was the duration of maternal antiretroviral therapy in HEU.

Abstract Atopic dermatitis (AD) is a highly heterogeneous chronic inflammatory skin disorder that is frequently associated with a plethora of comorbidities. AD is, therefore, considered a systemic disease impacted by a considerable burden and leading to poor quality of life, especially in patients with moderate-to-severe disease. Since atopic and non-atopic comorbidities can further worsen the disease course, accurate establishment of the patient’s individual intrinsic risk profile and needs is crucial and may help in guiding the selection of the best treatment option. Better quality of care for patients with AD can be delivered through a multidisciplinary team led by a dermatologist, for comprehensive patient management. The implementation of a multidisciplinary approach for AD could enhance the delivery of optimised and safe treatments, improve the standard of care and patient outcomes in the short and long term, and prevent or delay the lifelong impact of uncontrolled AD. Understanding the unmet needs, assessing correctly the patient risk profile and enhancing the shared patient–physician decision-making process can lead to disease control and quality-of-life improvement, especially in the context of the introduction of newer treatment for AD. This narrative review is a call for more data to establish standardised patient profiles and multidisciplinary strategies in AD management. In view on the fast-evolving treatments for AD, this review aims at highlighting the importance of a multidisciplinary approach to a comprehensive assessment and holistic care in patients with moderate-to-severe AD.

ABSTRACT: Age at first calving (AFC) represents the nonproductive period of ∼2 yr in Holstein cows, and thus, it has a relevant effect on the cost of rearing replacements in the dairy herd. In the present study, we aimed to evaluate genetic and genomic aspects of AFC in the Italian Holstein population. Data of 4,206,218 heifers with first calving between 1996 and 2020 were used. Age at first calving averaged 26.09 ± 3.07 mo and decreased across years. Heritability was estimated using a linear animal model which included the fixed effects of herd-year-season of birth and classes of gestation length, and the random animal additive genetic effect fitted to a pedigree-based relationship matrix. The EBV and genomically EBV (GEBV) were obtained, and they were standardized to mean 100 and standard deviation 5, where animals above the mean are those contributing to reduce AFC. Heritability estimates of AFC ranged from 0.031 to 0.045. The trend of sires' GEBV was favorable and indicated a reduced AFC across years. Approximate genetic correlations between GEBV of AFC and GEBV of other economically important traits were calculated on a subset of genotyped females born after 2015. Moderate favorable associations of AFC with production traits (0.39–0.51), udder depth (0.40), interval from first to last insemination in heifer (−0.43), and longevity (0.34) were assessed. Overall, the greatest lifetime productive performances and most favorable days open in first lactation were observed when heifers calved at 22 to 23 mo. In contrast, progeny of sires with GEBV of AFC above the mean yielded more milk, fat, and protein in first lactation, and had shorter days open than progeny of sires with GEBV of AFC below the mean. Results suggested that breeding strategies to improve AFC should be pursued, also considering genetic correlations between AFC and traits which are already part of the Italian Holstein breeding objective. The inclusion of AFC in an aggregate index is expected to contribute to enhance farm income.

Purpose of the article: Interleukin-23 inhibitors, such as tildrakizumab, have emerged as safe and effective options for the management of psoriasis. Yet their efficacy in elderly patients (aged 65 years or more), particularly in those with difficult-to-treat areas involvement, remains insufficiently explored. We conducted this real-life retrospective multicentric observational study to assess the effectiveness of tildrakizumab in elderly patients with moderate-to-severe psoriasis, with involvement of difficult-to-treat areas.Materials and methods: We enrolled forty-nine patients aged 65 years old or more (mean age 73.1 ± 6.0), all treated with tildrakizumab for at least 28 weeks. The effectiveness of tildrakizumab was assessed by Static Physician’s Global Assessment of Genitalia (sPGA-G), fingernail-PGA (f-PGA), palmoplantar PGA (pp-PGA), scalp-specific PGA (sc-PGA), and Psoriasis Area and Severity Index (PASI) scores.Results: Significant improvements in PASI scores were observed within 28 weeks of treatment, with 77.5%, 60%, and 45.2% of patients achieving PASI75, PASI90, and PASI100, respectively. The mean PASI decreased significantly from baseline (13.6 ± 9.9) to 1.3 ± 1.7 at week 28. More than 90% of patients had clear sPGA-G and pp-PGA scores and over 70% had clear f-PGA and sc-PGA scores after 28 weeks.Conclusions: Our findings suggest that tildrakizumab could be a valuable option for the treatment of elderly patients, including those with difficult-to-treat areas involvement.

Abstract Dupilumab‐associated ocular surface disease is a common clinical sign appearing in patients with atopic dermatitis (AD) just few months after dupilumab treatment start, developing in about 25% of patients. Atopic keratoconjunctivitis (AKC) is a well‐identified clinical entity, defined as a chronic inflammatory disease of eye that affects 25%–40% of patients with AD. Most clinical signs of ocular involvement in AD patients treated with dupilumab overlaps the AKC symptoms and signs. We supposed that Dupilumab‐associated ocular surface disease and AKC represent the same disease but differently called by dermatologists and ophthalmologists. AKC‐like disease may develop during dupilumab therapy as a consequence of alternative cytokines pathway activation (e.g. IL33) secondary to IL‐4/13 pathway block. The novel upadacitinib drug may bypass ILs pathway through Janus Kinases selective inhibition, avoiding positive or negative ILs feedback at the ocular surface level. In this case report, molecular analysis on conjunctival samples showed a lower ocular surface inflammation (lower expression of HLADR) although higher levels of IL4 and IL13 in a patient with AD and AKC during upadacitinib therapy, compared to prior dupilumab treatment. Target therapies in patients suffering from AD may prevent ocular and dermatological comorbidities improving quality of life before quality of skin and vision.

Abstract Background Wide consensus exists on the notion that low muscle mass is a predictor of negative health‐related events, such as disability, morbidity, and mortality. Indeed, the European Working Group on Sarcopenia in Older People 2 had identified muscle mass as the key component to confirm the diagnosis of sarcopenia. However, the lack of normative values for muscle mass across ages hampers the practical assessment of this important parameter. The aim of the present study was to produce cross‐sectional centile and normative values for calf circumference (a surrogate estimation of muscle mass) across a wide spectrum of ages using a large and unselected sample of community‐dwellers enrolled in the Longevity Check‐up 7+ (Lookup 7+) project. Methods This is a cross‐sectional study using the data of Lookup 7+ project, an ongoing study started in June 2015 and conducted in unconventional settings (i.e., exhibitions, malls, and health promotion campaigns). Candidate participants were considered eligible for enrolment if they were at least 45 years of age and provided written informed consent. Calf circumference was measured using an inextensible but flexible plastic tape in a sitting position with the knee and ankle at a right angle and the feet resting on the floor. Normative values for calf circumference from ages 45 to 80 + years were generated. Results A total of 11 814 participants were enrolled from 1 June 2015 to 30 September 2022. The mean age of participants included in the analyses was 61.8 years (standard deviation; 10.2 years; range: 45–98 years), and 6686 (57%) were women. Normative values for calf circumference were obtained for men and women, stratified by age groups. Accordingly, a calf circumference tape, with colour bands that demarcate the centiles range into which the patient falls, was created and validated. Conclusions Our study established age‐ and gender‐specific centile reference values for calf circumference. The calf circumference tape can be used to easily interpret the assessment in every‐day practice for the early detection of individuals with or at risk of sarcopenia and malnutrition.

Filomena Russo,1 Marco Galluzzo,2,3 Luca Stingeni,4 Severino Persechino,5 Leonardo Zichichi,6 Andrea Conti,7 Claudia Giofrè,8 Valentina Dini,9 Martina Vispi,10 Laura Atzori,11 Angelo Cattaneo,12 Aurora Parodi,13 Federico Bardazzi,14 Giuseppe Stinco,15 Paolo Dapavo,16 Giampiero Girolomoni,17 Maria Letizia Musumeci,18 Manuela Papini,19 Marina Venturini,20 Stefano Dastoli,21 Sergio Di Nuzzo,22 Maria Concetta Fargnoli,23 Gianluca Pagnanelli,24 Nicoletta Bernardini,25 Daniele Mario Gambini,26 Piergiorgio Malagoli,27 Carlo Mazzatenta,28 Ketty Peris,29 Iris Zalaudek,30 Gabriella Fabbrocini31 ,† Francesco Loconsole,32 Camilla Vassallo,33 Lucia Pietroleonardo,34 Francesca Prignano,35 Chiara Franchi,36 Anna Maria Offidani,37 Claudio Bonifati,38 Vito Di Lernia,39 Giovanni Gigante,40 Marta Silvia Bartezaghi,40 Matteo Franchi,41,42 Paola Ursoleo,40 Elisabetta Aloisi40 1Dermatology Section, Department of Medical, Surgical and Neurological Science, University of Siena, S. Maria Alle Scotte Hospital, Siena, Italy; 2Department of Systems Medicine, University of Rome “Tor Vergata”, Rome, Italy; 3Dermatology Unit, Fondazione Policlinico “Tor Vergata”, Rome, Italy; 4Section of Dermatology, Department of Medicine and Surgery, University of Perugia, Perugia, Italy; 5Dermatology Unit, NESMOS Department, Faculty of Medicine & Psychology, Sapienza University of Rome, Sant’Andrea University Hospital, Rome, Italy; 6Unit of Dermatology, San Antonio Abate Hospital, Trapani, Italy; 7Section of Dermatology, Department of Specialized Medicine, University of Modena and Reggio Emilia, Modena, Italy; 8U.O.C. Dermatologia, A.O. Papardo, Messina, Italy; 9Section of Dermatology, Department of Medicine and Oncology, University of Pisa, Pisa, Italy; 10Dermatology Unit, Misericordia Hospital, Grosseto, Italy; 11Dermatology Unit, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy; 12Dermatology Unit, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milano, Italy; 13Section of Dermatology, DiSSal University of Genoa, Ospedale-Policlinico San Martino IRCCS, Genova, Italy; 14Dermatology Division, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy; 15Section of Dermatology, Department of Medicine, University of Udine, Udine, Italy; 16Section of Dermatology, Department of Medical Sciences, University of Turin, Turin, Italy; 17Section of Dermatology, Department of Medicine, University of Verona, Verona, Italy; 18Section of Dermatology, Department of Medical and Surgical Specialties, University of Catania, Catania, Italy; 19Dermatology Clinic of Terni, University of Perugia, Perugia, Italy; 20Section of Dermatology, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy; 21Department of Health Sciences, Magna Graecia University, Catanzaro, Italy; 22Department of Medicine and Surgery, University of Parma, Parma, Italy; 23Section of Dermatology, Department of Biotechnological and Applied Clinical Science, University of L’Aquila, L’Aquila, Italy; 24Department of Dermatology, Istituto Dermopatico dell’Immacolata - IRCCS, Roma, Italy; 25Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Dermatology Unit, “Daniele Innocenzi”, Asl Latina, Italy; 26Dermatology Unit, ASST Papa Giovanni XXIII Hospital, Bergamo, Italy; 27Dermatology Unit, Azienda Ospedaliera San Donato Milanese, Milan, Italy; 28Dermatology Unit, Lucca Azienda USL Toscana Nord Ovest, Pisa, Italy; 29Department of Translational Medicine and Surgery, IRCCS A. Gemelli University Polyclinic Foundation, Sacred Heart Catholic University, Rome, Italy; 30Department of Dermatology, University of Trieste, Trieste, Italy; 31Section of Dermatology, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy; 32Department of Dermatology, University of Bari, Bari, Italy; 33Institute of Dermatology, IRCCS Policlinico San Matteo Foundation and University of Pavia, Pavia, Italy; 34Dermatology Unit, Vito Fazzi Hospital, Lecce, Italy; 35Dermatology Clinic, Department of Health Sciences, University of Florence, Florence, Italy; 36Dermatology Unit, IRCCS IO Galeazzi, Milan, Italy; 37Dermatological Clinic, Polytechnic University of the Marche Region, Ancona, Italy; 38Department of Dermatology, Istituto Dermatologico San Gallicano - IRCCS, Roma, Italy; 39Dermatology Unit, Arcispedale S. Maria Nuova IRCCS, Reggio Emilia, Italy; 40Novartis Farma SpA, Origgio, Italy; 41National Centre for Healthcare Research and Pharmacoepidemiology, Milan, Italy; 42Laboratory of Healthcare Research and Pharmacoepidemiology, Department of Statistics and Quantitative Methods, University of Milano Bicocca, Milan, Italy†Gabriella Fabbrocini passed away on 3 March 2023Correspondence: Filomena Russo, Dermatology Section, Department of Medical, Surgical and Neurological Science, University of Siena, S. Maria Alle Scotte Hospital, Siena, Italy, Email file.russo@libero.itPurpose: SUPREME, a phase IIIb study conducted in Italy, demonstrated safety and high efficacy of secukinumab for up to 72 weeks in patients with moderate-to-severe plaque-type psoriasis. SUPREME 2.0 study aimed to provide real-world data on the long-term drug survival and effectiveness of secukinumab beyond 72 weeks.Patients and Methods: SUPREME 2.0 is a retrospective observational chart review study conducted in patients previously enrolled in SUPREME study. After the end of the SUPREME study, eligible patients continued treatment as per clinical practice, and their effectiveness and drug survival data were retrieved from medical charts.Results: Of the 415 patients enrolled in the SUPREME study, 297 were included in SUPREME 2.0; of which, 210 (70.7%) continued secukinumab treatment throughout the 42-month observation period. Patients in the biologic-naïve cohort had higher drug survival than those in the biologic-experienced cohort (74.9% vs 61.7%), while HLA-Cw6–positive and HLA-Cw6–negative patients showed similar drug survival (69.3% and 71.9%). After 42 months, Psoriasis Area and Severity Index (PASI) 90 was achieved by 79.6% of patients overall; with a similar proportion of biologic-naïve and biologic-experienced patients achieving PASI90 (79.8% and 79.1%). The mean absolute PASI score reduced from 21.94 to 1.38 in the overall population, 21.90 to 1.24 in biologic-naïve and 22.03 to 1.77 in biologic-experienced patients after 42 months. The decrease in the absolute PASI score was comparable between HLA-Cw6–positive and HLA–Cw6-negative patients. The baseline Dermatology Life Quality Index scores also decreased in the overall patients (10.5 to 2.32) and across all study sub-groups after 42 months. Safety was consistent with the known profile of secukinumab, with no new findings.Conclusion: In this real-world cohort study, secukinumab showed consistently high long-term drug survival and effectiveness with a favourable safety profile.Keywords: psoriasis, secukinumab, real-world evidence, drug survival, SUPREME

AbstractBackground The Loggerhead sea turtle (Caretta caretta) is a marine reptile belonging to a monophyletic group of chelonians. As these animals are long-lived, they have the ability to accumulate pollutants.Aim To collect epidemiological data on toxic metals in marine Loggerhead sea turtles.Materials and Methods Forty Loggerhead sea turtles comprising 25 males and 15 females stranded freshly dead between 2013 and 2018 along the coasts of Sicily, Southern Italy, were examined for arsenic, cadmium, and lead accumulation in muscle and adipose tissues by means of a validated ICP-MS method. A modified K index as a growth condition factor, namely Fulton’s K index, was used. Samples were tested in duplicate. A Wilcoxon rank sum test was carried out to evaluate metal contents differences between muscle and adipose tissues and between genders.Results The Fulton’s K index suggested a good body condition of the C. caretta recovered with mean values of 5.34 ± 3.40 (n = 40; ±SD). Detectable concentrations of lead were found in 70% of the samples analysed with mean values of 0.65 ± 1.67 mg/kg wet weight and 0.51 ± 1.29 mg/kg wet weight in muscle and adipose tissues, respectively. No significant differences in arsenic, cadmium, and lead were detected between genders. In addition, no significant correlation was found between modified K index and concentrations of arsenic, cadmium, and lead.Clinical relevance Findings on muscle and adipose tissues suggest chronic exposure of Caretta caretta to high concentrations of especially lead which might negatively affect health and welfare of these marine turtles although body condition was good.

Introduction: Data about the long-term effectiveness of brodalumab could be valuable in assessing patient adherence to treatment and improving psoriasis management. Objective: The aim of our study was to evaluate the drug survival of brodalumab and identify any predictive factors for discontinuation. Methods: A multicenter retrospective study was conducted in patients with moderate-to-severe psoriasis who were treated for up to 3 years. We extracted data from patient files, related to the characteristics of the patients and the disease. Drug survival analysis was descriptively analyzed using Kaplan–Meier survival curves. Univariable and multivariable analyses were performed to assess baseline patient characteristics that predicted clinical response. Results: The study included 90 patients. Among them, 28 (31.1%) suspended brodalumab through the observation period. At weeks 52, 104 and 156 the median PASI score were 0.0 [0.0 – 0.8], 0.0 [0.0 – 1.0] and 0.0 [0.0 – 0.0], respectively. The estimated cumulative survival rates at weeks 52 and 104 were 86.32% and 78.09%, respectively. In the multivariable survival analysis, predictor factors for overall discontinuation included body mass index (BMI) (OR 1.10, 95% CI 1.03 - 1.18), baseline PASI (OR 1.06, 95% CI 1.02 - 1.10), and psoriatic arthritis (OR 5.05, 95% CI 0.89 - 13.50). Conclusions: Brodalumab has shown long-term effectiveness for up to 3 years. Considering baseline disease severity and patient characteristics could aid in optimizing the long-term management of psoriasis.