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Although recent studies have demonstrated associations between nonchromosomal birth defects and several pediatric cancers, less is known about their role on childhood leukemia susceptibility. Using data from the Childhood Cancer and Leukemia International Consortium, we evaluated associations between nonchromosomal birth defects and childhood leukemia. Pooling consortium data from 18 questionnaire-based and three registry-based case-control studies across 13 countries, we used multivariable logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between a spectrum of birth defects and leukemia. Our analyses included acute lymphoblastic leukemia (ALL, n = 13 115) and acute myeloid leukemia (AML, n = 2120) cases, along with 46 172 controls. We used the false discovery rate to account for multiple comparisons. In the questionnaire-based studies, the prevalence of birth defects was 5% among cases vs 4% in controls, whereas, in the registry-based studies, the prevalence was 11% among cases vs 7% in controls. In pooled adjusted analyses, there were several notable associations, including (1) digestive system defects and ALL (OR = 2.70, 95% CI: 1.46-4.98); (2) congenital anomalies of the heart and circulatory system and AML (OR = 2.86, 95% CI: 1.81-4.52) and (3) nervous system defects and AML (OR = 4.23, 95% CI: 1.50-11.89). Effect sizes were generally larger in registry-based studies. Overall, our results could point to novel genetic and environmental factors associated with birth defects that could also increase leukemia susceptibility. Additionally, differences between questionnaire- and registry-based studies point to the importance of complementary sources of birth defect phenotype data when exploring these associations.

Background. The Ilizarov method is a recognized technique for treating severe skeletal injuries, allowing for a comprehensive restoration of both bone and soft tissue components. Despite the fact that bone lengthening and transport are widely known techniques, distraction of a longitudinally split fragment is still used extremely rarely. The aim of the study is to describe a series of clinical cases involving patients operated on using this technique. Methods. We present a series of observations of five patients who underwent distraction of a longitudinally split fragment using the Ilizarov method between January 2006 and December 2022. Clinical information was obtained from case histories, all surgical interventions were documented. Postoperative examination was performed using radiography. Results. A case series demonstrates the successful application of this technique for reconstruction of partial bone defects resulting from trauma or osteomyelitis. The study included five patients (4 men and 1 woman) who underwent surgery 4.8-34.0 months after trauma for a partial defect of the proximal tibia ranging from 4 to 8 cm in length. Distraction was performed in different directions along the sagittal and longitudinal axes. The time of external fixation ranged from 3.5 to 4.8 months, the external fixation index ranged from 0.49 to 1.22. The ASAMI (Association for the Study and Application of the Methods of Ilizarov) functional score at the follow-up examination was excellent in all five patients. The ASAMI bone tissue assessment showed excellent results in all patients, except for one patient with residual equinus (good result). No other complications were reported. Conclusions. The Ilizarov method provides a minimally invasive and comprehensive approach to the elimination of partial bone defects, affecting simultaneously the skeletal and soft tissue components. Due to the longitudinal splitting during fragment transport and distraction osteogenesis, this method promotes bone and tissue regeneration and helps to avoid a volumetric bone defect and more complex segmental bone transport. Moreover, the role of transverse transport of the tibial cortex increases in the treatment of peripheral arterial diseases.

Background. Changes in the level of the patella position are a well-known complication of knee replacement, reconstruction of the anterior cruciate ligament, high tibial osteotomy and consequences of injuries. However, this problem has not been disclosed in the literature in relation to distraction osteogenesis using the Ilizarov method. The aim of the study is to describe such a rare iatrogenic complication as patella baja during limb lengthening by the Ilizarov method using a clinical case as an example. Case description. In 2017, a 17-year-old teenager was injured in a head-on collision of cars at high speed. The patient was diagnosed with an open fracture of the left femur and fibula and tibia of the left leg. He was treated in another clinic using the Ilizarov apparatus for osteosynthesis of the femur, tibia and proximal osteotomy of the tibia to move the bone to fill the distal bone defect. At the end of the treatment, the patient had a moderate limitation of the knee flexion (180-80°). In 2018, the patient was admitted to our clinic due to osteomyelitis at the level of the consolidated fracture. A new resection of the osteomyelitis lesion and proximal osteotomy for bifocal osteogenesis were performed. During the treatment, limitation of knee flexion (180-120°) was developed and radiographic signs of low position of the patella were obtained. Given the progression of patella baja (the Caton-Deschamps index = 0.51), we were forced to return the patient to the operating room to restore the correct height of the patella. Conclusions. The presented clinical case emphasizes the need for a more thorough assessment of the patella height after surgical treatment on the proximal tibia using the Ilizarov method. It is also noted that it is important to conduct a control MRI, which allows for a more detailed study of the initial position of the anterior tibial tubercle. In our case, early detection of complications allowed us to achieve complete recovery without any consequences.

Abstract Psoriasis is a chronic, immune-mediated, inflammatory skin disease, associated with multiple comorbidities and psychological and psychiatric disorders. The quality of life of patients with this disease is severely compromised, especially in moderate-to-severe plaque psoriasis. Secukinumab, a fully humanized monoclonal antibody, was the first anti-interleukin (IL)-17 biologic approved for treating psoriasis. Secukinumab demonstrated long-lasting efficacy and a good safety profile in individuals with plaque psoriasis, and it is associated with an improvement in health-related quality of life. While there is evidence that early treatment with systemic therapy can affect disease progression and improve long-term outcomes in other autoimmune diseases, evidence is limited in psoriasis, especially in real-world settings. This review provides an overview of studies describing the effectiveness of secukinumab in the treatment of psoriasis summarizing the literature and focusing on real-world evidence and early intervention.

Background. Indocyanine green (ICG) fluorescence imaging is a surgical tool with increasing applications in various surgical disciplines. During nonunion resection, the assessment of bone vascularization is currently based only on the surgeon’s experience. We introduced the use of indocyanine green (ICG) angiography in orthopedics. The aims of the study: 1) to use ICG fluorescence angiography to evaluate the bone perfusion in patients with atrophic nonunion, where poor or absent ICG flow reveals avascular tissue associated with bone necrosis requiring surgical resections; 2) to describe our case series of patients operated with this technique. Methods. We used ICG angiography in patients operated for tibial nonunion resection. We administered 0.5 mg/kg of ICG powder dissolved in sterile saline at 2.5 mg/ml concentration. The time from the injection to the beginning of appreciation of the green dye was measured. Non-viable bone was resected accordingly. Patient underwent routine follow-up. We enrolled all the suitable patients operated from April 2019 to June 2021 and matched three control patients for each of them. We reviewed their medical records and noted any relevant data. Results. We enrolled 4 cases and 12 controls, all male. The mean age was 30.8±6.9 years. The mean duration from trauma to surgery was 10.5 (0.7-25.0) months. The mean duration of surgery was 190.8±40.3 min. The defect size was 4.89±2.03 cm. ICG allowed rapid visualization of bone vascularization after 25-45 sec. No adverse events were observed. The mean external fixation time was 11.8±5.0 months. The mean external fixation index was 2.69±1.10. Seven patients needed a surgical revision during treatment. Three patients underwent reintervention after frame removal. There are no statistically significant differences between cases and controls. Conclusions. The research findings of this study are limited by the small number of observations. However, this technique is safe, easy, and rapid and may contribute to intraoperative decision of how much to resect. Using ICG could objectively demonstrate bone perfusion to help surgeons to avoid massive bone defects.

Abstract Introduction The introduction of biological therapies has revolutionized the treatment of moderate-to-severe plaque psoriasis. In particular, ixekizumab, an inhibitor of interleukin-17A, has shown great results in terms of efficacy and safety in both clinical trials and real-world experiences. However, there is a lack of long-term real-world data available for ixekizumab. Methods We conducted a multicenter real-life study to evaluate the effectiveness and safety of ixekizumab in patients with moderate-to-severe plaque psoriasis. Psoriasis Area and Severity Index score (PASI) was collected at baseline and after 1, 2, 3, 4, and 5 years. The occurrence of any adverse events was recorded at each time point. Results We enrolled 1096 patients treated with ixekizumab for at least 1 year. At week 52, the percentages of PASI 90 and PASI 100 were 85.04% and 69.07%, respectively. After 5 years of treatment with ixekizumab, out of 145 patients, a PASI 90 response was achieved by 86.90% of patients, while complete skin clearance was reached by 68.28% of patients. We did not observe any new significant safety findings throughout the study period. Conclusion This study supports the long-term effectiveness and safety of ixekizumab in a real-world setting.

Abstract Introduction Several systemic therapies have been approved for the treatment of severe AD. In particular, Janus kinase inhibitors (JAKi), including abrocitinib, baricitinib, and upadacitinib, recently received approval for the treatment of patients with severe AD after being evaluated in several clinical trials. However, a few concerns have been raised regarding their long-term safety and the management of these drugs in real-world clinical practice. In this article we described the results of a Delphi consensus aimed at describing the knowledge on JAKi and focusing, in particular, on providing clinical recommendations for dermatologists in daily practice regarding the use of these drugs. Methods Twelve Italian dermatologists reviewed the most recent literature regarding the efficacy and safety profiles of JAKi and proposed 24 statements. Results Agreement was reached for statements focusing on three main topics: (1) place in therapy of JAKi in patients with moderate-to-severe AD; (2) effectiveness and safety of JAK inhibitors in different phenotypes; (3) different approaches to the management of patients treated with JAKi in clinical practice. The panel proposed several recommendations regarding all the statements. Conclusion Given the wide use of JAKi in clinical practice, it is crucial to establish a specific follow-up for each patient’s phenotype in order to achieve the best possible clinical outcome and minimize potential adverse events.

Aim: Abrocitinib is a JAK-1 inhibitor approved for the treatment of moderate-to-severe atopic dermatitis (AD). We conducted a 16-week multicenter retrospective study to assess the short-term effectiveness and safety of abrocitinib in patients with moderate-to-severe AD.Our retrospective study included 85 adult patients from 14 Italian Dermatology Units affected by moderate-to-severe AD treated with abrocitinib 100/200 mg.Methods: Effectiveness of abrocitinib at weeks 4 and 16 was assessed by using the Eczema Area and Severity Index (EASI), the Investigator Global Assessment (IGA), the peak pruritus and sleep- Numerical Rating Scale (PP-NRS and S-NRS, respectively).Results: At week 16, improvement of at least 90% in EASI (EASI90) and IGA 0/1 was observed in 49.4% and 61.2% of patients, respectively. A reduction of at least 4 points in PP-NRS and S-NRS compared with baseline was achieved by 70.6% of patients for both endpoints. No significant safety reports were observed during the study period. Naïve patients had better rates of EASI 90 compared to patients who previously failed dupilumab.Conclusion: Our data confirm the effectiveness of abrocitinib in a real-world setting with better clinical responses at weeks 4 and 16, compared with Phase-III clinical trials. Longer analyses are required to further establish the safety profile of abrocitinib.

Purpose of the article: The aim of this multicenter observational study is to report data from real world on the use of bimekizumab in patients aged ≥ 65 years with moderate-to-severe plaque psoriasis. Elderly patients are poorly represented in clinical trials on bimekizumab for plaque psoriasis, and real-world studies are important to guide clinical choices.Materials and methods: A retrospective multicenter study was conducted in 33 dermatological outpatient clinics in Italy. Patients aged ≥ 65 years, with moderate-to-severe plaque psoriasis and treated with bimekizumab were enrolled. No exclusion criteria were applied. Bimekizumab was administered following the Italian Guidelines for the management of plaque psoriasis and according to the summary of product characteristics, in adult patients who were candidates for systemic treatments. Overall, 98 subjects were included, and received bimekizumab up to week 36. Clinical and demographic data were collected before the initiation of treatment with bimekizumab. At baseline and each dermatological examination (4, 16, and 36 weeks), clinical outcomes were measured by the following parameters: (1) PASI score; (2) site-specific (scalp, palmoplantar, genital, nail) Psoriasis Global Assessment (PGA). At each visit, the occurrence of any adverse events (AEs) was recorded, including serious AEs and AEs leading to bimekizumab discontinuation.Results: The mean PASI score was 16.6 ± 9.4 at baseline and significantly decreased to 4.3 ± 5.2 after 4 weeks (p

AbstractBackground Genital involvement in atopic dermatitis(AD) can have a significant impact on the patient’s quality of life. However, inspection of genital areas is not usually conducted during routine examination and patients may be reluctant to inform the clinician or show this area.Objective to evaluate the efficacy of tralokinumab in AD patients with genital involvement.Methods Adult patients with moderate/severe AD and genital involvement receiving tralokinumab have been analyzed. Primary endpoints were EASI, DLQI, PP-NRS, genital-IGA (g-IGA) and genital itching (GI) at week 16.Results out of 48 patients with moderate/severe AD under treatment with tralokinumab, 12 patients (25%) showed a genital involvement. Seven patients reported itching in the genital area (58%), while none reported a positive history of genital infections. Median scores at T0 were EASI 17.5, PP-NRS 8 and DLQI 14. After 16 weeks of treatment, we observed a median EASI of 3, a median PP-NRS of 1 and a median DLQI of 1. Finally, concerning the genital response, after 16 weeks of treatment, we observed a statistically significant decrease in mean GI and g-IGA scores.Conclusion despite the small size of our sample, tralokinumab can be considered as a valid treatment option for AD with genital involvement.

AbstractPurpose Tildrakizumab is a selective inhibitor of IL-23 approved for the treatment of moderate-to-severe plaque psoriasis in two dosages. We conducted a 16-week multicenter retrospective study to compare the effectiveness and safety of tildrakizumab 200 mg versus tildrakizumab 100 mg in patients with a high disease burden or high body weight.Materials and methods Our retrospective study included 134 patients treated with tildrakizumab 200 mg and 364 patients treated with tildrakizumab 100 mg from 28 Italian Dermatology Units affected by moderate-to-severe plaque psoriasis. The patients had a body weight above 90 kg or a high disease burden (Psoriasis Area and Severity Index [PASI] ≥ 16 or the involvement of difficult-to-treat areas). We evaluated the effectiveness of tildrakizumab at the week-16 visit in terms of PASI90, PASI100 and absolute PASI ≤ 2.Results After 16 weeks of treatment with tildrakizumab 200 mg, PASI90 was reached by 57.5% of patients and PASI100 by 39.6% of patients. At the same time point, 34.3% and 24.2% of patients treated with tildrakizumab 100 mg achieved PASI90 and PASI100, respectively.Conclusions Our data suggest that tildrakizumab 200 mg has better effectiveness than tildrakizumab 100 mg in patients with a body weight ≥ 90 kg and a high disease burden.

BackgroundTherapy resistance in cancer is often driven by a subpopulation of cells that are temporarily arrested in a non-proliferative G0 state, which is difficult to capture and whose mutational drivers remain largely unknown.ResultsWe develop methodology to robustly identify this state from transcriptomic signals and characterise its prevalence and genomic constraints in solid primary tumours. We show that G0 arrest preferentially emerges in the context of more stable, less mutated genomes which maintain TP53 integrity and lack the hallmarks of DNA damage repair deficiency, while presenting increased APOBEC mutagenesis. We employ machine learning to uncover novel genomic dependencies of this process and validate the role of the centrosomal gene CEP89 as a modulator of proliferation and G0 arrest capacity. Lastly, we demonstrate that G0 arrest underlies unfavourable responses to various therapies exploiting cell cycle, kinase signalling and epigenetic mechanisms in single-cell data.ConclusionsWe propose a G0 arrest transcriptional signature that is linked with therapeutic resistance and can be used to further study and clinically track this state.

In recent years, many countries have introduced Computational Thinking (CT) concepts into compulsory education as part of general curriculum reform efforts. A systematic review of academic and grey literature has been conducted to analyse the state of the art in implementing CT in primary and secondary education. In total, 1977 publications were identified, out of which 98 met the inclusion criteria for the review. The results show that, despite a lack of consensus on a common definition, a core set of key CT skills is addressed in primary and lower secondary education. Implementation approaches that emerged from the analysis are discussed and presented according to the European Commission's Joint Research Centre (2016) classification: (i) embedding CT across the curriculum as a transversal theme/skill set; (ii) integrating CT as a separate subject; and (iii) incorporating CT skills within other subjects such as Mathematics and Technology. New approaches to formative assessment of CT are emerging, reflecting different conceptualisations and differences in contextual and motivational aspects of CT curriculum integration. However, further investigation is needed to understand better how gender/equity/inclusion issues impact the quality of computing education integration.

Electrical engines are built under electromagnetism concepts to create mechanical power, those can be seen as simple machines, as it depends on reluctance, even being called as “reluctance motor”, what gives this engine the possibility of being widely used for many purposes. The main objective of this research is to minimize copper losses of a single-phase 6x6 variable reluctance synchronous motor. For that, a Particle Swarm Optimization (PSO) algorithm will be used to obtain the optimum configuration through the Finite Elements Method (FEM). In this context, electric motor design equations were dimensioned based on similar machines. The next procedure was to use FEMM (Finite Element Method Magnetics) software, that allows the magnetic flow density analysis inside the motor air gap. Finally, it is noteworthy that the copper losses results were analyzed before and after the variable reluctance motor optimization with computational tools.

Abstract Objective Ictal central apnea (ICA) is a frequent correlate of focal seizures, particularly in temporal lobe epilepsy (TLE), and regarded as a potential electroclinical biomarker of sudden unexpected death in epilepsy (SUDEP). Aims of this study are to investigate morphometric changes of subcortical structures in ICA patients and to find neuroimaging biomarkers of ICA in patients with focal epilepsy. Methods We prospectively recruited focal epilepsy patients with recorded seizures during a video‐EEG long‐term monitoring with cardiorespiratory polygraphic recordings from April 2020 to September 2022. Participants were accordingly subdivided into two groups: patients with focal seizures with ICA (ICA) and without (noICA). A pool of 30 controls matched by age and sex was collected. All the participants underwent MRI scans with volumetric high‐resolution T1‐weighted images. Post‐processing analyses included a whole‐brain VBM analysis and segmentation algorithms performed with FreeSurfer. Results Forty‐six patients were recruited (aged 15–60 years): 16 ICA and 30 noICA. The whole‐brain VBM analysis showed an increased gray matter volume of the amygdala ipsilateral to the epileptogenic zone (EZ) in the ICA group compared to the noICA patients. Amygdala sub‐segmentation analysis revealed an increased volume of the whole amygdala, ipsilateral to the EZ compared to controls [F(1, 76) = 5.383, pFDR = 0.042] and to noICA patients ([F(1, 76) = 5.383, pFDR = 0.038], specifically of the basolateral complex (respectively F(1, 76) = 6.160, pFDR = 0.037; F(1, 76) = 5.121, pFDR = 0.034). Interpretation Our findings, while confirming the key role of the amygdala in participating in ictal respiratory modifications, suggest that structural modifications of the amygdala and its subnuclei may be valuable morphological biomarkers of ICA.

Abstract Background Brodalumab, a fully human anti‐interleukin (IL)‐17 monoclonal antibody that blocks IL‐17RA, is approved in Europe for the treatment of adult patients with moderate‐to‐severe plaque psoriasis who are candidates for systemic treatment. Objectives This study evaluated the achievement and maintenance of therapeutic response for 1 year in psoriasis patients treated with brodalumab in the Italian clinical practice. Methods Real‐world, multicenter, observational, retrospective and prospective study. The retrospective phase ranged from enrolment visit to initiation of brodalumab (12 ± 4 weeks before). The prospective phase ranged from enrolment to a routine follow‐up visit set after 52 ± 4 weeks. Results One hundred eighty‐four patients were eligible and 164 completed the observation period (median 11.9 months; Q1–Q3: 11.4–12.3). At enrolment, the mean duration of disease was 13.9 years (standard deviation; 13.3), 94% of patients (N = 172) had ≥1 clinical manifestation of psoriasis, mainly erythema and itching, and 95.6% had received ≥1 antipsoriatic treatment before brodalumab. Patients who reached an absolute Psoriasis Area and Severity Index (PASI) score ≤3 at week 12 and maintained it ≤3 through week 52 were 97 (64.7%). At week 12, 72.7% of patients achieved PASI 75, 54.5% PASI 90 and 42.0% PASI 100. At Week 52, 92.9% of patients achieved PASI 75, 84.4% PASI 90 and 61.7% PASI 100. A static Physician's Global Assessment (sPGA) score = 0 was obtained by 55.0% of patients after 12 weeks of brodalumab and by 77.0% after 52 weeks. A Dermatology Life Quality Index ≤1 was reported by 71.9% of patients after 12 weeks and by 89.9% after 52 weeks of treatment. No significant outcome differences were shown among patient subgroups defined by previous antipsoriatic treatments (none, systemic other than biologics or biologic) at either brodalumab initiation or any of the subsequent study visits. Conclusions In this real‐world setting, brodalumab was rapidly effective on skin lesions and quality of life both in biologic‐naïve and biologic‐experienced moderate‐to‐severe psoriasis patients, with a favourable safety profile.

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

(1) Background/Objectives: Nail psoriasis (NP) is a chronic and difficult-to-treat disease, which causes significant social stigma and impairs the patients’ quality of life. Moreover, nail psoriasis is a true therapeutic challenge for clinicians. The presence of nail psoriasis can be part of a severe form of psoriasis and can have predictive value for the development of psoriatic arthritis. Our real-world-evidence multicenter study aims to evaluate the efficacy of bimekizumab in nail psoriasis. (2) Methods: A retrospective analysis of a multicenter observational study included 834 patients affected by moderate-to-severe psoriasis, in 33 Dermatologic Units in Italy, treated with bimekizumab from December 2022 to September 2023. Clinimetric assessments were based on Psoriasis Area and Severity Index (PASI), Dermatology Life Quality Index (DLQI), and Physician’s Global Assessment of Fingernail Psoriasis (PGA-F) for the severity of nail psoriasis at 0, 12, 24, and 36 weeks. (3) Results: Psoriatic nail involvement was present in 27.95% of patients. The percentage of patients who achieved a complete clearance of NP in terms of PGA-F 0 was 31.7%, 57%, and 88.5% at week 4, 16, and 36, respectively. PASI 100 was achieved by 32.03% of patients at week 4, by 61.8% at week 16, and by 78.92% of patients at week 36. The mean baseline PASI was 16.24. The mean DLQI values for the entire group of patients at baseline, at week 4, at week 16, and at week 36 were 14.62, 3.02, 0.83, and 0.5, respectively. (4) Conclusions: Therapies that promote the healing of both the skin and nails in a short time can also ensure a lower risk of subsequently developing arthritis which is disabling over time. Bimekizumab proved to be particularly effective to treat NP, with a fast response in terms of complete clearance, with over 88.5% of patients free from NP after 36 weeks. The findings of our real-world study showed that patients with moderate-to-severe PsO and concomitant NP had significantly faster and more substantial improvements in NP up to 36 weeks with respect to previous research findings. Considering the rapid healing of the nail, the dual inhibition of IL17 A and F might have a great value in re-establishing the dysregulation of keratin 17 at the nail level.

Introduction: Genital involvement is observed in approximately 60% of patients with psoriasis, presenting clinicians with formidable challenges in treatment. While new biologic drugs have emerged as safe and effective options for managing psoriasis, their efficacy in challenging-to-treat areas remains inadequately explored. Intriguingly, studies have shown that interleukin (IL)-17 inhibitors exhibit effectiveness in addressing genital psoriasis. Objectives: We aimed to determine the effectiveness profile of bimekizumab in patients affected by moderate-to-severe plaque psoriasis with involvement of genitalia. Methods: Bimekizumab, a dual inhibitor of both IL-17A and IL-17F, was the focus of our 16-week study, demonstrating highly favorable outcomes for patients with genital psoriasis. The effectiveness of bimekizumab was evaluated in terms of improvement in Static Physician's Global Assessment of Genitalia (sPGA-G) and Psoriasis Area and Severity Index. Results: Sixty-five adult patients were enrolled. Remarkably, 98.4% of our participants achieved a clear sPGA-G score (s-PGA-g=0) within 16 weeks. Moreover, consistent improvements were observed in PASI scores, accompanied by a significant reduction in the mean Dermatology Life Quality Index (DLQI), signifying enhanced quality of life. Notably, none of the patients reported a severe impairment in their quality of life after 16 weeks of treatment. In our cohort of 65 patients, subgroup analyses unveiled that the effectiveness of bimekizumab remained unaffected by prior exposure to other biologics or by obesity. Conclusions: Our initial findings suggest that bimekizumab may serve as a valuable treatment option for genital psoriasis. Nevertheless, further research with larger sample sizes and longer-term follow-up is imperative to conclusively validate these results.

Psoriasis is often associated with abdominal obesity and type-2 diabetes (T2D). The inflammatory process in psoriasis can target adipose tissue depots, especially those surrounding the heart and coronary arteries, exposing to an increased risk of cardiovascular diseases. A 50-year-old female patient referred to us for abdominal obesity and T2D, which were not controlled with lifestyle modifications. She had suffered from psoriasis for some years and was treated with guselkumab, without success. Epicardial adipose tissue (EAT) attenuation and pericoronary adipose tissue (PCAT) attenuation for each coronary, defined as mean attenuation expressed in Hounsfield unit (HU), were assessed by routine coronary computed tomography angiography. At baseline, EAT attenuation was −80 HU and PCAT attenuation of the right coronary artery (RCA) was −68 HU, values associated with an increased cardiac mortality risk. Psoriasis area and severity index (PASI) was 12.0, indicating severe psoriasis, while dermatology life quality index (DLQI) was 20, indicating a negative effect on the patient’s life. Semaglutide (starting with 0.25 mg/week for 4 weeks, increased to 0.50 mg/week for 16 weeks, and then to 1 mg/week) was started. After 10 months, semaglutide treatment normalized glycated hemoglobin and induced weight loss, particularly at abdominal level, also followed by a reduction in computed tomography-measured EAT volume. EAT attenuation and PCAT attenuation of RCA decreased, showing an important reduction of 17.5 and 5.9% respectively, compared with baseline. PASI and DLQI decreased by 98.3 and 95% respectively, indicating an improvement in psoriasis skin lesions and an important amelioration of the patient’s quality of life, compared with baseline.

IntroductionThe development of several effective biological drugs for moderate-to-severe plaque psoriasis has dramatically changed the lives of patients. Despite the wide use of interleukin (IL) inhibitors, limited data are available to date regarding long-term treatment persistence.MethodThis multicenter retrospective real-world study evaluated 5932 treatment courses across 5300 patients, all treated with interleukin inhibitors. Drug survival was expressed by using the Kaplan-Meier estimator for each biological drug at 6, 12, 24, 36 and 48 months. We also stratified by discontinuation associated with primary or secondary ineffectiveness.ResultsIn our study, the most prescribed drugs were secukinumab (1412), ixekizumab (1183), and risankizumab (977). After four years of follow-up, risankizumab emerged as the treatment with the highest drug survival overall, as 91.6% of patients were still on treatment. The overall probability of drug survival at four years was comparable for tildrakizumab (83.5%), ixekizumab (82.6%), guselkumab (82.4%) and brodalumab (81.8%). When evaluating only patients who discontinued the treatment because of ineffectiveness, once again risankizumab was the molecule with the highest drug survival at 4 years (93.4%), this time followed by ixekizumab (87%). Our study, in which all IL inhibitors were adequately represented, confirmed a slightly better treatment persistence for IL-23 inhibitors, consistent with other real-world studies.ConclusionOur experience showed that IL-23 inhibitors, and risankizumab in particular, had a higher probability of drug survival overall during a 4-year follow-up. Risankizumab and ixekizumab were less likely to be discontinued because of ineffectiveness after four years.

ABSTRACT: The aim of this study was to examine the effects of frozen storage for 12 mo on the concentrations of lipids and cholesterol and fatty acid profile of wooden chicken breast meat. A total of 120 samples of chicken breasts were selected, according to the degree of “wooden breast” myopathy [“severe,” “moderate,” and “normal” (absence of myopathy)], from male chickens slaughtered at 42 d of age, from Cobb 500 strain. Part of the samples (n = 20/grade of severity) were evaluated on the day of collection and the remainder were packaged, frozen and stored at −18°C for up to 12 mo. At the beginning (collection day) and at the end of the proposed freezing period (12 mo), analyses of lipid, cholesterol, and fatty acid profile were carried out. Percentage of saturated (SFA), monounsaturated (MUFA), and polyunsaturated (PUFA) fatty acids were evaluated. Meats affected by wooden breast myopathy had lower levels of PUFA that exert beneficial effects on health, such as DHA, EPA and ARA, and this profile is impaired by prolonged storage (12 mo), which results in important nutritional losses for the consumer.

Purpose Ixekizumab is a high-affinity monoclonal antibody that selectively targets interleukin (IL)-17A approved for the treatment of moderate-to-severe plaque psoriasis. The objective of this study was to describe the real-world long-term effectiveness of ixekizumab in patients with plaque psoriasis in Italy. Materials and Methods A retrospective study was conducted in patients affected by moderate-to-severe plaque psoriasis who were continuously treated with ixekizumab for at least 12 months. Patient data was obtained at 4-weeks, 12-weeks and 6-, 12-, 18- and 24-months after baseline (June 2017 and September 2019) from 10 sites. Results were analyzed by complete case approach, with sensitivity analysis performed to evaluate the impact of missing data. Results A total of 198 patients were enrolled in the study. At Month 24, 94.3% of patients achieved PASI75 response, while 85.1 and 71.8% achieved PASI90 and PASI100, respectively; and 91.1% of the patients achieved absolute PASI score ≤2. Patients experienced psoriasis improvement at 4 weeks after starting treatment, and improvement was maintained with continued ixekizumab use. The quality of life of patients also improved significantly starting at Week 12, with sustained effect in the long term. Conclusion This 24-month observational cohort study confirmed that ixekizumab is effective in the long-term management of patients with moderate-to-severe plaque psoriasis.

Abstract Background Therapy resistance in cancer is often driven by a subpopulation of cells that are temporarily arrested in a non-proliferative G0 state, which is difficult to capture and whose mutational drivers remain largely unknown. Results We develop methodology to robustly identify this state from transcriptomic signals and characterise its prevalence and genomic constraints in solid primary tumours. We show that G0 arrest preferentially emerges in the context of more stable, less mutated genomes which maintain TP53 integrity and lack the hallmarks of DNA damage repair deficiency, while presenting increased APOBEC mutagenesis. We employ machine learning to uncover novel genomic dependencies of this process and validate the role of the centrosomal gene CEP89 as a modulator of proliferation and G0 arrest capacity. Lastly, we demonstrate that G0 arrest underlies unfavourable responses to various therapies exploiting cell cycle, kinase signalling and epigenetic mechanisms in single-cell data. Conclusions We propose a G0 arrest transcriptional signature that is linked with therapeutic resistance and can be used to further study and clinically track this state.

In recent years, many countries have introduced Computational Thinking (CT) concepts into compulsory education as part of general curriculum reform efforts. A systematic review of academic and grey literature has been conducted to analyse the state of the art in implementing CT in primary and secondary education. In total, 1977 publications were identified, out of which 98 met the inclusion criteria for the review. The results show that, despite a lack of consensus on a common definition, a core set of key CT skills is addressed in primary and lower secondary education. Implementation approaches that emerged from the analysis are discussed and presented according to the European Commission’s Joint Research Centre (2016) classification: (i) embedding CT across the curriculum as a transversal theme/skill set; (ii) integrating CT as a separate subject; and (iii) incorporating CT skills within other subjects such as Mathematics and Technology. New approaches to formative assessment of CT are emerging, reflecting different conceptualisations and differences in contextual and motivational aspects of CT curriculum integration. However, further investigation is needed to understand better how gender/equity/inclusion issues impact the quality of computing education integration.

Marina Talamonti,1 Filomena Russo,2 Giovanna Malara,3,4 Katharina Hansel,5 Manuela Papini,6 Angelo Cattaneo,7 Aurora Parodi,8 Andrea Chiricozzi,9,10 Piergiorgio Malagoli,11 Federico Bardazzi,12 Valeria Brazzelli,13 Paolo Dapavo,14 Paolo Gisondi,15 Cristina Zane,16 Concetta Potenza,17 Franca Cantoresi,18 Maria Concetta Fargnoli,19 Sara Trevisini,20 Pina Brianti,21 Leonardo Pescitelli,22 Giovanni Gigante,23 Marta Bartezaghi,23 Luisa Caputo,23 Elisabetta Aloisi,23 Antonio Costanzo24,25 On behalf of the SUPREME Study Group1Dermatology, University of Rome Tor Vergata, Rome, Italy; 2Department of Medical, Surgical and Neurological Science, Dermatology Section, University of Siena, S. Maria alle Scotte Hospital, Siena, Italy; 3Dermatology Unit, Hospital “Bianchi Melacrino Morelli”, Reggio, Calabria, Italy; 4Department of Dermatology, Papardo Hospital, Messina, Italy; 5Section of Dermatology, Department of Medicine and Surgery, University of Perugia, Perugia, Italy; 6Dermatologic Clinic of Terni, Department of Medicine and Surgery, University of Perugia, Perugia, Italy; 7U.O. Dermatologia, Fondazione IRCCS Ca’ Granda - Ospedale Maggiore Policlinico, Milano, Italy; 8Di.S.Sal. Section of Dermatology, Ospedale Policlinico San Martino, University of Genova, Genova GE, 16132, Italy; 9UOC di Dermatologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli - IRCCS, Rome, Italy; 10Dermatologia, Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy; 11Psocare Unit, I.R.C.C.S Policlinico San Donato, Milano, Italy; 12Dermatology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; 13Dermatology, Fondazione IRCCS Policlinico San Matteo and University of Pavia, Pavia, Italy; 14Department of Biomedical Science and Human Oncology, Second Dermatologic Clinic, University of Torino, Torino, Italy; 15Section of Dermatology and Venereology, Department of Medicine, University of Verona, Verona, Italy; 16Dermatology Department, ASST Spedali Civili di Brescia, University of Brescia, Brescia, Italy; 17Dermatology Unit “Daniele Innocenzi”, Department of Medico-Surgical Sciences and Biotechnologies, Faculty of Pharmacy and Medicine, Sapienza University of Rome – Polo Pontino, Latina, Italy; 18Dermatology Unit, Department of Medicine, University of Roma, Roma, Italy; 19Dermatology, Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, L’Aquila, Italy; 20Department of Dermatology, University of Trieste, Trieste, Italy; 21Dermatology and Cosmetology Unit - San Raffaele Hospital, Milan, Italy; 22Department of Health Sciences, Dermatology Clinic, University of Firenze, Firenze, Italy; 23Novartis Farma SpA, Origgio, Italy; 24Unit of Dermatology, IRCCS Humanitas Research Hospital, Milano, Italy; 25Department of Biomedical Sciences, Humanitas University, Milano, ItalyCorrespondence: Marina Talamonti, Dermatology-Department of Systems Medicine, University of Rome Tor Vergata, PTV – Policlinico Tor Vergata, V.le Oxford 81, Rome, 00133, Italy, Tel +39 0620902743, Fax +39 0620902742, Email talamonti.marina@gmail.comPurpose: Secukinumab is a fully human monoclonal antibody that inhibits interleukin (IL)-17A approved for the treatment of moderate to severe plaque psoriasis in adults and children. We compared the efficacy and safety of secukinumab in patients aged < 65 years (adult patients) versus patients aged ≥ 65 years (elderly patients) in a post-hoc analysis of the SUPREME study.Patients and Methods: Patients with moderate to severe plaque psoriasis received subcutaneous secukinumab 300 mg per week for the first 5 weeks, then 300 mg per month. We compared the following outcomes in patients aged ≥ 65 years vs < 65 years: baseline characteristics; PASI50/75/90/100 response rates (improvements ≥ 50%/75%/90%/100% in Psoriasis Area and Severity Index (PASI) from baseline); changes in Dermatology Life Quality Index (DLQI); Hospital Anxiety and Depression Scale (HAD-A, HAD-D) score changes; treatment-emergent adverse events (TEAEs).Results: Secukinumab was slightly less effective in elderly patients than in adult patients (response rates at week 16: PASI90, 69.4% vs 80.9%, p = 0.4528; PASI100, 44.4% vs 56.7%, p = 0.8973). Elderly and adult patients showed a similar time course of changes in absolute PASI scores. Patients aged ≥ 65 years had a statistically significantly lower improvement in quality of life (mean DLQI reduction) than patients aged < 65 years at week 16 [− 5.4 (± 4.3) vs − 8.8 (± 6.9), p = 0.0065] and at week 24 [− 5.3 (± 4.4) vs − 9.2 (± 7.1), p = 0.0038]. Secukinumab treatment resulted in comparable mean reductions in anxiety and depression scores in both cohorts at 24 weeks [HAD-A, − 1.3 (± 3.3) vs − 2.1 (± 3.8), p = 0.9004; HAD-D, − 1.0 (± 3.3) vs − 1.5 (± 3.1), p = 0.4598]. The frequency of TEAEs in the two cohorts was similar (16.7% vs 14.6%, p = 0.7391).Conclusion: Secukinumab is a valid option for the management of moderate to severe psoriasis in elderly patients.Keywords: psoriasis, biologics, interleukin-17A, secukinumab, elderly

Abstract Aims Sacubitril/valsartan has changed the treatment of heart failure with reduced ejection fraction (HFrEF), due to the positive effects on morbidity and mortality, partly mediated by left ventricular (LV) reverse remodelling (LVRR). The aim of this multicenter study was to identify echocardiographic predictors of LVRR after sacubitril/valsartan administration. Methods and results Patients with HFrEF requiring therapy with sacubitril/valsartan from 13 Italian centres were included. Echocardiographic parameters including LV global longitudinal strain (GLS) and global peak atrial longitudinal strain by speckle tracking echocardiography were measured to find the predictors of LVRR [= LV end‐systolic volume reduction ≥10% and ejection fraction (LVEF) improvement ≥10% at follow‐up] at 6 month follow‐up as the primary endpoint. Changes in symptoms [New York Heart Association (NYHA) class] and neurohormonal activations [N‐terminal pro‐brain natriuretic peptide (NT‐proBNP)] were also evaluated as secondary endpoints; 341 patients (excluding patients with poor acoustic windows and missing data) were analysed (mean age: 65 ± 10 years; 18% female, median LVEF 30% [inter‐quartile range: 25−34]). At 6 month follow‐up, 82 (24%) patients showed early complete response (LVRR and LVEF ≥ 35%), 55 (16%) early incomplete response (LVRR and LVEF

Red-ruffed Fruitcrow (Pyroderus scutatus scutatus) occurs in humid forests of Brazil. Paraguay, and Argentina. The bird has disappeared from many regions of Brazil due to deforestation but is still found in well-preserved forests as well as fragments surrounding large urban areas. The reproduction of the P. s. scutatus subspecies is not well known, with only 1 nest described. Given this scenario, we provide another nest description and information on this subspecies' reproduction and chicks, and document insect and small vertebrate feeding at a location near the largest urban area in South America. This record was made in 2018. in an Atlantic Forest reserve next to the city of Sao Paulo. We found 2 large chicks at a nest that differs from a previously described nest in having a simpler structure. Our record is remarkable because this nest was found in the degraded area of a forest fragment close to the large urban area, which is very different from the well-preserved areas of Atlantic Forest where the previously known nest was found. Since this reserve is close to a continuous and well-preserved region of Atlantic Forest, and has areas that are in good condition, we speculate that the location of this nest may have been chosen due to an available food supply. The discovery of this nest highlights the importance of forest fragments for the conservation of this cotingid. Received 21 September 2020. Accepted 17 September 2022. Key words: Atlantic Forest, behavior. Brazil, Cotingidae. natural history. O pavo {Pyroderus scutatus scutatus) ocorre nas matas limidas do Brasil. Paraguai c Argentina. Dcsapareccu de muitas regides do sudeste do Brasil devido ao desmatamento. mas ainda e encontrada tanto em regides florestais preservadas, como fragmentos do cntorno de grandes areas urbanas. A reproducao do P. s. scutatus e pouco conhecida. tendo apenas um ninho descrito. Com base neste cenario, apresentamos a descricSo de um novo ninho. informacoes sobre reproducao. filhotes e alimentaeao de insetos e pequenos vertebrados dessa subespecic em Lima Iocalidade proxima da maior area urbana da America do Sul. O registro foi feito em 2018. cm uma rescrva de Mata Atlantica ao lado da cidade de Sao Paulo. Encontramos dois filhotes grandes cm um ninho difcrcnte de um anterior conhecido, por ter uma estrutura mais simples. Nosso registro e notavel porque este ninho foi encontrado na area degradada de um fragmento florestal proximo da area urbana. bem difercnte das areas bem preservadas de Mata Atlantica onde os ninhos antcriormente conhecidos foram encontrados. Pcla reserva estar proxima dc uma regiao continua e bem prcscrvada da Mala Atlantica e ter areas em mclhor estado de conservacao. cspeculamos dc que o local pode ter sido escolhido devido a otcrta de alimentos disponiveis. A descoberta deste ninho mostra o potencial dos fragmentos florestais para a conservacao desta especic de eotingideo. Palavras-chave: Brasil. comportamento, Cotingidae, historia natural, Mata Atlantica., Species of the family Cotingidae are Neotropical forest birds that occur widely in South America. Among the existing genera, the monospecific Pyroderus is represented by the Redruffed Fruitcrow (Pyroderus scutatus), [...]