Search

Background: Confirmatory data on long-term effectiveness and safety of ixekizumb in psoriatic patients from real-world studies are needed. Objectives: The primary aim was to evaluate the 3-year drug survival of ixekizumab in the treatment of patients with moderate-to-severe plaque psoriasis, in a multicenter real-world setting. The secondary aim was to assess the influence of predictive factors on the drug survival of ixekizumab. Methods: A retrospective analysis was performed on a cohort of patients with chronic plaque psoriasis, who received at least one dose of ixekizumab before December 2018. The drug survival analysis was performed, descriptively analyzed using Kaplan-Meier survival curves. Multivariable Cox regression analyses were carried out including variables considered of clinical importance. Results: A total of 306 patients was enrolled. The overall drug survival at 12, 24 and 36 months of treatment with ixekizumab was 92.11%, 83.85% and 80.19%, respectively. A higher probability (HR 2.34) of drug withdrawal was found among patients who had already received an anti-IL-17 agent compared with bio-naive patients (p 0.017). Conclusions: We found that ixekizumab is a biological agent characterized by a long term effectiveness, not influenced by several clinical factors and associated with a good safety profile.

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

BackgroundPsoriasis is a chronic immune-mediated inflammatory skin disease which can also involve joints. It is often associated with burdensome comorbidities which negatively impact prognosis and quality of life (QoL). Biologic agents have been shown to be effective in controlling disease progression, but their use is associated with higher costs compared with traditional systemic treatments. The economic analysis of the CANOVA (EffeCtiveness of biologic treAtmeNts for plaque psOriasis in Italy: an obserVAtional longitudinal study of real-life clinical practice) study aims to assess the costs and cost-effectiveness of biologics in a real-world context in Italy.MethodsThe annualised overall direct costs of moderate-to-severe plaque psoriasis management, the annualised cost of biologic drugs and the cost per responder in the Italian National Health System perspective were assessed. More specifically, the cost per response and cost per sustained response of the most prescribed biologic therapies for the treatment of moderate-to-severe plaque psoriasis within the CANOVA study were assessed using the Psoriasis Area Severity Index (PASI) at several score levels (75, 90 and 100%).ResultsThe most frequently used biologic therapies for plaque psoriasis were secukinumab, ustekinumab, adalimumab originator, and ixekizumab. Cost of biologics was the driver of expenditure, accounting for about 98% of total costs. Adalimumab originator was the biologic with the lowest cost per responder ratio (range: €7848 - €31,378), followed by secukinumab (range: €9015 - €33,419). Ustekinumab (range: €11,689 – €39,280) and ixekizumab (range: €11,092 – €34,289) ranked respectively third and fourth, in terms of cost-effectiveness ratio. As concerns the cost per sustained response analysis, secukinumab showed the lowest value observed (€21,375) over the other options, because of its high response rate (86% vs. 60–80%), which was achieved early in time.ConclusionBiologic therapy is a valuable asset for the treatment of moderate-to-severe plaque psoriasis. Concomitant assessment of treatment costs against the expected therapeutic response over time can provide physicians and payers additional insights which can complement the traditional risk-benefit profile assessment and drive treatment decisions.

Most patients with psoriasis present with localized mild-to-moderate disease. In this case, the application of topical treatments in the first-line setting is recommended in most cases. Among different topical options, the fixed-dose combination of betamethasone dipropionate (BD) and vitamin D analogue (Cal) aerosol foam (Enstilar®, Leo Pharma) is approved as first-line topical therapy for the treatment of psoriasis in USA and the EU, due to its high efficacy and its favorable administration scheme. The PSO-LONG was the first trial to report on the long-term efficacy and safety of the Cal/DB foam treatment for the proactive management of psoriasis and now, the indications of Cal/BD foam included its use in the psoriasis maintenance treatment. However, the precise role of this treatment and the potential therapeutic schemes in the long-term management of psoriasis need further clarification. This Position Paper, authored by a group of Italian Expert Dermatologists, critically discusses the long-term management of psoriasis with Cal/BD foam in clinical practice. In particular, the biological rationale in the proactive treatment with Cal/BD foam and current evidence regarding this therapeutic approach are presented, along with its application also in patients with moderate-to-severe disease, difficult-to-treat lesions, or within combination regimens. In addition, strategies to improve adherence to long-term treatment of psoriasis are discussed,.

Many authors consider the Ilizarov method as the best choice for correction of complex multiplanar foot deformities. Fifty-one patients, for a total of 55 feet, underwent V or Y osteotomy (respectively 32 and 23), 12 were due to congenital clubfoot outcomes, 11 were from post-traumatic pathologies, 9 from hemimelia, 7 from Charcot-Marie-Tooth, 5 from poliomyelitis, 3 from spina bifida, 2 from myopathy, 2 from poly-epiphyseal dysplasia, 1 from achondroplasia, 1 from arthrogryposis, 1 patient from Charcot's foot and 1 rheumatoid arthritis. All patients were contacted to undergo AOFAS and EQ-5D-5L questionnaire. The mean distraction time was 74.0 days (±25.3) and it was longer for V osteotomy (63.1 ± 21.1 vs 81.8 ± 25.4 days for Y and V respectively, p = .006). The average fixation time was 97.9 days (± 61.2), 90 days in the Y and 103 days in the V osteotomy groups. The mean preoperative foot length was longer in the group of Y osteotomy patients (158.7 ± 21.3 mm vs 133.5 ± 21.6 mm, p.001). The mean length postoperatively was substantially the same (Y group 164.0 mm vs V group 167.4 mm, p.562). The V osteotomy produces an elongation ratio of 440% with respect to that produced from the Y osteotomy (ratio length/distraction V/Y 0.44/0.1), with only 19% more in the distraction days. (81.8 V group vs 63.1 Y group). While the V osteotomy allows a lengthening of about 27%, the Y osteotomy, despite having correction potential superimposable to the V osteotomy, minimizes the elongation component.

Several studies have attempted to characterise the origin of canine transmissible venereal tumour (CTVT). However, the participation of cancer stem cells (CSC) has not been reported OBJECTIVES: Herein we describe the expression patterns of CSC markers CD44, CD34, CD90 and CD133 in CTVT METHODS: Thirty-eight samples were selected and assessed through flow cytometry and immunohistochemistry RESULTS AND CONCLUSIONS: Twenty-two tumours were classified as plasmacytoid and 16 as mixed. Almost all tumours showed high CD44 and low CD34 levels. CD133 and CD90 expression varied among tumours. Cytological groups did not differ in the proportion of CSC markers. Our results suggest that CSC subpopulations might participate in CTVT.

This study examined the differences of muscle strength, electromyography (EMG) and whole-body kinematics during maximum cross-step table tennis topspin between advanced and intermediate players. Ten advanced and ten intermediate players performed both voluntary isokinetic contraction test and forehand topspin strokes with maximum-effort towards cross-court target zone. The results indicated that advanced players generated significantly greater maximum racket speeds during forward swing phase (P < 0.05). At the instant of the topspin stroke, significantly smaller shoulder horizontal flexion and elbow flexion angles, but larger joint angular velocities in advanced players (P < 0.05). Moreover, advanced players exhibited longer muscle firing duration of anterior deltoid and biceps brachii as well as higher root mean squares and EMG integrals of the abdominal external oblique, anterior deltoid and biceps brachii muscles than the intermediate players (P < 0.05). Furthermore, the isokinetic results showed higher shoulder abduction/adduction, hip flexion/extension and knee flexion torques at fast speed (240°/s) and higher elbow flexion torque at medium speed (120°/s) in advanced players (P < 0.05). The findings suggest that higher activation of the deltoid, biceps and abdominal external oblique muscles as well as larger muscle strength under higher speed conditions would be the plausible key factors to maximise racket and joint angular velocities in forehand topspin.

Objective: COVID-19 toes represent the main dermatological COVID-19 cutaneous manifestation in pediatric patients. Its diagnosis exposes the whole family to social stigma and this aspect was not previously evaluated. Patients and methods: This was a multicenter, case-control, observational study that compared the family impact of COVID-19 toes vs. psoriasis (PsO). We enrolled 46 pediatric patients (23 with psoriasis and 23 with COVID-19 toes, age and gender matched) and their parents/caregivers that had to fill the Dermatitis Family Impact (DFI) questionnaire. Results: DFI index did not differ significantly between both subgroups (p=0.48), and in psoriatic patients did not correlate with both Psoriasis Area Severity Index (PASI) (p=0.59) and itch-VAS (p=0.16). Conclusions: COVID-19 toes, a transitory dermatosis, exerted a similar impact/perturbation on family dynamics than PsO, a well-known stigmatizing, chronic inflammatory dermatosis.

Luca Stingeni,1 Giovanna Malara,2,3 Andrea Conti,4 Luisa Di Costanzo,5 Carlo Giovanni Carrera,6 Martina Burlando,7 Piergiorgio Malagoli,8 Maria Letizia Musumeci,9 Federico Bardazzi,10 Valeria Brazzelli,11 Paolo Amerio,12 Clara De Simone,13,14 Sara Trevisini,15 Anna Balato,16 Matteo Megna,17 Francesco Loconsole,18 Catia De Felice,19 Marta Bartezaghi,20 Alice Rausa,20 Elisabetta Aloisi,20 Roberto Orsenigo,20 Antonio Costanzo21,22 On behalf of the SUPREME Study Group1Dermatology Section, Medical and Surgical Department, University of Perugia, Perugia, Italy; 2Dermatology Unit, Hospital “Bianchi Melacrino Morelli”, Reggio Calabria, Italy; 3Department of Dermatology, Papardo Hospital, Messina, Italy; 4Dermatologic Unit, Department of Surgery, Infermi Hospital, AUSL Romagna, Rimini, Italy; 5Department of Dermatology, “Gaetano Rummo” Hospital, Benevento UOC Dermatologia, AO G. Rummo, Benevento, Italy; 6U.O. Dermatologia, Fondazione IRCCS Ca’ Granda - Ospedale Maggiore Policlinico, Milano, Italy; 7IRCCS San Martino Polyclinic Hospital, Di.S.Sal. Section of Dermatology, Genoa, Italy; 8Dermatology Unit IRCCS Policlinico San Donato, Milan, Italy; 9Dermatology Clinic, University of Catania, Catania, Italy; 10Division of Dermatology, University Hospital Policlinico “S. Orsola-Malpighi”, Bologna, Italy; 11Institute of Dermatology, Foundation IRCCS Policlinico San Matteo and University of Pavia, Pavia, Italy; 12Dermatologic Clinic, G. D’Annunzio University, Chieti, Italy; 13Istituto di Dermatologia, Università Cattolica del Sacro Cuore, Rome, Italy; 14Fondazione Policlinico Universitario A. Gemelli – IRCCS, Rome, Italy; 15Dermatology Department, University of Trieste, Trieste, Italy; 16Dermatology Unit, University of Campania “Luigi Vanvitelli”, Naples, Italy; 17Section of Dermatology, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy; 18Department of Biomedical Sciences and Human Oncology, University of Bari, Bari, Italy; 19Department of Clinical Dermatology, Centre for the Study and Treatment of Psoriasis, San Gallicano Dermatological Institute, IRCCS, Rome, Italy; 20Novartis Farma SpA, Origgio, Italy; 21Unit of Dermatology, IRCCS Humanitas Research Hospital, Milan, Italy; 22Department of Biomedical Sciences, Humanitas University, Milan, ItalyCorrespondence: Luca Stingeni, Dermatology Section, Medical and Surgical Department, University of Perugia, Perugia, Italy, Tel +39075-5783881, Email luca.stingeni@unipg.itPurpose: Psoriasis, a common systemic inflammatory disorder, presents with gender-related differences in the quality of life (QoL) and treatment outcomes. This post hoc analysis from the Phase 3b SUPREME study explored gender-related differences in patient characteristics and efficacy of secukinumab 300 mg on Psoriasis Area and Severity Index (PASI) 75/90/100 and impact on QoL using the Dermatology Life Quality Index (DLQI) in patients with moderate to severe psoriasis through week 24.Patients and Methods: The proportion of patients achieving PASI 75/90/100 was computed using a nonresponder imputation approach. Differences between cohorts were analyzed using a logistic regression model. The mean change from baseline in DLQI was computed using the Wilcoxon test.Results: Among the 433 patients (males: 71.6%), females had a higher DLQI than males at baseline (13.1 vs 9.5; P< 0.0001). Males had a slightly higher response for PASI 90 than females at week 16 (80.7% vs 78.1%; P=0.0779) and 24 (83.2% vs 79.7%; P=0.0319). No differences were observed between genders in PASI 100/75 responses at week 24. Both genders showed an improvement in DLQI with secukinumab at week 24 (− 10.9 vs − 8.1, respectively, in females vs males; P=0.0004).Conclusion: In summary, secukinumab was effective in the treatment of psoriasis, irrespective of gender.Keywords: plaque psoriasis, PASI, patient-reported outcomes, Dermatology Quality of Life Index, Hospital Anxiety and Depression Scale

Echocardiography has been included as a first-line tool in several international guidelines for the management of patients with various cardiac diseases. Beyond diagnosis, echocardiographic examination helps in characterizing the severity of the condition since the very first stages. In particular, the application of second-level techniques, speckle tracking echocardiography in particular, can also reveal a subclinical dysfunction, while the standard parameters are in the normality range. The present review describes the potentialities of advanced echocardiography in different settings, including arterial hypertension, atrial fibrillation, diastolic dysfunction, and oncological patients, thus opening up potential starting points for its application as a clinical routine changer.

Background: Guselkumab is a humanized monoclonal antibody that binds selectively to the p19 subunit of interleukin-23, which has shown efficacy in patients with previous incomplete response to ustekinumab in the NAVIGATE clinical trial. Objectives: We conducted a 104-week multicenter retrospective study to assess the effectiveness and safety of guselkumab in patients affected by plaque psoriasis with an inadequate response to ustekinumab in a real-life setting. Methods: Our retrospective study included 233 adults affected by moderate-to-severe plaque psoriasis, enrolled in 14 different Italian centers, and treated with guselkumab after failing therapy with ustekinumab. Patient characteristics and PASI (Psoriasis Area and Severity Index) score at each visit (baseline, weeks 16, 52 and 104) were recorded. The percentages of patients achieving 75%, 90% and 100% (PASI 75, PASI 90 and PASI 100) improvement in PASI, compared with baseline, were registered. Results: At week 52, PASI 75 was reached by 89.88% of patients, PASI 90 by 71.43%, PASI 100 by 58.83% and absolute PASI ≤ 2 by 90.48%. At week 104, similar effectiveness results were observed. Compared to the NAVIGATE trial, we observed higher rates of PASI 75/90/100. Patients with the involvement of difficult-to-treat areas were significantly less likely to achieve PASI90 and PASI100 at week 16. Obese patients had significantly lower rates of PASI75 and PASI≤2 at week 52. At week 104, comparable responses were observed among all patients' subgroups, regardless of BMI status, involvement of difficult-to-treat areas, presence of cardiometabolic comorbidities and concomitant psoriatic arthritis. No significant safety findings were reported throughout the study. Conclusion: Our data suggest that the efficacy of guselkumab in patients with inadequate response to ustekinumab for plaque psoriasis in "real-life" clinical practice is comparable with NAVIGATE study with higher percentages of patients achieving PASI90 and PASI100 at weeks 16, 52 and 104.

Coronary flow reserve is the capacity of the coronary circulation to augment the blood flow in response an increase in myocardial metabolic demands and has a powerful prognostic significance in different clinical situations. It might assess with invasive and noninvasive technique. Transthoracic echocardiography Doppler is an emerging diagnostic technique, noninvasive, highly feasible, safe for patient and physician, without radiation, and able to detect macrovascular and microvascular anomalies in the coronary circulation. This review aims to describe the benefit and limits of echocardiographic assessment of coronary flow reserve.

Existing knowledge about fires has been challenged by changes in forests and wildfire regimes. We carried out a systematic literature review involving both a global and a case study approach (Portugal) to investigate the configuration of the social dimensions of wildfires in academic literature. We advance two interlocking claims: (i) human dimensions of wildfires are often simplified into shallow indicators of anthropogenic activities lacking social and historical grounding, and (ii) fire knowledge of Indigenous peoples and/or other forest and fire users and professionals remains overlooked. These arguments were manifest from the global-scale review and were confirmed by the case study of Portugal. The individual perceptions, memories and cultural practices of forest and fire users and professionals and the historical co-developments of fires, people and forests have been missing from wildfire research. Including and highlighting those perspectives will both add to existing knowledge and inform policies related to fire management by making them socially meaningful.

Introduction: Treat-to-target strategies are used in several chronic diseases to improve outcomes. Treatment goals have also been suggested for psoriasis, but there is currently no consensus on targets, and guidance is needed to implement this strategy in clinical practice. The project ‘Treat to Target Italia’ was launched by a scientific board (SB) of 10 psoriasis experts to generate expert consensus recommendations. Methods: On the basis of the published literature, their clinical experience, and the results of a survey among Italian dermatologists, the SB identified four relevant topics: (1) clinical remission; (2) quality of life; (3) abrogation of systemic inflammation; (4) safety. They drafted 20 statements addressing these four topics and submitted them to a panel of 28 dermatologists, in a Delphi process, to achieve consensus (greater than 80% agreement). Results: Consensus was reached on all statements. Treatment goals defining clinical remission should include a 90% improvement from baseline in the Psoriasis Area and Severity Index (PASI90 response) or an absolute PASI score of less than or equal to 3. Patient’s quality of life and satisfaction are important targets. If PASI targets are achieved, there should be no or very low impact of psoriasis on quality of life [Dermatology Life Quality Index (DLQI) score less than or equal to 3]. If PASI or DLQI goals are not achieved within 3–4months, treatment should be changed. Abrogation of systemic inflammation may be crucial for preventing or delaying inflammatory comorbidities. Safety is an equally important target as efficacy. Conclusion: These 20 consensus statements define the parameters of a treat-to-target strategy for psoriasis in Italy. It is hoped that use of these in the management of patients with psoriasis will improve treatment outcomes and patient health-related quality of life.

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.

Invertebrate Survival Journal, Vol 20 No 1 (2023)

PDF file - 66K, Describes the putative target mRNA validation

PDF file - 58K, Describes the types of infecting HPV among the 20 positive genotyped selected samples

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 6month 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±10years; 18% female, median LVEF 30% [inter-quartile range: 25-34]). At 6month follow-up, 82 (24%) patients showed early complete response (LVRR and LVEF≥35%), 55 (16%) early incomplete response (LVRR and LVEF&nbsp

Acute right ventricular (RV) failure is common in patients hospitalized with COVID-19. Compared to the conventional echocardiographic parameters, right ventricular longitudinal strain (RVLS) is more sensitive and accurate for the diagnosis of RV systolic dysfunction.Our purpose was to investigate the sustained RV dysfunction echo-quantified by RVLS in patients recovered from severe COVID-19. Furthermore, we aimed to assess whether disseminated intravascular coagulation (DIC) has a key role to predict the impaired RV strain.Of 198 consecutive COVID-19 patients hospitalized from March 1, 2020, to April 15, 2020, 45 selected patients who survived from severe COVID-19 were enrolled in the study and referred to our echo-lab for transthoracic echocardiography 6-months after discharge. RVLS was calculated as the mean of the strain values of RV free wall. DIC was defined with a validated scoring system: DIC score equal to or more than 5 is compatible with overt-DIC. Categories of acute respiratory distress syndrome (ARDS) were defined based on PaOA total 26 of 45 patients showed impaired RVLS at 6-months' follow-up. DIC score was significantly higher in patients with worse RVLS than in those with better RVLS (4.8 ± .5 vs. 3.6 ± .6, p =.03). Stages of ARDS did not modulate this relationship. Finally, overt-DIC results the only independent predictor of sustained RV dysfunction (OR 1.233, 95% CI 1.041-1.934, p =.043).Sustained RV impairment frequently occurs in patients recovered from severe COVID-19. DIC plays a key role, resulting in an independent predictor of sustained RV dysfunction.

This study aims to investigate table tennis players’ personality traits and motives in the frame of the Big Five personality model and the self-determination theory (SDT) of motivation. A total of 447 Italian table tennis players ranging in level of play between the regional and international levels participated in the study. They completed a self-report questionnaire measuring their personality traits and motives to play table tennis. Findings showed conscientiousness as the most distinctive trait of table tennis players. No differences were detected between elite and non-elite players. Table tennis players are mainly motivated by factors belonging to the intrinsic pole of the self-determination motivational continuum. External reinforcements represent a minimal incentive to play this sport both for elite and non-elite athletes. The current findings help clarify the relationships between personality traits, playing certain types of sports, and achieving different performance levels. We conclude by outlining implications for applied sport psychology.

Background: Although long-term management of psoriasis is paramount, this approach is challenging in clinical practice. In the recent PSO-LONG trial, a fixed-dose combination of betamethasone dipropionate (BD) and calcipotriol (Cal) foam applied twice a week on non-consecutive days for 52 weeks (proactive treatment) reduced the risk of relapse. However, the role of Cal/BD foam in the long-term management of psoriasis needs further clarifications. The ProActive Management (PAM) program, a nationwide Italian project, aims at reaching a consensus on the role of proactive management of psoriasis. Methods: A steering committee generated some statements through the nominal group technique (NGT). The statements were voted by an expert panel in an adapted Delphi voting process. Results: Eighteen statements were proposed, and the majority of them (14/18) reached a consensus during the Delphi voting. The need to provide long-term proactive topical treatment to reduce the risk of relapse for the treatment of challenging diseases sites or in patients where phototherapy or systemic therapies are contraindicated/ineffective was widely recognized. A consensus was reached about the possibility to associate the proactive treatment with systemic and biological therapies, without the need for dose intensification, thus favoring a prolonged remission. Moreover, the proactive treatment was recognized as more effective than weekend therapy in increasing time free from relapses. Approaches to improve adherence, on the other hand, need further investigation. Conclusions: The inclusion in guidelines of a proactive strategy among the effective treatment options will be a fundamental step in the evolution of a mild-moderate psoriasis therapeutic approach.

EffeCtiveness of biologic treAtmeNts for plaque psOriasis in Italy: An obserVAtional (CANOVA) study was aimed at providing real-world evidence of the effectiveness of biologics in Italian patients with moderate–severe psoriasis. It was an observational, retro-prospective cohort study conducted in 17 Italian dermatology clinics. Adult patients with moderate–severe plaque psoriasis, who started a biologic treatment between 24 weeks and 24 months before enrolment, were included. With a follow-up visit at 6months after enrolment, each patient had at least 12 months of observation. The primary objective was to describe the clinical response rates (PASI 75) after 16/24/52 weeks from biologic treatment start. Secondary outcomes were sustained response, quality of life, and treatment satisfaction. Of the 669 eligible patients (64% males), 52% were naïve to biologics, though a mean duration of psoriasis since first diagnosis of 18.6 years (SD 13.2). The most frequently prescribed biologics were secukinumab (41%), ustekinumab (25%), TNF-inhibitors (22%) and ixekizumab (12%). PASI 75 was achieved by 86% of patients (95% CI: 82%–89%) at 16 weeks, 90% (87%–93%) at 24 weeks, and 91% (89%–94%) at 52 weeks. Patients achieving PASI 90 and PASI 100 at 52 weeks were 75% (71%–79%) and 53% (49%–57%), respectively. Sustained PASI 75 response after 1year from treatment start was achieved by 78% (74%–82%) of patients. Mean DLQI total score was 2.3 (SD 3.9) at enrollment and decreased at the final visit to 1.8 (3.6). A high level of treatment satisfaction was expressed by patients over the study period. This large real-world study confirms in the clinical practice the good effectiveness and acceptability of biologics in psoriasis patients.

Background: Psoriatic arthritis (PsA) is an inflammatory condition which can affect up to 41% of psoriatic patients [1]. In 40-60% of patients, PsA can determine cartilage destruction and joint deformities, hereby heavily impacting physical function and quality of life, even increasing the risk of death compared to the general population[1]. PsA manifestations usually develop after psoriasis onset, therefore dermatologists play a crucial role in the detection of early signs of arthritis. In our study, we aimed to identify simply detectable clinical and ecographic signs of early PsA and to assess their reliability. Materials and methods: We assessed the opinion of a group of expert dermatologists, who were asked to express their opinion on the level of association between the selected anamnestic, clinical or instrumental signs and the onset of psoriatic arthritis by giving a score to each item. Results: Psoriatic onycopathy, signs of dactylitis and ultrasonographic alterations of selected joints were, respectively, the dermatologic, rheumatologic and imaging signs which had the strongest significance in the opinion of the experts. Conclusions: These signs should be carefully looked for during dermatological examinations in order to detect early PsA.

The epithelial to mesenchymal transition (EMT) is a key cellular process underlying cancer progression, with multiple intermediate states whose molecular hallmarks remain poorly characterised. To fill this gap, we present a method to robustly evaluate EMT transformation in individual tumours based on transcriptomic signals. We apply this approach to explore EMT trajectories in 7180 tumours of epithelial origin and identify three macro-states with prognostic and therapeutic value, attributable to epithelial, hybrid E/M and mesenchymal phenotypes. We show that the hybrid state is relatively stable and linked with increased aneuploidy. We further employ spatial transcriptomics and single cell datasets to explore the spatial heterogeneity of EMT transformation and distinct interaction patterns with cytotoxic, NK cells and fibroblasts in the tumour microenvironment. Additionally, we provide a catalogue of genomic events underlying distinct evolutionary constraints on EMT transformation. This study sheds light on the aetiology of distinct stages along the EMT trajectory, and highlights broader genomic and environmental hallmarks shaping the mesenchymal transformation of primary tumours.

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.

Patients with atopic dermatitis (AD) display a defective skin barrier, consequently they may experience inflammatory flares with different exposures, including masks. Actually, beside scattering case reports, no study focused on the possible AD flaring due to masks.In this multicenter prospective study AD patients with facial manifestation were followed with teledermatology and evaluated by two board-certified dermatologists at the baseline (T0) and after 1 month (T1) in which patients started to wear masks6 hours per day. Demographics and clinical parameters, included and not limited to Eczema Area and Severity Index (EASI) and Dermatology Life Quality Index (DLQI), were carefully collected and analyzed.We enrolled 57 AD patients (M/F 28/29, 33.91 ± 12.26 yoa) that wore surgical masks (38 (66.7%)), community masks (11 (19.3%) and N95 (8 (14.0%)). Both DLQI and EASI increase during the time period (p0.0001). DLQI variation was not influenced by age, BMI, and gender, mask type used and AD therapy (p=0.99), whilst EASI variation was significantly influenced by BMI, gender, and therapy (p=0.004).Mask wearing may prove detrimental to patients with atopic eczema and the same may not necessarily be the case for asthma patients.

The aim of the present study was to compare service and reception in winning and defeated Table Tennis athletes. The sample of the survey consisted of 64 games (34 men and 30 women) of the A1 Table Tennis Greek national league, where a total of 5,065 points were analysed between 33 male athletes and 18 female athletes, who are among the best 32 of the official Hellenic Table Tennis Federation ranking. The variables analysed were: service grip, service execution length, reception technique, reception movement, the point conquest of the serving athlete and the point advantage in the first three hits. The non-parametric-square test(x2) showed that statistically significant differences were found between winning and defeated men, in the length of the service, with winners having a more effective service and more offensive reception. As for the female athletes, statistically significant differences were found in the grip and length of the service between winning and defeated women, while it was found that the winners have better service, perform defensive shots in the reception, and have an advantage in the first three hits. The above findings will help high-level athletes, coaches, physical trainers and performance analysts in understanding the importance of serving and receiving in high-level Table Tennis.

The Conopophagidae family has only one report of predation of small vertebrates, being an anuran observed for the genus Conopophaga. Here, we present a record of predation on a small anuran amphibian by Conopophaga melanops. The record was made in 2008 in a Southeast Brazil. A recently dead individual of Fritziana mitus, with several lesions on its body, was observed next to an adult female of C. melanops captured in a mist net. We found only two records of predation of small vertebrates by C. melanops, being an anuran and a lizard. The three available records occurred during the reproductive period of C. melanops, indicating that the prey may serve as a resource to feed the young. This type of behavior, as well as the predator-prey relationship, should be better investigated in the field, especially in the Atlantic Forest, region with a high bird and frog diversity.

Psoriasis is one of the commonest inflammatory skin diseases determining a very high impact on patients' quality of life and daily activities and relationships. Several biologic therapies have been approved through the years for the treatment of moderate-to-severe plaque psoriasis, and efficacy and safety profile have been analyzed in clinical trials. Ixekizumab is an immunoglobulin G subclass 4 monoclonal antibody that selectively targets and binds IL-17A with high specificity and affinity. Inhibiting IL-17A activity, ixekizumab reduces and turns down levels of inflammation, resulting in the clinical improvement of the disease. Long-term efficacy and safety profile of ixekizumab have been investigated and reported in the UNCOVER trials, but in literature there are only few studies based on real life experience. We present the efficacy and safety profile of ixekizumab in a cohort of 779 patients affected by moderate-to-severe plaque psoriasis and treated with ixekizumab in 11 Italian dermatology hospitals, with a follow-up of care until 192 weeks.

Este artigo pretende analisar o fenômeno dos empréstimos segundo o modelo gerativista da Morfologia Distribuída (MD), visto que algumas características da gramática dos falantes podem ser esclarecidas pelo estudo desses dados. O aparato da MD é capaz de explicar esse fenômeno e suas propriedades de uma maneira bem elegante e condizente com as produções observadas. Nesse contexto, analisamos, principalmente, ocorrências de empréstimos do inglês nas línguas coreana e portuguesa, com o intuito de evidenciar a importância de um estudo dessa natureza fora de um viés lexicalista e/ou diacrônico, dado que a existência de empréstimos é um fenômeno extremamente produtivo e comum a todas as línguas. Dessa forma, nossa hipótese é a de que nossa faculdade da linguagem possui propriedades que explicam o funcionamento dessas formas emprestadas, não importando a tipologia das línguas em foco ou a relação que possam estabelecer entre si.

Obiettivo dell’articolo, sviluppando (e reinterpretando) un interessante suggerimento formulato da Christoph Engel, è quello di avviare un (preliminare) confronto fra alcune delle principali tesi di Friedrich Müller in merito all’interpretazione giuridica e al ragionamento giudiziale, da un lato, e, dall’altro, alcuni dei principali contributi offerti, sui medesimi temi, da John Dewey. Mettendo in luce ed indagando talune interessanti analogie (così come le non meno considerevoli differenze) fra le due posizioni, l’articolo esplora altresì alcuni problemi centrali connessi con il ruolo del giudice nel quadro delle istituzioni della democrazia costituzionale.

Wearing masks is an optimal preventive strategy during COVID-19 pandemic, but it may increase facial sebum production. However, few case reports have described seborrheic dermatitis (SeBD) and psoriasis (PsO) flares due to masks. Hence, we conducted a multicenter study to clarify the possibility of increased SeBD and PsO flares in association with mask wearing during the COVID-19 pandemic.This multicenter study enrolled patients with a diagnosis of facial SeBD and PsO. All dermatological consultations were conducted in teledermatology at baseline (T0) and after 1 month (T1) Of6 hours/day wearing mask. PsO patients were assessed using PsO Area and Severity Index (PASI) and self-administered PASI (SAPASI), whilst SeBD patients with symptom scale of seborrheic dermatitis' (SSSD) and seborrheic dermatitis area and severity index (SEDASI).A total of 33 (20 males, 13 females, average age 43.61±9.86) patients with PsO and 33 (20 males, 13 females, average age 44.00±8.58) with SeBD were enrolled. After 1 month, PsO patients displayed higher values of both PASI and SAPASI (P0.0001), while SeBD patients experienced a flare, as testified by the increment of both SSSD and SEDASI (P0.0001). Mask type did not seem to influence the flare severity.Masks remain an optimal preventive strategy during COVID-19 pandemic, but patients with PsO and SeBD may experience facial flares. Thus, therapeutic approach should be more aggressive in these groups of patients to counteract the triggering effect of masks.

Background Multimodality imaging approach is becoming more and more common in evaluating the severity and outcome of aortic stenosis (AS). Aim To assess the outcome of asymptomatic AS and the usefulness of aortic calcium score (CS) by computed tomography (CT) for solving the dilemma of low flow, low gradients (LFLG) severe AS. Methods 70 (81.4±8.4 years) prospective asymptomatic patients with AS were followed for 2.77±2.01 years with a trans-thoracic echo (TTE) every 6 months. End-points were all cause mortality, aortic valve replacement (AVR or TAVR), aortic velocity and gradients progression and symptoms occurrence. Prevalence of LFLG-AS was investigated and these patients underwent CT for CS calculation at the end of follow-up (FU), Figure 1. Results Baseline TTE results from the 70 pts were: peak velocity 3.1±0.8m/sec; peak gradient 44±21mmHg; mean gradient 26±14 mmHg; AVA 1±0.3 cm2; DVI 0.31±0.1; Svi 33.8±18 ml/m2; EF: 55±9% with an AS being mild in 32.9%, moderate in 28.4%, severe in 27.1%; 36.8% of severe AS were LFLG. During FU, 23 (32.8%) pts died (5.7% LFLG) and 13 (18.5%) underwent AVR/TAVR. Predictors of mortality were aortic gradients (p=0.03), AVA (p=0.008), DVI (p Conclusions Asymptomatic AS in elderly people is associated with high mortality risk and rapid progression. AVA remains the best predictor of outcome. In severe LFLG AS, calcium score correlates with symptoms occurrence, progression of valve disease, LV hypertrophy and function and also with RV function. Funding Acknowledgement Type of funding sources: None.

Silicon (Si) is a beneficial element for the growth of various crops, but its effect on plant metabolism is still not completely elucidated. Even if Si is not classified as an essential element for plants, the literature has reported its beneficial effects in a variety of species. In this work, the influence of Si foliar application on berry composition was evaluated on four grapevine cultivars. The berries of Teroldego and Oseleta (red grapes) and Garganega and Chardonnay (white grapes) were analyzed after foliar application of silicon by comparing the treated and control groups. A targeted metabolomic approach was used that focused on secondary metabolites, amino acids, sugars, and tartaric acid. Measurements were performed using liquid chromatography coupled with a diode array detector and mass spectrometry (LC-DAD-MS

Topic modeling is a popular technique in machine learning and natural language processing, where a corpus of text documents is classified into themes or topics using word frequency analysis. This approach has proven successful in various biological data analysis applications, such as predicting cancer subtypes with high accuracy and identifying genes, enhancers, and stable cell types simultaneously from sparse single cell epigenomics data. The advantage of using a topic model is that it not only serves as a clustering algorithm, but it can also explain clustering results by providing word probability distributions over topics.Our study proposes a novel topic modeling approach for clustering single cells and detecting topics (gene signatures) in single-cell datasets that measure multiple omics simultaneously. We applied this approach to examine the transcriptional heterogeneity of luminal and triple negative breast cancer cells using patient-derived xenograft models with acquired resistance to chemotherapy and targeted therapy. Through this approach, we identified protein-coding genes and long noncoding RNAs (lncRNAs) that group thousands of cells into biologically similar clusters, accurately distinguishing drug-sensitive and resistant breast cancer types. In comparison to standard state-of-the-art clustering analyses, our approach offers optimal partitioning of genes into topics and cells into clusters simultaneously, producing easily interpretable clustering outcomes. Additionally, we demonstrate that an integrative clustering approach, which combines the information from mRNAs and lncRNAs treated as disjoint omics layers, enhances the accuracy of cell classification.