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BACKGROUND Dupilumab has been demonstrated to be an effective treatment for patients with moderate-to-severe atopic dermatitis (AD) in clinical trials. However, evidence of real-world experience with dupilumab in a broader population is limited to date. METHODS Adult patients with moderate-to-severe AD, defined as an Eczema Area Severity Index (EASI) score of 24 or higher, treated with dupilumab at ten Italian academic centers, were included in the study. Physician-reported outcome measures (EASI), patient-reported outcome measures (pruritus and sleep score, Dermatology Life Quality Index, DLQI) and serological markers [immunoglobulin (Ig) E and eosinophil count] after 16 weeks were analyzed. RESULTS We enrolled 543 patients with moderate-to-severe AD. Two patients (0.4%) discontinued treatment. The median ± interquartile percentage change from baseline to 16 weeks of treatment in the EASI score was -87.5±22.0 (p

Background: Benralizumab is effective in severe eosinophilic asthma (SEA), but suboptimal responses are observed in some patients. Although several factors have been associated with benralizumab response, no cluster analysis has yet been undertaken to identify different responsiveness sub-phenotypes. Objective: To identify SEA sub-phenotypes with differential responsiveness to benralizumab. Methods: One hundred and five patients diagnosed with SEA who had completed 6months of benralizumab treatment were included in a hierarchical cluster analysis based on a set of clinical variables that can be easily collected in routine practice (age, age at disease onset, disease length, allergen sensitization status, blood eosinophil count, IgE levels, FEV1% predicted, nasal polyposis, bronchiectasis). Results: Four clusters were identified: Clusters 2 and 3 included patients with high levels of both IgE and eosinophils (type-2 biomarkers high), whereas Clusters 1 and 4 included patients with only one type-2 biomarker at a high level: IgE in Cluster 1 and eosinophils in Cluster 4. Clusters 2 and 3 (both type-2 biomarkers high) showed the highest response rate to benralizumab in terms of elimination of exacerbations (79% and 80% respectively) compared to Clusters 1 and 4 (52% and 60% respectively). When super-response (the absence of exacerbation without oral corticosteroid use) was assessed, Cluster 2, including patients with more preserved lung function than the other clusters, but comparable exacerbation rate, oral corticosteroid use and symptom severity, was the most responsive cluster (87.5% of patients). Conclusions: Our cluster analysis identified benralizumab differential response sub-phenotypes in SEA, with the potential of improving disease treatment and precision management.

Objectives To assess the feasibility and safety of a repeated SHort course Accelerated RadiatiON therapy (SHARON) regimen in the palliative setting of Head and Neck (H&N) cancer in older adults. Material and Methods Patients with histological confirmed H&N cancers, age ≥ 80 years, expected survival >3 months, and Eastern Cooperative Oncology Group (ECOG) performance status of ≤3 were enrolled. Patients were treated in cohorts of six patients: a total dose of 20 Gy was delivered in 2 consecutive days with a twice-daily fractionation (5 Gy per fraction) and at least 8-h interval. If no Grade 3 toxicity was registered, a second enrollment started with another cohort of six patients to whom were administered two cycles (total dose of 40 Gy). The primary endpoint was to evaluate the feasibility of the two cycles of treatment. Secondary endpoints were evaluation of symptoms control rate, symptoms-free survival (SFS), and Quality of Life (QoL) scores. Results Seventeen consecutive patients (median age: 85 years) were treated. Nine patients were treated with one cycle and 8 patients with two cycles. No G3 toxicity was reported in either cohort. With a median follow-up time of 4 months, 3-month SFS in the first and second cohorts was 83.3%, and 87.5%, respectively. The overall palliative response rate was 88%. Among 13 patients reporting pain, 8 (61.5%) showed an improvement or resolution of their pain. Conclusion Repeated short course accelerated radiotherapy in a palliative setting of H&N cancers is safe and well-tolerated in older adults.

Background/aim Late toxicity and long-term outcomes of a phase I-II trial on patients with prostate cancer treated with an integrated boost to the dominant intraprostatic lesion (DIL) are reported. Patients and methods Patients were treated using intensity-modulated radiotherapy, with a simultaneous integrated boost to the DIL, defined on staging magnetic resonance imaging, delivering 72 Gy in 1.8 Gy/fraction to prostate/seminal vesicles and 80 Gy in 2 Gy/fraction to the DIL. The primary endpoint was acute toxicity and secondary endpoints were late toxicity and biochemical disease-free survival. Results Forty-four patients were enrolled. The median follow-up was 120 (range=25-150) months. Five-year rates of grade 3 late gastrointestinal and genitourinary toxicity were 2.3% and 4.5%, respectively; only one grade 4 late genitourinary toxicity was recorded. Five-year biochemical relapse-free and overall survival rates were 95.3% and 95.5%, respectively. Conclusion The treatment was well tolerated and achieved excellent results in terms of outcome in patients with low-intermediate Gleason's score and low risk of nodal metastasis.

Background/aim To compare the predictive efficacy of National Comprehensive Cancer Network (NCCN) and European Association of Urology (EAU) risk stratification systems in radiotherapy of prostate cancer. Patients and methods One-thousand-nine-hundred-nine patients treated with definitive (1,074), adjuvant (381), and salvage radiotherapy (454) were analysed. Results Both systems significantly predicted biochemical-relapse-free-survival, metastasis-free-survival, and disease-free-survival, while only the NCCN system correlated with local-control in the definitive radiotherapy group. In the adjuvant setting, both systems failed to predict all outcomes. In the salvage setting, only the NCCN system significantly predicted biochemical-relapse-free-survival, metastasis-free-survival and disease-free-survival. Conclusion This analysis confirms the efficacy of both systems in definitive radiotherapy and suggests the utility of the NCCN also in salvage radiotherapy.

Stereotactic body radiotherapy (SBRT) has been shown to achieve high local control rates in limited metastatic burden of disease. Few papers reported on the efficacy of SBRT in nodal oligometastases. The primary aim of the present paper was to analyze the treatment outcome in this setting. Data from DESTROY-1 and SRS-DESTROY-2 phase I clinical trials were reviewed and analyzed. These trials were based on a 5 fractions and a single fraction regimens, respectively. End-points of this analysis were toxicity rates, overall response rate (ORR), and local control (LC). Patients treated between December 2003 and January 2018, with any metastatic site, and primary tumor type and histology were included. One hundred-eighty-one patients (M/F: 93/88; median age: 67, range 37–88) treated with SBRT on 253 nodal lesions were analyzed. Initially, the used technique was 3D-CRT (20.9%), while subsequently treatments were delivered by VMAT (79.1%). The total dose to the PTV ranged between 12Gy/single fraction to 50Gy/5 fractions. With a median follow-up of 21months (2–124), no grade 3 acute or late toxicity was recorded. ORR based on functional imaging was 92.5% with a complete response rate of 76%. Two- and three-year actuarial LC were 81.6% and 76.0%, respectively. Our large pooled analysis confirms the efficacy and safety of SBRT/SRS in patients with nodal metastases and identifies clinical and treatment variables able to predict complete response and local control rate.

Background This case is the first report describing rapid, successful treatment of severe atopic dermatitis (AD) and comorbid type-2 inflammatory diseases in the same patient, with dupilumab treatment, with no side-effects. Case presentation We report on effects of dupilumab in a patient with severe AD, a long-standing history of a mild, perennial allergic rhino-conjunctivitis, moderate asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). Conclusions Patients suffering from AD, asthma, allergic rhinitis and CRSwNP may be eligible for dupilumab single treatment that is possibly advantageous also from the pharmaco-economic standpoint.

Dupilumab, an inhibitor of interleukin (IL)-4/13 activity, is a biological agent approved for the treatment of moderate-to-severe atopic dermatitis (AD)1 . Our aim was to assess the long-term effectiveness and safety of dupilumab in a clinical real-life setting.

Corrado Pelaia,1 Claudia Crimi,2 Alida Benfante,3 Maria Filomena Caiaffa,4 Cecilia Calabrese,5 Giovanna Elisiana Carpagnano,6 Domenico Ciotta Jnr,7 Maria D’Amato,8 Luigi Macchia,9 Santi Nolasco,2 Girolamo Pelaia,1 Simona Pellegrino,7 Nicola Scichilone,3 Giulia Scioscia,10 Giuseppe Spadaro,11 Giuseppe Valenti,12 Alessandro Vatrella,7 Nunzio Crimi2 1Department of Health Sciences, University “Magna Graecia” of Catanzaro, Catanzaro, Italy; 2Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy; 3Department of Biomedicine and Internal and Specialistic Medicine, University of Palermo, Palermo, Italy; 4Allergology and Clinical Immunology Unit, University of Foggia, Foggia, Italy; 5Department of Translational Medical Sciences, University of Campania “Luigi Vanvitelli”, Foggia, Italy; 6Department of Basic Medical Sciences, Neuroscience and Sense Organs, Section of Respiratory Disease, University “Aldo Moro” of Bari, Bari, Italy; 7Department of Medicine, Surgery and Dentistry, University of Salerno, Salerno, Italy; 8Division of Pneumology, “V. Monaldi” University Hospital, Naples, Italy; 9Allergology and Clinical Immunology Unit, University “Aldo Moro” of Bari, Bari, Italy; 10Department of Medical and Surgical Sciences, Institute of Respiratory Diseases, University of Foggia, Foggia, Italy; 11Allergology and Immunology Unit, University “Federico II” of Naples, Naples, Italy; 12Allergology and Pulmonology Unit, Provincial Outpatient Center of Palermo, Palermo, ItalyCorrespondence: Corrado PelaiaDepartment of Health Sciences, University “Magna Graecia” of Catanzaro, Catanzaro, ItalyTel + 39 0961 3647007Email pelaia.corrado@gmail.comBackground: Benralizumab can be utilized as add-on biological treatment of severe eosinophilic asthma. However, so far only a few real-life studies have been published with regard to the use of this anti-IL-5 receptor humanized monoclonal antibody.Objective: The primary aim of this multicenter observational investigation has been to assess the therapeutic effects of benralizumab in patients with severe uncontrolled, corticosteroid refractory eosinophilic asthma. The secondary objective was to evaluate the efficacy of benralizumab with regard to positive or negative skin prick test (SPT).Methods: Clinical, functional, and laboratory parameters were evaluated in order to verify the therapeutic actions of benralizumab in atopic and non atopic subjects with difficult-to-treat eosinophilic asthma. Moreover, a comparative evaluation was carried out in relation to the presence or absence of SPT positivity.Results: After 6 months of add-on biological therapy with benralizumab, our 111 patients experienced a marked improvement of their severe eosinophilic asthma, expressed by significant changes in asthma exacerbation rate, prednisone intake, daily use of short-acting β2-adrenergic agonists (SABA), asthma control test (ACT) score, asthma quality of life questionnaire (AQLQ) score (56 patients), forced expiratory volume in one second (FEV1), forced vital capacity (FVC), blood eosinophil count, blood basophil count (59 patients), and fractional exhaled nitric oxide (FeNO) levels (39 patients). In addition, significantly more effective outcomes were detected in patients with positive SPT, when compared to subjects with negative SPT, only in regard to asthma exacerbation number, ACT score, and daily SABA utilization. No significant correlation was found between serum IgE concentrations and each of all measured parameters.Conclusion and Clinical Relevance: Taken together, the results of this real-world study indicate that in both allergic and non-allergic subjects benralizumab can be used as a valuable pharmacotherapeutic option for add-on biological therapy of severe eosinophilic asthma, regardless of SPT positivity or negativity.Keywords: severe eosinophilic asthma, allergic and non-allergic phenotypes, asthma exacerbations, IL-5 receptor, benralizumab

HCV infection has been hypothesized as a contributor of poor CD4+ recovery in patients living with HIV (PLWHIV). Aim of this study was to evaluate CD4+, CD8+ cells and CD4/CD8 ratio trends before and after HCV treatment with direct acting agents (DAA) in PLWHIV. HIV/HCV patients enrolled in ICONA and HepaICONA cohorts with HIV-RNA≤50copies/ml who achieved a sustained viral response after DAA treatment were studied. A linear regression model was used to investigate CD4+, CD8+ and CD4/CD8 changes 12months before and after DAA treatment. A total of 939 HIV/HCV patients were included, 225 (24.0%) female, median age: 53years (IQR 50–56). At DAA initiation, CD4+ T cell count was 12.5kPa. Trends of CD4+ and CD4/CD8 ratio were similar before and after DAA in all study populations (CD4+ change +17.6 cells/mm3 (95%CI −33.5; 69.4, p=0.494); CD4/CD8 change 0.013 (95%CI −0.061; 0.036, p=0.611). However, patients treated with ribavirin (RBV)-free DAA showed a significant decrease in CD8+ cells (−204.3 cells/mm3, 95%CI −375.0;-33.4, p=0.019), while patients treated with RBV experienced CD8+ cell increase (+141.2 cells/mm3, 95%CI 40.3; 242.1, p=0.006). In conclusion, HCV eradication following DAA treatment does not seem to have an impact on CD4+ T cell recovery in PLWHIV. However, a fast decline of CD8+T cells has been observed in patients treated without RBV, suggesting a favourable effect of HCV clearance on the general state of immune activation.

Introduction There is, so far, no universal definition of severe asthma. This definition usually relies on: number of exacerbations, inhaled therapy, need for oral corticosteroids, and respiratory function. The use of such parameters varies in the different definitions used. Thus, according to the parameters chosen, each patient may result in having severe asthma or not. The aim of this study was to evaluate how the choice of a specific definition of severe asthma can change the allocation of patients. Methods Data collected from the Severe Asthma Network Italy (SANI) registry were analyzed. All the patients included were then reclassified according to the definitions of U-BIOPRED, NICE, WHO, ATS/ERS, GINA, ENFUMOSA, and TENOR. Results 540 patients, were extracted from the SANI database. We observed that 462 (86%) met the ATS/ERS criteria as well as the GINA criteria, 259 (48%) the U-Biopred, 222 (41%) the NICE, 125 (23%) the WHO, 313 (58%) the Enfumosa, and 251 (46%) the TENOR criteria. The mean eosinophil value were similar in the ATS/ERS, U-Biopred, and Enfumosa (528, 532 and 516 cells/mcl), higher in WHO and Tenor (567 and 570 cells/mcl) and much higher in the NICE classification (624 cells/mcl). Lung function tests resulted similarly in all groups, with WHO (67%) and ATS/ERS-GINA (73%), respectively, showing the lower and upper mean FEV1 values. Conclusions The present observations clearly evidence the heterogeneity in the distribution of patients when different definitions of severe asthma are used. However, the recent definition of severe asthma, provided by the GINA document, is similar to that indicated in 2014 by ATS/ERS, allowing mirror reclassification of the patients examined. This lack of homogeneity could complicate the access to biological therapies. The definition provided by the GINA document, which reflects what suggested by ATS/ERS, could partially overcome the problem.

Background and aims Severe asthma is burdened by frequent exacerbations and use of oral corticosteroids (OCS) which worsen patients’ health and increase healthcare spending. Aim of this study was to assess the clinical and economic effect of adding mepolizumab (MEP) for the treatment of these patients. Methods Patients >18 years old, referred to 8 asthma clinics, starting MEP between May 2017 and December 2018, were enrolled and followed-up for 12 months. Information in the 12 months before mepolizumab were collected retrospectively. The evaluation parameters included: OCS use, number of exacerbations/hospitalizations, concomitant therapies, comorbidity, and annual number of working days lost due to the disease. The primary objective was to compare the annual total cost per patient pre- and post-MEP. Secondary outcomes included rates of exacerbations and number of OCS-dependent patients. Results 106 patients were enrolled in the study: 46 male, median age 58 years. Mean annual cost pre- and post-MEP (cost of biologic excluded) was €3996 and €1,527, respectively. Total savings due to MEP resulted in €2469 (95%CI 1945–2993), 62% due to exacerbations reduction and 33% due to productivity increase. Such savings could fund about 22% of the total cost of MEP for one year. The introduction of MEP induced a clinical benefit by reducing both OCS-dependent patients (OR = 0.12, 95%CI 0.06–0.23) and exacerbation rate (RR = 0.19, 95%CI 0.15–0.24). Conclusions Patients with severe eosinophilic asthma experienced a clinical benefit in asthma control adding MEP to standard therapy. Biologic therapy can be, partially, funded by the savings produced by patients’ improvement.

AimThe efficacy of low-dose fractionated radiotherapy (LDFRT) and chemotherapy (CHT) combination has large preclinical but little clinical evidence. Therefore, the aim of this review was to collect and analyze the clinical results of LDRT plus concurrent CHT in patients with advanced cancers.MethodsA systematic literature search was conducted on PubMed using the PRISMA methodology. Only studies based on the combination of LDFRT (< 1 Gy/fraction) and CHT were included. Endpoints of the analysis were tumor response, toxicity, and overall survival, with particular focus on any differences between LDFRT-CHT and CHT alone.ResultsTwelve studies (307 patients) fulfilled the selection criteria and were included in this review. Two studies were retrospective, one was a prospective pilot trial, six were phase II studies, two were phase I trials, and one was a phase I/II open label study. No randomized controlled trials were found. Seven out of eight studies comparing clinical response showed higher rates after LDFRT-CHT compared to CHT alone. Three out of four studies comparing survival reported improved results after combined treatment. Three studies compared toxicity of CHT and LDFRT plus CHT, and all of them reported similar adverse events rates. In most cases, toxicity was manageable with only three likely LDFRT-unrelated fatal events (1%), all recorded in the same series on LDFRT plus temozolomide in glioblastoma multiforme patients.ConclusionNone of the analyzed studies provided level I evidence on the clinical impact of LDFRT plus CHT. However, it should be noted that, apart from two small series of breast cancers, all studies reported improved therapeutic outcomes and similar tolerability compared to CHT alone. Systematic Review Registrationwww.crd.york.ac.uk/prospero/, identifier CRD42020206639.

Evaluate primary health care functions from the perspective of patients with tuberculosis from slums in the city of Buenos Aires, Argentina.Cross-sectional observational study with adult patients with tuberculosis (TB) and without TB (NoTB), living in slums (S) and outside them (NoS). Participants' perceptions were evaluated using the Primary Care Assessment Tool for users (abbreviated version), which measures four main domains (first contact, ongoing care, coordination with specialists, and comprehensiveness) and selected secondary domains. A Likert scale was used, ranging from "No, not at all" (1 point) to "Yes, definitely" (4 points). Scores ≥ 3 were considered to indicate adequate performance of functions. Averages were calculated for each domain, as well as two overall scores: with and without secondary domains.83 participants were included (20 TB-S, 21 TB-NoS, 19 NoTB-S, and 23 NoTB-NoS). The evaluated functions were perceived as inadequate. The TB-S group gave the lowest overall scores, not reaching 3 points in any domain. There were no significant differences in domains or overall scores between groups. Participants with TB gave lower scores in all domains, except in family-centered care, where they gave a significantly higher score than NoTB participants. The overall score without secondary domains was lower for TB participants than for the NoTB groups.According to the perception of participants with TB and without TB, primary health care functions are not satisfactory, either in slums or outside them.Evaluar las funciones de la atención primaria de salud desde la perspectiva de los pacientes con tuberculosis (TB) provenientes de villas de emergencia de la Ciudad Autónoma de Buenos Aires, Argentina.Estudio observacional transversal con pacientes adultos con TB y sin TB (NoTB), residentes en villas de emergencia (V) y fuera de ellas (NoV). La percepción de los participantes se evaluó mediante el cuestionario Primary Care Assessment Tool-usuarios (versión abreviada) que mide cuatro dimensiones principales (primer contacto, longitudinalidad de los cuidados, coordinación entre servicios e integralidad) y algunas secundarias. Se utilizó una escala de Likert, desde “No, en absoluto” (1 punto) hasta “Sí, sin duda” (4 puntos). Puntajes ≥ 3 se consideraron como cumplimiento adecuado de las funciones. Se calcularon promedios para cada dominio y dos puntajes globales: con y sin dominios secundarios.Se incluyeron 83 participantes (20 TB-S, 21 TB-NV, 19 NoTB-S y 23 NoTB-NoS). Las funciones evaluadas se percibieron como no adecuadas. El grupo TB-S tuvo los puntajes globales más bajos y en ningún dominio alcanzó 3 puntos. No hubo diferencias significativas en los dominios ni los puntajes globales entre grupos. Los participantes con TB dieron menores puntajes en todos los dominios, excepto en enfoque familiar que fue significativamente mayor que los de los participantes NoTB; el puntaje global sin dominios secundarios fue menor en los participantes con TB que en los NoTB.Según la percepción de los participantes con TB y sin TB, las funciones de la atención primaria de salud no son satisfactorias, tanto dentro de las villas de emergencia como fuera de ellas.Avaliar as funções da atenção primária à saúde da perspectiva de pacientes com tuberculose (TB) provenientes de comunidades desfavorecidas na cidade de Buenos Aires, Argentina.Estudo observacional transversal com pacientes adultos com ou sem TB (TB, NãoTB), residentes ou não de comunidades desfavorecidas (C, NãoC). Avaliamos as percepções dos participantes utilizando questionário Primary Care Assessment Tool-usuários (versão reduzida), que mede quatro dimensões principais (primeiro contato, longitudinalidade da atenção, coordenação entre serviços e integralidade), bem como algumas dimensões secundárias. Utilizamos uma escala de Likert de 4 pontos, variando de “definitivamente não” (1 ponto) a “definitivamente sim” (4 pontos). Considerou-se que pontuações ≥3 indicavam o cumprimento adequado das funções. Calculamos as médias para cada domínio e duas pontuações globais: com e sem domínios secundários.Ao todo, 83 participantes foram incluídos no estudo (20 TB-C, 21 TB-NãoC, 19 NãoTB-C e 23 NãoTB-NãoC). As funções avaliadas foram percebidas como inadequadas. O grupo TB-C apresentou a pontuação global mais baixa, não alcançando 3 pontos em nenhum domínio. Não houve diferenças significativas entre os grupos nos domínios nem na pontuação global. Os participantes com TB deram pontuações mais baixas em todos os domínios, exceto no enfoque familiar, no qual a pontuação foi significativamente mais alta que a dos participantes sem TB; a pontuação global sem domínios secundários foi mais baixa nos participantes com TB que nos sem TB.De acordo com as percepções dos participantes com e sem TB, as funções da atenção primária à saúde são insatisfatórias, tanto dentro como fora das comunidades desfavorecidas.

Objective: This study analysed whether the persistence of both reversible airway obstruction (RAO) and elevated BE counts was associated to reduced asthma control and accelerated lung function decline in treated severe asthmatics. Methods: About 202 severe asthmatics were studied after 12–120months of step-5 treatment associated to anti-IgE therapy. Following treatments, reversibility tests, after inhaling 400 mcg of Salbutamol, were performed. FEV1>12% or ≤12% changes differentiated RAO+ from RAO− subjects. Blood eosinophil (BE) counts after treatment were considered. Results: Pre-/post-treatment bronchodilator FEV1% and ACT were lower (61% [50–71], 74.4% [62.5–83.7] and 20[18–22]), whereas BE were higher (380 cells/µl [170–590]) in RAO+ compared to RAO− subjects (77% [64–88], p=0.0001, 81.8% [66.1–94.3], p=0.0001, 21[18–23], p=0.045 and 230 cells/µl [80–360], p=0.003). A negative relationship between SABA-induced FEV1% changes and pre-bronchodilator FEV1% (β=−0.551%; p=0.0001) and ACT (β=−0.059; p=0.038) was found. Conversely, post-treatment BE levels were positively related (β=145.565 cells/µl; p=0.003) to FEV1>12% increases. A rising trend of pre-/post-bronchodilator FEV1% in time was observed in RAO− subjects with BE300 cells/µl reaching lower values after more than 36months of step-5 treatment (59.6% [39.9–72.1] vs 74[66.5–89.2] of RAO+ individuals with BE300 cells/µl [p=0.009]). Conclusion: Persistent SABA-induced FEV1>12%, especially when associated to BE>300 cells/ml, may be a marker of accelerated lung function decline in severe asthmatics despite maximal step-5 treatment. The highest bronchodilation associated to the lowest BE levels should be the main goal of asthma treatment to prevent such decline.

Recently, dupilumab, an anti-IL-4Rα antibody, has become available for the treatment of moderate-to-severe atopic dermatitis (AD).1-4 Baseline patient characteristics that can be used as predictors of response to dupilumab treatment in AD patients have not yet been identified.

Background: Recent studies have reported improvement of outcomes (progression-free survival, overall survival, and prolongation of androgen deprivation treatment-free survival) with stereotactic body radiotherapy (SBRT) in non-small cell lung cancer and prostate cancer. The aim of this retrospective, multicenter study (MITO RT-01) was to define activity and safety of SBRT in a very large, real-world data set of patients with metastatic, persistent, and recurrent ovarian cancer (MPR-OC). Materials and Methods: The endpoints of the study were the rate of complete response (CR) to SBRT and the 24-month actuarial local control (LC) rate on “per-lesion” basis. The secondary endpoints were acute and late toxicities and the 24-month actuarial late toxicity-free survival. Objective response rate (ORR) included CR and partial response (PR). Clinical benefit (CB) included ORR and stable disease (SD). Toxicity was evaluated by the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC) and Common Terminology Criteria for Adverse Events (CTCAE) scales, according to center policy. Logistic and Cox regression were used for the uni- and multivariate analysis of factors predicting clinical CR and actuarial outcomes. Results: CR, PR, and SD were observed in 291 (65.2%), 106 (23.8%), and 33 (7.4%) lesions, giving a rate of CB of 96.4%. Patient aged ≤60 years, planning target volume (PTV) ≤18 cm3, lymph node disease, and biologically effective dose α/β10 > 70 Gy were associated with higher chance of CR in the multivariate analysis. With a median follow-up of 22 months (range, 3–120), the 24-month actuarial LC rate was 81.9%. Achievement of CR and total dose >25 Gy were associated with better LC rate in the multivariate analysis. Mild toxicity was experienced in 54 (20.7%) patients; of 63 side effects, 48 were grade 1, and 15 were grade 2. The 24-month late toxicity-free survival rate was 95.1%. Conclusions: This study confirms the activity and safety of SBRT in patients with MPR-OC and identifies clinical and treatment parameters able to predict CR and LC rate. Implications for Practice: This study aimed to define activity and safety of stereotactic body radiotherapy (SBRT) in a very large, real life data set of patients with metastatic, persistent, recurrent ovarian cancer (MPR-OC). Patient age 70 Gy were associated with higher chance of complete response (CR). Achievement of CR and total dose >25 Gy were associated with better local control (LC) rate. Mild toxicity was experienced in 20.7% of patients. In conclusion, this study confirms the activity and safety of SBRT in MPR-OC patients and identifies clinical and treatment parameters able to predict CR and LC rate.

Background The clinical and laboratory features of patients enrolled in the Severe Asthma Network in Italy (SANI) registry, a web-based observatory collecting demographic, clinical, functional and inflammatory data of patients with severe asthma were evaluated, with a special emphasis to chronic rhinosinusitis with nasal polyposis (CRSwNP). Methods For each eligible patients the following information has been collected: demographic data, clinical features, asthma control in the previous month according to the GINA (Global INitiative for Asthma) Guidelines and standardized questionnaires, concomitant regular and on demand treatments and inflammatory markers. Results 695 patients with severe asthma enrolled in 66 SANI centers were analyzed. The prevalence of chronic rhinosinusitis with nasal polyposis was 40.6%. Atopic dermatitis and bronchiectasis was significantly more frequent in patients with CRSwNP than in subjects without nasal polyposis; similarly, FeNO values are significantly higher in subject with CRSwNP than in patients without nasal polyposis. Finally, patients with CRSwNP had a significantly higher number of asthma exacerbations per year, more days on oral corticosteroids and were more likely to be OCS long term users. Conclusion OCS sparing is needed in patients with severe asthma, mainly in subjects with CRSwNP, adopting adequate strategies such as a better adherence to the treatment with inhaled therapy according to the GINA recommendations, the use of biologic agents and a multidisciplinary approach of the patient.

We aimed at evaluating the characteristics of HIV-1 molecular transmission clusters (MTCs) among natives and migrants living in Italy, diagnosed between 1998 and 2018. Phylogenetic analyses were performed on HIV-1 polymerase (pol) sequences to characterise subtypes and identify MTCs, divided into small (SMTCs, 2&ndash, 3 sequences), medium (MMTCs, 4&ndash, 9 sequences) and large (LMTCs, &ge, 10 sequences). Among 3499 drug-na&iuml, ve individuals enrolled in the Italian Cohort Naive Antiretroviral (ICONA) cohort (2804 natives, 695 migrants), 726 (20.8%, 644 natives, 82 migrants) were involved in 228 MTCs (6 LMTCs, 36 MMTCs, 186 SMTCs). Migrants contributed 14.4% to SMTCs, 7.6% to MMTCs and 7.1% to LMTCs, respectively. HIV-1 non-B subtypes were found in 51 MTCs, noteworthy was that non-B infections involved in MTCs were more commonly found in natives (n = 47) than in migrants (n = 4). Factors such as Italian origin, being men who have sex with men (MSM), younger age, more recent diagnosis and a higher CD4 count were significantly associated with MTCs. Our findings show that HIV-1 clustering transmission among newly diagnosed individuals living in Italy is prevalently driven by natives, mainly MSM, with a more recent diagnosis and frequently infected with HIV-1 non-B subtypes. These results can contribute to monitoring of the HIV epidemic and guiding the public health response to prevent new HIV infections.

Objectives To describe: (i) factors associated with rapid and delayed ART initiation; (ii) rates of 12 week virological response; and (iii) virologically controlled retention in care by 1 year from ART initiation according to timing of start in a real-life setting. Methods All individuals in the Icona cohort diagnosed with HIV in 2016–17 who initiated ART were grouped according to the time between HIV diagnosis and ART initiation: Group 1, ≤7 days; Group 2, 8–14 days; Group 3, 15–30 days; Group 4, 31–120 days; and Group 5, >120 days. Multivariable logistic regression models were used to identify factors associated with: (i) the probability of rapid (Group 1) and very delayed (Group 5) ART initiation; (ii) the 12 week virological response (by a modified snapshot algorithm); and (iii) the probability of retention in care at 1 year (on ART with HIV-RNA Results A total of 1247 individuals were included [82 (6.6%) in Group 1, 115 (9.2%) in Group 2, 267 (21.4%) in Group 3, 641 (51.4%) in Group 4 and 142 (11.4%) in Group 5]. Main predictors of rapid ART start (Group 1) were low CD4 cell count and high HIV-RNA at first contact with the infectious diseases centre. There was no association between probability of virological response and timing of ART initiation. Overall, 90% of individuals remained on ART after 1 year, 91% with undetectable HIV-RNA. Participants of Italian nationality, those with higher CD4 cell count and lower HIV-RNA at ART initiation were more likely to be retained in care after 1 year. Conclusions In our high-income observational setting, we did not observe differences in the 1 year rate of virological response and retention in care according to timing of ART initiation.

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) affects around 60% of patients with severe eosinophilic asthma (SEA). Benralizumab was recently approved for SEA add-on treatment. Objective: To assess the real-world effectiveness of benralizumab in SEA with or without CRSwNP. Methods: We conducted a multicenter observational study, including patients with SEA treated with benralizumab for 24 weeks in 12 Italian specialized facilities. Asthma exacerbations, Asthma Control Test (ACT), lung function, oral corticosteroid (OCS) dosage, and eosinophil and basophil count in peripheral blood were recorded at baseline and after 4, 12, and 24 weeks. The 22-item Sino-Nasal Outcome Test (SNOT-22) and Lund-Mackay scores were assessed at baseline and after 24 weeks in SEA+CRSwNP. Results: A total of 137 patients with late-onset SEA were included; 57.7% (79 of 137) showed the copresence of CRSwNP. Overall, severe asthma exacerbations decreased from 4 (3-6) to 0 (0-2) (P < .0001) after 24 weeks of treatment, and significant improvements were observed as early as 4 weeks in ACT score, OCS dosage, forced expiratory volume in the 1st second (FEV1)%, FEV1 (L), forced vital capacity (FVC)%, FEV1/FVC% (P < .0001), and forced expiratory flow between 25% and 75% of FVC (FEF25-75)% (P = .0022). Eosinophils and basophils in peripheral blood were rapidly depleted. In patients with SEA+CRSwNP, SNOT-22 decreased from 46 (39.5-64.5) to 32 (19-46) (P < .0001). Furthermore, in comparison with SEA, they showed enhanced responses with regard to ACT minimal clinically important difference (P = .0387), FEV1% (P = .017), FEV1 (L) (P = .02), and FEF25-75% (P = .0362). Conclusions: These real-world data suggest that benralizumab can represent a valid add-on therapeutic option for patients with SEA, especially with comorbid CRSwNP.

Pancreatic cancer (PaC) will soon be one of the main causes of cancer mortality. Furthermore, its incidence is higher in the older population and radiotherapy (RT) represents a treatment option. The aim of this review was to evaluate feasibility and outcome of RT in older patients with PaC. A systematic literature review of patients aged ≥65 years with PaC treated with RT was performed using the PRISMA methodology. Eleven papers (1830 patients) fulfilled our inclusion criteria and were analyzed. RT was prescribed either alone or as an adjuvant treatment. Prescribed RT dose ranged from 22.0 to 70.0 Gy with conventional fractionation or hypo-fractionated schedule and delivered by three-dimensional conformal RT, intensity modulated RT or stereotactic body RT. Grade ≥ 3 acute and grade ≥ 2 late toxicity rates ranged between 0.0% and 52.6% (median: 0.5%) and between 0.0% and 15.0% (median: 0%), respectively. Median overall survival and two-year survival rate were 11.3 months (range: 6.4–69.0 months) and 49.0% (range 6.6–75.5%), respectively. RT in older patients seems to be tolerable and safe particularly in terms of late toxicity irrespective of the treatment settings. Therefore, RT can represent a treatment option in PaC even in an older population. Further analyses and prospective trials enrolling older patients are needed to better define the risk/benefit ratio in different treatment settings.

Gustatory perception has been poorly explored in Parkinson's disease (PD). Aim of this study was to assess the flavor ability in PD patients, using the "flavor test" (FT), a new standardized and validated tool to examine the flavor perception. Thirty-eight patients (17 F and 21 M) and 36 control subjects (15 F and 21 M) comparable for age and gender were enrolled. All the subjects underwent the flavor test (FT), the Sniffin' Sticks test (SST), and the gustometry test (GT), based on the basic four tastants ("salty," "sour," "sweet," and "bitter"). PD patients presented a FT score significantly lower than controls (p

Several severe asthma comorbidities have been identified: an emerging one is bronchiectasis. We evaluated the frequency of bronchiectasis on severe asthma in a real-life setting, through the 'Severe Asthma Network Italy' (SANI) registry.SANI registry encompasses demographic, clinical, functional and inflammatory data of Italian severe asthmatics. Data obtained by the enrolled patients were analyzed, focusing the attention on those patients with concomitant clinically relevant bronchiectasis.About 15.5% patients have bronchiectasis. Bronchiectasis diagnosis was associated with a higher prevalence of chronic rhinosinusitis with nasal polyps (54.6% vs. 38%, p = 0.001) and higher serum IgE levels (673.4 vs. 412.1 kUI/L, p = 0.013). Patients with bronchiectasis had worse asthma control (ACT: 16.7 vs 18.2, p = 0.013), worse quality of life (AQLQ: 4.08 vs. 4.60, p = 0.02) and lower lung function (FEVsevere asthma associated with bronchiectasis represents a particularly severe asthma variant, possibly driven by an eosinophilic endotype. We, therefore, suggest that bronchiectasis should necessarily be assessed in severe asthmatic patients.

Purpose A concomitant boost (CB) in patients treated with postoperative radiotherapy after conservative surgery of invasive breast cancer (BC) has been suggested for treatment time reduction and therapy intensification. The aim of this analysis was to assess long-term tolerability of a CB in patients treated with postoperative intensity Modulated Accelerated RAdiotherapy (MARA). Patients and methods In this phase I-II trial, 321 patients with intermediate-high risk BC (pT1-4 with at least one of the following characteristics: pre or perimenopausal status, pN2-3, positive or close margins) were enrolled. Patients were treated with forward-planned intensity modulated radiotherapy (IMRT) and CB. A total dose of 50 Gy (2 Gy/fraction) and 60 Gy (2.4 Gy/fraction) was prescribed to the whole breast and the tumor bed, respectively. The potential impact of hypertension, diabetes, smoking habit, alcohol consumption, chemotherapy, and hormone therapy on both skin and subcutaneous late toxicity-free survival (LTFS) was evaluated. Survival curves were calculated using the Kaplan-Meier method. Results Median follow-up was 52 months (range: 3-115). Regional node irradiation, adjuvant chemotherapy and hormonal therapy were prescribed to 29.3%, 65.4% and 81.0% of patients, respectively. Five-year G2 and G3 skin LTFS were 95.6% and 100.0%, respectively. Five-year G2 and G3 subcutaneous LTFS were 80.0% and 98.6%, respectively. Only diabetes showed a significant correlation with worse G3 subcutaneous LTFS (p: 0.024). Five-year loco-regional control, metastasis-free survival, disease-free survival, and overall survival were 98.0%, 91.8%, 89.7% and 96.3%, respectively. Conclusion IMRT combined with CB was associated with a low risk of > G2 late toxicities (0.0% and 1.4% for skin and subcutaneous tissue, respectively). The cumulative actuarial incidence of local recurrences was 2.0% despite the exclusion of low-risk patients. Our results suggest that CB is safe and effective in patients with intermediate-high risk BC. Trial registration ClinicalTrials.gov: NCT03471741.

Introduction Since the community spread of Coronavirus disease 2019 (COVID-19), the practice of oncologic care at our comprehensive cancer center has changed. Postponing cancer treatment without consideration of its implications could cost more lives than can be saved. In this special situation, we must continue to provide our cancer patients with the highest quality of medical services assuring the safety. This article provides general guidance on supporting curative treatment strategies in vulvar cancer patients. Methods At our institution, a vulvar cancer multidisciplinary team (Vul.Can MDT) of specialists is responsible for personalized treatment of this disease. The phase 2 period necessarily requires specific procedures for both outpatient and inpatient pathways and to provide strategies concerning the management of vulvar cancer patients even in case of an eventually concomitant SARS-CoV-2 infection. In brief, an accurate remote and in person triage must be provided routinely and patients submitted to specific diagnostic tests prior to every major treatment or procedure (surgery, RT, and CT) or in case of suspicion for COVID-19 syndrome. The decisional workflow for these women often old and frail, have been rapidly adjusted by our Vul.Can MDT to mitigate the potential risks of COVID-19. Results The team produced two types of recommendations concerning: (1) safety regulations of care pathways, patients and health care providers, (2) personalized treatment strategies. We present a protocol that can be applied in clinical practice: the flowcharts provided, include the modulation of treatment intensity designed for surgical procedures and radiation, stratified for FIGO stage of disease and intention. Conclusion We suggest that our proposals are applicable in this setting of patients, considering anyway current international recommendations and guidelines.

Background Dupilumab is an anti-IL-4Rα antibody used in the treatment of patients with moderate-to-severe atopic dermatitis (msAD). This study explored the potential benefit of dupilumab in perennial allergic rhinoconjunctivitis (PAR) and perennial allergic asthma (PAA) caused by indoor allergens in adults with msAD. Methods This multicentric, prospective, observational, real-life study included adult patients with msAD who had been treated with dupilumab in 16 Italian care centres. Efficacy outcomes regarding AD, PAR and PAA were collected at baseline and 16 weeks. Safety was also assessed. Results We enrolled 123 patients with msAD. Between baseline and 16 weeks of treatment, the following measurements decreased statistically significantly: Eczema Area and Severity Index, SCOring AD, Patient-Oriented Eczema Measure, pruritus score, sleep score, Dermatology Life Quality Index and IgE. Dupilumab treatment in patients with comorbid PAR (n = 41) was associated with significant improvements in PAR disease control (measured using a Rhinitis Control Scoring System) and in PAR Quality of life (QoL) (measured using the Rhinoconjunctivitis QoL Questionnaire scores). In 32 patients with comorbid PAA, dupilumab significantly improved PAA control (measured using the Asthma Control Test and five-item Asthma Control Questionnaire scores) and disease-related QoL (measured using the Asthma QoL Questionnaire scores). Thirty-five patients (28.5%) developed conjunctivitis during the study period. Conclusion These results support the benefits of dupilumab for adult patients with PAR and/or PAA associated with msAD.

To investigate the present attitude of the Italian Radiation Oncologists in the management of breast cancer (BC) concerning hypofractionated radiotherapy (hRT), partial-breast irradiation (PBI), re-irradiation (rRT) and radiotherapy after neoadjuvant chemotherapy (post-NAC RT). A nationwide, 21-point questionnaire was distributed online via SurveyMonkey. Seventy-four Italian Radiotherapy Centers answered to the survey. In most cases, the responding centers treated more than 100 BC patients/year between January 2016 and December 2017. Almost half of responding centers (49%) treated patients with hRT, out of these, 95% as routine practice for early-stage BC. Dose prescriptions ranged between 39 and 45 Gy indicating a high use of moderate hRT. The chest wall and regional lymph nodes were irradiated with hRT by 13% and 15% of the responding centers, respectively. PBI was used by 60% of responders, with different techniques. Only 0.6% of participants perform rRT after BC recurrence. Finally, only 11% of the interviewed centers responded to their attitude toward post-NAC RT, which, however, was indicated in 97% of patients after breast-conserving surgery. This survey shows a fairly good use of hRT and a moderate practice of PBI in Italy. Some practices like hRT to the chest wall and regional lymph nodes as well as rRT need further verification. Likewise, the management of post-NAC RT is very heterogeneous. Future national clinical collaborative studies are advocated in order to investigate these controversial topics about breast cancer radiotherapy.

Telomeres length and telomerase activity are currently considered aging molecular stigmata. Water is a major requirement for our body and water should be alkaline. Recent reports have shown that aging is related to a reduced water intake. We wanted to investigate the effect of the daily intake of alkaline water on the molecular hallmark of aging and the anti-oxidant response. We watered a mouse model of aging with or without alkaline supplementation. After 10 months, we obtained the blood, the bone marrow and the ovaries from both groups. In the blood, we measured the levels of ROS, SOD-1, GSH, and the telomerase activity and analysed the bone marrow and the ovaries for the telomeres length. We found reduced ROS levels and increased SOD-1, GSH, telomerase activity and telomeres length in alkaline supplemented mice. We show here that watering by using alkaline water supplementation highly improves aging at the molecular level.

BackgroundStereotactic body radiotherapy (SBRT) has shown promising results in the clinical setting of oligometastatic, persistent, or recurrent disease in several malignancies including ovarian cancer.Primary ObjectiveThe MITO-RT3/RAD trial is a prospective, multicenter phase II study aimed at identifying potential predictors of response and clinical outcome after SBRT treatment.Study HypothesisRadiotherapy delivered by pre-defined SBRT treatment schedules and shared constraints could improve the rate of complete response.Trial DesignAll patients accrued will be treated with a radiotherapy dose in the range of 30–50 Gy by 1, 3, or 5 SBRT daily fractions to all sites of active metastatic disease according to diagnostic imaging. Schedules of treatment and dose prescription have been established before considering target sites and healthy organ dose constraints. Follow-up and monitoring of side effects will be carried out every 3 months for the first year with imaging and clinical evalutation, and every 4 months within the second year; thereafter, surveillance will be carried out every 6 months. The best response on a per lesion basis will be evaluated by computed tomographic (CT) scan, positron emission tomography/CT, or magnetic resonance imaging in case of brain lesions, every 3 months.Major Inclusion/Exclusion CriteriaThe study includes patients with oligometastatic, persistent, or recurrent ovarian cancer for which salvage surgery or other local therapies are not feasible due to any relative contra-indication to further systemic therapy because of serious co-morbidities, previous severe toxicity, unavailability of potentially active systemic therapy, or patient refusal.Primary EndpointThe primary endpoint of the study is the clinical complete response rate to SBRT by imaging on a per lesion basis.Sample SizeApproximately 205 lesions will be treated (90 lymph nodes and 115 parenchyma lesions).Estimated Dates for Completing Accrual and Presenting ResultsFifty-two centers have expressed their intention to participate. Enrollment should be completed by March 2023 and analysis will be completed in September 2023.Trial RegistrationNCT04593381.

The prognosis of prostate cancer (PC) is generally favorable but the incidence of metastases is relatively high after the treatment of the primary tumor, especially in high-risk patients. Fractionated stereotactic body radiotherapy (SBRT) or single fraction stereotactic body radiosurgery (SRS) are emerging treatment options in this setting. However, data on SBRT/SRS in patients with metastatic castration-resistant PC (mCRPC) are largely lacking, particularly in subjects with nodal lesions. Therefore, we evaluated outcomes and toxicity recorded in mCRPC patients with nodal oligoprogression. Patients included in this analysis had ≤ 5 metastatic sites without visceral lesions and underwent SBRT/SRS on nodal metastases. Thirty-eight patients carrying out 61 nodal metastases were analyzed. The median SRS dose was 20Gy (range 12–24Gy) and the most common schedule was 20Gy (44.8%). The median SBRT dose was 45Gy (range 20–50Gy) and the most common regimen was 45Gy in 5 fractions (37.9%). Thirty-seven patients (97.4%) showed only grade 0–1 acute toxicity while one patient reported grade 2 dysphagia. In terms of late toxicity, one grade 2 laryngeal, one grade 1 skin and one grade 1 gastrointestinal toxicities were recorded. Two-year actuarial local control (LC), distant progression-free survival, progression-free survival (PFS) and overall survival were 94.0, 47.2, 47.2, and 90.2%, respectively. Two-year next line systemic therapy-free survival (NEST-FS) was 67.7%. In conclusion, the efficacy in terms of LC of SBRT/SRS in patients with nodal metastases from PC was confirmed. Moreover, this analysis suggests the efficacy in terms of PFS and NEST-FS also in the setting of oligoprogressive PC. In fact, about one-third of patients were free from progressive disease and two-third of subjects did not require hormonal therapy switch or discontinuation three years after treatment.

Background/aim Non-melanoma skin cancers (NMSC) are the most common neoplasms worldwide and their incidence has been proven to increase in recent years and their treatment should aim at cancer cure as well as cosmetic and functional results. The aim of the study was to report the results of our mono-institutional series of high-dose-rate radiotherapy (cHDR-RT) in NMSC, based on a homogenous technique and two different treatment schedules. Patients and methods All patients affected by NMSC who were consecutively evaluated and treated at our Interventional Oncology Center from October 2018 to August 2020, were included. Patients underwent cHDR-RT using flap applicators and remotely afterloaded Ir-192 sources. Results Overall, 51 patients were treated for a total of 67 lesions. Local control (LC) and disease-specific survival (DSS) were 94.0% and 100%, respectively. Grade 1, grade 2, grade 3 and grade 4 acute toxicity rates were 24.6%, 3.5%, 3.5%, and 0.0%, respectively. The cosmetic results were graded as excellent/good, fair, and poor in 73.7%, 19.3%, and 7.0%. Conclusion cHDR-RT of NMSC is an effective alternative to surgery due to excellent outcomes both in terms of local control and aesthetic results especially in the face.

Kaposi sarcoma (KS) is a rare angioproliferative disorder, which is usually associated with human herpesvirus-8 infection. Electrochemotherapy (ECT) may be an option in the treatment of KS skin lesions due to the high response rate noted in neoplastic lesions of different histological types. The aim of the present systematic review was to analyse the available evidence on using ECT in the treatment of KS skin lesions. Tumor response, local control and toxicity were analyzed. In the three included studies, the complete response rate was 65-100% and the overall response rate in all studies was 100%. The treatment was well tolerated with mild and transient toxicity. However, further studies are required to fully analyze long-term disease control and to compare ECT with other local therapies used for KS.

Introduction: An education strategy was employed in our department to increase the rate of patients with uncomplicated painful bone metastases undergoing single fractionation radiotherapy (SFRT). The purpose of this report is to analyze the results of this strategy over a 5 year period. Materials and Methods: In January 2015, two meetings were organized in our department. In the first, data from an audit on the current SFRT rate were shown. In the second, evidence of SFRT efficacy in the relief of pain from uncomplicated bone metastases was presented. In addition, during the weekly discussion of clinical cases, the opportunity to use the SFRT was systematically recalled. Using our institutional database, all patients treated with radiotherapy for uncomplicated painful bone metastases in the period between 2014 (year considered as a reference) and 2019 were retrieved. Data regarding treatment date (year), radiotherapy fractionation, and tumor, patients, and radiation oncologists characteristics were collected. Results: A total of 627 patients were included in the analysis. The rate of patients undergoing SFRT increased from 4.0% in 2014 to 63.5% in 2019 ( p 80 years), lung cancer as the primary tumor, treatment prescribed by a radiation oncologist dedicated to palliative treatments, and treatment date (2014 vs 2015–2019). Conclusions: This retrospective single-center analysis showed that a simple but intensive and prolonged departmental education strategy can increase the rate of patients treated with SFRT by nearly 16 times.

Background The aim of this study was to investigate the impact of anti-HBc (HBcAb) positivity on the progression of liver fibrosis (Fibrosis-4 score >3.25) in the Italian cohort of HIV-infected individuals naïve to antiretroviral treatment (ICONA). Methods All patients with FIB-4 Results Patients who were HBcAb+/HCV-/HBs antigen (HBsAg)- and HCV+/HBcAb+/HBsAg- or HBsAg+/HBcAb+/HCV- had CD4+ cell counts below the nadir and significantly higher prevalence of AIDS diagnosis at baseline than the other groups (P < .0001). A Cox regression model adjusted for age, HIV transmission mode, country of birth, and alcohol consumption showed a higher relative risk (HR) of progression to FIB-4 >3.25 in HCV+/HBcAb+/HBsAg- patients (HR, 7.2; 95% CI, 3 8–13.64). Conclusions HBcAb+ contributes to liver damage in HIV+/HCV+/HBcAb+/HBsAg- subjects. A careful monitoring for signs of previous HBV infection is needed in this kind of patients.

Purpose: To investigate the potential benefits of a hypofractionated radiotherapy boost (HRB) after chemotherapy (CT) and concomitant chemoradiotherapy (CRT) in locally advanced pancreatic cancer (LAPC) patients. Primary endpoints were early and late toxicity, local control (LC) and pain-free progression (PFP) assessment. Two-years overall survival (OS), metastasis-free survival (MFS) and disease-free survival (DFS) were secondary endpoints. Materials and methods: Patients (pts) affected by unresectable non-metastatic LAPC, previously treated with CT and CRT in upfront or sandwich setting, were selected for sequential HRB. Total prescribed dose was 30Gy in 5 fractions (fr) to pancreatic primary lesion. Dose de-escalation was allowed in case of failure in respecting organs at risk constraints. Early and late toxicity were assessed according to CTCAE v.4.0 classification. The Kersh-Hazra scale was used for pain assessment. Local Control, PFP, MFS and DFS were calculated from the date of HRB to the date of relapse or the date of the last follow-up. Results: Thirty-one pts affected by unresectable, non-metastatic LAPC were consecutively enrolled from November 2004 to October 2019. All pts completed the planned HRB. Total delivered dose varied according to duodenal dose constraint: 20Gy in 5 fr (N: 6; 19.4%), 20Gy in 4 fr (N: 5; 16.2%), 25Gy in 5 fr (N: 18; 58.0%) and 30Gy in 6 fr (N: 2; 6.4%). Early and late toxicity were assessed in all pts: no Grade 3 or 4 acute gastrointestinal toxicity and no late gastrointestinal complications occurred. Median LC was 19months (range 1–156) and 1- and 2-year PFP were 85% and 62.7%, respectively (median 28months; range 2–139). According to the Kersh-Hazra scale, four pts had a Grade 3 and four pts had a Grade 1 abdominal pain before HRB. At the last follow-up only 3/31 pts had residual Grade 1 abdominal pain.Median MFS was 18months (range 1–139). The 2-year OS after HRB was 57.4%, while 2-year OS from diagnosis was 77.3%. Conclusion: Treatment intensification with hypofractionated radiotherapy boost is well tolerated in pts affected by unresectable LAPC previously treated with CT/CRT. Its rates of local and pain control are encouraging, supporting its introduction in clinical practice. Timing, schedule and dose of HRB need to be further investigated to personalize therapy and optimize clinical advantages.

BackgroundIn radiation oncology, automation of treatment planning has reported the potential to improve plan quality and increase planning efficiency. We performed a comprehensive dosimetric evaluation of the new Personalized algorithm implemented in Pinnacle3 for full planning automation of VMAT prostate cancer treatments.Material and MethodsThirteen low-risk prostate (without lymph-nodes irradiation) and 13 high-risk prostate (with lymph-nodes irradiation) treatments were retrospectively taken from our clinical database and re-optimized using two different automated engines implemented in the Pinnacle treatment system. These two automated engines, the currently used Autoplanning and the new Personalized are both template-based algorithms that use a wish-list to formulate the planning goals and an iterative approach able to mimic the planning procedure usually adopted by experienced planners. In addition, the new Personalized module integrates a new engine, the Feasibility module, able to generate an “a priori” DVH prediction of the achievability of planning goals. Comparison between clinically accepted manually generated (MP) and automated plans generated with both Autoplanning (AP) and Personalized engines (Pers) were performed using dose-volume histogram metrics and conformity indexes. Three different normal tissue complication probabilities (NTCPs) models were used for rectal toxicity evaluation. The planning efficiency and the accuracy of dose delivery were assessed for all plans.ResultsFor similar targets coverage, Pers plans reported a significant increase of dose conformity and less irradiation of healthy tissue, with significant dose reduction for rectum, bladder, and femurs. On average, Pers plans decreased rectal mean dose by 11.3 and 8.3 Gy for low-risk and high-risk cohorts, respectively. Similarly, the Pers plans decreased the bladder mean doses by 7.3 and 7.6 Gy for low-risk and high-risk cohorts, respectively. The integral dose was reduced by 11–16% with respect to MP plans. Overall planning times were dramatically reduced to about 7 and 15 min for Pers plans. Despite the increased complexity, all plans passed the 3%/2 mm γ-analysis for dose verification.ConclusionsThe Personalized engine provided an overall increase of plan quality, in terms of dose conformity and sparing of normal tissues for prostate cancer patients. The Feasibility “a priori” DVH prediction module provided OARs dose sparing well beyond the clinical objectives. The new Pinnacle Personalized algorithms outperformed the currently used Autoplanning ones as solution for treatment planning automation.

Postmastectomy radiotherapy (PMRT) has been shown to improve the overall survival for invasive breast cancer patients. However, it represents a challenging treatment geometry and individualized planning strategies with complex field arrangements are usually adopted to decrease radiotoxicity to heart and lungs. Automated treatment planning has the potential to improve plan quality consistency and planning efficiency. Herein, we describe the application of the Pinnacle3 Autoplanning engine as a valuable technological resource able to allow the treatment of challenging patients theoretically unfit for radiotherapy for major cardiac and pulmonary comorbidities. Treatment was planned for three left-sided chest wall and regional lymph-nodes postmastectomy breast cancer patients. A deep inspiration breath-hold (DIBH) technique was used aiming to reduce the OARs irradiation. Three manually generated plans (hybrid-IMRT (HMRT), hybrid-VMAT (HVMAT) and full VMAT (MP-VMAT) and a fully automated plan created by the Autoplanning engine (AP-VMAT) were optimized in order to ensure a safe radiation therapy to the patients. The plans were evaluated based on planning target volumes (PTVs) coverage, dose homogeneity index (HI), conformity index (CN), dose to organs at risk (OARs) and normal tissue complication probabilities (NTCPs) of pericarditis, long term mortality and pneumonitis. Despite the use of deep moderated breath-hold, all human-driven plans failed to reach the stringent dose objectives for OARs. All plans provided an optimal coverage for chest wall and lymph-nodal area. AP-VMAT delivered the lowest mean dose to the heart (3.4 to 4.9 Gy) and ipsilateral lung (7.5 to 12.5 Gy) reporting the lowest NTCP for pneumonitis (

Objective: The objective of this study was to assess the effectiveness and safety of dupilumab in treating elderly patients with atopic dermatitis from baseline to 52 weeks. Methods: A retrospective observational real-life study was conducted in a group of elderly patients with severe atopic dermatitis treated with dupilumab for 52 weeks. Inclusion criteria were: age ≥ 65 years; diagnosis of atopic dermatitis made by an expert dermatologist; Eczema Area and Severity Index ≥ 24; and a contraindication, side effects, or failure to respond to cyclosporine. The primary outcome was the mean percentage reduction in the Eczema Area and Severity Index score from baseline to week 52. Secondary measures includedthe mean percentage reduction in the Pruritus and Sleep Numerical Rating Scales and the Dermatology Life Quality Index, and the types and rates of adverse events from baseline to week 52. Results: One hundred and five patients were eligible for the study. Flexural dermatitis was the most frequent clinical phenotype (63.8%). The coexistence of more than one clinical phenotype was found in 70/105 (66.6%) patients. We observed a reduction in all disease severity scores from baseline to week 52 (p < 0.001). Adverse events were recorded in 30/105 (28.6%) patients, with conjunctivitis and injection-site reaction the most frequent. Conclusions: In this study, dupilumab is an effective and safe treatment for the long-term management of atopic dermatitis in patients aged over 65 years.

Raffaele Campisi,1 Claudia Crimi,1 Santi Nolasco,2 Bianca Beghè,3 Leonardo Antonicelli,4 Gabriella Guarnieri,5 Nicola Scichilone,6 Morena Porto,2 Luigi Macchia,7 Giulia Scioscia,8 Maria Pia Foschino Barbaro,8 Alberto Papi,9 Nunzio Crimi1,2 1Respiratory Medicine Unit, A.O.U. Policlinico “G. Rodolico -San Marco”, Catania, Italy; 2Department of Clinical and Experimental Medicine, Section of Respiratory Diseases, University of Catania, Catania, Italy; 3Respiratory Medicine Unit, Department of Medicine, University of Modena and Reggio Emilia, Modena, Italy; 4Allergy Unit, Department of Internal Medicine, Ancona University Hospital, Ancona, Italy; 5Department of Cardiac, Thoracic and Vascular Sciences, University-City Hospital of Padova, Padova, Italy; 6University of Palermo, PROMISE Department, University of Palermo, Palermo, Italy; 7Department of Emergency and Organ Transplantation, School and Chair of Allergology and Clinical Immunology, University of Bari, Bari, Italy; 8Department of Medical and Surgical Sciences, Institute of Respiratory Diseases, University of Foggia, Foggia, Italy; 9Respiratory Medicine Unit, S. Anna University Hospital, Ferrara, ItalyCorrespondence: Claudia CrimiRespiratory Medicine Unit, A.O.U. Policlinico “G. Rodolico - San Marco”, Catania, ItalyEmail dott.claudiacrimi@gmail.comIntroduction: Dupilumab is a monoclonal antibody targeting IL-4Rα recently licensed for severe asthma (SA). A Named Patients Program (NPP) was created in Italy before its commercial availability for SA patients with no other available therapeutic options. We aimed to assess the real-world effectiveness of dupilumab in patients with SA and unmet needs.Methods: We performed a multicentre retrospective study, including SA patients admitted to the NPP treated with dupilumab for 12 months. Data on the number of exacerbations, Asthma Control Test (ACT), pre-bronchodilator FEV1%, oral corticosteroids (OCSs) use, FeNO and eosinophils count in peripheral blood were recorded at baseline and after 3, 6, and 12 months.Results: We included 18 SA patients (mean age 53.3± 12.4 years, 66.7% female). Eleven (61.1%) were OCSs dependent. Five patients (27.8%) received previous anti-IgE and/or anti-IL-5 agents. A significant improvement in ACT score (from 15.7± 5.1 to 18.8± 4.8, p=0.023), OCSs intake [10 (5– 25) mg/day to 0 (0– 5) mg/day, p=0.0333] and FeNO [from 25 (20– 80) ppb to 21 (10.9– 55.3) ppb, p=0.0190] was already detected after 3 months of treatment. After 12 months, a statistically significant decrease in the number of exacerbations from 2 (0– 3) to 0 (0– 1) (p< 0.0068) and increase in FEV1% from 73.5± 19.5% to 87.1± 19.2% (p=0.0407) and ACT to a mean value of 22.4± 1.7 (p< 0.0001) and the interruption of OCSs in all the patients (p< 0.0001) was observed. A transient increase in the eosinophil count was observed in five patients (above 1000 cells/μL in 2 cases) after 3 months, without any clinical effect.Conclusion: Dupilumab improved all the explored clinical outcomes after 12 months, and the transient hypereosinophilia did not modify treatment response. These real-world data confirm the results reported in randomized controlled trials and provide an important opportunity to characterize the clinical impact of the treatment in a non-trial setting. Further real-world studies with a larger cohort of patients are needed to confirm these findings.Keywords: severe asthma, Named Patient Program, oral corticosteroids, real-world, dupilumab

Simple Summary Locally advanced vulvar cancer (LAVC) requires a multidisciplinary management. The aim of this paper is to conduct a review of all relevant studies regarding the role of radiotherapy in LAVC. Based on the available evidence, radiotherapy, with or without concurrent chemotherapy, has a relevant role in neoadjuvant, adjuvant or exclusive treatments. A multidisciplinary and multidimensional assessment can also be useful to identify the most suitable approach, in view of a better treatment personalization. Abstract Locally advanced vulvar cancer (LAVC) is a challenging disease, requiring multidisciplinary management. The aim of this review is to propose an integrated clinical approach including radiotherapy (RT) in the multidisciplinary management of LAVC to customize the treatment. A review of the literature was conducted on PubMed, Scopus, and Cochrane library to acquire all relevant studies on RT in LAVC. Based on the available evidence, RT, with or without concurrent chemotherapy, has a relevant role as adjuvant and exclusive treatment or in the neoadjuvant setting. However, multicentric prospective trials are needed to define the best treatment options based on tumor and patient characteristics. A multidisciplinary and multidimensional assessment can also be useful to identify the most suitable approach, considering patients’ age and comorbidities, in view of a better treatment personalization.

To the Editor Since the end of February 2020 Italy, first non- Asian Country, has reported an ever increasing number of COronaVIrus Disease 19 (COVID-19) patients, which has reached over 200,000 confirmed Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) infected subjects and resulted in more than 34000 deaths (data updated to June 19th, 20201).Patients with asthma are potentially more severely affected by by SARS-CoV-2 infection 2 and it is well established that respiratory viral infections are associated with severe adverse outcomes in patients with asthma, including increased risk of asthma exacerbation episodes 3. Nonetheless, according to the epidemiological studies published so far, chronic pulmonary diseases are not amongst the most common clinical conditions in COVID-19 patients4About 5-10% of entire asthma population, are severe asthmatics5 and one would expect increased vulnerability to SARS-CoV-2 infection, but no data is so fare available ti confirm this hypothesis.We investigated the incidence of COVID-19, describing its clinical course, in the population of the Severe Asthma Network in Italy (SANI), one of the largest registry for severe asthma worldwide6, and in an additional Center (Azienda Ospedaliero Univeristaria di Ferrara, Ferrara, Italy). All centers, have been contacted and inquired to report confirmed (i.e. patients with positive test result for the virus SARS-CoV-2 from analysis of nasopharyngeal or oropharyngeal swab specimens) or highly suspect cases of COVID-19 (i.e. patients with symptoms, laboratory findings and lung imaging typical of COVID-19 but without access to nasopharyngeal or oropharyngeal swab specimens because of clinical contingencies/emergency) among their cohorts of severe asthma. Demographic and clinical data of the entire cohort of severe asthmatics enrolled in the study and all reported cases of confirmed or suspect cases of COVID-19, have been obtained from the registry platform and collected from the additional Center. Additional data about COVID-19 symptoms, treatment and clinical course have been collected for all cases reported.Ethical issues and statistical analysis are reported in the online supplementary material.Twenty-six (1.73%) out of 1504 severe asthmatics had confirmed (11 out of 26) or highly suspect COVID-19 (15 out 26); eighteen (69.2%) were females and mean age was 56.2 ± 10 years. The geographical distribution of COVID-19 cases is presented in Figure 1.Nine (34.6%) infected patients experienced worsening of asthma during the COVID-19 symptomatic period; four of them needed a short course of oral corticosteroids for controlling asthma exacerbation symptoms.The most frequent COVID-19 symptoms reported were fever (100% of patients), malaise (84.6%), cough (80.8%), dyspnea (80.8%), headache (42.3%) and loss of smell (42.3%). Four patients (15.3%) have been hospitalized, one of which in intensive care unit; among hospitalized patients, two (7.7%) died for COVID-19 interstitial pneumonia. No deaths have been reported among the non-hospitalized patients.Severe asthmatics affected by COVID-19, had a significantly higher prevalence of non-insulin-dependent diabetes mellitus (NIDDM) compared to non-infected severe asthma patients (15.4% vs 3.8%, p=0.002; odds ratio: 4.7). No difference was found in other comorbidities (including rhinitis, chronic rhinosinusitis with or without nasal polyps, bronchiectasis, obesity, gastroesophageal reflux, arterial hypertension, cardiovascular diseases).Twenty-one patients with COVID-19 were on biological treatments: 15 (71%) were on anti-IL-5 or anti-IL5R agents (Mepolizumab n= 13; Benralizumab n=2 - counting for the 2.9% of all severe asthmatics treated with anti-IL5 in our study population) and 6 (29%) were on anti IgE (Omalizumab - 1.3% of all severe asthmatics treated with omalizumab in our study population).Table I summarizes demographic and clinical characteristics of the 26 COVID-19 patients.In conclusion, in our large cohort of severe asthmatics, COVID-19 was infrequent, not supporting the concept of asthma as a particularly susceptible condition to SARS-COV2 infection 2. This is in line with the first published large epidemiological data on COVID-19 patients, in which asthma is under-reported as comorbidity4. The COVID-19 related mortality rate in our cohort of patients was 7.7%, lower than the COVID-19 mortality rate in the general population (14.5% in Italy 1). These findings suggest that severe asthmatics are not at high risk of the SARS-CoV-2 infection and of severe forms of COVID-19. There are potentially different reasons for this. Self-containment is the first, because of the awareness of virus infections acting as a trigger for exacerbations, and therefore they could have acted with greater caution, scrupulously respecting social distancing, lockdown and hygiene rules of prevention, and being more careful in regularly taking asthma medications.Another possible explanation stands in the intrinsic features of type-2 inflammation, that characterizes a great proportion of severe asthmatics. Respiratory allergies and controlled allergen exposures are associated with significant reduction in angiotensin-converting enzyme 2 (ACE2) expression 7, the cellular receptor for SARS-CoV-2. Interestingly, ACE2 and Transmembrane Serine Protease 2 (TMPRSS2) (another protein mediating SARS-CoV-2 cell entry) have been found highly expressed in asthmatics with concomitant NIDDM8, the only comorbidity that was more frequent reported in our COVID-19 severe asthmatics.The third possible explanation refers to the possibility that inhaled corticosteroids (ICS) might prevent or mitigate the development of Coronaviruses infections. By definition, patients with severe asthma are treated with high doses of ICS 5 and this may have had a protective effect for SARS-CoV-2 infection.Noteworthy, among the patients of our case-series of severe asthmatics with COVID-19, the proportion of those treated anti-IL5 biologics was higher (71%) compared to the number of patients treated with anti-IgE (29%). Although the number of cases is too small to draw any conclusion, it is tempting to speculate that different biological treatments can have specific and different impact on antiviral immune response. In addition we may speculate of the consequence of blood eosinophils reduction: eosinopenia has been reported in 52-90% of COVID-19 patients worldwide and it has been suggested as a risk factor for more severe COVID-19 9.In conclusion, in our large cohort of severe asthmatics only a small minority experienced symptoms consistent with COVID-19, and these patients had peculiar clinical features including high prevalence of NIDDM as comorbidity. Further real-life registry-based studies are needed to confirm our findings and to extend the evidence that severe asthmatics are at low risk of developing COVID-19.

Atherosclerotic plaque instability and rupture in patients with asymptomatic carotid artery stenosis (ACAS) is a leading cause of major adverse cardiac events (MACE). This could be mainly evidenced in patients with pre-diabetes. Indeed, the altered glucose homeostasis and insulin resistance could cause over-inflammation of atherosclerotic plaque, favoring its conversion to unstable phenotype with rupture and MACE. Notably, metformin therapy reducing the metabolic distress and the inflammatory burden could reduce MACE in ACAS patients with pre-diabetes. In this setting, the microRNAs (miRs) could be used as molecular biomarkers of atherosclerosis progression, plaque rupture, and worse prognosis in normoglycemics (NG) versus pre-diabetics metformin users (PDMU) versus pre-diabetics non-metformin users (PDNMU). However, our study aimed to investigate a wide miRNA panel in peripheral blood exosomes from patients with ACAS divided in NG versus PDMU versus PDNMU, and to associate the circulating miRNA expression profiles with MACE at 2 years of follow-up after endarterectomy. The study included 234 patients with ACAS divided into NG (n = 125), PDNMU (n = 73), and PDMU (n = 36). The miRs’ expression profiles of circulating exosomes were determined at baseline and at 2 years of follow-up by Affymetrix microarrays from the patients’ plasma samples from any study cohort. Then we collected and analyzed MACE at 2 years of follow-up in NG versus PDMU versus PDNMU. Prediabetics versus NG had over-inflammation (p &lt, 0.05) and over expressed miR-24 and miR-27 at baseline. At 2 years of follow-up, PDNMU versus NG, PDMU versus NG, and PDNMU versus PDMU over-expressed inflammatory markers and miR-24, miR-27, miR-100, miR-126, and miR-133 (p &lt, 0.05). Finally, at the end of follow-up, we observed a significant difference about MACE comparing PDNMU versus NG (n = 27 (36.9%) versus n = 8 (6.4%), p &lt, 0.05), PDNMU versus PDMU (n = 27 (36.9%) versus n = 6 (16.6%), 0.05), and PDMU versus NG (n = 6 (16.6%) versus n = 8 (6.4%), 0.05). Admission glucose values (HR (hazard ratio) 1.020, CI (confidence of interval) 95% (1.001–1.038), p = 0.029), atheromatous carotid plaque (HR 5.373, CI 95% (1.251–11.079), p = 0.024), and miR-24 (HR 3.842, CI 95% (1.768–19.222), p = 0.011) predicted MACE at 2 years of follow-up. Specific circulating miRs could be over-expressed in pre-diabetics and specifically in PDNMU versus PDMU after endarterectomy. MiR24, hyperglycemia, and atheromatous plaque could predict MACE at 2 years of follow-up.

Summary Background The EU-supported ATHENA project stems from a previous study suggesting that moderate wine consumption reduced the side-effects of radiotherapy (RT) in breast cancer patients, an effect possibly due to non-alcoholic anthocyanin fractions of wine. Objective To evaluate the role of anthocyanins on RT skin side effects in breast cancer patients. Methods Randomized, controlled, double-blind clinical trial. Patients were assigned to an intensity modulated radiation therapy (IMRT) either for three or five weeks, then randomized to receive three times a day a water-soluble anthocyanin (125 mg)-rich extract of corn cob or a placebo. Supplementation started one week before till the end of RT. Skin characteristics were detected by a standardized, non-invasive Cutometer® dual-MPA580, providing quantitative indices of skin maximal distensibility (R0), elasticity (R2, R5, R7) and viscoelasticity (R6); a Mexameter® MX18 probe evaluated the skin erythema (Er) and melanin (M). Measures were performed before (T0), at the end of RT and of supplementation (T1), and 1, 6 and 12 months after RT (T2-T4). Acute and late skin toxicity were scored according to the RTOG/EORTG scale. Selected biomarkers were measured at T0 and T1. Results 193 patients previously assigned to 3- or 5-week RT schedules were randomized to either anthocyanin (97) or placebo (96) supplementation. RT induced changes in skin parameters: R0, R2, R5 and R7 decreased, while R6 increased; the changes in R0 and R6 continued in the same direction up to one year, while the others recovered towards basal values; Er and M peaked at T1 and T2, respectively, and returned to basal values at T4. Comparable skin changes were apparent in anthocyanin and placebo groups. A moderate RT-induced increase in total and HDL cholesterol and triglycerides was prevented by anthocyanins. Conclusions Anthocyanin supplementation did not prevent RT-induced local skin toxicity. The supplementation was well tolerated and safe.

Objective: The aim of our systematic review was to assess the role of interventional radiotherapy (IRT, brachytherapy) in the management of primary and/or recurrent vulvar carcinoma. Evidence acquisition: A systematic research using PubMed, Scopus and Cochrane library was performed. ClinicalTrials.gov was searched for ongoing or recently completed trials, and PROSPERO was searched for ongoing or recently completed systematic reviews. Only full-text English-language articles related to IRT for treatment of primary or recurrent VC were identified and reviewed. Conference paper, survey, letter, editorial, book chapter and review were excluded. Time restriction (1990–2018) as concerns the years of the publication was considered. Evidence synthesis: Primary disease: the median 5-year LC was 43.5% (range 19–68%); the median 5-year DFS was 44.5% (range 44–81%); the median 5-year OS was 50.5% (range 27–85%). Recurrent disease: the median 5-year DFS was 64% (range 56–72%) and the median 5-year OS was 45% (range 33%-57%). Acute ≥ grade 2 toxicity was reported in three patients (1.6%). The severe late toxicity rates (grade 3–4) ranged from 0% to 14.3% (median 7.7%). Conclusion: IRT as part of primary treatment for primary and/or recurrent vulvar cancer is associated with promising clinical outcomes.

Background Smell and taste dysfunctions (STDs) are symptoms associated with COVID-19 syndrome, even if their incidence is still uncertain and variable. Aims In this study, the effects of SARS-CoV-2 infection on chemosensory function have been investigated using both a self-reporting questionnaire on smell and flavor perception, and a simplified flavor test. Methods A total of 111 subjects (19 hospitalized [HOS] and 37 home-isolated [HI] COVID-19 patients, and 55 healthy controls [CTRL]) were enrolled in the study. They received a self-evaluation questionnaire and a self-administered flavor test kit. The flavor test used consists in the self-administration of four solutions with a pure olfactory stimulus (coffee), a mixed olfactory-trigeminal stimulus (peppermint), and a complex chemical mixture (banana). Results After SARS-CoV-2 infection, HOS and HI patients reported similar prevalence of STDs, with a significant reduction of both smell and flavor self-estimated perception. The aromas of the flavor test were recognized by HI and HOS COVID-19 patients similarly to CTRL; however, the intensity of the perceived aromas was significantly lower in patients compared to controls. Conclusion Data reported here suggests that a chemosensory impairment is present after SARS-CoV-2 infection, and the modified “flavor test” could be a novel self-administering objective screening test to assess STDs in COVID-19 patients. Clinical trial registration no. NCT04840966; April 12, 2021, retrospectively registered

Background Mid- and long-term sequelae of COVID-19 on cardiorespiratory fitness are unknown. Aim of the study was to assess the mid-term impact of mild-moderate COVID-19 on cardiorespiratory fitness evaluated by cardiopulmonary exercise testing (CPET) in elite athletes. Methods 13 elite cross-country skiers with previous mild-moderate COVID-19 symptoms underwent CPET before resuming seasonal training (COVID athletes). 13 elite detrained cross-country skiers, matched for principal confounding factors, were taken as controls (control group). Resting peripheral oxygen saturation, pulmonary function test, echocardiography, bioelectrical impedance analysis and CPET (modified XELG2, Woodway, USA) were performed in all participants. Results Median recovery time in COVID athletes was 34 days (IQR 33-38 days). COVID athletes reached earlier the onset of the aerobic threshold (4'48" vs 6'28", R2=0.15, F=4.37, p Conclusions Elite cross-country athletes, previously affected by mild-moderate COVID-19, reached earlier the aerobic threshold than controls, whereas the remaining CPET parameters did not differ between groups. Such changes were not associated with any detectable difference in resting pulmonary and cardiac examination. Subjects affected by mild-moderate COVID-19 may require a longer time course of re-adaptation to aerobic exercise.

In February 2020, a 71-year-old woman discovered a left breast lump and underwent surgery revealing the presence of invasive breast cancer (pT2N1a). She also suffered in the past from a lung cancer for which underwent complete surgical removal and from a severe valvular disease. Chemotherapy or radiotherapy were excluded due to the patient's comorbidities at the beginning, and prescribed only hormonal therapy. In light of the radiotherapy indication albeit the several comorbidities, a dosimetric study was proposed for exploiting the radiation treatment feasibility by all cutting-edge technologies available in our arsenal. Chest wall as well supraclavicular nodes were contoured according to RTOG guidelines. Active Breathing Coordinator device to treat the patient by moderate deep inspiration breath hold technique and the AlignRT® surface imaging system were used. Four different plans were compared: a plan mixing three dimensional and intensity modulated radiotherapy (HMRT plan), a plan mixing three dimensional and volumetric arc technique (HVMAT plan), a fully manual VMAT plan and a fully automated VMAT plan (AP-VMAT). Stringent objectives were applied to spare healthy organs. AP-VMAT alone fulfilled the objective of 4 Gy heart mean dose, lowered below 1% the NTCP estimates for lung pneumonitis and was able to reduce heart and homolateral lung doses, below 5 Gy. No differences between techniques were found in term of contralateral breast mean dose. Therefore, the fully automated VMAT plan was proposed for therapy. Patient underwent the radiotherapy treatment on chest wall and lymph-nodal area with 2 Gy per fraction up to a total dose of 50 Gy, without the appearance of severe acute toxicity. Six months later, no adverse events e.g. skin fibrosis, or heart failure, or disease recurrence have been reported. This case highlights how the new technologies can potentially change the therapeutic approach. Summary: We report a challenging case of left post mastectomy radiation treatment patient affected by severe preexisting comorbidities treated in our radiotherapy Unit by cutting edge technologies, showing how technological advances could allow a radiotherapy treatment in patients who would not be considered eligible in the past.