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The efficacy and safety of sublingual immunotherapy (SLIT) are currently supported by clinical trials, metaanalysis and post-marketing surveys. Practice parameters for clinical use of SLIT are proposed here by a panel of Italian specialists, with reference to evidence based criteria. Indications to SLIT include allergic rhinoconjunctivitis, asthma, and isolated conjunctivitis (strength of recommendation: grade A). As to severity of the disease, SLIT is indicated in moderate/severe intermittent rhinitis, persistent rhinitis and mild to moderate asthma (grade D). SLIT may be safely prescribed also in children aged three to five years (grade B), and its use in subjects aged more than 60 years is not prevented when the indications and contraindication are ascertained (grade D). The choice of the allergen to be employed for SLIT should be made in accordance with the combination of clinical history and results of skin prick tests (grade D). Polysensitisation, i.e. the occurrence of multiple positive response does not exclude SLIT, which may be done with the clinically most important allergens (grade D). As to practical administration, co-seasonal, pre co-seasonal, and continuous schedules are available, being the latter recommended for perennial allergens or for pollens with particularly prolonged pollination, such as Parietaria (grade D). For pollens with relatively short pollination, such as grasses and trees (cypress, birch, alder, hazelnut, olive) the pre coseasonal and perennial schedules are preferred (grade C). The build-up phases suggested by manufacturers can be safely used (grade A), but they can be modified according to the patient’s tolerance (grade C). A duration of SLIT of 3-5 years is recommended to ensure a long-lasting clinical effect after the treatment has been terminated (grade C).

Surgically addressing tumors poses a challenge, requiring a tailored, multidisciplinary approach for each patient based on the unique aspects of their case. Innovative therapeutic regimens combined to reliable reconstructive methods can contribute to an extended patient's life expectancy. This study presents a detailed comparative investigation of near-infrared therapy protocols, examining the impact of non-fractionated and fractionated irradiation regimens on cancer treatment. The therapy is based on the implantation of graphene oxide/poly(lactic-co-glycolic acid) three-dimensional printed scaffolds, exploring their versatile applications in oncology by the examination of pro-inflammatory cytokine secretion, immune response, and in vitro and in vivo tumor therapy. The investigation into cell death patterns (apoptosis vs necrosis) underlines the pivotal role of protocol selection underscores the critical influence of treatment duration on cell fate, establishing a crucial parameter in therapeutic decision-making. In vivo experiments corroborated the profound impact of protocol selection on tumor response. The fractionated regimen emerged as the standout performer, achieving a substantial reduction in tumor size over time, surpassing the efficacy of the non-fractionated approach. Additionally, the fractionated regimen exhibited efficacy also in targeting tumors in proximity but not in direct contact to the scaffolds. Our results address a critical gap in current research, highlighting the absence of a standardized protocol for optimizing the outcome of photodynamic therapy. The findings underscore the importance of personalized treatment strategies in achieving optimal therapeutic efficacy for precision cancer therapy.

We report a case of synchronous bilateral orbital metastases from primary lobular breast cancer with the radiographic imaging features of a diffuse orbital soft tissue inflammatory process. A 77-year-old lady with a history of lobular breast cancer and bilateral quadrantectomy 15 years earlier was referred to our Ocular Oncology Unit. She complained about double vision and ocular pain. Through an ophthalmological examination, she presented significant bilateral proptosis and complete ophthalmoplegia. Magnetic resonance imaging showed a diffuse soft tissue infiltration of both orbits with mild T2w fat-sat hyperintensity and T1-isointensity relative to extra-ocular muscles and a diffuse involvement of both the intra- and extra-conal compartments. Significant enlargement of the extraocular muscles without sparing the muscle tendons and eyelids soft tissue swelling were also evident. Post-contrast images showed a diffuse and bilateral contrast enhancement of the involved tissues. Due to the inconclusive imaging findings, a bilateral orbital incisional biopsy was planned. The histopathological and immunohistochemical diagnosis was of lobular breast carcinoma and the patient underwent external beam radiotherapy with consistent clinical improvement. In conclusion, post-menopausal women presenting with a history of breast carcinoma and clinical and radiographic findings suggestive of acute bilateral orbital inflammatory disease should be biopsied to rule out metastatic disease even several years from the primary tumour.

The beneficial effects of vitamin D in humans are numerous and various, and include neuronal, immune and bone homeostasis, and regulation of cardiovascular function. Recent studies have related vitamin D levels to cancer cell proliferation, but meta-analyses on this subject have provided controversial results. This review deals with the antioxidant and anti-inflammatory function of Vitamin D in chronic diseases, focusing mainly on cancer, immune diseases, cardiomyopathies. Vitamin D contributes significantly to reducing pro-oxidant biomarkers, both systemic and in specific tissues, involved in the development, progression, and recurrence of cancer, chronic and cardiometabolic diseases. The overall picture provided by this work highlights the need for new randomised controlled trials on oral Vitamin D supplementation in patients affected by cancer, or neurological and cardiovascular disorders, with the purpose of lowering risk factors for relapse of these diseases and improving patients' quality of life.

Abstract Purpose The complexity of multimodal approaches in cancer management has lately led to the establishment of multidisciplinary tumor boards (MDTBs) to define targeted, patient-centered treatment strategies. However, few data are available regarding the application of this approach in Ocular Oncology. Hereby, the Authors analyze the implementation and outcomes of a trained MDTB in a tertiary ocular oncology referral center. Methods A retrospective descriptive analysis of MDTB meetings discussing patients with ocular and periocular cancers, over a 12-months period, was carried out. Data were grouped by main site involved, topics discussed and final clinical decisions therefore taken. Meetings were held by a constant ‘Core team’ or – when required – by a broader ‘Extended team’. Results During the observational period 86 cases were discussed. In 27 patients ocular surface tissues were involved (31%), in 25 patients orbital tissues (29%), in 22 patients eyelids (26%), and in 12 patients intraocular tissues (14%). In 13 cases (15%) naïve or referred new patients, in 34 cases (40%) imaging or histopathologic reports and in 39 cases (45%) treatment plans were discussed. Regarding final decisions, a treatment plan was scheduled in 47 cases (55%) and a diagnostic ascertainment was required in 27 patients (31%); locally advanced and/or systemic diseases were referred or teamed up with other specialists in 12 cases (14%). Conclusions Ocular Oncology multidisciplinary team, by sharing expertise of different specialists, ensures a comprehensive evaluation of patients improving the accuracy of diagnosis and staging upon which planning a proper treatment. Further studies are needed to assess if this approach may also improve the outcomes and prognosis of patients.

Abstract The HSV-1 tegument protein Us11 counteracts the antiviral defense mechanisms by precluding the host protein shutoff. Previous works demonstrated that Us11 prevents heat-and staurosporine-induced apoptosis and inhibits autophagy. Therefore, in the present study, we investigated the hypothesis that HSV-1, through Us11, could recruit caspase-8, a key enzyme regulating programmed cell death. We first show that HSV-1 promotes the accumulation of caspase-8-p18 active fragments in both semi permissive THP-1 cells and fully permissive HEp-2 cells to HSV-1 replication. Using a recombinant virus R3630 (ΔUs11/ΔUs12) and a plasmid encoding Us11-recombinant protein we have proven that Us11 promotes p18 accumulation, which does not trigger the apoptotic signaling. Additional, in an in vitro model, we demonstrated that Us11-recombinant protein induces caspase-8-p18 cleavage by physically interacting with the caspase-8 recombinant protein. Finally, we found that, during HSV-1 replication, activated-caspase-8 cleaves Atg3 protein to potentially block autophagy and support its replication.

A 40-year-old male patient presented with diffuse radiolucent lesions on the upper maxilla at the apex of the incisors, canines, premolars, and molars. Surgical excision of the lesions was performed, and the biopsy specimens were submitted for histological analysis: the lesions of the first quadrant were found to be a squamous odontogenic tumor, a rare benign neoplasm of odontogenic origin. The purpose of this article is to describe the clinical, radiographic and histological aspects of odontogenic squamous tumor.

Recensione di: A. Baldi, The Author in Criticism. Calvino's Authorial Image in Italy, the United States, and the United Kingdom, Fairleigh Dickinson University Press, 2020, p. 296, ISBN 9781683931911, € 114.55.

Pierluigi Paggiaro,1 Simona Barbaglia,2 Stefano Centanni,3,4 Davide Croce,5 Enrico Desideri,6 Saffi Giustini,7,8 Claudio Micheletto,9 Antonino Musarra,10 Nicola Scichilone,11 Ugo Trama,12 Maria Teresa Zedda,7,13 Giorgio Walter Canonica14 1Department of Surgery, Medicine, Molecular Biology, and Critical Care, University of Pisa, Pisa, Italy; 2Associazione Nazionale Pazienti “Respiriamo Insieme”, Padova, Italy; 3Department of Health Sciences, Università degli Studi di Milano, Milan, Italy; 4Respiratory Unit, ASST Santi Paolo e Carlo, Milan, Italy; 5Center for Health Economics, Social and Health Care Management, LIUC-Università Cattaneo, Castellanza, Italy; 6Fondazione Innovazione e Sicurezza in Sanità, Rome, Italy; 7Italian General Practitioners’ Association “SIMG”, Florence, Italy; 8Local Health Unit of Montale, Pistoia, Italy; 9Cardio-Thoracic Department, Respiratory Unit, Integrated University Hospital, Verona, Italy; 10Allergy Unit, National Healthcare System, Reggio Calabria, Italy; 11Biomedical Department of Internal and Specialist Medicine, University of Palermo, Palermo, Italy; 12Dirigente UOD 06 Politica del Farmaco e Dispositivi, Naples, Italy; 13General Practice, Cagliari, Italy; 14Personalized Medicine Asthma & Allergy Clinic, Humanitas University and Research Hospital-IRCCS, Milan, ItalyCorrespondence: Pierluigi PaggiaroDepartment of Surgery, Medicine, Molecular Biology and Critical Care, University of Pisa, Via Paradisa No. 2, Pisa, 56124, ItalyTel +39 050 995365Fax +39 050 580124Email pierluigi.paggiaro@unipi.itIntroduction: People with severe asthma (SA) often have poor disease control and quality of life, and are at high risk of exacerbations, lung function decline and asthma-related death. The present expert opinion article aimed to identify unmet needs in the management of SA in Italy, and propose possible solutions to address these needs.Methods: At five multidisciplinary events in Italy, attendees identified factors that interfered with the effective management of SA and suggested how these barriers could be overcome. A core group of 12 Italian experts (pulmonologists, general practitioners, allergists, payers and patients) identified the main issues and proposed possible solutions based on the results from the meetings and relevant articles from the literature.Results and Conclusions: We reviewed the gap between real-world practice and guidelines, oral corticosteroid overuse, SA-related mortality, and barriers to effective SA treatment. Common themes were lack of awareness about SA among both patients and clinicians, and lack of networking/information exchange between those involved in the treatment of SA. Participants agreed on the need to implement patient education and create multidisciplinary groups of specialists to improve SA management through multidisciplinary educational initiatives, meetings with local experts, development of a flow chart for referral/connection with local experts and specialized centers. Clinical instruments that might help specialists improve SA management included referral networks, integrated care pathways, phenotyping and treatment algorithms, exacerbation tracking, and examination of electronic medical records for patients with uncontrolled asthma. The following actions need to be implemented in Italy: i) maximize the use of advanced therapies, eg, biologics; ii) increase/improve education for physicians and patients; iii) improve multidisciplinary communication and care coordination; iv) introduce regional and local protocols for SA diagnosis and treatment; and v) change the structure of healthcare services to reduce specialist waiting times and facilitate access to biologic therapies.Keywords: biologic therapy, expert opinion, oral corticosteroids, severe asthma, unmet needs

Against a backdrop of limited research focusing on dark-side characteristics in alliances, the authors argue that Machiavellianism in an alliance influences strategies pertaining to gaining new knowledge and using power to achieve better performance effectiveness. They develop a model using theories-in-use procedures and drawing from both Machiavellian intelligence and achievement goal perspectives, which they test in a quasi-longitudinal study of 199 marketing alliances. The results suggest that Machiavellianism relates negatively to collaborative learning and positively to learning anxiety and use of power. The findings also indicate that collaborative learning enhances performance, whereas learning anxiety and use of power result in underperformance. Collaborative learning, learning anxiety, and use of power fully mediate Machiavellianism's impact on performance. Finally, Machiavellianism's relationships with collaborative learning and learning anxiety are moderated positively and negatively, respectively, by partners' collaborative history. This evidence provides managers with a more in-depth understanding about the nature, functioning, and performance relevance of Machiavellianism in alliance partnerships. [ABSTRACT FROM AUTHOR]

In the recent years, it was recognized that type-2 inflammation links many forms of nasal polyposis with severe asthma. Thus, some biological drugs developed for severe asthma appeared to exert an effect on nasal polyposis. So far, there are several trials supporting this concept; therefore, some monoclonal antibodies for severe asthma were assessed also in polyposis, with promising results. Since different specialists are involved in the management of nasal polyposis (eg, pulmonologists, ENT, allergists), it was felt that an educational and informative document was needed to better identify the indications of biologicals in nasal polyposis. We collected the main Italian Scientific Societies, and prepared (under the Allergic Rhinitis and its Impact on Asthma, ARIA) a document endorsed by all Societies, to provide a provisional statement for the future use of monoclonal antibodies as a medical treatment for polyposis. It is the first nationwide endorsed document on this aspect. The current pathogenic knowledge and the experimental evidence are herein reviewed, and some suggestions for a correct prescription and follow-up are provided.

The risks of overusing short-acting β 2 -agonists (SABA), including an increase in asthma-related deaths, are many and well known. The Global Initiative on Asthma (GINA) 2019 and 2020 updates recommend as-needed inhaled corticosteroid (ICS)/formoterol as the preferred rescue medication in mild asthma as monotherapy and also in moderate to severe asthma when the maintenance and reliever therapy (MART) strategy is used. Using SABA for symptom relief, however, was the standard of treatment for many years, and consequently this practice persists, particularly in patients not taking ICS regularly. Here, we examine the rationale for this shift from a long-standing recommendation for as-needed SABA treatment to the use of as-needed ICS/formoterol and consider clinical evidence on strategies for asthma treatment and patient management.