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Abstract Recent literature has shown that triple therapy is more effective than dual therapy for individuals with uncontrolled asthma. However, the comparative efficacy between different triple therapies remains unclear. The objective of this study was to determine the comparative efficacy of extra-fine single-inhaler medium-dose (MD) or high-dose (HD) of beclometasone/formoterol/glycopyrronium bromide (BDP/FOR/GLY) compared to other triple therapies in patients whose asthma remains uncontrolled with MD or HD inhaled corticosteroids and long-acting β2-agonists. A systematic literature review identified randomized control trials on adult patients with uncontrolled asthma. Two separate networks were constructed according to patients’ previous inhaled-corticosteroid dosage. Network meta-analyses evaluated severe and moderate-to-severe exacerbations, pre-dose forced expiratory volume, and asthma control questionnaire responses at 52 (± 3) weeks. Among single-inhaler triple therapies, MD BDP/FOR/GLY significantly reduced the risk of severe exacerbations (RR [95% CrI] compared to MD fluticasone/umeclidinium/vilanterol: 0.65 [0.49, 0.89]), while HD BDP/FOR/GLY demonstrated an improved trend in reducing severe and moderate-to-severe exacerbations versus HD indacaterol acetate/glycopyrronium bromide/mometasone, fluticasone/umeclidinium/vilanterol, and salmeterol/fluticasone + tiotropium. HD BDP/FOR/GLY and HD BDP/FOR + tiotropium did not differ significantly. Compared to relevant single-inhaler triple therapies, MD and HD BDP/FOR/GLY are associated with a significant benefit or trend for improvement in terms of reducing the rate of severe and moderate-to-severe exacerbations.

Eleonora Volpato,1,2,* Vincenzo Pennisi,3,* Alfio Pennisi,3 Alessio Piraino,4 Paolo I Banfi,2 Salvatore D’Antonio,5 Stefano Centanni,6 Luca Cavalieri,7 Mattia Ramaccia,7 Filomena Bugliaro,8 Simona Barbaglia,9 Antonietta Cappuccio,10 Roberta Termini,10 Maria Giulia Marini10 1Dipartimento di Psicologia, Università Cattolica del Sacro Cuore, Milan, Italy; 2IRCCS Fondazione Don Carlo Gnocchi, Milan, Italy; 3Centro di riabilitazione Mons. Giosuè Calaciura, Biancavilla, Catania, Italy; 4Chiesi Farmaceutici S.p.A, Parma, Italy; 5Associazione Pazienti BPCO e altre patologie respiratorie, Rome, Italy; 6ASST- Santi Paolo e Carlo - Università degli Studi di Milano, Milan, Italy; 7Chiesi Italia S.p.A, Parma, Italy; 8Federasma e Allergie OdV - Federazione Italiana Pazienti, Prato, Italy; 9Associazione Nazionale Pazienti RESPIRIAMO INSIEME-APS, Padua, Italy; 10Healthcare Area, ISTUD, Milan, Italy*These authors contributed equally to this workCorrespondence: Eleonora Volpato, Department of Psychology, Università Cattolica del Sacro Cuore, Via Nirone, 15, Milan, CAP 20123, Italy, Tel +393293872692, Email eleonora.volpato@unicatt.itBackground: Despite the effectiveness of inhalation therapy, uncontrolled or severe asthma remains prevalent challenges in respiratory care Narrative Medicine (NM) offers a linguistic approach to comprehending illness experiences, thereby providing a framework for advancing healthcare.Aim: The primary aim of this study was to gather narratives from individuals grappling with severe or uncontrolled asthma and their Healthcare Professionals (HCPs), in order to explore the intricate interplay among quality of care, quality of life, psychological and social determinants, and adherence patterns.Methods: A cross-sectional NM study was conducted in Italy from February to December 2023, encompassing 135 patients with uncontrolled or severe asthma (54.7% male; mean age: 56.7 years) and 47 HCPs (64.9% male; mean age: 54.3 years). A mixed-method approach was adopted to scrutinize themes, language nuances, emotional expressions, and narrative classifications.Results: Patients with uncontrolled or severe asthma reported an average illness duration of 4.46 years, with exacerbations occurring over the past 20.9 months. Pulmonologists (83% of HCPs) played a predominant role in diagnosing and treating the disease in 96.1% of patients. Additionally, participants with severe asthma reported higher healthcare needs. The most reported emotions were fatigue (25.96%) and a sense of suffocation (11.53%). Upon commencing treatment, while experiencing physical improvement, patients predominantly expressed feelings of “submission/dependence” on medication (28%), followed by “fear” (21%) and “serenity/joy” (21%). HCPs, primarily pulmonologists (83%), emphasized the importance of raising awareness among specialists and General Practitioners (GPs), disseminating information, optimizing prescriptions, implementing phenotyping, tailoring therapy, and considering paediatric needs.Conclusion: These findings contribute to a deeper understanding of patient perspectives, facilitate personalized interventions, and underscore the factors influencing therapeutic adherence in uncontrolled or severe asthma.Keywords: uncontrolled asthma, severe asthma, adherence, quality of life, narrative medicine

Urticaria is a mast cell-dependent skin disease characterized by the presence of hives, angioedema, or both in the absence of systemic symptoms. It may be acute, or chronic. (1) Acute urticaria (AU) is common in children, affecting boys and girls equally. Chronic urticaria (CU) affects adult women more (3). AU affects more than 20% of the population and CU 0.1 and 1.5%. There are many pathologies that do not meet the clinical criteria for urticaria, despite being called urticarias, which leads to erroneous diagnoses and inconclusive epidemiology. This review attempts to clarify when we should consider urticaria as such and what are the diagnoses that can be considered urticaria without being so.

Objetivo: Elaborar un algoritmo de tratamiento en pacientes con alergia a la penicilina. Métodos: Estudio retrospectivo, efectuado en pacientes adultos con alergia a la penicilina, que permanecieran en el grupo 3 o 4 de la clasificación establecida, y asistieron a consulta ambulatoria en el Departamento de Neumología y Alergia del Hospital Central del Instituto de Previsión Social, entre enero de 2021 y diciembre de 2022. A cada paciente se realizó una prueba de provocación con amoxicilina, previo consentimiento informado. Resultados: Se registraron 60 pacientes, a quienes se logró eliminar el rotulo de alergia a la penicilina y a quienes se corrigió su historia clínica, con beneficios financieros para el paciente y el servicio de salud de Paraguay. Conclusión: Las etiquetas de alergia a la penicilina pueden suponer una prescripción irracional de antibióticos, estancia hospitalaria prolongada y mayor necesidad de consulta. La estratificación del riesgo, solo por características históricas, es capaz de identificar de manera segura a los pacientes ideales para las pruebas de desafío directo. Este estudio demuestra la viabilidad del primer programa de desetiquetado de penicilina aplicable en un entorno ambulatorio, que puede realizarse incluso fuera de los servicios de alergia de los hospitales. Palabras clave: Alergia; Alergia a la penicilina; Amoxicilina; Paraguay; Estratificación de riesgo; Viabilidad; Prescripción de antibióticos.

Hydrogen is assuming a pivotal role in the energy sector, intending to lead the decarbonization and overcome the fossil fuel use. In evaluating its key applications, the role of hydrogen in mobility stands out. It could transform one of the most polluting sectors, drastically reducing emissions without changing the drivers’ needs. In this perspective, the focus should be placed on hydrogen refueling infrastructures, which are a key factor, along with fuel cell vehicles, for extending the hydrogen chain in the mobility sector. Given this, the study analyzes the hydrogen refueling station performance, investigating the hydrogen flow features, and estimating the evolution of pressure and temperature within the vehicle tank. An ad-hoc model for hydrogen performance analysis is used by customizing its main blocks. In addition, the main safety aspects of the hydrogen refueling stations are evaluated. The behavior of each component of the refueling infrastructure, such as hydrogen storage tanks, compressors, and cooling systems, is examined and introduced in the model, characterizing the whole system. The model is then validated by comparing its performance with experimental data. The results show the pressure, temperature, and mass flow rate between the dispenser and the vehicle tank. These findings could help boost hydrogen use in mobility since crucial aspects are investigated and important information is provided for promising integrated systems, based on the interconnection between infrastructures and vehicles.

The zooxanthellate jellyfish Cassiopea andromeda (Forsskål, 1775), a Lessepsian species increasingly common in the western and central Mediterranean Sea, was investigated here to assess its potential as a source of bioactive compounds from medusa specimens both collected in the wild (the harbor of Palermo, NW Sicily) and reared under laboratory-controlled conditions. A standardized extraction protocol was used to analyze the biochemical composition of the two sampled populations in terms of protein, lipid, and pigment contents, as well as for their relative concentrations of dinoflagellate symbionts. The total extracts and their fractions were also biochemically characterized and analyzed for their in vitro antioxidant activity to quantify differences in functional compounds between wild and reared jellyfish. The two populations were similar in terms of extract yield, but with substantial differences in biomass, the number of zooxanthellae, protein and lipid contents, and fatty acid composition. The hydroalcoholic extracts obtained from jellyfish grown under controlled conditions showed greater antioxidant activity due to the presence of a higher content of bioactive compounds compared to wild jellyfish. This study could be the basis for considering the sustainable breeding of this holobiont or other similar organisms as a source of valuable compounds that can be used in the food, nutraceutical, or pharmaceutical sectors.

Rising concerns about climate change, the need to innovate and connect diverse energy sectors, and the challenge of energy dependency are boosting global interest in hydrogen-based technologies [...]

The various forms of anthropogenic pollution are regarded as a serious threat to marine coastal areas. The overproduction and mismanagement of petroleum derivatives, such as tar and plastics, have resulted in a significant correlation between these two pollutants. The aggregation of tar, microplastics (MPs), and natural materials can create plastitar blocks, which are common in coastal areas. These raise concern about the undeniable negative impact on the marine ecosystem and the associated biota, and serve as a recognizable and understandable indication of environmental decline. Here, the composition of the 11 plastitar blocks collected on the Ionian side of the Apulia region (Italy) was characterized both in tar and plastics using nuclear magnetic resonance (NMR) spectroscopy and Fourier transform infrared (FTIR) spectroscopy, respectively. Of the 250 particles extracted from the tar, 208 were identified as plastics, predominantly Polyethylene. The majority of these were in the form of pellets (90%), with fragments accounting for 5% and films and filaments representing the remaining 5%. This study provides new data that can be used to enhance the understanding of the distribution and baseline information about this novel form of pollution in Italian waters.

IntroductionAlthough hereditary male neoplasms are quite rare, individuals harbouring germline BRCA1/2 pathogenic variants (PVs) may have a risk of developing tumours associated with Hereditary Breast and Ovarian Cancer (HBOC) syndrome, including male breast (MBC), prostate (PCa) and pancreatic (PC) cancers, and melanoma. Women and men showed a comparable genetic architecture of cancer susceptibility, but there are some gender-specific features. Since little is known about cancer genetic susceptibility in male population, our study was aimed at investigating the frequency of BRCA1/2 PVs in men with HBOC syndrome-associated tumors, in order to understand whether differences in gender may reflect in the prevalence and spectrum of germline alterations.Patients and methodsWe retrospectively collected and analysed clinical information of 352 HBOC-associated male cancer patients genetically tested for germline BRCA1/2 PVs by Next-Generation Sequencing analysis, enrolled, from February 2018 to January 2024, at the “Regional Center for the prevention, diagnosis and treatment of rare and heredo-familial tumors of adults” of the University-Hospital Policlinico “P. Giaccone” of Palermo (Italy).ResultsOur investigation revealed that 7.4% of patients was carrier of a germline BRCA PV, with an almost total prevalence of BRCA2 alterations. In particular, 65.4% of BRCA-positive patients developed MBC, 19.2% had PC, 11.6% developed PCa, and only 3.8% had melanoma. Specifically, MBC individuals showed a BRCA-associated genetic predisposition in 17% of cases, whereas patients with PCa or PC exhibited a lower frequency of BRCA2 PVs, taking into account the current national criteria for access to germline genetic testing.DiscussionOur study showed a high heterogeneity in prevalence of germline BRCA2 PVs among men which could reflect a potential gender-specific genetic heterogeneity. Therefore, BRCA-associated male tumours could be due to BRCA2 PVs different from those usually detected in women. In the event that it is demonstrated, in future, that male cancers are genetically distinct entities from those female this could improve personalized risk evaluation and guide therapeutic choices for patients of both sexes, in order to obtain a gender equality in cancer care.

Drylands represent the main earth biome, providing ecosytemic services to a large number of people. Along these environments, woodlands are often dominated by multi-stemmed trees, which are exploited by local inhabitants to obtain forest products for their livelihood. In central-west Argentina, Neltuma flexuosa (algarrobo) woodlands are distributed across different landform units, varying in topographical and soil characteristics. This research aimed to reconstruct stem-growth time until harvestable diameter was achieved, and biological rotation age according to topo-edaphic variability in three algarrobo forests using dendrochronological methods. Results indicated that landform heterogeneity modulated species radial growth, influencing stem increments and cutting cycle period. In this sense, a decreasing trend in tree productivity emerged along a loamy-to-sandy textured soil gradient. These findings provide useful novel information for N. flexuosa forest management, suggesting the need to account for spatial landform/soil heterogeneity when examining desert forest dynamics. Highlights: • Neltuma flexuosa provides forest product (poles) to Central Monte Desert (Argentina) local inhabitants. • N. flexuosa wood productivity was assessed for different topo-edaphic landforms. • Cutting cycle was reached at younger ages at river and paleo-river landforms. • Wood extraction must consider landscape heterogeneity.

Luca Richeldi,1 Pietro Schino,2 Elena Bargagli,3 Alberto Ricci,4 Alberto Rocca,5 Francesca Marchesani,6 Alfio Pennisi,7 Gianna Camiciottoli,8,9 Maria D’Amato,10 Francesco Macagno,1 Ulrica Scaffidi Argentina,11 Eleonora Ingrassia,11 Alessio Piraino11 1Division of Pulmonary Medicine, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy; 2Miulli Hospital, Acquaviva Delle Fonti, Bari, Italy; 3Respiratory Diseases Unit, Department of Medical and Surgical Sciences, Neuro Sciences, Siena University Hospital, Siena, Italy; 4Department of Medical-Surgical Sciences and Translational Medicine, Via di Grottarossa 1035, Sapienza University of Rome, Rome, Italy; 5Department of Respiratory Medicine, Bellaria Hospital, Bologna, Italy; 6Division of Pneumology, Ospedale di Macerata, Macerata, Italy; 7Department of Respiratory Medicine, Hospital Clinic “Casa di Cura Riabilitativa Calaciura”, Catania, Italy; 8Department of Biomedical, Experimental and Clinical Sciences, University of Florence, Florence, Italy; 9Department of Cardiothoracovascular, Careggi University Hospital, Firenze, Italy; 10UOSD Malattie Respiratorie ”Federico II”, Ospedale Monaldi, Napoli, 80131, Italy; 11Medical Affairs, Chiesi Italia S.p.A, Parma, ItalyCorrespondence: Ulrica Scaffidi Argentina, Chiesi Italia S.P.A, Via Giacomo Chiesi 1, Parma, 43122, Italy, Tel +39 0521 1689690 ; +39 346 82 61 074, Email u.scaffidiargentina@chiesi.comPurpose: The TRITRIAL study assessed the effects of beclometasone dipropionate/formoterol fumarate/glycopyrronium (BDP/FF/G) fixed combination in patients with chronic obstructive pulmonary disease (COPD) in a real-world setting, focusing on patient’s experience and perspective through the use of patients reported outcomes.Patients and Methods: TRITRIAL was a multicenter, prospective, observational study conducted on patients with moderate-severe COPD treated with BDP/FF/G fixed therapy for 12 months. The main objective was to evaluate the impact of BDP/FF/G on health status through the COPD Assessment Test (CAT) score. Additional assessments included adherence and satisfaction, measured by the TAI-10/12 questionnaire and a specifically designed eight-item questionnaire, quality of life through the EQ-5D-5L test, sleep quality through the COPD and Asthma Sleep Impact Scale (CASIS), as well as safety and disease-related outcomes.Results: Data from 655 patients were analyzed in the study. The mean total CAT score significantly improved (from 22.8 at baseline to 18.1 at 6 months and 16.5 at 12 months; p < 0.0001), as well as all the eight CAT sub-items, which decreased on average by 0.5– 0.9 points during the study. Adherence and usability of the inhaler also improved during the study, with a decrease in poor compliance (from 30.1% to 18.3%) and an increase in good compliance (from 51.8% to 58.3%) according to the TAI score. Patients also benefited from significantly improved quality of life (EQ Index from 0.70 to 0.80; EQ-5D VAS score from 55.1 to 63.1) and sleep quality (CASIS score from 41.1 to 31.8). Finally, patients reported a significant reduction in exacerbation during the past 12 months.Conclusion: TRITRIAL showed that the BDP/FF/G fixed combination is effective and safe in patients with moderate-severe COPD and poorly controlled disease, improving patients’ HRQoL, sleep quality, adherence and inhaler usability and reducing COPD symptoms and the risk of exacerbation in a real-life setting.Keywords: beclometasone/formoterol/glycopyrronium, chronic obstructive pulmonary disease, real-world, fixed triple therapy, adherence, patient-reported outcomes

IntroductionPeritoneal dialysis (PD)-related peritonitis is one of the leading causes of discontinuation of PD and is considered a critically important outcome for patients on PD. However, there is no universally accepted method of measuring this outcome in clinical trials.MethodsWe convened an online consensus workshop to establish a core outcome measure for PD-related peritonitis in clinical trials.ResultsA total of 53 participants, including 18 patients and caregivers, from 12 countries engaged in breakout discussions in this workshop. Transcripts were analyzed thematically. We identified the following 3 themes: (i) feasibility and applicability across diverse settings, which reflected the difficulty with implementing laboratory-based measures in resource-limited environments; (ii) ensuring validity, which included minimizing false positives and considering the specificity of symptoms; and (iii) being meaningful and tangible to patients, which meant that the measure should be easy to interpret, reflect the impact that symptoms have on patients, and promote transparency by standardizing the reporting of peritonitis among dialysis units.ConclusionA core outcome measure for PD-related peritonitis should include both symptom-based and laboratory-based criteria. Thus, the International Society for Peritoneal Dialysis (ISPD) definition of peritonitis is acceptable. However, there should be consideration of reporting suspected peritonitis in cases where laboratory confirmation is not possible. The measure should include all infections from the time of catheter insertion and capture both the rate of infection and the number of patients who remain peritonitis free. A core outcome measure with these features would increase the impact of clinical trials on the care and decision-making of patients receiving PD.

Background/Objectives: The severity of acute lung injury is significantly impacted by age and sex in patients with hemorrhagic shock. AMP-activated protein kinase (AMPK) is a crucial regulator of energy metabolism but its activity declines with aging. Humanin is a mitochondrial peptide that exerts cytoprotective effects in response to oxidative stressors and is associated with longevity. Using a mouse model of hemorrhagic shock that mimics the clinical condition of adult patients, we investigated whether treatment with a humanin analog, humanin-G, mitigates lung injury and whether its mechanisms of action are dependent on the catalytic AMPKα1 subunit activation. Methods: Male and female AMPKα1 wild-type (WT) and knock-out (KO) mice (8–13 months old) were subjected to hemorrhagic shock by blood withdrawal, followed by resuscitation with shed blood and lactated Ringer’s solution. The mice were treated with PEGylated humanin-G or vehicle and euthanized 3 h post-resuscitation. Results: Sex- and genotype-related differences were observed after hemorrhagic shock as lung neutrophil infiltration was more pronounced in the male AMPKα1 WT mice than the female WT mice; also, the male AMPKα1 KO mice experienced a significant decline in mean arterial blood pressure when compared to the male WT mice after resuscitation. The scores of histological lung injury were similarly elevated in all the male and female AMPKα1 WT and KO mice when compared to the control mice. At molecular analysis, acute lung injury was associated with the downregulation of AMPKα1/α2 catalytic subunits in the WT mice, whereas an increased activation of the signal transducer and activator of transcription-3 (STAT3) was observed in all the vehicle-treated groups. The in vivo administration of humanin-G ameliorated histological lung damage in all the groups of animals and ameliorated mean arterial blood pressure in the male AMPKα1 KO mice. The in vivo administration of humanin-G lowered lung neutrophil infiltration in the male and female AMPKα1 WT mice only but not in the KO mice. The beneficial results of humanin-G correlated with the lung cytosolic and nuclear activation of AMPKα in the male and female AMPKα1 WT groups, whereas STAT3 activation was not modified. Conclusions: In adult age, hemorrhage-induced acute lung injury manifests with sex-dependent characteristics. Humanin-G has therapeutic potential and the AMPKα1subunit is an important requisite for its inhibitory effects on lung leucosequestration, but not for the amelioration of lung alveolar structure or the hemodynamic effects of the peptide.

Fulvio Braido,1,2 Enrico Arnaboldi,1,2 Sara Barile,3 Luca Cavalieri,4 Eleonora Ingrassia,4 Maria Russo,1,2 Alessio Piraino4 1Respiratory Unit for Continuity of Care, IRCCS, Ospedale Policlinico San Martino, Genova, Italy; 2Department of Internal Medicine (DiMI), University of Genova, Genova, Italy; 3Chiesi Farmaceutici S.p.A., Parma, Italy; 4Chiesi Italia S.p.A ., Parma, ItalyCorrespondence: Fulvio Braido, Respiratory Unit for Continuity of Care, IRCCS, Ospedale Policlinico San Martino, Genova, Italy, Email fulvio.braido@unige.itAbstract: In this article, we discuss the importance of real-world data in the treatment of patients with asthma and specifically the role of maintenance and reliever therapy (MART) with beclometasone dipropionate (BDP)/formoterol fumarate dihydrate (FF) delivered through a dry-powder inhaler (DPI) that contains an extrafine formulation. We also present the design of the NEWTON study. This multinational, multicenter, prospective, observational study will evaluate the real-world use of extrafine BDP/FF via a DPI as maintenance therapy and MART in patients with moderate to severe asthma. The study’s primary outcome will be the proportion of patients improving their asthma control. Digitally collected patient-reported outcomes, such as the 5-item Asthma Control Questionnaire, the EuroQol 5-dimension 5-level, and the Test of the Adherence to Inhalers, will be used to assess the patient’s asthma control, quality of life, and treatment adherence. Moreover, a new patient-reported outcome, the “Speed of change in health feeling” questionnaire, will be validated in a subgroup of patients. Overall, the results of this study will provide a real-life assessment of patients who perceived clinical benefits in a large cohort of asthmatics in Europe treated as per current clinical practice.Keywords: asthma, dry-powder inhaler, beclometasone dipropionate/formoterol fumarate, observational study

A care challenge that clinicians and other healthcare professionals face very frequently is the complications of bedridden syndrome. Respiratory involvement readily occurs in these patients for whom medical therapy alone is not sufficient. In this clinical case, the authors describe the results of chest physiotherapy in an elderly patient who had developed complete atelectasis of the left lung, attributable to two mechanisms: obstructive, due to mucus plugging, and compressive, due to pleural effusion. The patient was accessed in the authors’ Respiratory Rehabilitation Department, San Raffaele Pisana Scientific Institute for Research, Hospitalization and Healthcare (IRCCS), Rome, Italy, with dyspnoea at rest and high O2 requirement (venturi mask fraction of inspired O2: 40%), demonstrated by severe respiratory failure on blood gas analysis (partial pressure of O2/fraction of inspired O2: 155). Physical examination revealed marked reduction of lung sounds, especially on the left side, with diffuse rhonchi. A chest CT scan was performed to demonstrate complete left lung collapse that would have required invasive therapeutic procedures, such as bronchoscopy. However, given the high risk of periprocedural complications and the patient’s refusal, a chest physiotherapy programme was started. The lung was able to re-expand 7 days later, as evidenced by X-ray and improved gas exchange. The manuscript describes the physiotherapeutic techniques used and collects the main scientific evidence on them. The main purpose is to highlight the role of respiratory physiotherapy as an effective, safe, co-adjuvant treatment, and sometimes alternative to invasive manoeuvres in the treatment of frail patients.