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Abstract Background The potential efficacy of early combination therapy, based on an antiviral plus a monoclonal antibody, for COVID-19 in severely immunocompromised patients is matter of debate. Objectives Our aim was to describe the impact on clinical outcomes of COVID-19 treatments in severely immunocompromised individuals, evaluating differences between a combination and a monotherapy. Methods We included severely immunocompromised outpatients with mild-to-moderate COVID-19 who received an early treatment (either monotherapy with nirmatrelvir/ritonavir or remdesivir or the combination of an antiviral plus sotrovimab). We then assessed differences between the two treatment strategies on three main outcomes (30-day mortality, access to emergency department, hospitalization), separately and as a composite by using a propensity score weighted (PSW) approach. Results Eighty one severely immunocompromised patients were included, 39 receiving early combination therapy and 42 receiving monotherapy. No significant difference was observed in the 30-day mortality rate and hospitalization rate between subjects in the two groups, while access to the emergency department following treatment administration was significantly higher in people who received a combination therapy. After applying the PSW, it was observed that combination therapy impacted favourably on the composite outcome, in a statistically significant fashion. In addition, PSW approach for mortality showed that age was the only significant factor influencing the death as stand-alone outcome. Conclusions Early combination therapy showed a favourable impact on a composite outcome (including mortality, hospitalizations and access to emergency department) in severely immunocompromised hosts who were all vaccinated. However, further studies are needed to support our results.

Abstract Many emerging commercial services are based on the sharing or pooling of resources for common use with the aim of reducing costs. Businesses such as delivery-, mobility-, or transport-as-a-service have become standard in many parts of the world, fulfilling on-demand requests for customers in live settings. However, it is known that many of these problems are NP-hard, and therefore both modeling and solving them accurately is a challenge. Here we focus on one such routing problem, the Ride Pooling Problem (RPP), where multiple customers can request on-demand pickups and drop-offs from shared vehicles within a fleet. The combinatorial optimization task is to optimally pool customer requests using the limited set of vehicles, akin to a small-scale flexible bus route. In this work, we propose a quadratic unconstrained binary optimization (QUBO) program and introduce efficient formulation methods for the RPP to be solved using metaheuristics, and specifically emerging quantum optimization algorithms.

Abstract Introduction Cefiderocol is a siderophore cephalosporin showing activity against various carbapenem-resistant Gram-negative bacteria (CR-GNB). No data currently exist about real-world use of cefiderocol in terms of types of therapy (e.g., empirical or targeted, monotherapy or combined regimens), indications, and patient characteristics. Methods In this multicenter, prospective study, we aimed at describing the use of cefiderocol in terms of types of therapy, indications, and patient characteristics. Results Cefiderocol was administered as empirical and targeted therapy in 27.5% (55/200) and 72.5% (145/200) of cases, respectively. Overall, it was administered as monotherapy in 101/200 cases (50.5%) and as part of a combined regimen for CR-GNB infections in the remaining 99/200 cases (49.5%). In multivariable analysis, previous isolation of carbapenem-resistant Acinetobacter baumannii odds ratio (OR) 2.56, with 95% confidence interval (95% CI) 1.01–6.46, p = 0.047] and previous hematopoietic stem cell transplantation (OR 8.73, 95% CI 1.05–72.54, p = 0.045) were associated with administration of cefiderocol as part of a combined regimen, whereas chronic kidney disease was associated with cefiderocol monotherapy (OR 0.38 for combined regimen, 95% CI 0.16–0.91, p = 0.029). Cumulative 30-day mortality was 19.8%, 45.0%, 20.7%, and 22.7% in patients receiving targeted cefiderocol for infections by Enterobacterales, A. baumannii, Pseudomonas aeruginosa, and any metallo-β-lactamase producers, respectively. Conclusions Cefiderocol is mainly used for targeted treatment, although empirical therapies account for more than 25% of prescriptions, thus requiring dedicated standardization and guidance. The almost equal distribution of cefiderocol monotherapy and cefiderocol-based combination therapies underlines the need for further study to ascertain possible differences in efficacy between the two approaches.

Abstract Sperm length is highly variable across species and many questions about its variation remain open. Although variation in body mass may affect sperm length evolution through its influence on multiple factors, the extent to which sperm length variation is linked to body mass remains elusive. Here, we use the Pareto multi-task evolution framework to investigate the relationship between sperm length and body mass across tetrapods. We find that tetrapods occupy a triangular Pareto front, indicating that trade-offs shape the evolution of sperm length in relation to body mass. By exploring the factors predicted to influence sperm length evolution, we find that sperm length evolution is mainly driven by sperm competition and clutch size, rather than by genome size. Moreover, the triangular Pareto front is maintained within endotherms, internal fertilizers, mammals and birds, suggesting similar evolutionary trade-offs within tetrapods. Finally, we demonstrate that the Pareto front is robust to phylogenetic dependencies and finite sampling bias. Our findings provide insights into the evolutionary mechanisms driving interspecific sperm length variation and highlight the importance of considering multiple trade-offs in optimizing reproductive traits.

Credere (‘aver fede’, ‘aver fiducia’ in latino) definisce l’essenza sia del danaro che della religione. Se avere fiducia in qualcuno comporta dargli/le credito personale/economico, credere in Dio coinvolge la fede nella salvezza ultraterrena. Entrambe queste relazioni riflettono la fiducia che ciò che è stato prestato verrà restituito; quello che è stato rettamente investito sarà moltiplicato. Inoltre, così come ogni vicenda di credito è una storia di rischio ed incertezza (i debitori possono non riuscire a restituire il danaro e le istituzioni di credito, alla fin dei conti, sono sempre gestori di rischio), ogni vicenda di fede è una storia di speranza nella redenzione e nella grazia, che va chiaramente oltre il controllo umano – cosicché l’incertezza qui riappare di nuovo. L’originalità di questo saggio sta nella comprensione della moneta in connessione alla fede religiosa. A tale scopo, lo scritto adotta un approccio comparativo sulla nozione di fiducia (credere) nella finanza occidentale ed islamica, e come essa modelli diversamente l’interazione tra moneta (credito) e religione (fede) nelle loro economie morali. Partendo dalla relazioni tra credere (‘aver fiducia’) e credito che interconnette finanza, economia, moralità, e religione come se fossero gli angoli di un ‘aquilone del danaro’ (sezione 1), il saggio si addentra sugli sfondi teologici della finanza occidentale ed islamica, così da interpretarne i modelli alternativi di gestione del credito e del rischio (capitalismo su base di interesse pecuniario vs condivisione del rischio, mutualità, e cooperazione) come manifestazioni specifiche dei loro rispettivi credi religiosi, anche in relazione alla natura degli investimenti di impatto sociale (sezioni 2, 3 e 4). Per concludere la discussione, considerazioni finali sono proposte sulla relazione tra fiducia, danaro e religione secondo le linee interpretative di Weber sul capitalismo e nella concettualizzazione della finanza islamica, e come esse testimonino la persistenza di una cultura di differenziazione della modernità (sezione 5). / 𝐶𝑟𝑒𝑑𝑒𝑟𝑒 (‘𝑡𝑜 𝑏𝑒𝑙𝑖𝑒𝑣𝑒’, ‘𝑡𝑜 𝑡𝑟𝑢𝑠𝑡’ 𝑖𝑛 𝑡ℎ𝑒 𝐿𝑎𝑡𝑖𝑛 𝑙𝑎𝑛𝑔𝑢𝑎𝑔𝑒) 𝑑𝑒𝑓𝑖𝑛𝑒𝑠 𝑡ℎ𝑒 𝑒𝑠𝑠𝑒𝑛𝑐𝑒 𝑏𝑜𝑡ℎ 𝑜𝑓 𝑚𝑜𝑛𝑒𝑦 𝑎𝑛𝑑 𝑟𝑒𝑙𝑖𝑔𝑖𝑜𝑛. 𝐼𝑓 𝑡𝑟𝑢𝑠𝑡𝑖𝑛𝑔 𝑠𝑜𝑚𝑒𝑜𝑛𝑒 𝑚𝑒𝑎𝑛𝑠 𝑔𝑖𝑣𝑖𝑛𝑔 𝑡ℎ𝑒𝑚 𝑝𝑒𝑟𝑠𝑜𝑛𝑎𝑙/𝑒𝑐𝑜𝑛𝑜𝑚𝑖𝑐 𝑐𝑟𝑒𝑑𝑖𝑡, 𝑏𝑒𝑙𝑖𝑒𝑣𝑖𝑛𝑔 𝑖𝑛 𝐺𝑜𝑑 𝑖𝑛𝑣𝑜𝑙𝑣𝑒𝑠 𝑓𝑎𝑖𝑡ℎ 𝑖𝑛 𝑎𝑓𝑡𝑒𝑟𝑙𝑖𝑓𝑒 𝑠𝑎𝑙𝑣𝑎𝑡𝑖𝑜𝑛. 𝐵𝑜𝑡ℎ 𝑡ℎ𝑒𝑠𝑒 𝑟𝑒𝑙𝑎𝑡𝑖𝑜𝑛𝑠 𝑟𝑒𝑓𝑙𝑒𝑐𝑡 𝑡ℎ𝑒 𝑡𝑟𝑢𝑠𝑡 𝑡ℎ𝑎𝑡 𝑤ℎ𝑎𝑡 ℎ𝑎𝑠 𝑏𝑒𝑒𝑛 𝑙𝑒𝑛𝑡 𝑤𝑖𝑙𝑙 𝑏𝑒 𝑟𝑒𝑡𝑢𝑟𝑛𝑒𝑑; 𝑤ℎ𝑎𝑡 ℎ𝑎𝑠 𝑏𝑒𝑒𝑛 𝑟𝑖𝑔ℎ𝑡𝑒𝑜𝑢𝑠𝑙𝑦 𝑖𝑛𝑣𝑒𝑠𝑡𝑒𝑑 𝑤𝑖𝑙𝑙 𝑏𝑒 𝑚𝑢𝑙𝑡𝑖𝑝𝑙𝑖𝑒𝑑. 𝑀𝑜𝑟𝑒𝑜𝑣𝑒𝑟, 𝑗𝑢𝑠𝑡 𝑎𝑠 𝑎𝑛𝑦 𝑠𝑡𝑜𝑟𝑦 𝑜𝑓 𝑐𝑟𝑒𝑑𝑖𝑡 𝑖𝑠 𝑎 𝑠𝑡𝑜𝑟𝑦 𝑜𝑓 𝑟𝑖𝑠𝑘 𝑎𝑛𝑑 𝑢𝑛𝑐𝑒𝑟𝑡𝑎𝑖𝑛𝑡𝑦 (𝑑𝑒𝑏𝑡𝑜𝑟𝑠 𝑚𝑎𝑦 𝑛𝑜𝑡 𝑏𝑒 𝑎𝑏𝑙𝑒 𝑡𝑜 𝑟𝑒𝑡𝑢𝑟𝑛 𝑚𝑜𝑛𝑒𝑦, 𝑎𝑛𝑑 𝑐𝑟𝑒𝑑𝑖𝑡 𝑖𝑛𝑠𝑡𝑖𝑡𝑢𝑡𝑖𝑜𝑛𝑠 𝑎𝑟𝑒 𝑎𝑙𝑤𝑎𝑦𝑠, 𝑎𝑓𝑡𝑒𝑟 𝑎𝑙𝑙, 𝑟𝑖𝑠𝑘 𝑚𝑎𝑛𝑎𝑔𝑒𝑟𝑠), 𝑎𝑛𝑦 𝑠𝑡𝑜𝑟𝑦 𝑜𝑓 𝑓𝑎𝑖𝑡ℎ 𝑖𝑠 𝑎 𝑠𝑡𝑜𝑟𝑦 𝑜𝑓 ℎ𝑜𝑝𝑒 𝑖𝑛 𝑟𝑒𝑑𝑒𝑚𝑝𝑡𝑖𝑜𝑛 𝑎𝑛𝑑 𝑔𝑟𝑎𝑐𝑒, 𝑤ℎ𝑖𝑐ℎ 𝑐𝑙𝑒𝑎𝑟𝑙𝑦 𝑔𝑜𝑒𝑠 𝑏𝑒𝑦𝑜𝑛𝑑 ℎ𝑢𝑚𝑎𝑛 𝑐𝑜𝑛𝑡𝑟𝑜𝑙 – ℎ𝑒𝑛𝑐𝑒, 𝑢𝑛𝑐𝑒𝑟𝑡𝑎𝑖𝑛𝑡𝑦 ℎ𝑒𝑟𝑒 𝑟𝑒𝑎𝑝𝑝𝑒𝑎𝑟𝑠 𝑎𝑔𝑎𝑖𝑛. 𝑇ℎ𝑒 𝑜𝑟𝑖𝑔𝑖𝑛𝑎𝑙𝑖𝑡𝑦 𝑜𝑓 𝑡ℎ𝑖𝑠 𝑎𝑟𝑡𝑖𝑐𝑙𝑒 𝑙𝑖𝑒𝑠 𝑖𝑛 𝑡ℎ𝑒 𝑢𝑛𝑑𝑒𝑟𝑠𝑡𝑎𝑛𝑑𝑖𝑛𝑔 𝑜𝑓 𝑚𝑜𝑛𝑒𝑦 𝑎𝑠 𝑐𝑜𝑛𝑛𝑒𝑐𝑡𝑒𝑑 𝑡𝑜 𝑟𝑒𝑙𝑖𝑔𝑖𝑜𝑢𝑠 𝑏𝑒𝑙𝑖𝑒𝑓. 𝐹𝑜𝑟 𝑡ℎ𝑖𝑠 𝑝𝑢𝑟𝑝𝑜𝑠𝑒, 𝑖𝑡 𝑡𝑎𝑘𝑒𝑠 𝑎 𝑐𝑜𝑚𝑝𝑎𝑟𝑎𝑡𝑖𝑣𝑒 𝑝𝑒𝑟𝑠𝑝𝑒𝑐𝑡𝑖𝑣𝑒 𝑜𝑛 𝑡ℎ𝑒 𝑛𝑜𝑡𝑖𝑜𝑛 𝑜𝑓 𝑡𝑟𝑢𝑠𝑡 (𝑐𝑟𝑒𝑑𝑒𝑟𝑒) 𝑖𝑛 𝑊𝑒𝑠𝑡𝑒𝑟𝑛 𝑎𝑛𝑑 𝐼𝑠𝑙𝑎𝑚𝑖𝑐 𝑓𝑖𝑛𝑎𝑛𝑐𝑒, 𝑎𝑛𝑑 ℎ𝑜𝑤 𝑡𝑟𝑢𝑠𝑡 𝑑𝑖𝑓𝑓𝑒𝑟𝑒𝑛𝑡𝑙𝑦 𝑠ℎ𝑎𝑝𝑒𝑠 𝑡ℎ𝑒 𝑖𝑛𝑡𝑒𝑟𝑎𝑐𝑡𝑖𝑜𝑛 𝑏𝑒𝑡𝑤𝑒𝑒𝑛 𝑚𝑜𝑛𝑒𝑦 (𝑐𝑟𝑒𝑑𝑖𝑡) 𝑎𝑛𝑑 𝑟𝑒𝑙𝑖𝑔𝑖𝑜𝑛 (𝑓𝑎𝑖𝑡ℎ) 𝑖𝑛 𝑡ℎ𝑒𝑖𝑟 𝑚𝑜𝑟𝑎𝑙 𝑒𝑐𝑜𝑛𝑜𝑚𝑖𝑐𝑠. 𝑀𝑜𝑣𝑖𝑛𝑔 𝑓𝑟𝑜𝑚 𝑡ℎ𝑒 𝑟𝑒𝑙𝑎𝑡𝑖𝑜𝑛𝑠ℎ𝑖𝑝 𝑏𝑒𝑡𝑤𝑒𝑒𝑛 𝑐𝑟𝑒𝑑𝑒𝑟𝑒 (‘𝑡𝑜 𝑡𝑟𝑢𝑠𝑡’) 𝑎𝑛𝑑 𝑐𝑟𝑒𝑑𝑖𝑡 𝑡ℎ𝑎𝑡 𝑖𝑛𝑡𝑒𝑟𝑐𝑜𝑛𝑛𝑒𝑐𝑡𝑠 𝑓𝑖𝑛𝑎𝑛𝑐𝑒, 𝑒𝑐𝑜𝑛𝑜𝑚𝑖𝑐𝑠, 𝑚𝑜𝑟𝑎𝑙𝑖𝑡𝑦, 𝑎𝑛𝑑 𝑟𝑒𝑙𝑖𝑔𝑖𝑜𝑛 𝑎𝑠 𝑖𝑓 𝑡ℎ𝑒𝑦 𝑤𝑒𝑟𝑒 𝑡ℎ𝑒 𝑐𝑜𝑟𝑛𝑒𝑟𝑠 𝑜𝑓 𝑎 ‘𝑚𝑜𝑛𝑒𝑦 𝑘𝑖𝑡𝑒’ (𝑠𝑒𝑐𝑡𝑖𝑜𝑛 1), 𝑡ℎ𝑒 𝑎𝑟𝑡𝑖𝑐𝑙𝑒 𝑑𝑒𝑙𝑣𝑒𝑠 𝑖𝑛𝑡𝑜 𝑡ℎ𝑒 𝑡ℎ𝑒𝑜𝑙𝑜𝑔𝑖𝑐𝑎𝑙 𝑏𝑎𝑐𝑘𝑔𝑟𝑜𝑢𝑛𝑑𝑠 𝑜𝑓 𝑊𝑒𝑠𝑡𝑒𝑟𝑛 𝑎𝑛𝑑 𝐼𝑠𝑙𝑎𝑚𝑖𝑐 𝑓𝑖𝑛𝑎𝑛𝑐𝑒, 𝑠𝑜 𝑡𝑜 𝑖𝑛𝑡𝑒𝑟𝑝𝑟𝑒𝑡 𝑡ℎ𝑒𝑖𝑟 𝑎𝑙𝑡𝑒𝑟𝑛𝑎𝑡𝑖𝑣𝑒 𝑚𝑜𝑑𝑒𝑙𝑠 𝑜𝑓 𝑐𝑟𝑒𝑑𝑖𝑡 𝑎𝑛𝑑 𝑟𝑖𝑠𝑘 𝑚𝑎𝑛𝑎𝑔𝑒𝑚𝑒𝑛𝑡 (𝑖𝑛𝑡𝑒𝑟𝑒𝑠𝑡-𝑏𝑎𝑠𝑒𝑑 𝑐𝑎𝑝𝑖𝑡𝑎𝑙𝑖𝑠𝑚 𝑣𝑠 𝑟𝑖𝑠𝑘-𝑠ℎ𝑎𝑟𝑖𝑛𝑔, 𝑚𝑢𝑡𝑢𝑎𝑙𝑖𝑡𝑦, 𝑎𝑛𝑑 𝑐𝑜𝑜𝑝𝑒𝑟𝑎𝑡𝑖𝑜𝑛) 𝑎𝑠 𝑠𝑝𝑒𝑐𝑖𝑓𝑖𝑐 𝑚𝑎𝑛𝑖𝑓𝑒𝑠𝑡𝑎𝑡𝑖𝑜𝑛𝑠 𝑜𝑓 𝑡ℎ𝑒𝑖𝑟 𝑟𝑒𝑠𝑝𝑒𝑐𝑡𝑖𝑣𝑒 𝑟𝑒𝑙𝑖𝑔𝑖𝑜𝑢𝑠 𝑐𝑟𝑒𝑒𝑑𝑠, 𝑎𝑙𝑠𝑜 𝑖𝑛 𝑟𝑒𝑙𝑎𝑡𝑖𝑜𝑛 𝑡𝑜 𝑡ℎ𝑒 𝑛𝑎𝑡𝑢𝑟𝑒 𝑜𝑓 𝑠𝑜𝑐𝑖𝑎𝑙𝑙𝑦 𝑜𝑟𝑖𝑒𝑛𝑡𝑒𝑑 𝑖𝑛𝑣𝑒𝑠𝑡𝑚𝑒𝑛𝑡𝑠 (𝑠𝑒𝑐𝑡𝑖𝑜𝑛𝑠 2, 3 𝑎𝑛𝑑 4). 𝑇𝑜 𝑐𝑜𝑛𝑐𝑙𝑢𝑑𝑒 𝑡ℎ𝑒 𝑑𝑖𝑠𝑐𝑢𝑠𝑠𝑖𝑜𝑛, 𝑓𝑖𝑛𝑎𝑙 𝑐𝑜𝑛𝑠𝑖𝑑𝑒𝑟𝑎𝑡𝑖𝑜𝑛𝑠 𝑎𝑟𝑒 𝑝𝑟𝑜𝑝𝑜𝑠𝑒𝑑 𝑜𝑛 𝑡ℎ𝑒 𝑟𝑒𝑙𝑎𝑡𝑖𝑜𝑛𝑠ℎ𝑖𝑝 𝑏𝑒𝑡𝑤𝑒𝑒𝑛 𝑡𝑟𝑢𝑠𝑡, 𝑚𝑜𝑛𝑒𝑦, 𝑎𝑛𝑑 𝑟𝑒𝑙𝑖𝑔𝑖𝑜𝑛 𝑎𝑐𝑐𝑜𝑟𝑑𝑖𝑛𝑔 𝑡𝑜 𝑊𝑒𝑏𝑒𝑟’𝑠 𝑖𝑛𝑡𝑒𝑟𝑝𝑟𝑒𝑡𝑖𝑣𝑒 𝑜𝑢𝑡𝑙𝑖𝑛𝑒 𝑜𝑓 𝑐𝑎𝑝𝑖𝑡𝑎𝑙𝑖𝑠𝑚 𝑎𝑛𝑑 𝑖𝑛 𝐼𝑠𝑙𝑎𝑚𝑖𝑐 𝑓𝑖𝑛𝑎𝑛𝑐𝑒 𝑐𝑜𝑛𝑐𝑒𝑝𝑡𝑢𝑎𝑙𝑖𝑠𝑎𝑡𝑖𝑜𝑛, 𝑎𝑛𝑑 ℎ𝑜𝑤 𝑡ℎ𝑒𝑦 𝑡𝑒𝑠𝑡𝑖𝑓𝑦 𝑡𝑜 𝑡ℎ𝑒 𝑝𝑒𝑟𝑠𝑖𝑠𝑡𝑒𝑛𝑐𝑒 𝑜𝑓 𝑎 𝑑𝑖𝑓𝑓𝑒𝑟𝑒𝑛𝑡𝑖𝑎𝑡𝑖𝑜𝑛 𝑐𝑢𝑙𝑡𝑢𝑟𝑒 𝑜𝑓 𝑚𝑜𝑑𝑒𝑟𝑛𝑖𝑡𝑦 (𝑠𝑒𝑐𝑡𝑖𝑜𝑛 5).

Bacterial infections are a common complication in patients with decompensated liver cirrhosis. The complex landscape of cirrhosis, characterized by immune paralysis and an exhausted response to exogenous triggers, explains the higher prevalence of such infections, particularly in advanced disease stages. In clinical practice, the onset of a bacterial infection can lead to further deterioration of hepatic and extra-hepatic function, potentially resulting in acute decompensation or acute-on-chronic liver failure. This has significant clinical implications, particularly for patients awaiting a transplant. In this review, we will discuss the latest evidence on the diagnosis and therapy of bacterial infections in patients with decompensated cirrhosis. Additionally, we will analyze the impact of bacterial infections in the context of liver transplantation, discussing debated topics such as the timing of transplantation in patients with infections, potential implications for prioritization, effects on post-operative recovery, grafts, and patient survival.

Abstract Intra-abdominal infections (IAIs) are common surgical emergencies and are an important cause of morbidity and mortality in hospital settings, particularly if poorly managed. The cornerstones of effective IAIs management include early diagnosis, adequate source control, appropriate antimicrobial therapy, and early physiologic stabilization using intravenous fluids and vasopressor agents in critically ill patients. Adequate empiric antimicrobial therapy in patients with IAIs is of paramount importance because inappropriate antimicrobial therapy is associated with poor outcomes. Optimizing antimicrobial prescriptions improves treatment effectiveness, increases patients’ safety, and minimizes the risk of opportunistic infections (such as Clostridioides difficile) and antimicrobial resistance selection. The growing emergence of multi-drug resistant organisms has caused an impending crisis with alarming implications, especially regarding Gram-negative bacteria. The Multidisciplinary and Intersociety Italian Council for the Optimization of Antimicrobial Use promoted a consensus conference on the antimicrobial management of IAIs, including emergency medicine specialists, radiologists, surgeons, intensivists, infectious disease specialists, clinical pharmacologists, hospital pharmacists, microbiologists and public health specialists. Relevant clinical questions were constructed by the Organizational Committee in order to investigate the topic. The expert panel produced recommendation statements based on the best scientific evidence from PubMed and EMBASE Library and experts’ opinions. The statements were planned and graded according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) hierarchy of evidence. On November 10, 2023, the experts met in Mestre (Italy) to debate the statements. After the approval of the statements, the expert panel met via email and virtual meetings to prepare and revise the definitive document. This document represents the executive summary of the consensus conference and comprises three sections. The first section focuses on the general principles of diagnosis and treatment of IAIs. The second section provides twenty-three evidence-based recommendations for the antimicrobial therapy of IAIs. The third section presents eight clinical diagnostic-therapeutic pathways for the most common IAIs. The document has been endorsed by the Italian Society of Surgery.

Although studies have suggested an association between lung infections and increased risk of neuronal disorders (e.g., dementia, cognitive impairment, and depressive and anxious behaviors), its mechanisms remain unclear. Thus, an experimental mice model of pulmonary sepsis was developed to investigate the relationship between lung and brain inflammation. Male Swiss mice were randomly assigned to either pneumosepsis or control groups. Pneumosepsis was induced by intratracheal instillation of Klebsiella pneumoniae, while the control group received a buffer solution. The model's validation included assessing systemic markers, as well as tissue vascular permeability. Depression- and anxiety-like behaviors and cognitive function were assessed for 30 days in sepsis survivor mice, inflammatory profiles, including cytokine levels (lungs, hippocampus, and prefrontal cortex) and microglial activation (hippocampus), were examined. Pulmonary sepsis damaged distal organs, caused peripheral inflammation, and increased vascular permeability in the lung and brain, impairing the blood-brain barrier and resulting in bacterial dissemination. After sepsis induction, we observed an increase in myeloperoxidase activity in the lungs (up to seven days) and prefrontal cortex (up to 24 h), proinflammatory cytokines in the hippocampus and prefrontal cortex, and percentage of areas with cells positive for ionized calcium-binding adaptor molecule 1 (IBA-1) in the hippocampus. Also, depression- and anxiety-like behaviors and changes in short-term memory were observed even 30 days after sepsis induction, suggesting a crosstalk between inflammatory responses of lungs and brain.

Abstract Background Infections are one of the most common causes of death after lung transplant (LT). However, the benefit of ‘targeted’ prophylaxis in LT recipients pre-colonized by Gram-negative (GN) bacteria is still unclear. Methods All consecutive bilateral LT recipients admitted to the Intensive Care Unit of the University Hospital of Padua (February 2016–2023) were retrospectively screened. Only patients with pre-existing GN bacterial isolations were enrolled and analyzed according to the antimicrobial surgical prophylaxis (‘standard’ vs. ‘targeted’ on the preoperative bacterial isolation). Results One hundred eighty-one LT recipients were screened, 46 enrolled. Twenty-two (48%) recipients were exposed to ‘targeted’ prophylaxis, while 24 (52%) to ‘standard’ prophylaxis. Overall prevalence of postoperative multi-drug resistant (MDR) GN bacteria isolation was 65%, with no differences between the two surgical prophylaxis (p = 0.364). Eleven (79%) patients treated with ‘standard’ prophylaxis and twelve (75%) with ‘targeted’ therapy reconfirmed the preoperative GN pathogen (p = 0.999). The prevalence of postoperative infections due to MDR GN bacteria was 50%. Of these recipients, 4 belonged to the ‘standard’ and 11 to the ‘targeted’ prophylaxis (p = 0.027). Conclusions The administration of a ‘targeted’ prophylaxis in LT pre-colonized recipients seemed not to prevent the occurrence of postoperative MDR GN infections.

Background Kaposi Sarcoma (KS) has been historically associated with HIV, especially in people with advanced immunosuppression. Its prevalence decreased over time, but management remains difficult especially when the diagnosis is late and there is a visceral involvement. Bone localization, and particularly the vertebral one, is rare. We herein present a case of vertebral localizations of KS and performed a review literature to assess demographic, clinical characteristics and treatment outcomes in people with HIV. Methods The systematic review was carried out by following the PRISMA guidelines and registering the protocol in PROSPERO database (n. registration: CRD42024548626). We included all cases of vertebral localizations of KS from January 1rst 1981 to December 31rst, 2023. Results Twenty-two cases, including ours, were ever reported in people with HIV, mostly males (95.4%), with a median age of 35 years (IQR: 32-44), median CD4+ T cell count of 80 cell/mm3 (IQR 13-111), 31.8% with high HIV viral load. Five people received HIV and KS diagnosis simultaneously. In all cases, but one, there were multiple sites involved. Most spine lesions were localized at thoracic and lumbar levels (59.1%), causing pathological fractures in 2 cases. Chemotherapy and radiotherapy were performed in 50% and 18.2% cases, respectively. 22.7% persons died, stability and improvement/disease regression were reported for 13.6% and 22.7% persons, respectively, while 9.9% had a significant disease progression and a person was lost to follow-up. Conclusions Despite progresses in treatment, late presentation of KS, especially with spine involvement may have a poor prognosis. More efforts are needed to promote access to HIV testing, especially when indicating conditions are present.

Background Recently, injectable cabotegravir/rilpivirine (ICAB/RPV) became available for HIV treatment. However, there are no real-life data on the impact of switching to ICAB/RPV on sleep disturbances (SD). Therefore, we aimed at assessing and investigating this aspect in our cohort. Methods A SD multidimensional assessment (Epworth Sleepiness scale, Insomnia severity Index, Berlin Questionnaire, and Pittsburg Sleep Quality Index, PSQI) was performed to all people who consented before starting ICAB/RPV and 12 wk after the switch. Demographics, life-style habits, laboratory, and clinical data were collected from medical health records. Results To June 2023, 46 people were included, 76.1% males, with a median age of 48.5 (IQR: 41–57), 50% had multimorbidity, 13% was on polypharmacy. Median age with HIV and CD4 + T cell count nadir were 10 (5–19.5) years and 360 (205–500) cell/mm3, respectively. The reason to start a long-acting strategy was person’s choice in all cases. Baseline antiretroviral regimens were mostly: tenofovir alafenamide/emtricitabine/rilpivirine (39.1%) and dolutegravir/lamivudine (32.6%). No significant changes were observed in any of the scores for each questionnaire, but for a worsening PSQI. 37% people reported a subjectively improved sleep quality, even if statistically significant changes were not observed in almost all the sleep parameters. Conclusions To the best of our knowledge, this is the first study exploring impact of switching to ICAB/RPV on SD. Despite integrase inhibitor have been associated with SD, we did not observed a negative impact on sleep quality after the switch to ICAB/RPV. More studies and with larger number of people are necessary to confirm our results.

Background: The introduction of rapid antigen tests revolutionized the approach to SARS-CoV-2 diagnosis, offering prompt and accurate results with high sensitivity and specificity. Although it is more cost- and time-saving than the gold standard, real-time polymerase chain reaction (RT-PCR), the efficacy in general population screening in both hospital- and community-based settings remains unknown. Moreover, rapid antigen testing is limited by qualitative results. This study aims to evaluate the diagnostic reliability of the LumiraDx™ rapid antigen test during the Omicron era and to investigate its quantitative (analogue-to-digital converter (ADC)) results in comparison with RT-PCR Ct values. Methods: This prospective study included all adult patients with mild-to-moderate SARS-CoV-2 symptoms who were not hospitalised and did not require oxygen supplementation, consented to participate, and attended the Infectious and Tropical Diseases Unit of Padua University Hospital from July 14th, 2022 to January 3rd, 2023. The patients underwent two different tests simultaneously: a nasal LumiraDx™ swab and a real-time RT-PCR assay performed on a nasopharyngeal swab. Sampling was repeated several times for a subset of subjects. Results: We enrolled 266 consecutive participants and collected 601 pairs of LumiraDx™ and RT-PCR samples. The most prevalent variant was BA.4/BA.5 Omicron (60.2 %). The sensitivity and specificity of LumiraDx™ test when compared to real-time RT-PCR results as the reference standard were 93.1 % and 79.75 %, respectively. No significant differences in diagnostic reliability were found based on the available characteristics, age, sex, symptom status, or COVID-19 variant, except for the days from symptom onset. According to the multilevel logistic regression analysis, the only independent variable significantly associated with test concordance was the Ct value (adjusted odds ratio (OR) = 0.56, p

Background: Almost 10% of women in reproductive age are diagnosed with ovarian endometriomas and can experience symptoms and infertility disorders. Ovarian endometriomas can be treated with medical or surgical therapy. Objective: To assess whether long-term therapy with dienogest or oral cyclic estrogen-progestogens is effective in reducing the size of ovarian endometriomas, alleviating associated symptoms, and reducing the requirement for surgery. Design: Prospective non-interventional cohort study. Methods: We enrolled childbearing women diagnosed with ovarian endometriomas. We collected demographic, clinical, and surgical data, including the evaluation of ovarian endometrioma-associated symptoms and pain using the visual analog scale. We grouped the women according to treatment regimen into dienogest, estrogen-progestogens, and no-treatment. Patient’s assessment was performed at baseline and after 12 months evaluating the largest ovarian endometrioma diameter (in millimeters) and the associated symptoms. Furthermore, we analyzed the impact of hormonal treatment in a sub-group of women fulfilling at baseline the criteria for a first-line surgical approach (ovarian endometrioma > 30 mm with visual analog scale > 8 or ovarian endometrioma > 40 mm before assisted reproductive treatments or any ovarian endometrioma(s) > 60 mm). Results: We enrolled 142 patients: 62, 38, and 42 in dienogest, estrogen-progestogens, and no-treatment groups, respectively. No significant differences were found regarding baseline characteristics. After 12 months, the mean largest ovarian endometrioma diameter increased in the no-treatment group (31.1 versus 33.8; p

Introduction Bronchiolitis obliterans syndrome (BOS) is the most common form of CLAD and is characterized by airflow limitation and an obstructive spirometry pattern without parenchymal opacities. The protein signature of BOS lesions concerns extracellular matrix organization and aberrant basement membrane composition. In this pilot study, we investigated the presence of COL4A5 in the serum of patients with BOS. Methods 41 patients who had undergone LTX were enrolled. Of these, 27 developed BOS and 14 (control group) were considered stable at the time of serum sampling. Of BOS patients, serum samples were analysed at the time of BOS diagnosis and before the clinical diagnosis (pre-BOS). COL4A5 levels were detected through the ELISA kit. Results Serum concentrations of COL4A5 were higher in pre-BOS than in stable patients (40.5 ± 13.9 and 24.8 ± 11.4, respectively, p = 0.048). This protein is not influenced by comorbidities, such as acute rejection or infections, or by therapies. Survival analysis also reveals that a higher level of COL4A5 was also associated with less probability of survival. Our data showed a correlation between concentrations of COL4A5 and FEV1 at the time of diagnosis of BOS. Conclusion Serum concentrations of COL4A5 can be considered a good prognostic marker due to their association with survival and correlation with functional parameters., Author(s): M. Armati [sup.1], S. Cattelan [sup.1], M. Guerrieri [sup.1], M. Messina [sup.1], B. Perea [sup.1], M. Genovese [sup.2], M. d'Alessandro [sup.1], S. Gangi [sup.1], P. Cameli, F. Perillo [sup.1], [...]

This study investigates the prevalence and patterns of transmitted drug resistance mutations (TDRMs) and HIV-1 subtypes among antiretroviral therapy (ART) naïve individuals in Veneto, Italy, from 2017 to 2024. This research aims to understand the dynamic landscape of TDRMs and HIV-1 genetic diversity to inform treatment strategies effectively. We included all adult ART-naïve people with HIV (PWH) from seven infectious disease units in Veneto, Italy. We collected the genotypic resistance testing conducted to predict drug susceptibility and subtype distribution using the Stanford HIVdb algorithm. We included 762 PWH, showing a slight but statistically significant decline in the B subtype among Italian PWH (p = 0.045) and an increase in non-B subtypes among foreigners, though it was not statistically significant (p = 0.333). The most frequent mutations were in Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs), especially in non-B subtypes, with a notable rise from 10.7% in 2017–2019 to 15.5% in 2020–2024. Notably, TDRMs were consistently detected, highlighting an ongoing challenge despite the stable prevalence observed over the years. In addition, the data revealed a concerning rise in mutations against newer drug classes, such as integrase inhibitors. Conclusively, the study underscores the necessity of continuous surveillance of HIV subtypes and resistance patterns to adapt ART regimens optimally. Despite the stable levels of drug resistance, the emergence of resistance against newer drugs necessitates ongoing vigilance and possible adjustment in treatment protocols to enhance clinical outcomes and manage HIV drug resistance effectively.

IntroductionCasirivimab and imdevimab (CAS/IMV) are two non-competing, high-affinity human IgG1 anti-SARS-CoV-2 monoclonal antibodies, that showed a survival benefit in seronegative hospitalized patients with COVID-19. This study aimed to estimate the day-28 risk of mechanical ventilation (MV) and death in individuals hospitalized for severe COVID-19 pneumonia and receiving CAS/IMV. Additionally, it aimed to identify variables measured at the time of hospital admission that could predict these outcomes and derive a prediction algorithm.MethodsThis is a retrospective, observational cohort study conducted in 12 hospitals in Italy. Adult patients who were consecutively hospitalized from November 2021 to February 2022 receiving CAS/IMV were included. A multivariable logistic regression model was used to identify predictors of MV or death by day 28 from treatment initiation, and β-coefficients from the model were used to develop a risk score that was derived by means of leave-one-out internal cross-validation (CV), external CV, and calibration. Secondary outcome was mortality.ResultsA total of 480 hospitalized patients in the training set and 157 patients in the test set were included. By day 28, 36 participants (8%) underwent MV and 28 died (6%) for a total of 58 participants (12%) experiencing the composite primary endpoint. In multivariable analysis, four factors [age, PaO2/FiO2 ratio, lactate dehydrogenase (LDH), and platelets] were independently associated with the risk of MV/death and were used to generate the proposed risk score. The accuracy of the score in the area under the curve (AUC) was 0.80 and 0.77 in internal validation and test for the composite endpoint and 0.87 and 0.86 for death, respectively. The model also appeared to be well calibrated with the raw data.ConclusionThe mortality risk reported in our study was lower than that previously reported. Although CAS/IMV is no longer used, our score might help in identifying which patients are not likely to benefit from monoclonal antibodies and may require alternative interventions.

Purpose The PRESTIGIO Registry was established in 2017 to collect clinical, virological and immunological monitoring data from people living with HIV (PLWH) with documented four-class drug resistance (4DR). Key research purposes include the evaluation of residual susceptibility to specific antiretrovirals and the validation of treatment and monitoring strategies in this population.Participants The PRESTIGIO Registry collects annual plasma and peripheral blood mononuclear cell samples and demographic, clinical, virological, treatment and laboratory data from PLWH followed at 39 Italian clinical centres and characterised by intermediate-to-high genotypic resistance to ≥1 nucleoside reverse transcriptase inhibitors, ≥1 non-nucleoside reverse transcriptase inhibitors, ≥1 protease inhibitors, plus either intermediate-to-high genotypic resistance to ≥1 integrase strand transfer inhibitors (INSTIs) or history of virological failure to an INSTI-containing regimen. To date, 229 people have been recorded in the cohort. Most of the data are collected from the date of the first evidence of 4DR (baseline), with some prebaseline information obtained retrospectively. Samples are collected from the date of enrollment in the registry.Findings to date The open-ended cohort has been used to assess (1) prognosis in terms of survival or development of AIDS-related or non-AIDS-related clinical events; (2) long-term efficacy and safety of different antiretroviral regimens and (3) virological and immunological factors predictive of clinical outcome and treatment efficacy, especially through analysis of plasma and cell samples.Future plans The registry can provide new knowledge on how to implement an integrated approach to study PLWH with documented resistance to the four main antiretroviral classes, a population with a limited number of individuals characterised by a high degree of frailty and complexity in therapeutic management. Given the scheduled annual updates of PLWH data, the researchers who collaborate in the registry can send study proposals at any time to the steering committee of the registry, which evaluates every 3 months whether the research studies can be conducted on data and biosamples from the registry and whether they are aimed at a better understanding of a specific health condition, the emergence of comorbidities or the effect of potential treatments or experimental drugs that may have an impact on disease progression and quality of life. Finally, the research studies should aim to be inclusive, innovative and in touch with the communities and society as a whole.Trial registration number NCT04098315.

Abstract The outbreak of Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, forced us to face a pandemic with unprecedented social, economic, and public health consequences. Several nations have launched campaigns to immunize millions of people using various vaccines to prevent infections. Meanwhile, therapeutic approaches and discoveries continuously arise; however, identifying infected patients that are going to experience the more severe outcomes of COVID-19 is still a major need, to focus therapeutic efforts, reducing hospitalization and mitigating drug adverse effects. Microbial communities colonizing the respiratory tract exert significant effects on host immune responses, influencing the susceptibility to infectious agents. Through 16S rDNAseq we characterized the upper airways’ microbiota of 192 subjects with nasopharyngeal swab positive for SARS-CoV-2. Patients were divided into groups based on the presence of symptoms, pneumonia severity, and need for oxygen therapy or intubation. Indeed, unlike most of the literature, our study focuses on identifying microbial signatures predictive of disease progression rather than on the probability of infection itself, for which a consensus is lacking. Diversity, differential abundance, and network analysis at different taxonomic levels were synergistically adopted, in a robust bioinformatic pipeline, highlighting novel possible taxa correlated with patients’ disease progression to intubation.

Abstract COVID-19-related acute respiratory distress syndrome (CARDS) is associated with high mortality rates. We still have limited knowledge of the complex alterations developing in the lung microenvironment. The goal of the present study was to comprehensively analyze the cellular components, inflammatory signature, and respiratory pathogens in bronchoalveolar lavage (BAL) of CARDS patients (16) in comparison to those of other invasively mechanically ventilated patients (24). In CARDS patients, BAL analysis revealed: SARS-CoV-2 infection frequently associated with other respiratory pathogens, significantly higher neutrophil granulocyte percentage, remarkably low interferon-gamma expression, and high levels of interleukins (IL)-1β and IL-9. The most important predictive variables for worse outcomes were age, IL-18 expression, and BAL neutrophilia. To the best of our knowledge, this is the first study that was able to identify, through a comprehensive analysis of BAL, several aspects relevant to the complex pathophysiology of CARDS.

Abstract Variational quantum algorithms are the leading candidate for advantage on near-term quantum hardware. When training a parametrized quantum circuit in this setting to solve a specific problem, the choice of ansatz is one of the most important factors that determines the trainability and performance of the algorithm. In quantum machine learning (QML), however, the literature on ansatzes that are motivated by the training data structure is scarce. In this work, we introduce an ansatz for learning tasks on weighted graphs that respects an important graph symmetry, namely equivariance under node permutations. We evaluate the performance of this ansatz on a complex learning task, namely neural combinatorial optimization, where a machine learning model is used to learn a heuristic for a combinatorial optimization problem. We analytically and numerically study the performance of our model, and our results strengthen the notion that symmetry-preserving ansatzes are a key to success in QML.

AbstractCircular Economy (CE) is critical to the United Nations 2030 agenda for sustainable development. This transition can be fostered by technologies from Industry 4.0 (I40), one of the main engines for digital transformation. Science has already documented models, theoretical frameworks, and case studies linking CE and I40 together. However, the research agenda still needs to address a gap regarding how practitioners use these technologies to pursue circularity. Based on a practitioner’s perspective, this article aims to understand how I40 technologies can support the transition to a CE. We distributed an open-ended survey and received 361 responses from organizations in 37 countries. This sample resulted in 154 usable records that were examined through content analysis. We identified a field-validated list of 31 information-technology (IT) capabilities, revealing that most initiatives are reactive – focused on reducing waste and recycling – rather than proactive. This article contributes to research to identify new IT capabilities for CE that emerge from practice and to provide a structured way for organizations to pursue circularity.

Abstract Heterostructures of Ga $$_2$$ 2 O $$_3$$ 3 with other materials such as Si, SiC or diamond, are a possible way of addressing the low thermal conductivity and lack of p-type doping of Ga $$_2$$ 2 O $$_3$$ 3 for device applications, as well as of improving device reliability. In this work we study the electrical and thermal properties of Ga $$_2$$ 2 O $$_3$$ 3 –SiO $$_2$$ 2 heterostructures. Here, thin-film gallium oxide with thickness ranging between 8 and 30 nm was deposited onto a silicon substrate with a thermal oxide by means of oxidised liquid gallium layer delamination. The resulting heterostructure is then characterised by means of X-ray photoelectron spectroscopy and transient thermoreflectance. The thin-film gallium oxide valence band offset with respect to the SiO $$_2$$ 2 is measured as 0.1 eV and predicted as $$-2.3$$ - 2.3 eV with respect to diamond. The thin-film’s out-of-plane thermal conductivity is determined to be 3 ±0.5 Wm $$^{-1}$$ - 1 K $$^{-1}$$ - 1 , which is higher than what has been previously measured for other polycrystalline Ga $$_2$$ 2 O $$_3$$ 3 films of comparable thickness.