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Long-acting injectable antiretroviral therapy (LAI-ART) could increase adherence to therapy, while maintaining excellent viro-immunologic control, reduce the risk of toxicity and drug interactions, and improve the overall quality of life of people living with HIV. The purpose of this study is to assess knowledge and acceptability to this new therapeutic modality in PLWH and their readiness to change their current treatment regimen in favour of the injectable one. An anonymous, multiple-choice self-completion questionnaire was offered at the Infectious and Tropical Diseases Unit of the ASST Spedali Civili of Brescia from June 2022 to June 2023 to every PLWH. We enrolled 500 subjects. Although just a few people are aware of the availability of LAI-ART (only 281 subjects, 56.2%), the acceptability toward this new therapeutic modality is quite good (432 subjects, 86.4%) and more than half of the study population have declared that they would like to replace oral therapy with intramuscular injections (320, 63%). Duration of HIV infection, gender and number of concomitant medications were not related to the cumulative propensity to LAI-ART, while age appeared to be an independent predictor (OR 0.97, 95%CI 0.95–0.98, p-value < 0.001). The selection of motivated patients seems critical to establish LAI-ART in clinical practice.

People living with HIV (PLWH) have a higher risk of herpes zoster (HZ) reactivation and postherpetic neuralgia (PHN) compared to general population. Our study aims to evaluate prevalence of HZ reactivation and PHN after vaccination with recombinant vaccine (RZV) in a population living with HIV, and to identify risk factors associated with recurrence. We conducted an observational study, enrolling all PLWH ≥18 years old vaccinated with RZV from January 2022 to December 2023. A questionnaire was proposed to the subjects at least 6 months after vaccination, inquiring about previous history of HZ and PHN, and recurrence after vaccination. We collected demographic characteristics, comorbidities, viro-immunological status, and medications. We performed a descriptive analysis and univariate logistic regressions to investigate risk factors associated with HZ reactivation and PHN persistence. We included 223 subjects. We estimated the prevalence of events among 145 subjects: we recorded 54 subjects with pre-vaccination HZ (prevalence 37.24 % [IC 95 %: 29.36% – 45.65 %]) and 13 with post-vaccination HZ (prevalence 8.97 % [IC 95 %: 4.86 % - 14.84 %]). The prevalence of pre-vaccination PHN was 19.23 % [IC 95 %: 11.18 % - 29.73 %], with mean NRS 6.33 [IC 95 %: 4.9–7.76]; no case of PHN was recorded after vaccination. Evaluating risk factors related to post-vaccination HZ, we didn't find any association with viro-immunological status, clinical history of HIV infection, or concomitant medications. We correlate HZ and age (OR 1.06, CI 95 % 1.01–1.13, p-value 0.031), haematological (OR 9.60, CI 95 % 1.70–49.9, p-value 0.007), oncological (OR 5.36, CI 95 % 1.04–22.8, p-value 0.028), and hepatic comorbidities (OR 3.67, CI 95 % 1.10–12.0, p-value 0.030). This is the first real-world study that highlights the excellent clinical response to RZV, with a low prevalence of HZ reactivation and complete resolution of PHN after the vaccination. Moreover, we identified clinical conditions promoting the recurrence HZ after vaccination.

Cognitive and motor performances decline with ageing, and this may be exacerbated in people with HIV (PWH) due to several factors. The study aimed to compare cognitive and fine motor performance between older adults with and without HIV. We conducted a cross-sectional study of participants ≥ 65 years in the GEPPO cohort using Mini-Addenbrooke's Cognitive Examination (MACE) and Grooved Pegboard Test (GPT). Quality of life, depression, anxiety, and sleep quality were also measured. PWH (n = 239) were younger (73.7 vs. 80.6 years) and more commonly males at birth (85 vs. 25%) than PWoH (n = 52). No significant differences in MACE scores were observed between groups (24 vs. 23, p > 0.900). Time to complete GPT was longer in PWoH (140 vs. 106 s, p = 0.004), with 56% exceeding normative GPT values vs. 24% in PWH (p < 0.001). In multivariate models, older age and lower education predicted worse MACE and GPT scores, whereas benzodiazepine/Z drug use predicted poorer fine motor skills. PWH reported lower quality of life but similar or better depression, anxiety, and sleep scores compared to PWoH. Older PWH show comparable cognitive but better fine motor performance than PWoH. Education and benzodiazepine use emerged as key modifiable or protective factors, underscoring the importance of targeted geriatric and mental health interventions.

Objectives Enlarged main pulmonary artery diameter (MPAD) resulted to be associated with pulmonary hypertension and mortality in a non-COVID-19 setting. The aim was to investigate and validate the association between MPAD enlargement and overall survival in COVID-19 patients. Methods This is a cohort study on 1469 consecutive COVID-19 patients submitted to chest CT within 72 h from admission in seven tertiary level hospitals in Northern Italy, between March 1 and April 20, 2020. Derivation cohort ( n  = 761) included patients from the first three participating hospitals; validation cohort ( n  = 633) included patients from the remaining hospitals. CT images were centrally analyzed in a core-lab blinded to clinical data. The prognostic value of MPAD on overall survival was evaluated at adjusted and multivariable Cox’s regression analysis on the derivation cohort. The final multivariable model was tested on the validation cohort. Results In the derivation cohort, the median age was 69 (IQR, 58–77) years and 537 (70.6%) were males. In the validation cohort, the median age was 69 (IQR, 59–77) years with 421 (66.5%) males. Enlarged MPAD (≥ 31 mm) was a predictor of mortality at adjusted (hazard ratio, HR [95%CI]: 1.741 [1.253–2.418], p  < 0.001) and multivariable regression analysis (HR [95%CI]: 1.592 [1.154–2.196], p  = 0.005), together with male gender, old age, high creatinine, low well-aerated lung volume, and high pneumonia extension (c-index [95%CI] = 0.826 [0.796–0.851]). Model discrimination was confirmed on the validation cohort (c-index [95%CI] = 0.789 [0.758–0.823]), also using CT measurements from a second reader (c-index [95%CI] = 0.790 [0.753;0.825]). Conclusion Enlarged MPAD (≥ 31 mm) at admitting chest CT is an independent predictor of mortality in COVID-19. Key Points • Enlargement of main pulmonary artery diameter at chest CT performed within 72 h from the admission was associated with a higher rate of in-hospital mortality in COVID-19 patients. • Enlargement of main pulmonary artery diameter (≥ 31 mm) was an independent predictor of death in COVID-19 patients at adjusted and multivariable regression analysis. • The combined evaluation of clinical findings, lung CT features, and main pulmonary artery diameter may be useful for risk stratification in COVID-19 patients.

The worldwide use of prone position (PP) for invasively ventilated patients with COVID-19 is progressively increasing from the first pandemic wave in everyday clinical practice. Among the suggested treatments for the management of ARDS patients, PP was recommended in the Surviving Sepsis Campaign COVID-19 guidelines as an adjuvant therapy for improving ventilation. In patients with severe classical ARDS, some authors reported that early application of prolonged PP sessions significantly decreases 28-day and 90-day mortality. Since January 2021, the COVID19 Veneto ICU Network research group has developed and implemented nationally and internationally the \"PROVENT-C19 Registry\", endorsed by the Italian Society of Anesthesia Analgesia Resuscitation and Intensive Care…'(SIAARTI). The PROVENT-C19 Registry wishes to describe 1. The real clinical practice on the use of PP in COVID-19 patients during the pandemic at a National and International level; and 2. Potential baseline and clinical characteristics that identify subpopulations of invasively ventilated patients with COVID-19 that may improve daily from PP therapy. This web-based registry will provide relevant information on how the database research tools may improve our daily clinical practice. This multicenter, prospective registry is the first to identify and characterize the role of PP on clinical outcome in COVID-19 patients. In recent years, data emerging from large registries have been increasingly used to provide real-world evidence on the effectiveness, quality, and safety of a clinical intervention. Indeed observation-based registries could be effective tools aimed at identifying specific clusters of patients within a large study population with widely heterogeneous clinical characteristics. The registry was registered (ClinicalTrial.Gov Trials Register NCT04905875) on May 28,2021.

Background To compare differences in the probability of COVID-19-related death between native Italians and immigrants hospitalised with COVID-19. Methods This retrospective study of prospectively collected data was conducted at the ASST Fatebenefratelli-Sacco Hospital in Milan, Italy, between 21 February and 31 November 2020. Uni- and multivariable Cox proportional hazard models were used to assess the impact of the patients' origin on the probability of COVID-19-related death. Results The study population consisted of 1,179 COVID-19 patients: 921 Italians (78.1%) and 258 immigrants (21.9%) who came from Latin America (99, 38%), Asia (72, 28%), Africa (50, 19%) and central/eastern Europe (37, 14%). The Italians were significantly older than the immigrants (median age 70 years, interquartile range (IQR) 58–79 vs 51 years, IQR 41–60; p < 0.001), and more frequently had one or more co-morbidities (79.1% vs 53.9%; p < 0.001). Mortality was significantly greater among the Italians than the immigrants as a whole (26.6% vs 12.8%; p < 0.001), and significantly greater among the immigrants from Latin America than among those from Asia, Africa or central/eastern Europe (21% vs 8%, 6% and 8%; p = 0.016). Univariable analysis showed that the risk of COVID-19-related death was lower among the immigrants (hazard ratio [HR] 0.43, 95% confidence interval [CI] 0.30–0.63; p < 0.0001], but the risk of Latin American immigrants did not significantly differ from that of the Italians (HR 0.74, 95% CI 0.47–1.15; p = 0.183). However, after adjusting for potential confounders, multivariable analysis showed that there was no difference in the risk of death between the immigrants and the Italians (adjusted HR [aHR] 1.04, 95% CI 0.70–1.55; p = 0.831), but being of Latin American origin was independently associated with an increased risk of death (aHR 1.95, 95% CI 1.17–3.23; p = 0.010). Conclusions Mortality was lower among the immigrants hospitalised with COVID-19 than among their Italian counterparts, but this difference disappeared after adjusting for confounders. However, the increased risk of death among immigrants of Latin American origin suggests that COVID-19 information and prevention initiatives need to be strengthened in this sub-population.

Immune checkpoint inhibitors (CI) have demonstrated clinical activity in Hodgkin Lymphoma (HL) patients relapsing after autologous stem cell transplantation (ASCT), although only 20% complete response (CR) rate was observed. The efficacy of CI is strictly related to the host immune competence, which is impaired in heavily pre-treated HL patients. Here, we aimed to enhance the activity of early post-ASCT CI (nivolumab) administration with the infusion of autologous lymphocytes (ALI). Twelve patients with relapse/refractory (R/R) HL (median age 28.5 years; range 18-65), underwent lymphocyte apheresis after first line chemotherapy and then proceeded to salvage therapy. Subsequently, 9 patients with progressive disease at ASCT received early post-transplant CI supported with four ALI, whereas 3 responding patients received ALI alone, as a control cohort. No severe adverse events were recorded. HL-treated patients achieved negative PET scan CR and 8 are alive and disease-free after a median follow-up of 28 months. Four patients underwent subsequent allogeneic SCT. Phenotypic analysis of circulating cells showed a faster expansion of highly differentiated NK cells in ALI plus nivolumab-treated patients as compared to control patients. Our data show anti-tumor activity with good tolerability of ALI + CI for R/R HL and suggest that this setting may accelerate NK cell development/maturation and favor the expansion of the “adaptive” NK cell compartment in patients with HCMV seropositivity, in the absence of HCMV reactivation.

Grapevine ( Vitis vinifera L.) is a crop of major economic importance. However, grapevine yield is guaranteed by the massive use of pesticides to counteract pathogen infections. Under temperate-humid climate conditions, downy mildew is a primary threat for viticulture. Downy mildew is caused by the biotrophic oomycete Plasmopara viticola Berl. & de Toni, which can attack grapevine green tissues. In lack of treatments and with favourable weather conditions, downy mildew can devastate up to 75% of grape cultivation in one season and weaken newly born shoots, causing serious economic losses. Nevertheless, the repeated and massive use of some fungicides can lead to environmental pollution, negative impact on non-targeted organisms, development of resistance, residual toxicity and can foster human health concerns. In this manuscript, we provide an innovative approach to obtain specific pathogen protection for plants. By using the yeast two-hybrid approach and the P. viticola cellulose synthase 2 ( Pv CesA2), as target enzyme, we screened a combinatorial 8 amino acid peptide library with the aim to identify interacting peptides, potentially able to inhibit Pv Cesa2. Here, we demonstrate that the NoPv1 peptide aptamer prevents P. viticola germ tube formation and grapevine leaf infection without affecting the growth of non-target organisms and without being toxic for human cells. Furthermore, NoPv1 is also able to counteract Phytophthora infestans growth, the causal agent of late blight in potato and tomato, possibly as a consequence of the high amino acid sequence similarity between P. viticola and P. infestans cellulose synthase enzymes.

Background Gender differences in asthma perception and control have been reported. The PROXIMA observational study assessed these outcomes in a cohort of Italian severe allergic asthma (SAA) patients. This post hoc analysis of the PROXIMA results was aimed at assessing gender differences in SAA in a real-world setting, focusing on disease perception and impact on quality of life (QoL). Methods The PROXIMA study was an observational, multicenter study, consisting of a cross-sectional and a prospective longitudinal phase, including adult outpatients diagnosed with SAA at step 4 requiring a therapeutic step-up. Patients on omalizumab treatment at baseline were included in the 12-month longitudinal phase. Disease control was assessed by the Asthma Control Questionnaire (ACQ) score, patients’ disease perception by the Brief Illness Perception Questionnaire (BIPQ), and QoL by the EuroQoL five-dimensional three-level questionnaire (EQ-5D-3 L) at baseline and after 6 and 12 months. Two regression models were used to evaluate the association between gender and BIPQ total score and EQ-5D-3L score, respectively. Results 357 patients (65% females) were analyzed for the cross-sectional phase and 99 (62.6% females) for the longitudinal phase. The prevalence of perennial and seasonal aeroallergens was similar between genders. ACQ score decreased similarly during omalizumab treatment at 6 and 12 months in both genders; no gender differences were observed in control rates. Asthma perception was worse among females at all study visits reaching statistical significance at 12 months (mean (SD) B-IPQ total score 41.8 (9.4) vs 35.6 (12.0); T test p-value (males vs females) < 0.05). Statistically significant gender differences were observed for some specific items, with males reporting less symptom experience, concern about the disease, and emotional impact at 12-months. The results of the multivariate regression model for repeated measures showed that overall treatment with omalizumab improved disease perception overtime regardless from gender. Males reported a significantly better QoL compared to females at both 6 and 12 months. Conclusions In this real-world setting, females confirmed to have a worse perception of asthma, feel it as more symptomatic and suffer a greater impact on their QoL, even though having similar baseline severity and obtaining similar level of control.

An unprecedented wave of patients with acute respiratory failure due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease 2019 (COVID-19) hit emergency departments (EDs) in Lombardy, starting in the second half of February 2020. This study describes the direct and indirect impacts of the SARS-CoV-2 outbreak on an urban major-hospital ED. Data regarding all patients diagnosed with COVID-19 presenting from February 1 to March 31, 2020, were prospectively collected, while data regarding non-COVID patients presenting within the same period in 2019 were retrospectively retrieved. ED attendance dropped by 37% in 2020. Two-thirds of this reduction occurred early after the identification of the first autochthonous COVID-19 case in Lombardy, before lockdown measures were enforced. Hospital admissions of non-COVID patients fell by 26%. During the peak of COVID-19 attendance, the ED faced an extraordinary increase in: patients needing oxygen (+239%) or noninvasive ventilation (+725%), transfers to the intensive care unit (+57%), and in-hospital mortality (+309%), compared with the same period in 2019. The COVID-19 outbreak determined an unprecedented upsurge in respiratory failure cases and mortality. Fear of contagion triggered a spontaneous, marked reduction of ED attendance, and, presumably, some as yet unknown quantity of missed or delayed diagnoses for conditions other than COVID-19.