Allestimento e trial clinico di un vaccino a DNA per il trattamento della leishmaniosi canina

This study aimed to evaluate the effect of a DNA vaccine based on two Leishmania antigens (Cpb1, PO) in leishmaniotic dogs. Twelve leishmaniotic dogs from a leishmaniasis-endemic area (Naples, Italy) received three consecutive injections of DNA vaccine at 15-days intervals. Another group of five leishmaniotic dogs received the same amount of pVAX-1 without the coding sequences of Leishmania antigens. Leishmania DNA load, INFγ, IL-4 mRNA expression levels and clinical parameters were tested before and after the therapy, every 3 months for a period of 12 months. Analysis of the data in the vaccinated dogs showed: i) a decrease Leishmania DNA load in lymph node samples, ii) an increase of INFγ and IL-levels in PBMC samples. All vaccinated dogs also showed an improvement in the clinical symptoms. Our results show that the vaccine developed in this study may represent a useful tool in the treatment of leishmaniotic dogs. However, since the duration of positive effects is limited in time, further trials are needed to evaluate the effectiveness of immunotherapy alone or in association with conventional therapy.</br

Epidemiology and genetic characterization of <i>Border Disease Virus</i> circulating in Sardinia

Border Disease Virus (BDV), a pestivirus from the Flaviviridae family, is an important pathogen of sheep and goats responsible for significant losses in farms around the world. In spite of the relevance of this pathogen there are only a few epidemiological studies on BDV infection and, as a consequence, the economic impact on small ruminant productions is probably under-estimated. The aims of this study are i) to determine the distribution of BDV in small ruminant farms in Sardinia and genetically characterize circulating strains ii) analyze the relation between seroprevalence, Somatic Cells Count (SCC) an milk yeld. ELISA was performed using “BVDV/MD/BDV p80 Protein Antibody Test Kit” (IDEXX) on serum of bulk tank milk (BTM) samples collected from Sardinian sheep flocks and goat herds between spring 2014 and 2015. The number of sampled farms corresponded to 8.5% of all registered farms in Sardinia. RNA was isolated using Qiamp Viral RNA mini kit from the cellular fraction of each ELISA positive BTV sample and amplified by rt-PCR using complementary primers to a highly conserved region in the untranslated regions (UTRs) of the viral genome. The amplicons were sequenced for phylogenetic analysis. Geographic distribution of collected specimen, seroprevalence and virological positive samples were analyzed via GIS (ESRI ARCGIS 10.3). ELISA screening shows a seroprevalence of 8.3% among goat farms and 10.5% among ovine farms. Ten from the ELISA positive samples were found rt-PCR positive. The sequence analysis indicates that all the amplified samples match with BDV genomes and the phylogenetic analysis revealed that all the viruses clustered in the same group classified as BDV-7. BDV-7 is the only group isolated in Sardinia so far

Association between maternal dupilumab exposure and pregnancy outcomes in patients with moderate‐to‐severe atopic dermatitis: A nationwide retrospective cohort study

Background There is limited epidemiological evidence on outcomes associated with dupilumab exposure during pregnancy; monitoring pregnancy outcomes in large populations is required. Objective To investigate the potential association between exposure to dupilumab in pregnant women with atopic dermatitis and any adverse pregnancy, neonatal, congenital and post-partum outcomes. Methods We performed a multicentre retrospective cohort study across 19 Italian tertiary referral hospital. Childbearing women were eligible if aged 18–49 years and carried out the pregnancy between 1 October 2018 and 1 September 2022. Results We retrospectively screened records of 5062 patients receiving dupilumab regardless of age and gender, identifying 951 female atopic dermatitis patients of childbearing age, 29 of whom had been exposed to the drug during pregnancy (3%). The median duration of dupilumab treatment prior to conception was 22.5 weeks (range: 3–118). The median time of exposure to the drug during pregnancy was 6 weeks (range: 2–24). All the documented pregnancies were unplanned, and the drug was discontinued in all cases once pregnancy status was reported. The comparison of the study cohort and the control group found no significant drug-associated risk for adverse pregnancy, congenital, neonatal or post-partum outcomes. The absence of a statistically significant effect of exposure on the event was confirmed by bivariate analysis and multivariate analysis adjusted for other confounding factors. Conclusions This cohort of pregnant patients exposed to dupilumab adds to the existing evidence concerning the safety of biologic agents in pregnancy. No safety issues were identified regarding the primary outcome assessed. In clinical practice, these data provide reassurance in case of dupilumab exposure during the first trimester. However, the continuous use of dupilumab throughout pregnancy warrants further research

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

Global disparities in surgeons’ workloads, academic engagement and rest periods: the on-calL shIft fOr geNEral SurgeonS (LIONESS) study

: The workload of general surgeons is multifaceted, encompassing not only surgical procedures but also a myriad of other responsibilities. From April to May 2023, we conducted a CHERRIES-compliant internet-based survey analyzing clinical practice, academic engagement, and post-on-call rest. The questionnaire featured six sections with 35 questions. Statistical analysis used Chi-square tests, ANOVA, and logistic regression (SPSS® v. 28). The survey received a total of 1.046 responses (65.4%). Over 78.0% of responders came from Europe, 65.1% came from a general surgery unit; 92.8% of European and 87.5% of North American respondents were involved in research, compared to 71.7% in Africa. Europe led in publishing research studies (6.6 ± 8.6 yearly). Teaching involvement was high in North America (100%) and Africa (91.7%). Surgeons reported an average of 6.7 ± 4.9 on-call shifts per month, with European and North American surgeons experiencing 6.5 ± 4.9 and 7.8 ± 4.1 on-calls monthly, respectively. African surgeons had the highest on-call frequency (8.7 ± 6.1). Post-on-call, only 35.1% of respondents received a day off. Europeans were most likely (40%) to have a day off, while African surgeons were least likely (6.7%). On the adjusted multivariable analysis HDI (Human Development Index) (aOR 1.993) hospital capacity &gt; 400 beds (aOR 2.423), working in a specialty surgery unit (aOR 2.087), and making the on-call in-house (aOR 5.446), significantly predicted the likelihood of having a day off after an on-call shift. Our study revealed critical insights into the disparities in workload, access to research, and professional opportunities for surgeons across different continents, underscored by the HDI

Subcortical brain volume, regional cortical thickness, and cortical surface area across disorders: findings from the ENIGMA ADHD, ASD, and OCD Working Groups

Objective Attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and obsessive-compulsive disorder (OCD) are common neurodevelopmental disorders that frequently co-occur. We aimed to directly compare all three disorders. The ENIGMA consortium is ideally positioned to investigate structural brain alterations across these disorders. Methods Structural T1-weighted whole-brain MRI of controls (n=5,827) and patients with ADHD (n=2,271), ASD (n=1,777), and OCD (n=2,323) from 151 cohorts worldwide were analyzed using standardized processing protocols. We examined subcortical volume, cortical thickness and surface area differences within a mega-analytical framework, pooling measures extracted from each cohort. Analyses were performed separately for children, adolescents, and adults using linear mixed-effects models adjusting for age, sex and site (and ICV for subcortical and surface area measures). Results We found no shared alterations among all three disorders, while shared alterations between any two disorders did not survive multiple comparisons correction. Children with ADHD compared to those with OCD had smaller hippocampal volumes, possibly influenced by IQ. Children and adolescents with ADHD also had smaller ICV than controls and those with OCD or ASD. Adults with ASD showed thicker frontal cortices compared to adult controls and other clinical groups. No OCD-specific alterations across different age-groups and surface area alterations among all disorders in childhood and adulthood were observed. Conclusion Our findings suggest robust but subtle alterations across different age-groups among ADHD, ASD, and OCD. ADHD-specific ICV and hippocampal alterations in children and adolescents, and ASD-specific cortical thickness alterations in the frontal cortex in adults support previous work emphasizing neurodevelopmental alterations in these disorders

Association between maternal dupilumab exposure and pregnancy outcomes in patients with moderate-to-severe atopic dermatitis: A nationwide retrospective cohort study

BackgroundThere is limited epidemiological evidence on outcomes associated with dupilumab exposure during pregnancy; monitoring pregnancy outcomes in large populations is required.ObjectiveTo investigate the potential association between exposure to dupilumab in pregnant women with atopic dermatitis and any adverse pregnancy, neonatal, congenital and post-partum outcomes.MethodsWe performed a multicentre retrospective cohort study across 19 Italian tertiary referral hospital. Childbearing women were eligible if aged 18-49 years and carried out the pregnancy between 1 October 2018 and 1 September 2022.ResultsWe retrospectively screened records of 5062 patients receiving dupilumab regardless of age and gender, identifying 951 female atopic dermatitis patients of childbearing age, 29 of whom had been exposed to the drug during pregnancy (3%). The median duration of dupilumab treatment prior to conception was 22.5 weeks (range: 3-118). The median time of exposure to the drug during pregnancy was 6 weeks (range: 2-24). All the documented pregnancies were unplanned, and the drug was discontinued in all cases once pregnancy status was reported. The comparison of the study cohort and the control group found no significant drug-associated risk for adverse pregnancy, congenital, neonatal or post-partum outcomes. The absence of a statistically significant effect of exposure on the event was confirmed by bivariate analysis and multivariate analysis adjusted for other confounding factors.ConclusionsThis cohort of pregnant patients exposed to dupilumab adds to the existing evidence concerning the safety of biologic agents in pregnancy. No safety issues were identified regarding the primary outcome assessed. In clinical practice, these data provide reassurance in case of dupilumab exposure during the first trimester. However, the continuous use of dupilumab throughout pregnancy warrants further research

Prevalent use of Combined Prophylaxis of Hepatitis B after liver transplantation in Italy: Results of a national survey in a large cohort

BACKGROUND: Prophylaxis of hepatitis B after liver transplantation with antiviral(s) and immunoglobulins efficiently protect the majority of recipients; however recent experiences suggest a decline of HBsag-positive candidates and the use of hepatitis B immunoglobulin-free schedules. MetHoDs: this national survey evaluated the epidemiology and clinical results of hepatitis B prophylaxis among 10,365 liver transplants performed in 25 years in 13 italian centers. RESULTSː With a percentage of 22, 2260 procedures were performed in HBsAg-positive recipients and 714 out of 1080 anti-HBc-positive grafts were used in HBsag-negative recipients; a total of 2974 patients (29%) were considered at risk of hepatitis B after liver transplantation. similar rates (18% of HBsag-positive candidates and 15% of anti-HBc-positive grafts) were registered in the last collected year. combined prophylaxis with Hepatitis B immunoglobulins remained prevalent among centers and was effective in 96% of HBsag-positive recipients and in 94% of HBsag-negative recipi-ents of anti-HBc-positive grafts.CONCLUSIONS: Data from this survey confirm: the excellent results of combined prophylaxis; the past and persistent use of Hepatitis B immunoglobulin-on and only rare -off prophylactic regimens, in contrast with the newest reports; the increasing use of anti-HBc-positive grafts; the past and present high prevalence of HBsag-positive recipients, due to an increase in candidates with either hepatocellular carcinoma and Hepatitis Delta Virus coinfection in the last years

Immunocompromised patients with acute respiratory distress syndrome : Secondary analysis of the LUNG SAFE database

The aim of this study was to describe data on epidemiology, ventilatory management, and outcome of acute respiratory distress syndrome (ARDS) in immunocompromised patients. Methods: We performed a post hoc analysis on the cohort of immunocompromised patients enrolled in the Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE) study. The LUNG SAFE study was an international, prospective study including hypoxemic patients in 459 ICUs from 50 countries across 5 continents. Results: Of 2813 patients with ARDS, 584 (20.8%) were immunocompromised, 38.9% of whom had an unspecified cause. Pneumonia, nonpulmonary sepsis, and noncardiogenic shock were their most common risk factors for ARDS. Hospital mortality was higher in immunocompromised than in immunocompetent patients (52.4% vs 36.2%; p < 0.0001), despite similar severity of ARDS. Decisions regarding limiting life-sustaining measures were significantly more frequent in immunocompromised patients (27.1% vs 18.6%; p < 0.0001). Use of noninvasive ventilation (NIV) as first-line treatment was higher in immunocompromised patients (20.9% vs 15.9%; p = 0.0048), and immunodeficiency remained independently associated with the use of NIV after adjustment for confounders. Forty-eight percent of the patients treated with NIV were intubated, and their mortality was not different from that of the patients invasively ventilated ab initio. Conclusions: Immunosuppression is frequent in patients with ARDS, and infections are the main risk factors for ARDS in these immunocompromised patients. Their management differs from that of immunocompetent patients, particularly the greater use of NIV as first-line ventilation strategy. Compared with immunocompetent subjects, they have higher mortality regardless of ARDS severity as well as a higher frequency of limitation of life-sustaining measures. Nonetheless, nearly half of these patients survive to hospital discharge. Trial registration: ClinicalTrials.gov, NCT02010073. Registered on 12 December 2013