Safety of Rotavirus Vaccination in Preterm Infants Admitted in Neonatal Intensive Care Units in Sicily, Italy: A Multicenter Observational Study

Rotavirus (RV) is among the most common vaccine-preventable diseases in children under five years of age. Despite the severity of rotavirus pathology in early childhood, rotavirus vaccination for children admitted to the neonatal intensive care unit (NICU), who are often born preterm and with various previous illnesses, is not performed. This multicenter, 3-year project aims to evaluate the safety of RV vaccine administration within the six main neonatal intensive care units of the Sicilian Region to preterm infants. Methods: Monovalent live attenuated anti-RV vaccination (RV1) was administered from April 2018 to December 2019 to preterm infants with gestational age ≥ 28 weeks. Vaccine administrations were performed in both inpatient and outpatient hospital settings as a post discharge follow-up (NICU setting) starting at 6 weeks of age according to the official immunization schedule. Any adverse events (expected, unexpected, and serious) were monitored from vaccine administration up to 14 days (first assessment) and 28 days (second assessment) after each of the two scheduled vaccine doses. Results: At the end of December 2019, 449 preterm infants were vaccinated with both doses of rotavirus vaccine within the six participating Sicilian NICUs. Mean gestational age in weeks was 33.1 (±3.8 SD) and the first dose of RV vaccine was administered at 55 days (±12.9 SD) on average. The mean weight at the first dose was 3388 (SD ± 903) grams. Only 0.6% and 0.2% of infants reported abdominal colic and fever above 38.5 ◦C in the 14 days after the first dose, respectively. Overall, 1.9% EAEs were observed at 14 days and 0.4% at 28 days after the first/second dose administration. Conclusions: Data obtained from this study confirm the safety of the monovalent rotavirus vaccine even in preterm infants with gestational age ≥ 28 weeks, presenting an opportunity to improve the vaccination offer both in Sicily and in Italy by protecting the most fragile infants who are more at risk of contracting severe rotavirus gastroenteritis and nosocomial RV infection

Efficacy of a new technique - INtubate-RECruit-SURfactant-Extubate - "IN-REC-SUR-E" - in preterm neonates with respiratory distress syndrome: Study protocol for a randomized controlled trial

Background: Although beneficial in clinical practice, the INtubate-SURfactant-Extubate (IN-SUR-E) method is not successful in all preterm neonates with respiratory distress syndrome, with a reported failure rate ranging from 19 to 69 %. One of the possible mechanisms responsible for the unsuccessful IN-SUR-E method, requiring subsequent re-intubation and mechanical ventilation, is the inability of the preterm lung to achieve and maintain an "optimal" functional residual capacity. The importance of lung recruitment before surfactant administration has been demonstrated in animal studies showing that recruitment leads to a more homogeneous surfactant distribution within the lungs. Therefore, the aim of this study is to compare the application of a recruitment maneuver using the high-frequency oscillatory ventilation (HFOV) modality just before the surfactant administration followed by rapid extubation (INtubate-RECruit-SURfactant-Extubate: IN-REC-SUR-E) with IN-SUR-E alone in spontaneously breathing preterm infants requiring nasal continuous positive airway pressure (nCPAP) as initial respiratory support and reaching pre-defined CPAP failure criteria. Methods/design: In this study, 206 spontaneously breathing infants born at 24+0-27+6 weeks' gestation and failing nCPAP during the first 24 h of life, will be randomized to receive an HFOV recruitment maneuver (IN-REC-SUR-E) or no recruitment maneuver (IN-SUR-E) just prior to surfactant administration followed by prompt extubation. The primary outcome is the need for mechanical ventilation within the first 3 days of life. Infants in both groups will be considered to have reached the primary outcome when they are not extubated within 30 min after surfactant administration or when they meet the nCPAP failure criteria after extubation. Discussion: From all available data no definitive evidence exists about a positive effect of recruitment before surfactant instillation, but a rationale exists for testing the following hypothesis: a lung recruitment maneuver performed with a step-by-step Continuous Distending Pressure increase during High-Frequency Oscillatory Ventilation (and not with a sustained inflation) could have a positive effects in terms of improved surfactant distribution and consequent its major efficacy in preterm newborns with respiratory distress syndrome. This represents our challenge. Trial registration: ClinicalTrials.gov identifier: NCT02482766. Registered on 1 June 2015

Off-label long acting injectable antipsychotics in real-world clinical practice: a cross-sectional analysis of prescriptive patterns from the STAR Network DEPOT study

Introduction Information on the off-label use of Long-Acting Injectable (LAI) antipsychotics in the real world is lacking. In this study, we aimed to identify the sociodemographic and clinical features of patients treated with on- vs off-label LAIs and predictors of off-label First- or Second-Generation Antipsychotic (FGA vs. SGA) LAI choice in everyday clinical practice. Method In a naturalistic national cohort of 449 patients who initiated LAI treatment in the STAR Network Depot Study, two groups were identified based on off- or on-label prescriptions. A multivariate logistic regression analysis was used to test several clinically relevant variables and identify those associated with the choice of FGA vs SGA prescription in the off-label group. Results SGA LAIs were more commonly prescribed in everyday practice, without significant differences in their on- and off-label use. Approximately 1 in 4 patients received an off-label prescription. In the off-label group, the most frequent diagnoses were bipolar disorder (67.5%) or any personality disorder (23.7%). FGA vs SGA LAI choice was significantly associated with BPRS thought disorder (OR = 1.22, CI95% 1.04 to 1.43, p = 0.015) and hostility/suspiciousness (OR = 0.83, CI95% 0.71 to 0.97, p = 0.017) dimensions. The likelihood of receiving an SGA LAI grew steadily with the increase of the BPRS thought disturbance score. Conversely, a preference towards prescribing an FGA was observed with higher scores at the BPRS hostility/suspiciousness subscale. Conclusion Our study is the first to identify predictors of FGA vs SGA choice in patients treated with off-label LAI antipsychotics. Demographic characteristics, i.e. age, sex, and substance/alcohol use co-morbidities did not appear to influence the choice towards FGAs or SGAs. Despite a lack of evidence, clinicians tend to favour FGA over SGA LAIs in bipolar or personality disorder patients with relevant hostility. Further research is needed to evaluate treatment adherence and clinical effectiveness of these prescriptive patterns

Insight from an Italian Delphi Consensus on EVAR feasibility outside the instruction for use: the SAFE EVAR Study

BACKGROUND: The SAfety and FEasibility of standard EVAR outside the instruction for use (SAFE-EVAR) Study was designed to define the attitude of Italian vascular surgeons towards the use of standard endovascular repair (EVAR) for infrarenal abdominal aortic aneurysm (AAA) outside the instruction for use (IFU) through a Delphi consensus endorsed by the Italian Society of Vascular and Endovascular Surgery (Societa Italiana di Chirurgia Vascolare ed Endovascolare - SICVE). METHODS: A questionnaire consisting of 26 statements was developed, validated by an 18 -member Advisory Board, and then sent to 600 Italian vascular surgeons. The Delphi process was structured in three subsequent rounds which took place between April and June 2023. In the first two rounds, respondents could indicate one of the following five degrees of agreement: 1) strongly agree; 2) partially agree; 3) neither agree nor disagree; 4) partially disagree; 5) strongly disagree; while in the third round only three different choices were proposed: 1) agree; 2) neither agree nor disagree; 3) disagree. We considered the consensus reached when >70% of respondents agreed on one of the options. After the conclusion of each round, a report describing the percentage distribution of the answers was sent to all the participants. RESULTS: Two -hundred -forty-four (40.6%) Italian Vascular Surgeons agreed to participate the first round of the Delphi Consensus; the second and the third rounds of the Delphi collected 230 responders (94.3% of the first -round responders). Four statements (15.4%) reached a consensus in the first rounds. Among the 22 remaining statements, one more consensus (3.8%) was achieved in the second round. Finally, seven more statements (26.9%) reached a consensus in the simplified last round. Globally, a consensus was reached for almost half of the proposed statements (46.1%). CONCLUSIONS: The relatively low consensus rate obtained in this Delphi seems to confirm the discrepancy between Guideline recommendations and daily clinical practice. The data collected could represent the source for a possible guidelines' revision and the proposal of specific Good Practice Points in all those aspects with only little evidence available

The Role of Attitudes Toward Medication and Treatment Adherence in the Clinical Response to LAIs: Findings From the STAR Network Depot Study

Background: Long-acting injectable (LAI) antipsychotics are efficacious in managing psychotic symptoms in people affected by severe mental disorders, such as schizophrenia and bipolar disorder. The present study aimed to investigate whether attitude toward treatment and treatment adherence represent predictors of symptoms changes over time. Methods: The STAR Network \u201cDepot Study\u201d was a naturalistic, multicenter, observational, prospective study that enrolled people initiating a LAI without restrictions on diagnosis, clinical severity or setting. Participants from 32 Italian centers were assessed at three time points: baseline, 6-month, and 12-month follow-up. Psychopathological symptoms, attitude toward medication and treatment adherence were measured using the Brief Psychiatric Rating Scale (BPRS), the Drug Attitude Inventory (DAI-10) and the Kemp's 7-point scale, respectively. Linear mixed-effects models were used to evaluate whether attitude toward medication and treatment adherence independently predicted symptoms changes over time. Analyses were conducted on the overall sample and then stratified according to the baseline severity (BPRS < 41 or BPRS 65 41). Results: We included 461 participants of which 276 were males. The majority of participants had received a primary diagnosis of a schizophrenia spectrum disorder (71.80%) and initiated a treatment with a second-generation LAI (69.63%). BPRS, DAI-10, and Kemp's scale scores improved over time. Six linear regressions\u2014conducted considering the outcome and predictors at baseline, 6-month, and 12-month follow-up independently\u2014showed that both DAI-10 and Kemp's scale negatively associated with BPRS scores at the three considered time points. Linear mixed-effects models conducted on the overall sample did not show any significant association between attitude toward medication or treatment adherence and changes in psychiatric symptoms over time. However, after stratification according to baseline severity, we found that both DAI-10 and Kemp's scale negatively predicted changes in BPRS scores at 12-month follow-up regardless of baseline severity. The association at 6-month follow-up was confirmed only in the group with moderate or severe symptoms at baseline. Conclusion: Our findings corroborate the importance of improving the quality of relationship between clinicians and patients. Shared decision making and thorough discussions about benefits and side effects may improve the outcome in patients with severe mental disorders

How future surgery will benefit from SARS-COV-2-related measures: a SPIGC survey conveying the perspective of Italian surgeons

COVID-19 negatively affected surgical activity, but the potential benefits resulting from adopted measures remain unclear. The aim of this study was to evaluate the change in surgical activity and potential benefit from COVID-19 measures in perspective of Italian surgeons on behalf of SPIGC. A nationwide online survey on surgical practice before, during, and after COVID-19 pandemic was conducted in March-April 2022 (NCT:05323851). Effects of COVID-19 hospital-related measures on surgical patients' management and personal professional development across surgical specialties were explored. Data on demographics, pre-operative/peri-operative/post-operative management, and professional development were collected. Outcomes were matched with the corresponding volume. Four hundred and seventy-three respondents were included in final analysis across 14 surgical specialties. Since SARS-CoV-2 pandemic, application of telematic consultations (4.1% vs. 21.6%; p < 0.0001) and diagnostic evaluations (16.4% vs. 42.2%; p < 0.0001) increased. Elective surgical activities significantly reduced and surgeons opted more frequently for conservative management with a possible indication for elective (26.3% vs. 35.7%; p < 0.0001) or urgent (20.4% vs. 38.5%; p < 0.0001) surgery. All new COVID-related measures are perceived to be maintained in the future. Surgeons' personal education online increased from 12.6% (pre-COVID) to 86.6% (post-COVID; p < 0.0001). Online educational activities are considered a beneficial effect from COVID pandemic (56.4%). COVID-19 had a great impact on surgical specialties, with significant reduction of operation volume. However, some forced changes turned out to be benefits. Isolation measures pushed the use of telemedicine and telemetric devices for outpatient practice and favored communication for educational purposes and surgeon-patient/family communication. From the Italian surgeons' perspective, COVID-related measures will continue to influence future surgical clinical practice

Études précliniques sur un foie extracorporel bioartificiel

For all patients suffering of acute liver failure, there is an urgent need of alternatives to liver transplantation. Due to a variety of factors, those patients do not always have easy access to an available organ and die waiting for a transplant. Therefore, it is imperative to find viable alternatives to liver transplantation. Among the various alternatives that emerged in recent years, our group has mainly investigated the concept of bioartificial liver. It is an extracorporeal circulation device equipped with artificial elements (activated charcoal and ionic resin) and a biological element (hepatic biomass) capable of supporting the failing organ. This device has the role of providing hepatic functions, lost due to the disease, helping the patient to remain alive until an organ is available or, otherwise, capable of promoting natural liver regeneration. This thesis retraces the evolution of these devices over time, describing their principle of operation and the main results proposed by the literature. The focus is then moved on the development of our liver supply device and the scientific path that allowed optimizing the hepatic biomass at best. This thesis work led to the development of a ready-to-use BAL device on animal models of acute liver failure.Pour tous les patients souffrant d'une insuffisance hépatique aigue, il existe un besoin urgent de solutions alternatives à la transplantation du foie. En raison de divers facteurs, ces patients n'ont pas toujours accès à un organe et meurent dans l’attente d’une greffe. Il est donc impératif de trouver des alternatives viables à la transplantation du foie. Parmi les différentes alternatives apparues ces dernières années, notre groupe a principalement étudié le concept de foie bioartificiel. Il s'agit d'un dispositif de circulation extracorporelle équipé d'éléments artificiels (charbon actif et résine ionique) et d'éléments biologiques (biomasse hépatique) capables de soutenir l'organe défaillant. Ce dispositif a pour rôle de fournir les fonctions hépatiques, perdues à cause de la maladie, afin d'aider le patient à rester en vie jusqu'à ce qu'un organe soit disponible ou de favoriser la régénération naturelle du foie. Cette thèse retrace l'évolution de ces dispositifs au cours du temps, en décrivant leur principe de fonctionnement et les principaux résultats proposés par la littérature. Un accent est ensuite mis sur le développement de notre dispositif de suppléance hépatique et sur la voie scientifique qui a permis d'optimiser au mieux la biomasse hépatique. Ce travail a conduit à la mise au point d'un dispositif BAL prêt à l'emploi sur des modèles de petits animaux en insuffisance hépatique aigue

Études précliniques sur un foie extracorporel bioartificiel

Pour tous les patients souffrant d'une insuffisance hépatique aigue, il existe un besoin urgent de solutions alternatives à la transplantation du foie. En raison de divers facteurs, ces patients n'ont pas toujours accès à un organe et meurent dans l’attente d’une greffe. Il est donc impératif de trouver des alternatives viables à la transplantation du foie. Parmi les différentes alternatives apparues ces dernières années, notre groupe a principalement étudié le concept de foie bioartificiel. Il s'agit d'un dispositif de circulation extracorporelle équipé d'éléments artificiels (charbon actif et résine ionique) et d'éléments biologiques (biomasse hépatique) capables de soutenir l'organe défaillant. Ce dispositif a pour rôle de fournir les fonctions hépatiques, perdues à cause de la maladie, afin d'aider le patient à rester en vie jusqu'à ce qu'un organe soit disponible ou de favoriser la régénération naturelle du foie. Cette thèse retrace l'évolution de ces dispositifs au cours du temps, en décrivant leur principe de fonctionnement et les principaux résultats proposés par la littérature. Un accent est ensuite mis sur le développement de notre dispositif de suppléance hépatique et sur la voie scientifique qui a permis d'optimiser au mieux la biomasse hépatique. Ce travail a conduit à la mise au point d'un dispositif BAL prêt à l'emploi sur des modèles de petits animaux en insuffisance hépatique aigue.For all patients suffering of acute liver failure, there is an urgent need of alternatives to liver transplantation. Due to a variety of factors, those patients do not always have easy access to an available organ and die waiting for a transplant. Therefore, it is imperative to find viable alternatives to liver transplantation. Among the various alternatives that emerged in recent years, our group has mainly investigated the concept of bioartificial liver. It is an extracorporeal circulation device equipped with artificial elements (activated charcoal and ionic resin) and a biological element (hepatic biomass) capable of supporting the failing organ. This device has the role of providing hepatic functions, lost due to the disease, helping the patient to remain alive until an organ is available or, otherwise, capable of promoting natural liver regeneration. This thesis retraces the evolution of these devices over time, describing their principle of operation and the main results proposed by the literature. The focus is then moved on the development of our liver supply device and the scientific path that allowed optimizing the hepatic biomass at best. This thesis work led to the development of a ready-to-use BAL device on animal models of acute liver failure

Adhesive coatings based on melanin-like nanoparticles for surgical membranes

Adhesive coatings for implantable biomaterials can be designed to prevent material displacement from the site of implant. In this paper, a strategy based on the use of melanin-like nanoparticles (MNPs) for the development of adhesive coatings for polysaccharidic membranes was devised. MNPs were synthesized in vitro and characterized in terms of dimensions and surface potential, as a function of pH and ionic strength. The in vitro biocompatibility of MNPs was investigated on fibroblast cells, while the antimicrobial properties of MNPs in suspension were evaluated on E. coli and S. aureus cultures. The manufacturing of the adhesive coatings was carried out by spreading MNPs over the surface of polysaccharidic membranes; the adhesive properties of the nano-engineered coating to the target tissue (intestinal serosa) were studied in simulated physiological conditions. Overall, this study opens for novel approaches in the design of naturally inspired nanostructured adhesive systems