Hospital Of Turin Research Articles

A novel scoring system proposal to guide surgical treatment indications for high grade gliomas in elderly patients: DAK-75.

High-grade gliomas are the most prevalent neurooncological desease in adults, their incidence increases with age, peaking in the seventh decade. This paper aims to address how to select patients for surgical resection by identifying pre-surgical predictors of 12-month mortality in newly diagnosed HGG patients aged ≥ 75years. A prognostic score will be proposed to guide surgical decisions based on expected survival. Retrospective observational single-center cohort study was carried out at the "Città della Salute e della Scienza-Molinette" University Hospital in Turin, Italy. All consecutive patients aged ≥ 75years newly diagnosed with HGG were included, regardless of whether they underwent surgical resection. Clinical, radiological, histological and molecular data were collected.Variables potentially available at the time of diagnosis were considered to develop a multivariable logistic regression predictive model, with 12-months overall survival as the dependent variable. 102 patients aged 75years or older received a new diagnosis of high-grade glioma, of whom 68 underwent surgical resection. Patients undergoing surgery were slightly younger (76.9 vs 79.0years, p = 0.007) and had better performance status (median KPS 80 vs 70). Most tumors undergoing surgery were localized in cortical or subcortical non-motor areas (p < 0.001) and less frequently deep-seated (p = 0.023) or multifocal (p < 0.001). A predictive model, the DAK-75 score, was developed: the AUROC of the final model was 0.822 (95% CI 0.741-0.902). The score includes clinical presentation, tumor location, and KPS, ranging from 0 to 20, categorizing risk scores into low-risk and high-risk groups (< or > 8). Higher scores corresponded to fewer surgical patients and higher one-year mortality rates (92.2% vs 47.1%, p < 0.001). DAK-75 score may represent a valuable tool in the decision-making process for neurosurgical intervention in elderly patients diagnosed with HGG. Further studies are needed to externally and prospectively validate the scoring system.

Combination of 2 Quantitative Immunoassays and Clinical Score Algorithm to Reduce False-Negative Results in Heparin-Induced Thrombocytopenia: Prevalence Study of Mauriziano Hospital in Turin, Italy.

Heparin-induced thrombocytopenia (HIT) is a serious adverse effect of heparin treatment caused by platelet-activating anti-platelet factor 4 (PF4)/heparin antibodies. Accurate diagnosis of HIT is essential but remains challenging. The aim of our study was to explore the performance of our optimized diagnostic laboratory algorithm, based on Chemiluminescence (CliA) and ELISA immunoassays, on suspected HIT patients. The study compared the prevalence of HIT diagnosis in A.O. Mauriziano with the literature. 163 consecutive patients were investigated for suspected HIT with CliA HemosIL Acustar HIT-IgG, Werfen. HIT was ruled out in all patients with CliA <0.13 U/mL. All patients with CliA >0.13 U/mL were further investigated with Zymutest-HIA anti-PF4 IgG ELISA immunoassay. In these patients, HIT was ruled out on the combination of CliA between 0.13 and 1.0 U/mL followed by ELISA assay <0.300 OD. HIT was ruled in patients whose plasma tested positive or doubtful with CliA and positive with ELISA immunoassay and confirmed positive with a platelet aggregation test (PAT). Suspicion of HIT was revealed with clinical 4Ts score or recent suggestive anamnestic history. Our diagnostic algorithm ruled out HIT diagnosis in 144/163 patients (88%) and predicted a positive PAT in 5/19 (26%) of CliA positive (4/5) or ELISA positive and CliA doubtful (1/5) patients. Our prevalence was 3.1%, comparable with the literature. The approach combining 2 quantitative immunoassays' (CliA and ELISA) results and 4Ts score probability was able to rule out the diagnosis within 1 h in 66% of patients with suspected HIT and within 24 h in 88% of patients. In the remaining 12% of cases, management decisions have to be based on individualized judgment while awaiting functional confirming results (48-72 h).

Fourier Transform Infrared Spectroscopy Application for Candida auris Outbreak Typing in a Referral Intensive Care Unit: Phylogenetic Analysis and Clustering Cut-Off Definition.

Recently Candida auris has emerged as a multi-resistant fungal pathogen, with a significant clinical impact, and is able to persist for a long time on human skin and hospital environments. It is a critical issue on the WHO fungal priority list and therefore it is fundamental to reinforce hospital surveillance protocols to limit nosocomial outbreaks. The purpose of this study was to apply Fourier transform infrared spectroscopy (FT-IR) to investigate the phylogenetic relationships among isolated strains from a C. auris outbreak at the University Intensive Care Unit of a Tertiary University hospital in Turin (Italy). To calculate a clustering cut-off, intra- and inter-isolate, distance values were analysed. The data showed the presence of a major Alfa cluster and a minor Beta cluster with a defined C. auris clustering cut-off. The results were validated by an external C. auris strain and Principal Component and Linear Discriminant Analyses. The application of FT-IR technology allowed to obtain important information about the phylogenetic relationships between the analysed strains, defining for the first time a "not WGS-based" clustering cut-off with a statistical-mathematical approach. FT-IR could represent a valid alternative to molecular methods for the rapid and cost-saving typing of C. auris strains with important clinical implications.

Outcomes and Impact of Pre-ECMO Clinical Course in Severe COVID-19-Related ARDS Treated with VV-ECMO: Data from an Italian Referral ECMO Center.

Background: The efficacy of veno-venous extracorporeal membrane oxygenation (VV-ECMO) as rescue therapy for refractory COVID-19-related ARDS (C-ARDS) is still debated. We describe the cohort of C-ARDS patients treated with VV-ECMO at our ECMO center, focusing on factors that may affect in-hospital mortality and describing the time course of lung mechanics to assess prognosis. Methods: We performed a prospective observational study in the intensive care unit at the "Città della Salute e della Scienza" University Hospital in Turin, Italy, between March 2020 and December 2021. Indications and management of ECMO followed the Extracorporeal Life Support Organization (ELSO) guidelines. Results: The 60-day in-hospital mortality was particularly high (85.4%). Non-survivor patients were more frequently treated with non-invasive ventilatory support and steroids before ECMO (95.1% vs. 57.1%, p = 0.018 and 73.2% vs. 28.6%, p = 0.033, respectively), while hypertension was the only pre-ECMO factor independently associated with in-hospital mortality (HR: 2.06, 95%CI: 1.06-4.00). High rates of bleeding (85.4%) and superinfections (91.7%) were recorded during ECMO, likely affecting the overall length of ECMO (18 days, IQR: 10-24) and the hospital stay (32 days, IQR: 24-47). Static lung compliance was lower in non-survivors (p = 0.031) and differed over time (p = 0.049), decreasing by 48% compared to initial values in non-survivors. Conclusions: Our data suggest the importance of considering NIS among the common ECMO eligibility criteria and changes in lung compliance during ECMO as a prognostic marker.

The digital era of pediatric urological clinical care: telemedicine for management of lower urinary tract symptoms and nocturnal enuresis - a comprehensive tertiary center insight.

Lower urinary tract symptoms (LUTS) and nocturnal enuresis (NE) are complex conditions requiring a long-term follow-up. Telemedicine is an emerging technological tool in the surgical field, and its availability exponentially grew during the COVID-19 pandemic, expanding its application fields, optimizing technical aspects, reducing costs, and ensuring high-quality standards. This work describes our experience with telemedicine in a Division of Pediatric Urology for the follow-up of enuresis and LUTS. A retrospective analysis of our telemedicine preliminary experience was conducted at Regina Margherita Children's Hospital in Turin, Italy. This study included all the patients aged <18 years who were monitored for enuresis and LUTS through telemedicine between September 1, 2021 and July 31, 2023. Clinical data and outcomes were analyzed, and patients and families were asked to voluntary fill an evaluation questionnaire on their satisfaction. Additionally, we focused on the post COVID-19 period, between September 2022 and July 2023, analyzing the data of two different patients' populations: the first one (G1) of patients choosing telemedicine outpatients visits (TOVs) and the second one (G2) of those choosing a face-to-face visit. One hundred five patients were enrolled. One hundred sixty-two TOVs were performed. The median age at first visit was 9.7±0.66 years (range 7-16 years). Diagnosis were: 77/105 (67%) NE and 28/105 (33%) LUTS. The average referred distance between the patients' residence and the hospital was 46.35±129.37 km (range 2-1300 kilometers) and the time taken to overcome it was 44.21±77.29 minutes (range 10-780 minutes). In 64/105 cases (61%) the follow-up was interrupted for total healing or symptoms resumption. Only two cases (2%) required the conversion to an in-person ambulatory consult, due to a social-linguistic barrier. 146/162 families (90%) filled the survey questionnaire at the end of each TOV, reporting in 94% of cases a high satisfaction level. In the comparative statistical analysis of the two patient groups, G1 (52 telemedicine office visits, [TOVs]) vs. G2 (25 face-to-face visits), the average referred distance was 17.78±7.98 km (range: 5-35 km) for G1, contrasting with 7.04±3.35 km (range: 2.5-14 km) for G2 (P=0.00001). Additionally, the waiting time before the visit was 3.96±2.90 minutes (range: 0-10 minutes) for G1, in contrast to 26.52±11.22 minutes (range: 5-44 minutes) for G2 (P=0.00001). Furthermore, a higher compliance with behavioral or pharmacological indications was observed in the G1 group, exhibiting lower adherence in only 12 out of 52 cases compared to 14 out of 25 cases in G2 (P=0.0091). Telemedicine is a proper solution and an effective tool to manage the therapeutic follow-up of NE and LUTS, ensuring suitable quality standards and reducing social costs, such as the loss of working days and transport costs. The implementation and complete integration of its use into the healthcare system should be the goals to pursue in order to take full advantage of all its potentials.

Multidrug-resistant pathogens and ventilator-associated pneumonia in critically ill COVID-19 and non-COVID-19 patients: a prospective observational monocentric comparative study

BackgroundThe COVID-19 pandemic has increased the incidence of ventilator-associated pneumonia (VAP) among critically ill patients. However, a comparison of VAP incidence in COVID-19 and non-COVID-19 cohorts, particularly in a context with a high prevalence of multidrug-resistant (MDR) organisms, is lacking.Material and MethodsWe conducted a single-center, mixed prospective and retrospective cohort study comparing COVID-19 patients admitted to the intensive care unit (ICU) of the “Città della Salute e della Scienza” University Hospital in Turin, Italy, between March 2020 and December 2021 (COVID-19 group), with a historical cohort of ICU patients admitted between June 2016 and March 2018 (NON-COVID-19 group). The primary objective was to define the incidence of VAP in both cohorts. Secondary objectives were to evaluate the microbial cause, resistance patters, risk factors and impact on 28 days, ICU and in-hospital mortality, duration of ICU stay, and duration of hospitalization).ResultsWe found a significantly higher incidence of VAP (51.9% - n = 125) among the 241 COVID-19 patients compared to that observed (31.2% - n = 78) among the 252 NON-COVID-19 patients. The median SOFA score was significantly lower in the COVID-19 group (9, Interquartile range, IQR: 7–11 vs. 10, IQR: 8–13, p < 0.001). The COVID-19 group had a higher prevalence of Gram-positive bacteria-related VAP (30% vs. 9%, p < 0.001), but no significant difference was observed in the prevalence of difficult-to-treat (DTR) or MDR bacteria. ICU and in-hospital mortality in the COVID-19 and NON-COVID-19 groups were 71% and 74%, vs. 33% and 43%, respectively. The presence of COVID-19 was significantly associated with an increased risk of 28-day all-cause hospital mortality (Hazard ratio, HR: 7.95, 95% Confidence Intervals, 95% CI: 3.10-20.36, p < 0.001). Tracheostomy and a shorter duration of mechanical ventilation were protective against 28-day mortality, while dialysis and a high SOFA score were associated with a higher risk of 28-day mortality.ConclusionCOVID-19 patients with VAP appear to have a significantly higher ICU and in-hospital mortality risk regardless of the presence of MDR and DTR pathogens. Tracheostomy and a shorter duration of mechanical ventilation appear to be associated with better outcomes.

Assessment of post-thrombectomy brain hemorrhage in acute ischemic stroke with dual-energy CT: how reliable is it in clinical practice?

Acute ischemic stroke is currently among the main causes of mortality in Western countries. The current guidelines suggest different flowcharts of diagnostic work-up and treatment modalities, including endovascular thrombectomy. Immediately after intra-arterial recanalization, a brain CT scan is usually performed to assess for the presence of peri-procedural complications; in this setting, it is very hard, if possible, to differentiate blood from iodinated contrast material, which is normally present in ischemic tissue because of BBB disruption. Dual-energy CT may be used for this purpose, exploiting its ability to discriminate different materials. We retrospectively studied 44 patients with acute ischemic stroke who were treated with endovascular recanalization at San Giovanni Bosco Hospital in Turin and were then scanned with DECT technology. Subsequent scan was used as standard, since iodine from contrast staining is usually reabsorbed in 24h and blood persists longer. A χ2 test of independence was performed to examine the relationship between blood detected by DECT scan after the endovascular procedure and the presence of blood in the same areas on the following scans, with a significant result: χ2 (1, N = 37) = 10.7086, p = 0.0010. Patients with blood detected on DECT scans had a double chance of having hemorrhagic infarction in follow-up scans, (RR 2.02). The sensitivity and specificity of DECT were respectively 70% and 90%, with an overall diagnostic accuracy of 76% and a positive and negative predictive value, respectively, of 95% and 53%. Dual-energy CT scan after endovascular recanalization in ischemic stroke identifies early hemorrhagic infarction with excellent specificity and good overall diagnostic accuracy, representing a reliable diagnostic tool in everyday clinical practice.

Esperienza del team vulnologico ai tempi del COVID-19

La pandemia di Coronavirus (COVID-19) ha aumentato in modo significativo il ricovero di pazienti prevalentemente a causa delle complicanze respiratorie, in particolar modo nelle unità di terapia intensiva. Durante la prima ondata i pazienti COVID-19 presentavano un numero maggiore di lesioni da pressione (LDP) acquisite in ospedale, rispetto ai pazienti non COVID-19. La fragilità di questi pazienti, le manovre necessarie al loro supporto respiratorio e l’utilizzo di numerosi dispositivi medici sono le motivazioni principali dell’elevato rischio di perdita dell’integrità cutanea. L’insorgenza di lesioni cutanee ha come conseguenze un aumento della degenza, dei costi relativi all’assistenza e, non meno importante, un impatto negativo sulla qualità di vita dei pazienti. Alla luce di tali premesse, il team vulnologico infermieristico dell’Ospedale HUB Mauriziano di Torino, nel periodo pandemico, ha pianificato ed effettuato un intervento di prevenzione/trattamento delle lesioni cutanee e di supporto degli operatori sanitari impegnati nell’assistenza ai pazienti COVID-19 nei reparti dell’ospedale. L’attività è stata svolta nel periodo dal 30/10/2020 al 30/04/2021. Nello studio sono stati arruolati 679 pazienti. In 361 pazienti (53,2%) sono state effettuate esclusivamente attività di tipo preventivo, 343 (95%) di questi pazienti non hanno sviluppato alcuna lesione. L’età, la durata del ricovero e il punteggio di Braden sono stati i fattori più rilevanti nei pazienti con LDP acquisite. In 318 (46,8%) pazienti, oltre ad interventi preventivi, sono stati effettuati trattamenti di lesioni preesistenti, in questo campione in 28 (8,8%) dei casi si è registrato un peggioramento delle lesioni. Infine, la quasi totalità degli operatori, 113 su 118 (96%), ha riconosciuto l’utilità del supporto degli specialisti in Wound Care attraverso la compilazione di un questionario online.

Pharmacogenetics and Pharmacokinetics of Posaconazole in Patients with Acute Myeloid Leukemia: Useful Tools for Antifungal Stewardship

DISCUSSION INTRODUCTION Antifungal prophylaxis with posaconazole in patients with acute myeloid leukemia (AML) undergoing induction chemotherapy is usually recommended [1]. Few studies described the clinical impact of suboptimal posaconazole plasma concentrations during prophylaxis, which may be associated with a higher risk of invasive fungal infections (IFI) and a strong impact on clinical outcome [2]. ENDPOINT: The primary endpoint of this study was to evaluate weekly posaconazole Cthrough plasma concentration in AML patients treated with induction chemotherapy. Since polymorphisms of genes encoding enzymes, transporters and transcription factors were also analyzed a possible association amongst plasma exposure, genetic polymorphisms, risk of breakthrough infection and clinical outcam was evaluated . MATERIALS AND METODS: This was a prospective, single center study at “City of Health and Science”, Molinette Hospital in Turin, Italy. Adult Patients with AML undergoing induction chemotherapy admitted to Haematological wards, were enrolled between March 2023 and July 2023. Antifungal prophylaxis with oral posaconazole, 300mg bid the first day and 300 mg qd thereafter was given. Biological samples (plasma for posaconazole quantificatication and whole blood for genetics) were obtained for each patient after loading dose and then posaconazole C trough were evaluated weekly (at 7, 14, 21 and 28 days). The Following genes were evaluated: UGT1A1, UGT1A3, ABCB1, ABCG2, ABCC2, ABCB11, SLCO1B1, SLCO1B3, SLC22A6, PXR, CAR, VDR, CYP27B1, CYP24A1, GC. The mortality was assessed at day 28 from hospital admission. Invasive fungal disease (IFD) was defined as the occurence of a proven or probable IFD according to the European Organization for Research and Treatment of Cancer/National insitute of Allergy and Infection Diseases Micoses Study Group Criteria (EORTC/MSG) revised definitions [3]. Furthermore, according to the clinical suspicion of breakthrough infection, the switch from prophylaxis to antifungal therapy was also recorded as well as antifungal restaging before treatment change. RESULTS: Twenty patients were included: 9 were women (45%) with a median age of 67 years old (±10.5) and a median Charlson Comorbidity Index of 5 (±1.3). Mean posaconazole C through plasma concentrations are reported in Table 1 and were in range for all the different timepoints. According to EORTC criteria, two patients (10%) had a probable IFI on day 14, and antifungal therapy with liposomal amphotericin B was started [3]. One of those patients had low C trough value at time of suspected breaktrough infection (T 14; 0.2 microg/L 9). The 28 day mortality was 10%, due to the haematological underlying disease. Regarding pharmacogenetic analysis, posaconazole C trough at day 7 and 14 was associated with ABCB1 1236 polymorphism with p=0.022 and p=0.038, respectively. Furthermore, VDR ApaI (p=0.010), VDR TaqI (p=0.023), VDR BsmI (p=0.042), ABCB11 (p=0.023) and UGT1A3 023 (p=0.023) genetic variants were reported in patients with probable IFI. There is a potential impact of the use of posaconazole plasma levels monitoring and associated pharmacogenetics to evaluate the risk of underexposure during antifungal prophylaxis, but also at antifungal restaging before treatment switch. These useful tools may help clinicians to identify patients with a higher risk for under-effective plasma concentrations of posaconazole and can be used to improve antifungal stewardship approach in this setting. The utility of such approaches should also be evaluated in azole-to-azole strategies BIBLIOGRAPHY Olivia White et al. Isavuconazonium or posaconazole for antifungal prophylaxis in patients with acute myeloid leukemia. J Oncol Pharm Pract 2023 May 15;10781552231175825. doi: 10.1177/10781552231175825.Tang LA et al. Risk factors for subtherapeutic levels of posaconazole tablet. J Antimicrob Chemother. 2017 Oct 1;72(10):2902-2905. doi: 10.1093/jac/dkx228. PMID: 29091205Peter Donnelly et al. Revision and update of the Consensus definition of Invasive Fungal Disease from the European Organization for Research adn Treatment of Cancer and the Mycoses study Group Education and Research Consortium. Clin Infect Dis 2020 Sep 12;71(6):1367-1376. doi: 10.1093/cid/ciz1008.

MAURIVAX: A Vaccination Campaign Project in a Hospital Environment for Patients Affected by Autoimmune Diseases and Adult Primary Immunodeficiencies.

Background: Patients with autoimmune diseases (ADs) and primary immunodeficiencies (PIDs) are characterized by an increased risk of noninvasive and widespread infections as they are considered frail patients. In addition, many flares of the underlying disease are reported after routine vaccinations. To date, the vaccination rate in these two populations is suboptimal. According to the latest guidelines, targeted interventions are needed, such as strengthening the network of vaccination activities. Our project aimed to propose a pilot network for carrying out the recommended vaccinations in frail patients. Methods: The Allergy and Immunology Center of the Mauriziano Hospital in Turin, Italy started the "Maurivax" project, a facilitated pathway for frail patients to administer the recommended vaccinations in the setting of a dedicated structure where they could be properly followed up. Results: From June 2022 to February 2023, 49 patients underwent a vaccination consultation: 45 of them (91.8%) were subsequently vaccinated. Among these, 36 subjects (80%) were affected by an active AD and were already in treatment with immunosuppressive therapy or about to start it. Seven patients (15.5%) had a confirmed diagnosis of PID or showed a clinical presentation that was highly suggestive of that condition. Overall, twenty-seven patients (60%) showed a high-grade immunosuppression and six (13.3%) had a low-grade immunosuppression. No patients had a disease flare within 30 days from vaccination and no severe reactions after vaccination was observed. Conclusions: Adherence and vaccination safety at our immunology hospital vaccine clinic dedicated to patients with ADs and PIDs were high. We propose an effective model for managing vaccinations in frail patients in a specialist hospital setting.

Cohort profile: the Turin prostate cancer prognostication (TPCP) cohort.

Prostate cancer (PCa) is the most frequent tumor among men in Europe and has both indolent and aggressive forms. There are several treatment options, the choice of which depends on multiple factors. To further improve current prognostication models, we established the Turin Prostate Cancer Prognostication (TPCP) cohort, an Italian retrospective biopsy cohort of patients with PCa and long-term follow-up. This work presents this new cohort with its main characteristics and the distributions of some of its core variables, along with its potential contributions to PCa research. The TPCP cohort includes consecutive non-metastatic patients with first positive biopsy for PCa performed between 2008 and 2013 at the main hospital in Turin, Italy. The follow-up ended on December 31st 2021. The primary outcome is the occurrence of metastasis; death from PCa and overall mortality are the secondary outcomes. In addition to numerous clinical variables, the study's prognostic variables include histopathologic information assigned by a centralized uropathology review using a digital pathology software system specialized for the study of PCa, tumor DNA methylation in candidate genes, and features extracted from digitized slide images via Deep Neural Networks. The cohort includes 891 patients followed-up for a median time of 10 years. During this period, 97 patients had progression to metastatic disease and 301 died; of these, 56 died from PCa. In total, 65.3% of the cohort has a Gleason score less than or equal to 3 + 4, and 44.5% has a clinical stage cT1. Consistent with previous studies, age and clinical stage at diagnosis are important prognostic factors: the crude cumulative incidence of metastatic disease during the 14-years of follow-up increases from 9.1% among patients younger than 64 to 16.2% for patients in the age group of 75-84, and from 6.1% for cT1 stage to 27.9% in cT3 stage. This study stands to be an important resource for updating existing prognostic models for PCa on an Italian cohort. In addition, the integrated collection of multi-modal data will allow development and/or validation of new models including new histopathological, digital, and molecular markers, with the goal of better directing clinical decisions to manage patients with PCa.

Vaccination and Trust in the National Health System among HIV+ Patients: An Italian Cross-Sectional Survey.

This study aimed to evaluate the knowledge, attitudes, and practises (KAP) of individuals living with HIV (PLWH) regarding vaccines and their trust in the Italian national health system (NHS). A cross-sectional survey was conducted at Amedeo di Savoia Hospital in Turin, Italy, involving 160 HIV-positive patients. Descriptive statistics were utilised to analyse variables such as vaccination status and intention, perceived risk of infection, and disease severity. The infections were categorised into sexually transmitted diseases and other vaccine-preventable diseases. Except for the perceived severity of infection, there were no significant differences in the percentages between the two infection groups for the variables examined. Concerning patients' perception of the Italian NHS, a high percentage of the sample believed in the information provided by healthcare workers (HCWs) (95.6%) and considered HCWs up-to-date on vaccines (93.1%). However, a considerable proportion expressed concerns about insufficient information on vaccine risks from HCWs (33.3%), perceived judgement by HCWs for vaccine refusal (40.3%), and suspected financial interests of HCWs in vaccination (19.5%). Some HIV+ patients may hesitate to be vaccinated or hold misconceptions about the severity of certain infectious diseases. Additionally, there are concerns about trust in the Italian NHS and communication by HCWs.

Retrospective comparison of monochorionic diamniotic twin pregnancies stratified by spontaneous or artificial conception.

To compare outcomes of monochorionic diamniotic (MCDA) twin pregnancies by invitro fertilization (IVF) vs. spontaneously conceived counterparts. Retrospective comparison. Data about MCDA twin pregnancies, conceived spontaneously or by IVF, attending the Twin Pregnancy Care Unit of Sant'Anna Hospital in Turin (Italy) between January 1st 2010 and March 31st 2022, were collected retrospectively. Obstetric, fetal, and neonatal outcomes of MCDA twin pregnancies by IVF were compared to those of spontaneously conceived counterparts. Data were described by univariate and multivariate analysis. 541 MCDA twin pregnancies were included in the study, among which 45 conceived by IVF and 496 spontaneously conceived. Women with IVF twins were older than those who conceived spontaneously (36.7±5.7 vs. 32.1±5.2 years; p<0.001). No significant difference in the prevalence ofpregnancy complications between the two groups was found, except for an increased incidence of hypertensive disorders among IVF pregnancies (17.8 vs. 8.5 %; p=0.039), which resulted nonsignificant after adjusting for maternal age and parity (aOR 1.9, 95 % CI 0.8-4.6). Data about 1,046 live born babies (90 conceived by IVF and 956 spontaneously) were also collected: perinatal outcomes did not differ between the two groups. Our results suggest that MCDA twin pregnancies following IVF are not at increased risk of adverse outcomes compared to spontaneous MCDA twin pregnancies.

Adrenal insufficiency management in the pediatric emergency setting and risk factors for adrenal crisis development

BackgroundIn patients with adrenal insufficiency (AI), adrenal crisis (AC) represents a clinical emergency. Early recognition and prompt management of AC or AC-risk conditions in the Emergency Department (ED) can reduce critical episodes and AC-related outcomes. The aim of the study is to report the clinical and biochemical characteristics of AC presentation to improve their timely recognition and proper management in a ED setting.MethodsSingle-centre, retrospective, observational study on pediatric patients followed at the Department of Pediatric Endocrinology of Regina Margherita Children’s Hospital of Turin for primary AI (PAI) and central AI (CAI).ResultsAmong the 89 children followed for AI (44 PAI, 45 CAI), 35 patients (21 PAI, 14 CAI) referred to the PED, for a total of 77 accesses (44 in patients with PAI and 33 with CAI). The main causes of admission to the PED were gastroenteritis (59.7%), fever, hyporexia or asthenia (45.5%), neurological signs and respiratory disorders (33.8%). The mean sodium value at PED admission was 137.2 ± 1.23 mmol/l and 133.3 ± 1.46 mmol/l in PAI and CAI, respectively (p = 0.05). Steroids administration in PED was faster in patients with CAI than in those with PAI (2.75 ± 0.61 and 3.09 ± 1.47 h from PED access, p = 0.83). Significant factors related to the development of AC were signs of dehydration at admission (p = 0.027) and lack of intake or increase of usual steroid therapy at home (p = 0.059). Endocrinological consulting was requested in 69.2% of patients with AC and 48.4% of subjects without AC (p = 0.032).Conclusionchildren with AI may refer to the PED with an acute life-threatening condition that needs prompt recognition and management. These preliminary data indicate how critical the education of children and families with AI is to improve the management at home, and how fundamental the collaboration of the pediatric endocrinologist with all PED personnel is in raising awareness of early symptoms and signs of AC to anticipate the proper treatment and prevent or reduce the correlated serious events.

Development of an organisational model for the preparation of the mRNA-bnt162B2 vaccine: the experience of the Clinical Galenics Laboratory of the Hospital Pharmacy of the Mauriziano Hospital, Turin

The centralised preparation of the mRNA-bnt162B2 vaccine at the Clinical Galenics Laboratory of the Hospital Pharmacy of the Mauriziano Hospital in Turin is an organisational model designed to guarantee the quality of the drug to be administered, the safety of both the vaccinee and the vaccinating personnel, and the traceability of all operations performed. The preparation in ready-for-use syringes individually packaged and labelled, according to the Good Manufacturing Practice (GMP) of the Official Pharmacopoeia, was entrusted to the Biomedical Laboratory Technician (BLT) under the responsibility of the Hospital Pharmacist. In compliance with the GMP, the model was developed through dedicated premises, specific staff training and written procedures concerning the handling of vaccines. The entire production process was guaranteed by: a Hospital Pharmacist and two interchangeable BLTs, one preparer and one assistant. They were necessary to maintain the aseptic technique and the cross-checking of all operations. Labels were prepared showing qualitative-quantitative composition, batch and expiry date, validity of the preparation, pharmacist's signature. The label applied to each syringe, together with the daily work plan, ensured traceability of the process at every stage. The efficient model proposed has always proved adaptable to the changes that characterised the vaccination campaign. From 27/12/2020 to 31/03/2022 a total of 48.017 doses were prepared. The centralisation of the vaccine preparation in the Clinical Galenics Laboratory of the Hospital Pharmacy also reduced handling errors, as well as the waste from unused residues, which proved to be only 0.08%.

Development of an organisational model for the preparation of the mRNA-bnt162B2 vaccine: the experience of the Clinical Galenics Laboratory of the Hospital Pharmacy of the Mauriziano Hospital, Turin

The centralised preparation of the mRNA-bnt162B2 vaccine at the Clinical Galenics Laboratory of the Hospital Pharmacy of the Mauriziano Hospital in Turin is an organisational model designed to guarantee the quality of the drug to be administered, the safety of both the vaccinee and the vaccinating personnel, and the traceability of all operations performed. The preparation in ready-for-use syringes individually packaged and labelled, according to the Good Manufacturing Practice (GMP) of the Official Pharmacopoeia, was entrusted to the Biomedical Laboratory Technician (BLT) under the responsibility of the Hospital Pharmacist.In compliance with the GMP, the model was developed through dedicated premises, specific staff training and written procedures concerning the handling of vaccines. The entire production process was guaranteed by: a Hospital Pharmacist and two interchangeable BLTs, one preparer and one assistant. They were necessary to maintain the aseptic technique and the cross-checking of all operations. Labels were prepared showing qualitative-quantitative composition, batch and expiry date, validity of the preparation, pharmacist’s signature. The label applied to each syringe, together with the daily work plan, ensured traceability of the process at every stage.The efficient model proposed has always proved adaptable to the changes that characterised the vaccination campaign. From 27/12/2020 to 31/03/2022 a total of 48.017 doses were prepared. The centralisation of the vaccine preparation in the Clinical Galenics Laboratory of the Hospital Pharmacy also reduced handling errors, as well as the waste from unused residues, which proved to be only 0.08%.

D.O.T. PAQUITOP, an Autonomous Mobile Manipulator for Hospital Assistance

The use of robotic technologies for caregiving and assistance has become a very interesting research topic in the field of robotics. Towards this goal, the researchers at Politecnico di Torino are developing robotic solutions for indoor assistance. This paper presents the D.O.T. PAQUITOP project, which aims at developing a mobile robotic assistant for the hospital environment. The mobile robot is composed of a custom omnidirectional platform, named PAQUITOP, a commercial 6 dof robotic arm, sensors for monitoring vital signs in patients, and a tablet to interact with the patient. To prove the effectiveness of this solution, preliminary tests were conducted with success in the laboratories of Politecnico di Torino and, thanks to the collaboration with the Onlus Fondazione D.O.T. and the medical staff of Molinette Hospital in Turin (Italy), at the hematology ward of Molinette Hospital.

Single-run UHPLC-MS/MS method for simultaneous quantification of endogenous steroids and their phase II metabolites in serum for anti-doping purposes

Anti-doping rule violations related to the abuse of endogenous anabolic androgenic steroids can be currently discovered by the urinary steroidal module of Athlete Biological Passport. Since this powerful tool is still subjected to some limitations due to various confounding factors altering the steroid profile, alternative strategies have been constantly proposed. Among these, the measurement of blood concentrations of endogenous steroid hormones by LC-MS is currently of increasing interest in anti-doping, bringing significant advantages for the detection of testosterone abuse in females and in individuals with deletion of UGT2B17 enzyme. Although various research groups have made significant efforts in method development, there is currently no accepted or harmonized anti-doping method for quantitative analysis of the various testosterone doping markers in blood. In this study we present a UHPLC-MS/MS method for the quantification of major circulating steroid hormones together with an extended panel of glucuro- and sulpho-conjugated phase II metabolites of androgens. Chromatographic setup was optimized by comparing the performance of three different C18 stationary phases and by the careful selection of mobile phases with the aim of separating all the target steroids, including numerous isomeric/isobaric compounds. MS parameters were fine-tuned to obtain the sensitivity needed for measuring the target analytes, that show specific serum concentrations ranging from low pg/mL for less abundant compounds to μg/mL for sulpho-conjugated steroids. Finally, sample preparation protocol was developed for the extraction of steroid hormones from 200 μL of serum and the performance was evaluated in terms of extraction recovery and matrix effect. The final method was then applied to authentic serum samples collected from healthy volunteers (40 males and 40 females) at the Blood Bank of the City of Health and Science University Hospital of Turin. The analysis of these samples allowed to obtain results on serum concentrations of the targeted steroids, with particular emphasis on previously undiscovered phase II metabolites, such as the isomers of 5-androstane-3,17-diol glucuronide. This preliminary application also enabled measuring dihydrotestosterone sulphate in male samples, efficiently separating this analyte from its isomer, epiandrosterone sulphate, which circulates in blood at high concentrations.The promising results of this study are encouraging for the measurement of blood steroid profile markers in serum and plasma samples for Athlete Biological Passport purposes.

479 ECHOCARDIOGRAPHIC ESTIMQTION OF CQRDIQC POWER IN CARDIOGENIC SHOCK: CORRELATION WITH INVASIVE HEMODYNAMICS AND PROGNOSTIC IMPLICATIONS.

Abstract Background Cardiac power output (CPO) is currently used for cardiogenic shock patient's evaluation including shock phenotyping, mechanical circulatory support selection and weaning algorithms. Despite its remarkable prognostic role, CPO use is limited by the need for a Swan-Ganz catheter. Aim of this study was to evaluate the feasibility and accuracy of echocardiographic estimation of CPO compared to RHC-derived measurement. We also aimed to investigate the prognostic role of non-invasive CPO in the specific setting of cardiogenic shock. Methods We performed blinded echocardiography in all consecutive heart failure (HF) patients undergoing RHC as a part of their evaluation at Cardiology Department of Città della Salute e della Scienza University hospital in Turin. Echocardiographic CPO was calculated as: (cardiac output * mean arterial pressure)/451. eCPO was subsequently assessed in 80 patients admitted for cardiogenic shock in cardiac ICU of centers participating at the Altshock registry during the first 24 hours from shock onset. Primary endpoint was in-hospital MACE (death, heart transplantation or LVAD implantation during the index hospitalization). Results 103 HF patients (57.6 ± 11.3 years, 63% males, median left ventricle ejection fraction 25% [IQR 20-51%]) were included in the derivation cohort. Mean invasive CPO was 0.72 ± 0.27 W, while eCPO was 0.74 ± 0.27 W. eCPO showed a good correlation with invasive CPO (Pearson r: 0.96, p&amp;lt;0.001). In the Altshock registry cohort (80 patients, 81% males, mean age 62.5 ± 14.4 years, in-hospital mortality 31.4%) eCPO &amp;lt;0.6 (HR 2,48 [95% CI 1,06 - 5,85], p=0,04), hemoglobin (p=0.005), systolic blood pressure (p=0.05) and SCAI class (p=0.02) were associated with increased risk of in-hospital MACE at univariate analysis. Echocardiographic CPO &amp;lt;0.6 remained significantly associated with MACE also after adjustment at multivariate Cox analysis (HR 2,87 [95% CI 1,03 - 7,96] p=0,043). Conclusion Echocardiographic estimation of CPO (eCPO) is feasible and showed a good agreement with invasive CPO. Reduced eCPO during the first 24 hours was associated with increased in-hospital MACE in cardiogenic shock patients.

979 ARRHYTHMOGENIC CARDIOMYOPATHY: LONG-TERM FOLLOW-UP OF A PROSPECTIVE MULTICENTRE COHORT

Abstract Background Arrhythmogenic cardiomyopathy (ACM) is an inherited heart muscle disease characterized by fibro-fatty replacement of predominantly right, left or biventricular myocardium. The clinical course of ACM is characterized by high risk of abrupt arrhythmic ventricular events, potentially leading to sudden cardiac death (SCD), and by progressive impairment of biventricular systolic function, which may lead to heart failure (HF)-related death, with an estimated overall yearly mortality ranging from 0.08% to 3.6% among studies. Aim This study sought to assess the long-term follow-up of a cohort of ACM patients from the Piedmont region of Italy, specifically evaluating the cumulative incidence of SCD, HF-related death and heart transplantat. Methods Patients who received a definite ACM diagnosis according to the latest available International Task Force Criteria (ITFC) at three different institutions in Piedmont (“Cardinal Massaia” Hospital of Asti, “Azienda Ospedaliera Ordine Mauriziano” of Turin and “Città della Salute e della Scienza” Hospital of Turin) between 1982 and March 2022 were prospectively enrolled. Clinical, electrocardiographic and imaging data were collected at baseline and during follow-up. The occurrence of two coprimary composite endpoints was evaluated, namely the arrhythmic composite endpoint of SCD or aborted SCD and the HF-related composite endpoint, including heart transplant for end-stage HF or cardiac death due to pump failure. Independent predictors of the coprimary composite endpoints were also assessed by means of multivariable analysis. Results The overall population included 97 patients; mean age at diagnosis was 38.2 ± 14.3 years; 66 (68%) patients were male. Median follow-up was 12.9 years (interquartile range 0-38 years). The composite arrhythmic outcome occurred in 10 (10.3%) patients and the composite HF outcome occurred in 13 (13.5%) patients. Overall, 19 (19.6%) patients died: seven (37%) patients died from SCD, four (21%) patients died of end-stage HF and eight (42%) patients died from non-cardiac causes. The cumulative incidence of cardiac death was 1.65% per year. Aborted SCD occurred in 3 (3%) patients, sustained ventricular tachycardias in 51 (52%), HF in 17 (18%) and atrial fibrillation in 21 (22%); forty-seven (48%) underwent an implantable cardioverter defibrillator implantation (ICD) and 8 (8%) patients underwent heart transplant. Mean interval between ACM diagnosis and heart transplant was 130.4 ± 75.3 months. At univariable analysis, the presence at baseline of terminal activation duration (TAD) ≥ 55 ms on surface electrocardiogram (p value 0.037), right atrium dilatation at transthoracic echocardiography (p value 0.021) and cardiac magnetic resonance imaging (p value 0.031) and palpitations as main clinical presentation (p value 0.017) were associated with the occurrence of the arrhythmic endpoint. At multivariable analysis, baseline TAD ≥ 55 msec was the only predictor of the composite arrhythmic endpoint (odds ratio 12.5, 95% confidence interval 1.29 to 121.26, p value 0.029). At univariable analysis, the presence of epsilon waves (p value 0.017), TAD ≥ 55 ms (p value 0.020) and T wave inversion in leads V1-V3 (p value 0.022) on surface electrocardiogram, HF (p value 0.018) or atrial arrhythmias (p value &amp;lt; 0.001) at presentation and New York Heart Association (NYHA) class III to IV at diagnosis (p value 0.002) were significantly associated with the composite HF-related endpoint. At multivariable analysis, the presence of atrial arrhythmias at presentation was the only predictor of the HF-related composite endpoint (odds ratio 10.8, 95% confidence interval 1.29 to 90.32, p value 0.028). Conclusions In this multicenter cohort of 97 ACM patients, the cumulative incidence of cardiac death was 1.65% per year at long-term follow-up. Arrhythmic death accounted for the majority of cardiac fatal events (64%), confirming the peculiar predisposition to SCD of ACM patients. Evolution towards end-stage HF and cardiac death due to pump failure were common.