Endovascular treatment of visceral artery pseudoaneurysms with ethylene-vinyl alcohol (evoh) copolymer-based non-adhesive liquid embolic agents (naleas)

Background and Objectives: Treatment of visceral artery pseudoaneurysms (VAPs) is always indicated regardless of their diameters, as their risk of rupture is significantly higher than that of visceral artery aneurysms. The invasiveness of surgery and its associated complications have led to a shift in favor of radiological interventions as the initial treatment of choice. However, there are still some unanswered questions on endovascular treatment of VAPs regarding the optimal endovascular technique and the efficacy and safety outcomes. The purpose of this multicenter study was to retrospectively evaluate the effectiveness and safety of endovascular treatment of visceral pseudoaneurysms using Ethylene-Vinyl Alcohol (EVOH) Copolymer-Based Non-Adhesive Liquid Embolic Agents (NALEAs). Materials and Methods: Consecutive patients who underwent endovascular embolization with EVOH-based NALEAs for visceral artery pseudoaneurysms between January 2018 and June 2023 were retrospectively evaluated. Results: 38 embolizations were performed. Technical success was achieved in all patients. The clinical success rate was high (92.1% overall), with no significant differences between ruptured and unruptured VAPs (p = 0.679). Seven patients (18.4%) experienced procedure-related complications, related to one case of non-target embolization, four splenic abscesses due to end-organ infarction, and two femoral pseudoaneurysms. The rates of procedure-related complications, end-organ infarction, and vascular access-site complications did not significantly differ between ruptured and unruptured VAPs (p > 0.05). Conclusions: Both ruptured and unruptured visceral pseudoaneurysms can be effectively and safely treated with NALEA-based endovascular embolization. We suggest considering the use of NALEAs, particularly in specific clinical cases that highlight their advantages, including patients with coagulopathy, fragile vessels, and embolization targets that are located at a considerable distance from the microcatheter tip and are otherwise difficult to reach

A machine-learning based bio-psycho-social model for the prediction of non-obstructive and obstructive coronary artery disease

Background: Mechanisms of myocardial ischemia in obstructive and non-obstructive coronary artery disease (CAD), and the interplay between clinical, functional, biological and psycho-social features, are still far to be fully elucidated. Objectives: To develop a machine-learning (ML) model for the supervised prediction of obstructive versus non-obstructive CAD. Methods: From the EVA study, we analysed adults hospitalized for IHD undergoing conventional coronary angiography (CCA). Non-obstructive CAD was defined by a stenosis < 50% in one or more vessels. Baseline clinical and psycho-socio-cultural characteristics were used for computing a Rockwood and Mitnitski frailty index, and a gender score according to GENESIS-PRAXY methodology. Serum concentration of inflammatory cytokines was measured with a multiplex flow cytometry assay. Through an XGBoost classifier combined with an explainable artificial intelligence tool (SHAP), we identified the most influential features in discriminating obstructive versus non-obstructive CAD. Results: Among the overall EVA cohort (n = 509), 311 individuals (mean age 67 ± 11 years, 38% females; 67% obstructive CAD) with complete data were analysed. The ML-based model (83% accuracy and 87% precision) showed that while obstructive CAD was associated with higher frailty index, older age and a cytokine signature characterized by IL-1β, IL-12p70 and IL-33, non-obstructive CAD was associated with a higher gender score (i.e., social characteristics traditionally ascribed to women) and with a cytokine signature characterized by IL-18, IL-8, IL-23. Conclusions: Integrating clinical, biological, and psycho-social features, we have optimized a sex- and gender-unbiased model that discriminates obstructive and non-obstructive CAD. Further mechanistic studies will shed light on the biological plausibility of these associations. Clinical trial registration: NCT02737982

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

The role of immune suppression in COVID-19 hospitalization: clinical and epidemiological trends over three years of SARS-CoV-2 epidemic

Specific immune suppression types have been associated with a greater risk of severe COVID-19 disease and death. We analyzed data from patients >17 years that were hospitalized for COVID-19 at the “Fondazione IRCCS Ca′ Granda Ospedale Maggiore Policlinico” in Milan (Lombardy, Northern Italy). The study included 1727 SARS-CoV-2-positive patients (1,131 males, median age of 65 years) hospitalized between February 2020 and November 2022. Of these, 321 (18.6%, CI: 16.8–20.4%) had at least one condition defining immune suppression. Immune suppressed subjects were more likely to have other co-morbidities (80.4% vs. 69.8%, p < 0.001) and be vaccinated (37% vs. 12.7%, p < 0.001). We evaluated the contribution of immune suppression to hospitalization during the various stages of the epidemic and investigated whether immune suppression contributed to severe outcomes and death, also considering the vaccination status of the patients. The proportion of immune suppressed patients among all hospitalizations (initially stable at <20%) started to increase around December 2021, and remained high (30–50%). This change coincided with an increase in the proportions of older patients and patients with co-morbidities and with a decrease in the proportion of patients with severe outcomes. Vaccinated patients showed a lower proportion of severe outcomes; among non-vaccinated patients, severe outcomes were more common in immune suppressed individuals. Immune suppression was a significant predictor of severe outcomes, after adjusting for age, sex, co-morbidities, period of hospitalization, and vaccination status (OR: 1.64; 95% CI: 1.23–2.19), while vaccination was a protective factor (OR: 0.31; 95% IC: 0.20–0.47). However, after November 2021, differences in disease outcomes between vaccinated and non-vaccinated groups (for both immune suppressed and immune competent subjects) disappeared. Since December 2021, the spread of the less virulent Omicron variant and an overall higher level of induced and/or natural immunity likely contributed to the observed shift in hospitalized patient characteristics. Nonetheless, vaccination against SARS-CoV-2, likely in combination with naturally acquired immunity, effectively reduced severe outcomes in both immune competent (73.9% vs. 48.2%, p < 0.001) and immune suppressed (66.4% vs. 35.2%, p < 0.001) patients, confirming previous observations about the value of the vaccine in preventing serious disease

GWAS meta-analysis of over 29,000 people with epilepsy identifies 26 risk loci and subtype-specific genetic architecture

Epilepsy is a highly heritable disorder affecting over 50 million people worldwide, of which about one-third are resistant to current treatments. Here we report a multi-ancestry genome-wide association study including 29,944 cases, stratified into three broad categories and seven subtypes of epilepsy, and 52,538 controls. We identify 26 genome-wide significant loci, 19 of which are specific to genetic generalized epilepsy (GGE). We implicate 29 likely causal genes underlying these 26 loci. SNP-based heritability analyses show that common variants explain between 39.6% and 90% of genetic risk for GGE and its subtypes. Subtype analysis revealed markedly different genetic architectures between focal and generalized epilepsies. Gene-set analyses of GGE signals implicate synaptic processes in both excitatory and inhibitory neurons in the brain. Prioritized candidate genes overlap with monogenic epilepsy genes and with targets of current antiseizure medications. Finally, we leverage our results to identify alternate drugs with predicted efficacy if repurposed for epilepsy treatment

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

The role of cytoskeleton networks on lipid-mediated delivery of DNA.

BackgroundLipid-mediated delivery of DNA is hindered by extracellular and intracellular barriers that significantly reduce the transfection efficiency of synthetic nonviral vectors.ResultsIn this study we investigated the role of the actin and microtubule networks on the uptake and cytoplasmic transport of multicomponent cationic liposome-DNA complexes in CHO-K1 live cells by means of confocal laser scanning microscopy and 3D single particle tracking. Treatment with actin (latrunculin B)- and microtubule-disrupting (nocodazole) reagents indicated that intracellular trafficking of complexes predominantly involves microtubule-dependent active transport. We found that the actin network has a major effect on the initial uptake of complexes, while the microtubule network is mainly responsible for the subsequent active transportation to the lysosomes.ConclusionCollectively, a strategy to improve the efficiency of lipid gene vectors can be formulated. We could find a lipid formulation that allows the nanoparticles to avoid the microtubule pathway to lysosomes

Current Choices and Management of Treatment in Persons with Severe Hemophilia A without Inhibitors: A Mini-Delphi Consensus

Background. Regular treatment to prevent bleeding and consequent joint deterioration (prophylaxis) is the standard of care for persons with severe hemophilia A, traditionally based on intravenous infusions of the deficient clotting FVIII concentrates (CFCs). In recent years, extended half-life (EHL) CFCs and the non-replacement agent emicizumab, subcutaneously administered, have reduced the treatment burden. Methods. To compare and integrate the opinions on the different therapies available, eight hemophilia specialists were involved in drafting items of interest and relative statements through the Estimate-Talk-Estimate (ETE) method (“mini-Delphi”), in this way reaching consensus. Results. Eighteen items were identified, then harmonized to 10, and a statement was generated for each. These statements highlight the importance of personalized prophylaxis regimens. CFCs, particularly EHL products, seem more suitable for this, despite the challenging intravenous (i.v.) administration. Limited real-world experience, particularly in some clinical settings, and the lack of evidence on long-term safety and efficacy of non-replacement agents, require careful individual risk/benefit assessment and multidisciplinary data collection. Conclusions. The increased treatment options extend the opportunities of personalized prophylaxis, the mainstay of modern management of hemophilia. Close, long-term clinical and laboratory follow-up of patients using newer therapeutic approaches by specialized hemophilia treatment centers is needed

Analytical Performance of Different Laboratory Methods for Measuring Susoctocog-Alfa

Recombinant porcine factor VIII (rpFVIII) is indicated for treating bleeding episodes in acquired haemophilia A, but there are few data regarding laboratory methods to adequately monitor treatment. This study involving three Italian laboratories aimed to evaluate the analytical performance of different assays for measuring rpFVIII. Five spiked rpFVIII samples (0.5–1.5 IU/mL) were analysed on three days, in triplicate, with eleven combinations of reagents (Werfen, Boston, MA, USA: SynthasIL and SynthaFax for one-stage assay, Chromogenix Coamatic FVIII for chromogenic assay), FVIII depleted plasmas (with or without von Willebrand factor—VWF) and calibrators (HemosIL human calibrator plasma, porcine calibrator diluted in FVIII deficient plasma with or without VWF). The assays were performed on ACL TOP analysers (Werfen, Boston, MA, USA). Intra- and inter-assay and inter-laboratory Coefficient of Variation (CV%) were calculated together with percentage of recovery (% recovery) on the expected value. The results showed that the reagent combinations reaching satisfactory analytical performance are: SynthasIL/human calibrator/deficient plasma+VWF (total recovery 99.4%, inter-laboratory CV 4.04%), SynthasIL/porcine calibrator/deficient plasma+VWF (total recovery 111%, inter-laboratory CV 2.75%) and Chromogenic/ porcine calibrator/deficient plasma+VWF (total recovery 96.6%, inter-laboratory CV 8.32%). This study highlights that the use of porcine standard (when available) and FVIII deficient plasma with VWF should be recommended