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Abstract Ventricular septal defect (VSD) is a serious complication of myocardial infarction (MI), with its global incidence significantly reduced in recent years due to advances in coronary reperfusion techniques. However, during the COVID-19 pandemic, there was an unexpected rise in the incidence of post-MI VSD, likely driven by delays in seeking treatment. This study retrospectively analyzed 10 cases of post-MI VSD treated at our hospitals from March 2018 to August 2023, comparing incidence rates across pre-pandemic, pandemic, and post-pandemic periods. The findings revealed a notable increase in VSD cases during the pandemic, with six cases occurring in two years, compared to only two cases in each of the pre-pandemic and post-pandemic periods. Despite these fluctuations, surgical intervention remained a crucial and effective treatment, with 60% of patients surviving the 30-day follow-up. The study underscores the impact of delayed treatment on VSD incidence during the pandemic and highlights the critical need for timely medical intervention to manage severe MI complications effectively.

Background/Objectives: Malpractice in cardiovascular surgery was addressed from the forensic pathology perspective, offering reflections on risk prevention in the Italian context. Litigation and risk management in healthcare, following the Italian law on safety of care, clinical risk management and professional liability, should be viewed in an integrated manner. Methods: We conducted a narrative review on litigation data and the principal areas of complaint in Italy regarding the cardiovascular field. The aim is to discuss human, communicative, organisational, technological and regulatory factors that may play a role in this phenomenon. Results: We discuss the importance of information and consent and the management and monitoring of competences, particularly in specialised activities, given the current human capital deficit. Furthermore, we focus on the centrality of the surgical indication focusing on benefit-risk balance in light of clinical guidelines and team-based evaluation, such as by an emergency heart team, to better tailor care to patients. At the facility level, the minimum volume of activity and the requirements for human resources, specialisations, technologies and organisation standards needed for health activity authorisation are highlighted as foundational to risk prevention. Furthermore, we discussed the availability of the minimum diagnostic and care tools in compliance with guidelines and the role of company clinical and organisational protocols. Conclusions: In the surgical, time-sensitive, highly specialised and technologically advanced sector, the importance of enterprise risk prevention and broad, value-based governance to ensure healthcare quality and safety is emphasised.

INTRODUCTION: Delirium is not commonly diagnosed in neonatal intensive care units and can adversely impact patient outcomes in the ICU setting. Recognition of delirium in the NICU is a necessary first step to address the potential impact on neonatal outcomes. METHODS: We conducted a quality improvement initiative implementing screening for neonatal delirium. We aimed to increase screening in NICU patients from 0% to 85% by March 2022. Interdisciplinary meetings were held with key stakeholders to develop a clinical algorithm. We used standardized tools for delirium screening. Our process measures included weekly nursing compliance with Richmond Agitation Sedation Scale/Cornell Assessment of Pediatric Delirium/ scoring documentation (Fig. 1) and patients referred to psychiatry. Outcome measures included the percentage of patients screened for delirium before discharge. We conducted Plan-Do-Study Act cycles to optimize the screening process in the electronic medical record (EMR). This included creating an order set, documentation flowsheets, and prompts in the EMR for patients. RESULTS: After initial implementation, we achieved an average weekly screening compliance of 76% (Fig. 1). Inclusion criteria expansion resulted in a downward compliance shift to 59%. Subsequently, the addition of the EMR checklist resulted in a center-line shift to a sustained average weekly screening compliance of 77%. An average of 82% of all eligible NICU patients received delirium screening before discharge (Fig. 2). CONCLUSIONS: Using quality improvement methodology, there was increased screening and recognition of delirium in our NICU. Future research efforts could focus on assessing preventive measures and the impact of neonatal delirium on patient outcomes.

Developmental exposure to environmental toxicants has been linked to the onset of neurological disorders and diseases. Despite substantial advances in the field of neurotoxicology, there remain significant knowledge gaps in our understanding of cellular targets and molecular mechanisms that mediate the neurotoxicological endpoints associated with exposure to both legacy contaminants and emerging contaminants of concern. Zebrafish are a powerful neurotoxicological model given their high degree sequence conservation with humans and the similarities they share with mammals in micro- and macro-level brain structures. Many zebrafish studies have effectively utilized behavioral assays to predict the neurotoxic potential of different compounds, but behavioral phenotypes are rarely able to predict the brain structures, cell types, or mechanisms affected by chemical exposures. Calcium-modulated photoactivatable ratiometric integrator (CaMPARI), a recently developed genetically-encoded calcium indicator, undergoes a permanent green to red switch in the presence of elevated intracellular Ca2+ concentrations and 405-nm light, which allows for a "snapshot" of brain activity in freely-swimming larvae. To determine whether behavioral results are predictive of patterns of neuronal activity, we assessed the effects of three common neurotoxicants, ethanol, 2,2',3,5',6-pentachlorobiphenyl (PCB 95), and monoethylhexyl phthalate (MEHP), on both brain activity and behavior by combining the behavioral light/dark assay with CaMPARI imaging. We demonstrate that brain activity profiles and behavioral phenotypes are not always concordant and, therefore, behavior alone is not sufficient to understand how toxicant exposure affects neural development and network dynamics. We conclude that pairing behavioral assays with functional neuroimaging tools such as CaMPARI provides a more comprehensive understanding of the neurotoxic endpoints of compounds while still offering a relatively high throughput approach to toxicity testing.

The Ma‘dan al-šifā’-i Sikandar-šāhī is an extensive Persian handbook of Ayurvedic medicine made for Miyān Bhuwa ibn Ḫawāṣṣ Ḫān, a vizir of Sultan Sikandar Lōdī (r. 1489-1517) to whom the book was dedicated. This treatise was thought to provide Indian Muslim physicians, unfamiliar with Sanskrit, with a comprehensive manual of Ayurvedic medicine and therapy. Miyān Bhuwa allocated considerable resources to achieving this translation project and hired scholars to translate the many parts of Ayurvedic books used to compile the Persian text. This article explores the reasons behind the production of the Ma‘dan al-šifā’ and proposes a new reading of this book. It argues that Miyān Bhuwa’s project was part of a broader process of incorporation of Ayurvedic materials within Persian texts which had already started about two centuries earlier and which allowed Muslim physicians to master new forms of interpretation, classification and treatment of diseases when compared with earlier Arabic and Persian medical books. It looks at the epistemic and the practical issues raised in the preface of the Ma‘dan al-šifā’, which directly questions the adequacy of how Greco-Arabic thought understood body temperament in the Indian environment. It inquires into the authorship of this Persian Ayurvedic handbook and suggests that probably Miyān Bhuwa only assembled the translations made from Sanskrit texts. The last part of the article looks at the conceptual structure of the Ma‘dan al-šifā’ and how the Sanskrit sources and their models shaped the organization of the sections of the Persian book. Moreover, it suggests that the overall framework of the book relied on the overlap of models of presentation of medical knowledge, a device meant to negotiate between the models of the Sanskrit sources and those of the Muslim readers.

The Supports Intensity Scale--Children's Version (SIS-C) was translated into Italian using a committee approach to translation. Latent modeling approaches enabled the leveraging of the large standardization sample from the U.S. (n = 4,015) to generate translation-specific norms from data collected in Italy (n = 435) for children and youth ranging ages 5-16 years placed in six evenly distributed age groups by country. Findings indicated the structure of the SIS-C (i.e., seven support need domains organized under an overall support needs construct), was supported in the Italian context. However, there were age-related differences in the U.S. and Italian samples. In the Italian sample, norms were established for the 5-8 years, 9-10 years, and 11-16 years age groups. Moreover, the Italian sample also differed from other European samples and SIS-C translations. The importance of understanding cultural contexts in interpreting findings from the SIS-C is discussed, along with ways in which SIS-C findings can be used to inform policy and practice in the Italian context.

Abstract Motivated by issues in the context of asymptotically flat spacetimes at null infinity, we discuss in the simplest example of a free massless scalar field in two dimensions several subtleties that arise when setting up the canonical formulation on a single or on two intersecting null hyperplanes with a special emphasis on the infinite-dimensional global and conformal symmetries and their canonical generators, the free data, a consistent treatment of zero modes, matching conditions, and implications for quantization of massless versus massive fields.

BackgroundDespite the high success rate of radiofrequency catheter ablation (RFCA) in Wolff-Parkinson-White Syndrome (WPW), localizing the successful ablation site can be challenging and may require multiple radiofrequency (RF) applications.ObjectiveThis study aims to evaluate the efficacy of a novel workflow for the automatic and precise identification of accessory pathway ablation site, named Delta Wave Automatic Mapping.MethodsPatients undergoing a first procedure for RF ablation of a manifest accessory pathway were included. Electro-Anatomical Mapping (EAM) was performed with the CARTO 3 system (Biosense Webster, Johnson & Johnson Medical S.p.a., Irvine, CA) leveraging auto-acquisition algorithms already present in the CARTO 3 software. Mapping and ablation were performed with an irrigated tip catheter with contact force sensor. Procedure success was defined as loss of pathway function after ablation. The number of RF applications required and time to effect were measured for each patient. Recurrences were evaluated during follow-up visits. Additionally, at the end of each procedure, historical predictors of ablation success were measured offline to evaluate their relationship with the successful ablation site found with the novel workflow.ResultsA total of 50 patients were analysed (62% APs right and 38% APs left). All 50 APs were successfully eliminated in each procedure with a median Time-to-effect (TTE) of 2.0 (IQR 1.2–3.5) seconds. No AP recurrences during a median follow-up of 10 (IQR 6–13) months were recorded. Offline analysis of successful ablation site revealed a pre-ablation delta/ventricular interval of ≤−10 msec in 52% of the patients and in 100% of the patients the signal related to the Kent bundle was identified.ConclusionsThe novel workflow efficiently localizes APs without requiring manual annotations. Historical endocardial parameters predicting success were measured offline for each case and they corresponded to the ablation target automatically annotated by the proposed workflow. This novel mapping workflow holds promise in enhancing the efficacy of RFCA in the presence of manifest APs.

Background and Objectives: In coronary artery bypass grafting (CABG) on pump, achieving optimal visualization is critical for surgical precision and safety. The use of blowers to clear the CABG anastomosis poses risks, including the formation of micro-embolic gas bubbles, which can be insidious and increase the risk of cerebral or myocardial complications. This retrospective study compares the effectiveness of the use of irrigation mist and CO2 versus a direct CO2 blower without irrigation in terms of visualization, postoperative fibrillation, and micro-embolic gas activity. Materials and Methods: The study involved 40 patients who underwent on-pump CABG, with 20 patients assigned to the irrigation mist and CO2 group (ClearView™) and 20 to the direct CO2 blower group. Primary outcomes included the quality of intraoperative visualization, the incidence of fibrillation at aortic de-clamping, and the presence of micro-embolic gas activity detected via transesophageal echocardiography (TEE) in the cardiac chambers. Results: Patients in the irrigation mist and CO2 group experienced superior visualization and reduced tissue desiccation. Fibrillation at the time of aortic de-clamping occurred in two patients (10%) using the irrigation mist and CO2, compared to eight patients (40%) using the direct CO2 blower. Additionally, TEE monitoring revealed lower levels of micro-embolic gas activity in the irrigation mist and CO2 group, indicating a potential reduction in gas embolization risk. Conclusions: The irrigation mist and CO2 system not only provides enhanced visualization during CABG but also significantly reduces the incidence of fibrillation during aortic de-clamping and micro-embolic gas activity. These findings suggest improved patient safety and outcomes, highlighting the irrigation mist and CO2 system as a potentially safer alternative to direct CO2 blowing in the context of myocardial revascularization.

Abstract Seismic anisotropy is a powerful tool to map deformation processes in the deep Earth. Below 660 km, however, observations are scarce and conflicting. In addition, the underlying crystal scale mechanisms, leading to microstructures and crystal orientations, remain poorly constrained. Here, we use multigrain X‐ray diffraction in the laser‐heated diamond anvil cell to investigate the orientations of hundreds of grains in pyrolite, a model composition of the Earth's mantle, at in situ pressure and temperature. Bridgmanite in pyrolite exhibits three regimes of microstructures, due to transformation and deformation at low and high pressure. These microstructures result in predictions of 1.5%–2% shear wave splitting between 660 and 2,000 km with reversals in fast S‐wave polarization direction at about 1,300 km depth. Anisotropy can develop in pyrolite at lower mantle conditions, but pressure has a significant impact on the plastic behavior of bridgmanite, and hence seismic observations, which may explain conflicting anisotropy observations.

Abstract We perform a detailed study of the covariance properties of the symplectic potential of general relativity on a null hypersurface, and of the different polarizations that can be used to study conservative as well as leaky boundary conditions. This allows us to identify a one-parameter family of covariant symplectic potentials. We compute the charges and fluxes for the most general phase space with arbitrary variations. We study five symmetry groups that arise when different restrictions on the variations are included. Requiring stationarity as in the original Wald-Zoupas prescription selects a unique member of the family of symplectic potentials, the one of Chandrasekaran, Flanagan and Prabhu. The associated charges are all conserved on non-expanding horizons, but not on flat spacetime. We show that it is possible to require a weaker notion of stationarity which selects another symplectic potential, again in a unique way, and whose charges are conserved on both non-expanding horizons and flat light-cones. Furthermore, the flux of future-pointing diffeomorphisms at leading-order around an outgoing flat light-cone is positive and reproduces a tidal heating plus a memory term. We also study the conformal conservative boundary conditions suggested by the alternative polarization and identify under which conditions they define a non-ambiguous variational principle. Our results have applications for dynamical notions of entropy, and are useful to clarify the interplay between different boundary conditions, charge prescriptions, and symmetry groups that can be associated with a null boundary.

While many genetic diseases have effective treatments, they frequently progress rapidly to severe morbidity or mortality if those treatments are not implemented immediately. Since front-line physicians frequently lack familiarity with these diseases, timely molecular diagnosis may not improve outcomes. Herein we describe Genome-to-Treatment, an automated, virtual system for genetic disease diagnosis and acute management guidance. Diagnosis is achieved in 13.5 h by expedited whole genome sequencing, with superior analytic performance for structural and copy number variants. An expert panel adjudicated the indications, contraindications, efficacy, and evidence-of-efficacy of 9911 drug, device, dietary, and surgical interventions for 563 severe, childhood, genetic diseases. The 421 (75%) diseases and 1527 (15%) effective interventions retained are integrated with 13 genetic disease information resources and appended to diagnostic reports ( https://gtrx.radygenomiclab.com ). This system provided correct diagnoses in four retrospectively and two prospectively tested infants. The Genome-to-Treatment system facilitates optimal outcomes in children with rapidly progressive genetic diseases.