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Data capture systems that acquire continuous hospital-based electrocardiographic (ECG) and physiologic (vital signs) data can foster robust research (i.e., large sample sizes from consecutive patients). However, the application of these systems and the data generated are complex and requires careful human oversight to ensure that accurate and high quality data are procured. This technical article will describe two different data capture systems created by our research group designed to examine false alarms associated with alarm fatigue in nurses. The following aspects regarding these data capture systems will be discussed: (1) history of development; (2) summary of advantages, challenges, and important considerations; (3) their use in research; (4) their use in clinical care; and (5) future developments.

BACKGROUND: Continuous electrocardiographic (ECG) monitoring is used to identify ventricular tachycardia (VT), but false alarms occur frequently. OBJECTIVE: The purpose of this study was to assess the rate of 30-day in-hospital mortality associated with VT alerts generated from bedside ECG monitors to those from a new algorithm among intensive care unit (ICU) patients. METHODS: We conducted a retrospective cohort study in consecutive adult ICU patients at an urban academic medical center and compared current bedside monitor VT alerts, VT alerts from a new-unannotated algorithm, and true-annotated VT. We used survival analysis to explore the association between VT alerts and mortality. RESULTS: We included 5679 ICU admissions (mean age 58 ± 17 years; 48% women), 503 (8.9%) experienced 30-day in-hospital mortality. A total of 30.1% had at least 1 current bedside monitor VT alert, 14.3% had a new-unannotated algorithm VT alert, and 11.6% had true-annotated VT. Bedside monitor VT alert was not associated with increased rate of 30-day mortality (adjusted hazard ratio [aHR] 1.06; 95% confidence interval [CI] 0.88-1.27), but there was an association for VT alerts from our new-unannotated algorithm (aHR 1.38; 95% CI 1.12-1.69) and true-annotated VT(aHR 1.39; 95% CI 1.12-1.73). CONCLUSION: Unannotated and annotated-true VT were associated with increased rate of 30-day in-hospital mortality, whereas current bedside monitor VT was not. Our new algorithm may accurately identify high-risk VT; however, prospective validation is needed.

BackgroundFalse ventricular tachycardia (VT) alarms are common during in-hospital electrocardiographic (ECG) monitoring. Prior research shows that the majority of false VT can be attributed to algorithm deficiencies.PurposeThe purpose of this study was: (1) to describe the creation of a VT database annotated by ECG experts and (2) to determine true vs. false VT using a new VT algorithm created by our group.MethodsThe VT algorithm was processed in 5320 consecutive ICU patients with 572,574 h of ECG and physiologic monitoring. A search algorithm identified potential VT, defined as: heart rate >100 beats/min, QRSs > 120 ms, and change in QRS morphology in >6 consecutive beats compared to the preceding native rhythm. Seven ECG channels, SpO2 , and arterial blood pressure waveforms were processed and loaded into a web-based annotation software program. Five PhD-prepared nurse scientists performed the annotations.ResultsOf the 5320 ICU patients, 858 (16.13%) had 22,325 VTs. After three levels of iterative annotations, a total of 11,970 (53.62%) were adjudicated as true, 6485 (29.05%) as false, and 3870 (17.33%) were unresolved. The unresolved VTs were concentrated in 17 patients (1.98%). Of the 3870 unresolved VTs, 85.7% (n = 3281) were confounded by ventricular paced rhythm, 10.8% (n = 414) by underlying BBB, and 3.5% (n = 133) had a combination of both.ConclusionsThe database described here represents the single largest human-annotated database to date. The database includes consecutive ICU patients, with true, false, and challenging VTs (unresolved) and could serve as a gold standard database to develop and test new VT algorithms.

Modelling objects at a large resolution or scale brings challenges in the storage and processing of data and requires efficient structures. In the context of modelling urban environments, we face both issues: 3D data from acquisition extends at geographic scale, and digitization of buildings of historical value can be particularly dense. Therefore, it is crucial to exploit the point cloud derived from acquisition as much as possible, before (or alongside) deriving other representations (e.g., surface or volume meshes) for further needs (e.g., visualization, simulation). In this paper, we present our work in processing 3D data of urban areas towards the generation of a semantic model for a city digital twin. Specifically, we focus on the recognition of shape primitives (e.g., planes, cylinders, spheres) in point clouds representing urban scenes, with the main application being the semantic segmentation into walls, roofs, streets, domes, vaults, arches, and so on.Here, we extend the conference contribution in Romanengo et al. (2023a), where we presented our preliminary results on single buildings. In this extended version, we generalize the approach to manage whole cities by preliminarily splitting the point cloud building-wise and streamlining the pipeline. We added a thorough experimentation with a benchmark dataset from the city of Tallinn (47,000 buildings), a portion of Vaihingen (170 building) and our case studies in Catania and Matera, Italy (4 high-resolution buildings). Results show that our approach successfully deals with point clouds of considerable size, either surveyed at high resolution or covering wide areas. In both cases, it proves robust to input noise and outliers but sensitive to uneven sampling density.

Based on the increase in the rates of social vulnerability of the Argentine population, an analysis was carried out regarding the quality of life and resilience of the population. Objective: To weigh resilience and quality of life in the parents and caregivers who attend the Child Development Centers of the Ministry of Social Development (CeDIS) of the City of Buenos Aires, relative to the broader Argentine population. Sample: non-probabilistic, intentional, 650 adult subjects participating in CeDIS. Results: Quality of life, health, future safety, and community satisfaction are more influential factors for CeDIS participants than they are to the general population of Argentina. Levels of resilience increase proportionally with quality of life, in line with the apparent correlation between quality of life levels and the dimensions of resilience. It could be inferred that improvements in quality of life would produce a greater increase in resilience levels.

Abstract Background Relapse and refractory (R/R) rates after first‐line R‐CHOP in diffuse large B cell lymphomas (DLBCL) are ~40% and ~15% respectively. Aims We conducted a retrospective real‐world analysis aimed at evaluating clinical outcomes of R/R DLBCL patients. Material and Methods Overall, 403 consecutive DLBCL patients treated in two large hematological centers in Torino, Italy were reviewed. Results At a median follow up of 50 months, 5‐year overall survival from diagnosis (OS‐1) was 66.5%, and 2‐year progression free survival (PFS‐1) was 68%. 134 (34.4%) patients relapsed (n = 46, 11.8%) or were refractory (n = 88, 22.6%) to R‐CHOP. Most employed salvage treatments included platinum salt‐based regimens in 38/134 (28.4%), lenalidomide in 14 (10.4%). Median OS and PFS after disease relapse or progression (OS‐2 and PFS‐2) were 6.7 and 5.1 months respectively. No significant difference in overall response rate, OS‐2 or PFS‐2 in patients treated with platinum‐based regimens versus other regimens was observed. By multivariate analysis, age between 60 and 80 years, germinal center B cell type cell of origin and extranodal involvement of

Conferences are spaces to meet and network within and across academic and technical fields, learn about new advances, and share our work. They can help define career paths and create long-lasting collaborations and opportunities. However, these opportunities are not equal for all. This article introduces 10 simple rules to host an inclusive conference based on the authors' recent experience organizing the 2021 edition of the useR! statistical computing conference, which attracted a broad range of participants from academia, industry, government, and the nonprofit sector. Coming from different backgrounds, career stages, and even continents, we embraced the challenge of organizing a high-quality virtual conference in the context of the Coronavirus Disease 2019 (COVID-19) pandemic and making it a kind, inclusive, and accessible experience for as many people as possible. The rules result from our lessons learned before, during, and after the organization of the conference. They have been written mainly for potential organizers and selection committees of conferences and contain multiple practical tips to help a variety of events become more accessible and inclusive. We see this as a starting point for conversations and efforts towards building more inclusive conferences across the world. * Translated versions of the English abstract and the list of rules are available in 10 languages in S1 Text: Arabic, French, German, Italian, Japanese, Korean, Portuguese, Spanish, Tamil, and Thai.

P21 is a protein secreted by all forms of Trypanosoma cruzi (T. cruzi) with recognized biological activities determined in studies using the recombinant form of the protein. In our recent study, we found that the ablation of P21 gene decreased Y strain axenic epimastigotes multiplication and increased intracellular replication of amastigotes in HeLa cells infected with metacyclic trypomastigotes. In the present study, we investigated the effect of P21 in vitro using C2C12 cell lines infected with tissue culture-derived trypomastigotes (TCT) of wild-type and P21 knockout (TcP21−/−) Y strain, and in vivo using an experimental model of T. cruzi infection in BALB/c mice. Our in-vitro results showed a significant decrease in the host cell invasion rate by TcP21−/− parasites as measured by Giemsa staining and cell count in bright light microscope. Quantitative polymerase chain reaction (qPCR) analysis showed that TcP21−/− parasites multiplied intracellularly to a higher extent than the scrambled parasites at 72h post-infection. In addition, we observed a higher egress of TcP21−/− trypomastigotes from C2C12 cells at 144h and 168h post-infection. Mice infected with Y strain TcP21−/− trypomastigotes displayed higher systemic parasitemia, heart tissue parasite burden, and several histopathological alterations in heart tissues compared to control animals infected with scrambled parasites. Therewith, we propose that P21 is important in the host–pathogen interaction during invasion, cell multiplication, and egress, and may be part of the mechanism that controls parasitism and promotes chronic infection without patent systemic parasitemia.

The field of distributional ecology has seen considerable recent attention, particularly surrounding the theory, protocols, and tools for Ecological Niche Modeling (ENM) or Species Distribution Modeling (SDM). Such analyses have grown steadily over the past two decades—including a maturation of relevant theory and key concepts—but methodological consensus has yet to be reached. In response, and following an online course taught in Spanish in 2018, we designed a comprehensive English-language course covering much of the underlying theory and methods currently applied in this broad field. Here, we summarize that course, ENM2020, and provide links by which resources produced for it can be accessed into the future. ENM2020 lasted 43 weeks, with presentations from 52 instructors, who engaged with >2500 participants globally through >14,000 hours of viewing and >90,000 views of instructional video and question-and-answer sessions. Each major topic was introduced by an “Overview” talk, followed by more detailed lectures on subtopics. The hierarchical and modular format of the course permits updates, corrections, or alternative viewpoints, and generally facilitates revision and reuse, including the use of only the Overview lectures for introductory courses. All course materials are free and openly accessible (CC-BY license) to ensure these resources remain available to all interested in distributional ecology.

Abstract Introduction Sickle cell disease (SCD) in pregnancy is associated with worse maternal and neonatal outcomes. There is limited available data describing the burden and outcomes of critically ill obstetric patients affected by SCD in low-income settings. Objectives We aimed to define SCD burden and impact on mortality in critically-ill obstetric patients admitted to an urban referral hospital in Sierra Leone. We hypothesized that SCD burden is high and independently associated with increased mortality. Methods We performed a registry-based cross-sectional study from March 2020 to December 2021 in the high-dependency unit (HDU) of Princess Christian Maternity Hospital PCMH, Freetown. Primary endpoints were the proportion of patients identified in the SCD group and HDU mortality. Secondary endpoints included frequency of maternal direct obstetric complications (MDOCs) and the maternal early obstetric warning score (MEOWS). Results Out of a total of 497 patients, 25 (5.5%) qualified to be included in the SCD group. MEOWS on admission was not different between patients with and without SCD and SCD patients had also less frequently reported MDOCs. Yet, crude HDU mortality in the SCD group was 36%, compared to 9.5% in the non SCD group (P

Abstract Tissue regeneration or healing both require efficient vascularization within a tissue-damaged area. Based on this concept, a remarkable number of strategies, aimed at developing new tools to support re-vascularization of damaged tissue have emerged. Among the strategies proposed, the use of pro-angiogenic soluble factors, as a cell-free tool, appears as a promising approach, able to overcome the issues concerning the direct use of cells for regenerative medicine therapy. Here, we compared the effectiveness of adipose mesenchymal stem cells (ASCs), use as cell suspension, ASC protein extract or ASC-conditioned-medium (i.e., soluble factors), combined with collagenic scaffold, in supporting in vivo angiogenesis. We also tested the capability of hypoxia in increasing the efficiency of ASC to promote angiogenesis, via soluble factors, both in vivo and in vitro. In vivo studies were performed using the Integra® Flowable Wound Matrix, and the Ultimatrix in sponge assay. Flow cytometry was used to characterize the scaffold- and sponge-infiltrating cells. Real-time PCR was used to evaluate the expression of pro-angiogenic factors by stimulating Human Umbilical-Vein Endothelial Cells with ASC-conditioned media, obtained in hypoxic and normoxic conditions. We found that, in vivo, ACS-conditioned media can support angiogenesis similar to ASCs and ASC protein extract. Also, we observed that hypoxia increases the pro-angiogenic activities of ASC-conditioned media, compared to normoxia, by generating a secretome enriched in pro-angiogenic soluble factors, with bFGF, Adiponectine, ENA78, GRO, GRO-a, and ICAM1-3, as most regulated factors. Finally, ASC-conditioned media, produced in hypoxic condition, induce the expression of pro-angiogenic molecules in HUVECs. Our results provide evidence that ASC-conditioned-medium can be proposed as a cell-free preparation able to support angiogenesis, thus providing a relevant tool to overcome the issues and restrictions associated with the use of cells.

The Channichthyidae, a monophyletic fish group belonging to the suborder Notothenioidei, are uniquely adapted to the polar environment. However, while their physiology has been extensively studied, studies on their ecology are relatively rare. Here, we investigated the trophic ecology of seven icefish species (Chaenodraco wilsoni, Chionobathyscus dewitti, Chionodraco hamatus, Dacodraco hunteri, Neopagetopis ionah, Pagetodes antarcticus and Pagetopsis macropterus) by using the traditional morphometric approach to assess the relationship between form and feeding function. The suction index (SI), the mechanical advantage in jaw closing (MA) and nine morphological traits related to feeding structures have been analysed. Icefish species are characterised by non-protractible, elongate jaws and a wide gape; such morphological features influence the low values of both MA and SI, supporting their ram-feeding habit. The ecomorphological differences among species resulted mainly determined by the anatomical structures related to SI. Such differences do not seem to be determined primarily by the type of prey, as is the case in other taxonomic groups of Notothenioidei, but rather by phylogenetic proximity. A 3D animation was developed to visualise the different feeding modes of two icefish species (C. hamatus and P. macropterus) which are characterised by different approaches to prey.

Abstract Species records from biological collections are becoming increasingly available online. This unprecedented availability of records has largely supported recent studies in taxonomy, biogeography, macroecology and biodiversity conservation. Biological collections vary in their documentation and notation standards, which have changed through time. For different reasons, neither collections nor data repositories perform the editing, formatting and standardisation of the data, leaving these tasks to the final users of the species records (e.g. taxonomists, ecologists and conservationists). These tasks are challenging, particularly when working with millions of records from hundreds of biological collections. To help collection curators and final users perform those tasks, we introduce plantR, an open‐source package that provides a comprehensive toolbox to manage species records from biological collections. The package is accompanied by the proposal of a reproducible workflow to manage this type of data in taxonomy, ecology and biodiversity conservation. It is implemented in R and designed to handle relatively large datasets as fast as possible. Initially designed to handle plant species records, many of the plantR features also apply to other groups of organisms, given that the data structure is similar. The plantR workflow includes tools to (a) download records from different data repositories, (b) standardise typical fields associated with species records, (c) validate the locality, geographical coordinates, taxonomic nomenclature and species identifications, including the retrieval of duplicates across collections, and (d) summarise and export records, including the construction of species lists with vouchers. Other R packages provide tools to tackle some of the workflow steps described above. But in addition to the new tools and resources related to data standardisation and validation, the greatest strength of plantR is to provide a comprehensive and user‐friendly workflow in one single environment, performing all tasks from data retrieval to export. Thus, plantR can help researchers better assess data quality and avoid data leakage in a wide variety of studies using species records.

Abstract Background Even though hyperglycemia is a well-known cardiovascular risk factor, the absolute risk of cardiovascular events varies to a great extent within each glycemic category. The aim of this study is to evaluate whether N-terminal pro-B natriuretic peptide (NT-ProBNP) could help identify subjects at higher cardiovascular risk, independently of blood glucose levels. Methods Serum NT-ProBNP levels were measured in 5502 people aged 45–79 years without heart failure from the general population (3380 with normoglycemia, 1125 with pre-diabetes and 997 with diabetes) that participated in the 1999–2004 cycles of the National Health and Nutrition Examination Survey. We applied Cox and Fine Gray models adjusted for cardiovascular risk factors to evaluate the association between NT-ProBNP levels and all-cause and cardiovascular mortality through December 2015. Results After a median follow-up of 13 years, 1509 participants died, 330 of cardiovascular causes. In the multivariable-adjusted models, compared with participants with NT-ProBNP

Prostate cancer (PCa) accounts as the most common non-cutaneous disease affecting males, and as the first cancer, for incidence, in male. With the introduction of the concept of immunoscore, PCa has been classified as a cold tumor, thus driving the attention in the development of strategies aimed at blocking the infiltration/activation of immunosuppressive cells, while favoring the infiltration/activation of anti-tumor immune cells. Even if immunotherapy has revolutionized the approaches to cancer therapy, there is still a window failure, due to the immune cell plasticity within PCa, that can acquire pro-tumor features, subsequent to the tumor microenvironment (TME) capability to polarize them. This review discussed selected relevant soluble factors [transforming growth factor-beta (TGFβ), interleukin-6 (IL-6), IL-10, IL-23] and cellular components of the innate immunity, as drivers of tumor progression, immunosuppression, and angiogenesis within the PCa-TME.

NADPH oxidase NOX2 produces superoxide, a reactive oxygen species essential in innate immunity. Here, the authors reveal the structure of the NOX2 core, rationalize disease-causing mutations, and suggest avenues for selective NOX2 pharmacological modulation.

Abstract Background False ventricular tachycardia (VT) alarms are common during in‐hospital electrocardiographic (ECG) monitoring. Prior research shows that the majority of false VT can be attributed to algorithm deficiencies. Purpose The purpose of this study was: (1) to describe the creation of a VT database annotated by ECG experts and (2) to determine true vs. false VT using a new VT algorithm created by our group. Methods The VT algorithm was processed in 5320 consecutive ICU patients with 572,574 h of ECG and physiologic monitoring. A search algorithm identified potential VT, defined as: heart rate >100 beats/min, QRSs > 120 ms, and change in QRS morphology in >6 consecutive beats compared to the preceding native rhythm. Seven ECG channels, SpO2, and arterial blood pressure waveforms were processed and loaded into a web‐based annotation software program. Five PhD‐prepared nurse scientists performed the annotations. Results Of the 5320 ICU patients, 858 (16.13%) had 22,325 VTs. After three levels of iterative annotations, a total of 11,970 (53.62%) were adjudicated as true, 6485 (29.05%) as false, and 3870 (17.33%) were unresolved. The unresolved VTs were concentrated in 17 patients (1.98%). Of the 3870 unresolved VTs, 85.7% (n = 3281) were confounded by ventricular paced rhythm, 10.8% (n = 414) by underlying BBB, and 3.5% (n = 133) had a combination of both. Conclusions The database described here represents the single largest human‐annotated database to date. The database includes consecutive ICU patients, with true, false, and challenging VTs (unresolved) and could serve as a gold standard database to develop and test new VT algorithms.

Survival from in-hospital cardiac arrest (IHCA) due to pulseless electrical activity/asystole remains poor. We aimed to evaluate whether electrocardiographic changes provide predictive information for risk of IHCA from pulseless electrical activity/asystole. We conducted a retrospective case-control study, utilizing continuous electrocardiographic data from case and control patients. We selected 3 consecutive 3-hour blocks (block 3, 2, and 1 in that order); block 1 immediately preceded cardiac arrest in cases, whereas block 1 was chosen at random in controls. In each block, we measured dominant positive and negative trends in electrocardiographic parameters, evaluated for arrhythmias, and compared these between consecutive blocks. We created random forest and logistic regression models, and tested them on differentiating case versus control patients (case block 1 vs control block 1), and temporal relation to cardiac arrest (case block 2 vs case block 1). Ninety-one cases (age 63.0 ± 17.6, 58% male) and 1,783 control patients (age 63.5 ± 14.8, 67% male) were evaluated. We found significant differences in electrocardiographic trends between case and control block 1, particularly in QRS duration, QTc, RR, and ST. New episodes of atrial fibrillation and bradyarrhythmias were more common before IHCA. The optimal model was the random forest, achieving an area under the curve of 0.829, 63.2% sensitivity, 94.6% specificity at differentiating case versus control block 1 on a validation set, and area under the curve 0.954, 91.2% sensitivity, 83.5% specificity at differentiating case block 1 versus case block 2. In conclusion, trends in electrocardiographic parameters during the 3-hour window immediately preceding IHCA differ significantly from other time periods, and provide robust predictive information.

BackgroundCheyne-Stokes respiration and periodic breathing (CSRPB) have not been studied sufficiently in the intensive care unit setting (ICU).ObjectivesTo determine whether CSRPB is associated with adverse outcomes in ICU patients.MethodsThe ICU group was divided into quartiles by CSRPB (86 patients in quartile 1 had the least CSRPB and 85 patients in quartile 4 had the most CSRPB). Adverse outcomes (emergent intubation, cardiorespiratory arrest, inpatient mortality and the composite of all) were compared between patients with most CSRPB (quartile 4) and those with least CSRPB (quartile 1).ResultsICU patients in quartile 4 had a higher proportion of cardiorespiratory arrests (5% versus 0%, (p=.042), and more adverse events over all (19% versus 8%, p=.041) as compared to patients in quartile 1.ConclusionsCSRPB can be measured in the ICU and it's severity is associated with adverse outcomes in critically ill patients.

Understanding the mechanisms driving community assembly has been a major focus of ecological research for nearly a century, yet little is known about these mechanisms in commensal communities, particularly with respect to their historical/evolutionary components. Here, we use a large-scale dataset of 4,440 vascular plant species to explore the relationship between the evolutionary distinctiveness (ED) (as measured by the ’species evolutionary history’ (SEH)) of host species and the phylogenetic diversity (PD) of their associated epiphyte species. Although there was considerable variation across hosts and their associated epiphyte species, they were largely unrelated to host SEH. Our results mostly support the idea that the determinants of epiphyte colonization success might involve host characteristics that are unrelated to host SEH (e.g., architectural differences between hosts). While determinants of PD of epiphyte assemblages are poorly known, they do not appear to be related to the evolutionary history of host species. Instead, they might be better explained by neutral processes of colonization and extinction. However, the high level of phylogenetic signal in epiphyte PD (independent of SEH) suggests it might still be influenced by yet unrecognized evolutionary determinants. This study highlights how little is still known about the phylogenetic determinants of epiphyte communities.

IntroductionMethimazole (MMI) represents the conventional therapeutic agent for Graves’ disease (GD) hyperthyroidism, but MMI efficacy is limited since it marginally affects the underlying autoimmune process. In a previous study, we randomly assigned 42 newly diagnosed GD patients with insufficient vitamin D (VitD) and selenium (Se) levels to treatment with MMI alone (standard) or combined with selenomethionine and cholecalciferol (intervention) and observed a prompter resolution of hyperthyroidism in the intervention group.MethodsIn the present study, we aimed to explore changes in peripheral T regulatory (Treg) and circulating natural killer (NK) cell frequency, circulating NK cell subset distribution and function, during treatment.ResultsAt baseline, circulating total CD3-CD56+NK cells and CD56bright NK cells were significantly higher in GD patients than in healthy controls (HC) (15.7 ± 9.6% vs 9.9 ± 5.6%, p=0.001; 12.2 ± 10.3% vs 7.3 ± 4.1%, p=0.02, respectively); no differences emerged in Treg cell frequency. Frequencies of total NK cells and CD56bright NK cells expressing the activation marker CD69 were significantly higher in GD patients than in HC, while total NK cells and CD56dim NK cells expressing CD161 (inhibitory receptor) were significantly lower. When co-cultured with the K562 target cell, NK cells from GD patients had a significantly lower degranulation ability compared to HC (p

El trabajo define los requisitos para el desarrollo de un sistema de información en una organización de salud de Mar del Plata, Argentina. Se combinan las metodologías participativas de investigación operativa soft y el proceso analítico de jerarquías para facilitar la toma de decisiones organizacionales. La propuesta contribuye al desarrollo efectivo y sistémico del proceso decisorio, considerando la infraestructura informacional, características de los decisores y condiciones estructurales y funcionales de la organización.

BackgroundThe utility of exercise-induced ST-segment depression for diagnosing ischemic heart disease (IHD) in women is unclear.HypothesisBased on evidence that IHD pathophysiology in women involves coronary vascular dysfunction, we hypothesized that coronary vascular dysfunction contributes to exercise electrocardiography (Ex-ECG) ST-depression in the absence of obstructive coronary artery disease, so-called false positive results. We tested our hypothesis in a pilot study evaluating the relationship between peripheral vascular endothelial function and Ex-ECG.MethodsTwenty-nine asymptomatic women without cardiac risk factors underwent maximal Bruce protocol exercise treadmill testing and peripheral endothelial function assessment using peripheral arterial tonometry (Itamar EndoPAT 2000) to measure reactive hyperemia index (RHI). The relationship between RHI and Ex-ECG ST-segment depression was evaluated using logistic regression and differences in subgroups using 2-tailed t tests.ResultsMean age was 54 ± 7 years, body mass index 25 ± 4 kg/m2 , and RHI 2.51 ± 0.66. Three women (10%) had RHI 0.05). RHI did not predict ST-segment depression.ConclusionsOur pilot study demonstrates high prevalence of exercise-induced ST-segment depression in asymptomatic, middle-aged, overweight women. Peripheral vascular endothelial dysfunction did not predict Ex-ECG ST-segment depression. Further work is needed to investigate the utility of vascular endothelial testing and Ex-ECG for IHD diagnostic and management purposes in women.

BackgroundPatients hospitalized for suspected acute coronary syndrome (ACS) are at risk for transient myocardial ischemia. During the "rule-out" phase, continuous ECG ST-segment monitoring can identify transient myocardial ischemia, even when asymptomatic. However, current ST-segment monitoring software is vastly underutilized due to false positive alarms, with resultant alarm fatigue. Current ST algorithms may contribute to alarm fatigue because; (1) they are not designed with a delay (minutes), rather alarm to brief spikes (i.e., turning, heart rate changes), and (2) alarm to changes in a single ECG lead, rather than contiguous leads.PurposeThis study was designed to determine sensitivity, and specificity, of ST algorithms when accounting for; ST magnitude (100μV vs 200μV), duration, and changes in contiguous ECG leads (i.e., aVL, I, - aVR, II, aVF, III; V1, V2, V3, V4, V5, V6, V6, I).MethodsThis was a secondary analysis from the COMPARE Study, which assessed occurrence rates for transient myocardial ischemia in hospitalized patients with suspected ACS using 12-lead Holter. Transient myocardial ischemia was identified from Holter using >100μV ST-segment ↑ or ↓, in >1 ECG lead, >1min. Algorithms tested against Holter transient myocardial ischemia were done using the University of California San Francisco (UCSF) ECG algorithm and included: (1)100μV vs 200μV any lead during a 5-min ST average; (2)100μV vs 200μV any lead >5min, (3) 100μV vs 200μV any lead during a 5-min ST average in contiguous leads, and (4) 100μV vs 200μV>5min in contiguous leads (Table below).ResultsIn 361 patients; mean age 63+12years, 63% male, 56% prior CAD, 43 (11%) had transient myocardial ischemia. Of the 43 patients with transient myocardial ischemia, 17 (40%) had ST-segment elevation events, and 26 (60%) ST-segment depression events. A higher proportion of patients with ST segment depression has missed ischemic events. Table shows sensitivity and specificity for the four algorithms tested.ConclusionsSensitivity was highly variable, due to the ST threshold selected, with the 100μV measurement point being superior to the 200μV amplitude threshold. Of all the algorithms tested, there was moderate sensitivity and specificity (70% and 68%) using the 100μV ST-segment threshold, integrated ST-segment changes in contiguous leads during a 5-min average.

Patients with suspected acute coronary syndrome (ACS) are at risk of transient myocardial ischemia (TMI), which could lead to serious morbidity or even mortality. Early detection of myocardial ischemia can reduce damage to heart tissues and improve patient condition. Significant ST change in the electrocardiogram (ECG) is an important marker for detecting myocardial ischemia during the rule-out phase of potential ACS. However, current ECG monitoring software is vastly underused due to excessive false alarms. The present study aims to tackle this problem by combining a novel image-based approach with deep learning techniques to improve the detection accuracy of significant ST depression change. The obtained convolutional neural network (CNN) model yields an average area under the curve (AUC) at 89.6% from an independent testing set. At selected optimal cutoff thresholds, the proposed model yields a mean sensitivity at 84.4% while maintaining specificity at 84.9%.

Abstract Aims Myocardial injury (MI) in coronavirus disease‐19 (COVID‐19) is quite prevalent at admission and affects prognosis. Little is known about troponin trajectories and their prognostic role. We aimed to describe the early in‐hospital evolution of MI and its prognostic impact. Methods and results We performed an analysis from an Italian multicentre study enrolling COVID‐19 patients, hospitalized from 1 March to 9 April 2020. MI was defined as increased troponin level. The first troponin was tested within 24 h from admission, the second one between 24 and 48 h. Elevated troponin was defined as values above the 99th percentile of normal values. Patients were divided in four groups: normal, normal then elevated, elevated then normal, and elevated. The outcome was in‐hospital death. The study population included 197 patients; 41% had normal troponin at both evaluations, 44% had elevated troponin at both assessments, 8% had normal then elevated troponin, and 7% had elevated then normal troponin. During hospitalization, 49 (25%) patients died. Patients with incident MI, with persistent MI, and with MI only at admission had a higher risk of death compared with those with normal troponin at both evaluations (P

This chapter is a review of studies that have examined false arrhythmia alarms during in-hospital electrocardiographic (ECG) monitoring in the intensive care unit. In addition, we describe an annotation effort being conducted at the UCSF School of Nursing, Center for Physiologic Research designed to improve algorithms for lethal arrhythmias (i.e., asystole, ventricular fibrillation, and ventricular tachycardia). Background: Alarm fatigue is a serious patient safety hazard among hospitalized patients. Data from the past five years, showed that alarm fatigue was responsible for over 650 deaths, which is likely lower than the actual number due to under-reporting. Arrhythmia alarms are a common source of false alarms and 90% are false. While clinical scientists have implemented a number of interventions to reduce these types of alarms (e.g., customized alarm settings; daily skin electrode changes; disposable vs. non-disposable lead wires; and education), only minor improvements have been made. This is likely as these interventions do not address the primary problem of false arrhythmia alarms, namely deficient and outdated arrhythmia algorithms. In this chapter we will describe a number of ECG features associated with false arrhythmia alarms. In addition, we briefly discuss an annotation effort our group has undertaken to improve lethal arrhythmia algorithms.

Trypanosoma cruzi is the causative protozoan of Chagas’ Disease, a neglected tropical disease that affects 6−7 million people worldwide. Interaction of the parasite with the host immune system is a key factor in disease progression and chronic symptoms. Although the human immune system is capable of controlling the disease, the parasite has numerous evasion mechanisms that aim to maintain intracellular persistence and survival. Due to the pronounced genetic variability of T. cruzi, co-infections or mixed infections with more than one parasite strain have been reported in the literature. The intermodulation in such cases is unclear. This study aimed to evaluate the co-infection of T. cruzi strains G and CL compared to their individual infections in human macrophages derived from THP-1 cells activated by classical or alternative pathways. Flow cytometry analysis demonstrated that trypomastigotes were more infective than extracellular amastigotes (EAs) and that strain G could infect more macrophages than strain CL. Classically activated macrophages showed lower number of infected cells and IL-4-stimulated cells displayed increased CL-infected macrophages. However, co-infection was a rare event. CL EAs decreased the production of reactive oxygen species (ROS), whereas G trypomastigotes displayed increased ROS detection in classically activated cells. Co-infection did not affect ROS production. Monoinfection by strain G or CL mainly induced an anti-inflammatory cytokine profile by decreasing inflammatory cytokines (IFN-γ, TNF-α, IL-1β) and/or increasing IL-4, IL-10, and TGF-β. Co-infection led to a predominant inflammatory milieu, with reduced IL-10 and TGF-β, and/or promotion of IFN-γ and IL-1β release. Infection by strain G reduced activation of intracellular signal transducer and activator of transcription (STAT) factors. In EAs, monoinfections impaired STAT-1 activity and promoted phosphorylation of STAT-3, both changes may prolong cell survival. Coinfected macrophages displayed pronounced activation of all STATs examined. These activations likely promoted parasite persistence and survival of infected cells. The collective results demonstrate that although macrophages respond to both strains, T. cruzi can modulate the intracellular environment, inducing different responses depending on the strain, parasite infective form, and co-infection or monoinfection. The modulation influences parasite persistence and survival of infected cells.

In recent years, there has been a growing interest in developing innovative anticancer therapies targeting the tumor microenvironment (TME). The TME is a complex and dynamic milieu surrounding the tumor mass, consisting of various cellular and molecular components, including those from the host organism, endowed with the ability to significantly influence cancer development and progression. Processes such as angiogenesis, immune evasion, and metastasis are crucial targets in the search for novel anticancer drugs. Thus, identifying molecules with “multi-tasking” properties that can counteract cancer cell growth at multiple levels represents a relevant but still unmet clinical need. Extensive research over the past two decades has revealed a consistent anticancer activity for several members of the T2 ribonuclease family, found in evolutionarily distant species. Initially, it was believed that T2 ribonucleases mainly acted as anticancer agents in a cell-autonomous manner. However, further investigation uncovered a complex and independent mechanism of action that operates at a non-cell-autonomous level, affecting crucial processes in TME-induced tumor growth, such as angiogenesis, evasion of immune surveillance, and immune cell polarization. Here, we review and discuss the remarkable properties of ribonucleases from the T2 family in the context of “multilevel” oncosuppression acting on the TME.

Background: Glucocorticoid therapy has emerged as an effective therapeutic option in hospitalized patients with coronavirus disease 2019 (COVID-19). This study aimed to focus on the impact of relevant clinical and laboratory factors on the protective effect of glucocorticoids on mortality. Methods: A sub-analysis was performed of the multicenter Cardio-COVID-Italy registry, enrolling consecutive patients with COVID-19 admitted to 13 Italian cardiology units between 01 March 2020 and 09 April 2020. The primary endpoint was in-hospital mortality. Results: A total of 706 COVID-19 patients were included (349 treated with glucocorticoids, 357 not treated with glucocorticoids). After adjustment for relevant covariates, use of glucocorticoids was associated with a lower risk of in-hospital mortality (adjusted HR 0.44; 95% CI 0.26–0.72; p = 0.001). A significant interaction was observed between the protective effect of glucocorticoids on mortality and PaO2/FiO2 ratio on admission (p = 0.042), oxygen saturation on admission (p = 0.017), and peak CRP (0.023). Such protective effects of glucocorticoids were mainly observed in patients with lower PaO2/FiO2 ratio (100 mg/L). Conclusions: The protective effects of glucocorticoids on mortality in COVID-19 were more evident among patients with worse respiratory parameters and higher systemic inflammation.

BackgroundAcute myocardial ischemia is a common cause of ventricular arrhythmias, yet recent ECG methods predicting susceptibility to ventricular tachyarrhythmia have not been fully evaluated during spontaneous ischemia. We sought to evaluate the clinical utility of alternans and non-alternans components of repolarization variability from the standard 10-second 12-lead ECG signals to risk stratify patients with acute chest pain.MethodsWe enrolled consecutive, non-traumatic, chest pain patients transported through Emergency Medical Services (EMS) to three tertiary care hospitals with cardiac catheterization lab capabilities in Pittsburgh, PA. ECG signals were manually annotated by an electrophysiologist, then automatically processed using a custom-written software. Both T wave alternans (TWA) and non-alternans repolarization variability (NARV) were calculated using the absolute RMS differences over the repolarization window between odd/even averaged beats and between consecutive averaged pairs, respectively. The primary study outcome was the presence of acute myocardial infarction (AMI) documented by cardiac angiography.ResultsAfter excluding patients with secondary repolarization changes (n=123) and those with excessive noise (n=90), our final sample included 537 patients (age 57±16years, 56% males). Patients with AMI (n=47, 9%) had higher TWA and NARV values (p

Cheyne-Stokes respiration (CSR) has been investigated primarily in outpatients with heart failure. In this study we compare CSR and periodic breathing (PB) between healthy and cardiac groups. We compared CSR and PB, measured during 24 hr of continuous 12-lead electrocardiographic (ECG) Holter recording, in a group of 90 hospitalized patients presenting to the emergency department with symptoms suggestive of acute coronary syndrome (ACS) to a group of 100 healthy ambulatory participants. We also examined CSR and PB in the 90 patients presenting with ACS symptoms, divided into a group of 39 (43%) with confirmed ACS, and 51 (57%) with a cardiac diagnosis but non-ACS. SuperECG software was used to derive respiration and then calculate CSR and PB episodes from the ECG Holter data. Regression analyses were used to analyze the data. We hypothesized SuperECG software would differentiate between the groups by detecting less CSR and PB in the healthy group than the group of patients presenting to the emergency department with ACS symptoms. Hospitalized patients with suspected ACS had 7.3 times more CSR episodes and 1.6 times more PB episodes than healthy ambulatory participants. Patients with confirmed ACS had 6.0 times more CSR episodes and 1.3 times more PB episodes than cardiac non-ACS patients. Continuous 12-lead ECG derived CSR and PB appear to differentiate between healthy participants and hospitalized patients.

Blood potassium concentration ([K+]) influences the electrocardiogram (ECG), particularly T-wave morphology. We developed a new method to quantify [K+] from T-wave analysis and tested its clinical applicability on data from dialysis patients, in whom [K+] varies significantly during the therapy. To elucidate the mechanism linking [K+] and T-wave, we also analysed data from long QT syndrome type 2 (LQT2) patients, testing the hypothesis that our method would have underestimated [K+] in these patients. Moreover, a computational model was used to explore the physiological processes underlying our estimator at the cellular level. We analysed 12-lead ECGs from 45 haemodialysis and 12 LQT2 patients. T-wave amplitude and downslope were calculated from the first two eigenleads. The T-wave slope-to-amplitude ratio (TS/A) was used as starting point for an ECG-based [K+] estimate (KECG). Leave-one-out cross-validation was performed. Agreement between KECG and reference [K+] from blood samples was promising (error: -0.09 ± 0.59 mM, absolute error: 0.46 ± 0.39 mM). The analysis on LQT2 patients, also supported by the outcome of computational analysis, reinforces our interpretation that, at the cellular level, delayed-rectifier potassium current is a main contributor of KECG correlation to blood [K+]. Following a comprehensive validation, this method could be effectively applied to monitor patients at risk for hyper/hypokalemia.

IntroductionThe relationship between the autonomic nervous system and restless legs syndrome (RLS) and periodic limb movements of sleep (PLMS) consists of varied and somewhat conflicting reports. In order to further elucidate these complexities, a retrospective analysis of polysomnography (PSG) records and clinical data was performed.MethodsRecords from 233 adult subjects were randomly selected and organized into one of four groups ("non-RLS/PLMS" [n=61], "RLS" [n=60], "PLMS" [n=58], and "RLS/PLMS" [n=54]). Heart rate variability (HRV) analysis was based on 5-minute samples of 2-lead electrocardiogram data isolated from PSG recordings during wakefulness and NREM sleep, and included mean RR interval (labeled "NN") and standard deviation of the RR intervals (labeled "SDNN"), and HRV power, very low frequency (VLF), low frequency (LF), and high frequency (HF) spectral bands.ResultsA significant reduction in the VLF band in the PLMS group as compared to the non-RLS/PLMS group (542±674 vs. 969±1025 ms2, p=0.038) was found in wakefulness. Statistically significant differences were seen in the PLMS group as compared to the non-RLS/PLMS group with a reduction in SDNN (p=0.001) and the HF (p=0.001) band, and an increase in HRV power (p=0.001), and the VLF (p=0.005) and LF (p=0.001) bands in NREM sleep.ConclusionsThe PLMS group exhibited reduced basal sympathetic activity in wakefulness, but basal sympathetic predominance during NREM sleep, distinguishing this group from the RLS and RLS/PLMS groups.

Despite some significant therapeutic breakthroughs leading to immunotherapy, a high percentage of patients with non-small cell lung cancer (NSCLC) do not respond to treatment on relapse, thus experiencing poor prognosis and survival. The unsatisfying results could be related to the features of the tumor immune microenvironment and the dynamic interactions between a tumor and immune infiltrate. Host–tumor interactions strongly influence the course of disease and response to therapies. Thus, targeting host-associated factors by restoring their physiologic functions altered by the presence of a tumor represents a new therapeutic approach to control tumor development and progression. In NSCLC, the immunogenic tumor balance is shifted negatively toward immunosuppression due to the release of inhibitory factors as well as the presence of immunosuppressive cells. Among these cells, there are myeloid-derived suppressor cells, regulatory T cells that can generate a tumor-permissive milieu by reprogramming the cells of the hosts such as tumor-associated macrophages, tumor-associated neutrophils, natural killer cells, dendritic cells, and mast cells that acquire tumor-supporting phenotypes and functions. This review highlights the current knowledge of the involvement of host-related factors, including innate and adaptive immunity in orchestrating the tumor cell fate and the primary resistance mechanisms to immunotherapy in NSCLC. Finally, we discuss combinational therapeutic strategies targeting different aspects of the tumor immune microenvironment (TIME) to prime the host response. Further research dissecting the characteristics and dynamic interactions within the interface host–tumor is necessary to improve a patient fitness immune response and provide answers regarding the immunotherapy efficacy, with the aim to develop more successful treatments for NSCLC.