Managing Iatrogenic Aortic Dissection: Insight from 3D-holographic Imaging and CT Computational Fluid Dynamic Simulations.

Iatrogenic aortic dissection is a rare but life-threatening complication of coronary artery bypass surgery. We report a case with incidentally detected iatrogenic aortic dissection related to aorta cross-clamping successfully managed with watchful follow-up. The decision-making was based on 3D hologram and fluid dynamic analysis guidance.

Opportunistic screening for osteoporosis using routine clinical care computed tomography brain studies.

OBJECTIVE: Osteoporosis and falls are both prevalent in the elderly, and CT brain (CTB) is frequently performed post head-strike. We aim to validate the relationship between frontal bone density (Hounsfield unit) from routine CTB and bone mineral density from dual-energy X-ray absorptiometry (DEXA) scan for opportunistic osteoporosis screening. MATERIALS AND METHODS: Patients who had a non-contrast CTB followed by a DEXA scan in the subsequent year were included in this multi-center retrospective study. The relationship between frontal bone density on CT and femoral neck T-score on DEXA was examined using ANOVA, Pearson's correlation, and receiver operating curve (ROC) analysis. Sensitivity, specificity, negative and positive predictive values, and area under the curve (AUC) were calculated. RESULTS: Three hundred twenty-six patients (205 females and 121 males) were analyzed. ANOVA analysis showed that frontal bone density was lower in patients with DEXA-defined osteoporosis (p < 0.001), while Pearson's correlation analysis demonstrated a fair correlation with femoral neck T-score (r = 0.3, p < 0.001). On subgroup analysis, these were true in females but not in males. On ROC analysis, frontal bone density weakly predicted osteoporosis (AUC 0.6, 95% CI 0.5-0.7) with no optimal threshold identified. HU < 610 was highly specific (87.5%) but poorly sensitive (18.9%). HU > 1200 in females had a strong negative predictive value for osteoporosis (92.6%, 95% CI 87.1-98.1%). CONCLUSION: Frontal bone density from routine CTB is significantly different between females with and without osteoporosis, but not between males. However, frontal bone density was a weak predictor for DEXA-defined osteoporosis. Further research is required to determine the role of CTB in opportunistic osteoporosis screening.

Determinants of Change in Physical Activity in Children during the Transition from Elementary to High School.

INTRODUCTION: Effective public health interventions targeting factors that influence physical activity are urgently needed to reduce the age-related decline in physical activity in youth. The purpose of this study was to identify associations between physical activity and a set of potential influences on physical activity in children as they transition from elementary to high school. METHODS: Participants were 951 children from South Carolina school districts who completed outcome and independent variable measures on at least two time points from the 5th to 11th grades in 2010-2017. The primary outcome variable was physical activity, measured by accelerometry. Independent variables included a comprehensive set of variables in the child, parent/home, school, and community domains. Children, parents and school administrators, and staff completed questionnaires to assess psychosocial and home, school, and neighborhood environmental influences. Growth curve analyses identified independent variables associated with physical activity over time, either as a main effect or as an interaction with age. RESULTS: As main effects, self-efficacy, self-schema, sport participation, weekday outdoor hours, importance of child participating in sports and physical activity, safe to play outside, and Physical Activity Resource Assessment weighted score were positively associated with physical activity. The associations between physical activity and enjoyment motivation, appearance motivation, weekend outdoor time, and home equipment exhibited significant interactions with age. Enjoyment motivation influenced physical activity during the earlier years, whereas the remaining three variables influenced physical activity in the later years. CONCLUSIONS: Interventions should target multiple domains of influences that may vary by age.

Pharyngeal mucosal closure in total laryngectomy: comparison between vertical and T-shaped closure.

Objective: The objective of this study was to compare the outcomes vertical and T-shaped pharyngoplasty closure techniques after total laryngectomy (TL) and to evaluate the factors associated with the development of pharyngocutaneous fistula. Materials and methods: We performed a retrospective study that included patients with a histopathological diagnosis of laryngeal cancer that underwent TL between 2009 and 2021. Results: Fifty-seven patients were included in the study. A total of 14 patients underwent a vertical closure of the neopharynx (24.6%), while 43 patients underwent a T-shaped closure (74.4%). Pharyngocutaneous fistula was the most common complication, observed in 40.4% of cases (n = 23). No difference in the rate of complications was observed between groups, with the exception of tracheal dehiscence which was reduced in patients with T-shaped closure (n = 2, 4.7% vs. n = 5, 35.7%, p = 0.002). Diabetes mellitus was more frequently observed in patients withthe development of pharyngocutaneous fistula (n = 7, 30.4% vs. n = 3, 8.8%, p = 0.03). Conclusions: Although complicationswere lower in the T-shaped closure group, we could not establish the superiority of either technique.

Objetivo: Evaluar los desenlaces de la técnica vertical en comparación con la técnica en T para el cierre de faringoplastia posterior a una laringectomía total, y evaluar los factores asociados con el desarrollo de fístula faringocutánea. Método: Estudio retrospectivo de pacientes con diagnóstico de cancer de laringe a quienes se realizó laringectomía total como tratamiento, de 2009 a 2021. Resultados: Se incluyeron 57 pacientes. A 14 (24.6%) se les realizó una faringoplastia con cierre en T y a 43 (74.4%) un cierre vertical. La fístula faringocutánea fue la complicación más frecuente, presente en el 40.4% de los casos (n = 23). No se observaron diferencias en el desarrollo de complicaciones entre grupos, con excepción de la dehiscencia traqueal, la cual fue menos frecuente en el grupo de cierre en T (n = 2, 4.7% vs. n = 5, 35.7%; p = 0.002). La diabetes mellitus se asoció con el desarrollo de fístula faringocutánea (n = 7, 30.4% vs. n = 3, 8.8%; p = 0.03). Conclusiones: Aunque se observó una tendencia a una disminución de las complicaciones en el grupo de cierre en T, no se encontró superioridad de una técnica sobre otra.

Machine learning enabled detection of COVID-19 pneumonia using exhaled breath analysis: a proof-of-concept study.

Detection of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) relies on real-time-reverse-transcriptase polymerase chain reaction (RT-PCR) on nasopharyngeal swabs. The false-negative rate of RT-PCR can be high when viral burden and infection is localized distally in the lower airways and lung parenchyma. An alternate safe, simple and accessible method for sampling the lower airways is needed to aid in the early and rapid diagnosis of COVID-19 pneumonia. In a prospective unblinded observational study, patients admitted with a positive RT-PCR and symptoms of SARS-CoV-2 infection were enrolled from three hospitals in Ontario, Canada. Healthy individuals or hospitalized patients with negative RT-PCR and without respiratory symptoms were enrolled into the control group. Breath samples were collected and analyzed by laser absorption spectroscopy (LAS) for volatile organic compounds (VOCs) and classified by machine learning (ML) approaches to identify unique LAS-spectra patterns (breathprints) for SARS-CoV-2. Of the 135 patients enrolled, 115 patients provided analyzable breath samples. Using LAS-breathprints to train ML classifier models resulted in an accuracy of 72.2%-81.7% in differentiating between SARS-CoV2 positive and negative groups. The performance was consistent across subgroups of different age, sex, body mass index, SARS-CoV-2 variants, time of disease onset and oxygen requirement. The overall performance was higher than compared to VOC-trained classifier model, which had an accuracy of 63%-74.7%. This study demonstrates that a ML-based breathprint model using LAS analysis of exhaled breath may be a valuable non-invasive method for studying the lower airways and detecting SARS-CoV-2 and other respiratory pathogens. The technology and the ML approach can be easily deployed in any setting with minimal training. This will greatly improve access and scalability to meet surge capacity; allow early and rapid detection to inform therapy; and offers great versatility in developing new classifier models quickly for future outbreaks.

Enhancing pre-transplant cardiac assessment: Validation and utility of the CAD-LT score with CCTA in liver transplant candidates.

BACKGROUND: Coronary computed tomography angiography (CCTA) is increasingly being used in the preoperative workup for liver transplantation (LT). We sought to assess the utility of integrating CCTA with the novel CAD-LT (Coronary Artery Disease in Liver Transplantation) score and its impact on reducing the need for invasive coronary angiography prior to LT. METHODS: We conducted a retrospective cohort study of consecutive patients (age ≥ 18 years) who underwent CCTA for LT workup between 2011 and 2018 at the Victorian Liver Transplant Unit, Melbourne, Australia. CAD-LT scores, a traditional risk factor-based criteria, were calculated, and patients stratified as low-, intermediate- or high-risk. RESULTS: Overall, 229 patients underwent CCTA. The mean age was 66 ± 5 years (82% male) with a modest-to-high risk factor burden (diabetes, 53%; hypertension, 46%; current or former smoker, 62%). The mean CAD-LT score of our cohort was 12.4 ± 4.0. No patients were classified as low-risk, 49 patients (21.4%) were deemed intermediate-risk and 180 patients (78.6%) were deemed high-risk. A high CAD-LT score (≥ 9) showed high sensitivity (95.3% [95% CI 86-98%]) and modest specificity (27.8% [95% CI 21-35%]) for the detection of obstructive coronary artery disease on CCTA, with a negative predictive value of 94%. Following multidisciplinary discussions, only 41 patients (18%) of patients proceeded to ICA of which 27% received percutaneous coronary intervention. CONCLUSIONS: The use of CCTA in patients deemed intermediate- to high-risk by the CAD-LT score has the potential to reduce the need for invasive coronary angiography in patients undergoing LT workup.

Automated inversion time selection for late gadolinium-enhanced cardiac magnetic resonance imaging.

OBJECTIVES: To develop and share a deep learning method that can accurately identify optimal inversion time (TI) from multi-vendor, multi-institutional and multi-field strength inversion scout (TI scout) sequences for late gadolinium enhancement cardiac MRI. MATERIALS AND METHODS: Retrospective multicentre study conducted on 1136 1.5-T and 3-T cardiac MRI examinations from four centres and three scanner vendors. Deep learning models, comprising a convolutional neural network (CNN) that provides input to a long short-term memory (LSTM) network, were trained on TI scout pixel data from centres 1 to 3 to identify optimal TI, using ground truth annotations by two readers. Accuracy within 50 ms, mean absolute error (MAE), Lin's concordance coefficient (LCCC) and reduced major axis regression (RMAR) were used to select the best model from validation results, and applied to holdout test data. Robustness of the best-performing model was also tested on imaging data from centre 4. RESULTS: The best model (SE-ResNet18-LSTM) produced accuracy of 96.1%, MAE 22.9 ms and LCCC 0.47 compared to ground truth on the holdout test set and accuracy of 97.3%, MAE 15.2 ms and LCCC 0.64 when tested on unseen external (centre 4) data. Differences in vendor performance were observed, with greatest accuracy for the most commonly represented vendor in the training data. CONCLUSION: A deep learning model was developed that can identify optimal inversion time from TI scout images on multi-vendor data with high accuracy, including on previously unseen external data. We make this model available to the scientific community for further assessment or development. CLINICAL RELEVANCE STATEMENT: A robust automated inversion time selection tool for late gadolinium-enhanced imaging allows for reproducible and efficient cross-vendor inversion time selection. KEY POINTS: • A model comprising convolutional and recurrent neural networks was developed to extract optimal TI from TI scout images. • Model accuracy within 50 ms of ground truth on multi-vendor holdout and external data of 96.1% and 97.3% respectively was achieved. • This model could improve workflow efficiency and standardise optimal TI selection for consistent LGE imaging.

MicroRNA Profiling of the Inflammatory Response after Early and Late Asthmatic Reaction.

A high proportion of house dust mite (HDM)-allergic asthmatics suffer from both an early asthmatic reaction (EAR) and a late asthmatic reaction (LAR) which follows it. In these patients, allergic inflammation is more relevant. MiRNAs have been shown to play an important role in the regulation of asthma's pathology. The aim of this study was to analyze the miRNA profile in patients with mild asthma and an HDM allergy after bronchial allergen provocation (BAP). Seventeen patients with EAR/no LAR and 17 patients with EAR plus LAR, determined by a significant fall in FEV1 after BAP, were differentially analyzed. As expected, patients with EAR plus LAR showed a more pronounced allergic inflammation and FEV1 delta drop after 24 h. NGS-miRNA analysis identified the down-regulation of miR-15a-5p, miR-15b-5p, and miR-374a-5p after BAP with the highest significance in patients with EAR plus LAR, which were negatively correlated with eNO and the maximum decrease in FEV1. These miRNAs have shared targets like CCND1, VEGFA, and GSK3B, which are known to be involved in airway remodeling, basement membrane thickening, and Extracellular Matrix deposition. NGS-profiling identified miRNAs involved in the inflammatory response after BAP with HDM extract, which might be useful to predict a LAR.

Trust and acceptability of data-driven clinical recommendations in everyday practice: A scoping review.

BACKGROUND: Increasing attention is being given to the analysis of large health datasets to derive new clinical decision support systems (CDSS). However, few data-driven CDSS are being adopted into clinical practice. Trust in these tools is believed to be fundamental for acceptance and uptake but to date little attention has been given to defining or evaluating trust in clinical settings. OBJECTIVES: A scoping review was conducted to explore how and where acceptability and trustworthiness of data-driven CDSS have been assessed from the health professional's perspective. METHODS: Medline, Embase, PsycInfo, Web of Science, Scopus, ACM Digital, IEEE Xplore and Google Scholar were searched in March 2022 using terms expanded from: "data-driven" AND "clinical decision support" AND "acceptability". Included studies focused on healthcare practitioner-facing data-driven CDSS, relating directly to clinical care. They included trust or a proxy as an outcome, or in the discussion. The preferred reporting items for systematic reviews and meta-analyses extension for scoping reviews (PRISMA-ScR) is followed in the reporting of this review. RESULTS: 3291 papers were screened, with 85 primary research studies eligible for inclusion. Studies covered a diverse range of clinical specialisms and intended contexts, but hypothetical systems (24) outnumbered those in clinical use (18). Twenty-five studies measured trust, via a wide variety of quantitative, qualitative and mixed methods. A further 24 discussed themes of trust without it being explicitly evaluated, and from these, themes of transparency, explainability, and supporting evidence were identified as factors influencing healthcare practitioner trust in data-driven CDSS. CONCLUSION: There is a growing body of research on data-driven CDSS, but few studies have explored stakeholder perceptions in depth, with limited focused research on trustworthiness. Further research on healthcare practitioner acceptance, including requirements for transparency and explainability, should inform clinical implementation.

Atherosclerosis on CT coronary angiography and the risk of long-term cardiovascular events after liver transplantation.

Computed tomography coronary angiography (CTCA) is increasingly utilized for preoperative risk stratification before liver transplantation (LT). We sought to assess the predictors of advanced atherosclerosis on CTCA using the recently developed Coronary Artery Disease-Reporting and Data System (CAD-RADS) score and its impact on the prediction of long-term major adverse cardiovascular events (MACE) following LT. We conducted a retrospective cohort study of consecutive patients who underwent CTCA for LT work-up between 2011 and 2018. Advanced atherosclerosis was defined as coronary artery calcium scores > 400 or CAD-RADS score ≥ 3 (≥50% coronary artery stenosis). MACE was defined as myocardial infarction, heart failure, stroke, or resuscitated cardiac arrest. Overall, 229 patients underwent CTCA (mean age 66 ± 5 y, 82% male). Of these, 157 (68.5%) proceeded with LT. The leading etiology of cirrhosis was hepatitis (47%), and 53% of patients had diabetes before transplant. On adjusted analysis, male sex (OR 4.6, 95% CI 1.5-13.8, p = 0.006), diabetes (OR 2.2, 95% CI 1.2-4.2, p = 0.01) and dyslipidemia (OR 3.1, 95% CI 1.3-6.9, p = 0.005) were predictors of advanced atherosclerosis on CTCA. Thirty-two patients (20%) experienced MACE. At a median follow-up of 4 years, CAD-RADS ≥ 3, but not coronary artery calcium scores, was associated with a heightened risk of MACE (HR 5.8, 95% CI 1.6-20.6, p = 0.006). Based on CTCA results, 71 patients (31%) commenced statin therapy which was associated with a lower risk of all-cause mortality (HR 0.48, 95% CI 0.24-0.97, p = 0.04). The standardized CAD-RADS classification on CTCA predicted the occurrence of cardiovascular outcomes following LT, with a potential to increase the utilization of preventive cardiovascular therapies.

Contemporary and Emerging MRI Strategies for Assessing Kidney Allograft Complications: Arterial Stenosis and Parenchymal Injury, From the AJR Special Series on Imaging of Fibrosis.

MRI plays an important role in the evaluation of kidney allografts for vascular complications as well as parenchymal insults. Transplant renal artery stenosis, the most common vascular complication of kidney transplant, can be evaluated by MRA using gadolinium and nongadolinium contrast agents as well as by unenhanced MRA techniques. Parenchymal injury occurs through a variety of pathways, including graft rejection, acute tubular injury, BK polyomavirus infection, drug-induced interstitial nephritis, and pyelonephritis. Investigational MRI techniques have sought to differentiate among these causes of dysfunction as well as to assess the degree of interstitial fibrosis or tubular atrophy (IFTA)-the common end pathway for all of these processes-which is currently evaluated by invasively obtained core biopsies. Some of these MRI sequences have shown promise in not only assessing the cause of parenchymal injury but also assessing IFTA noninvasively. This review describes current clinically used MRI techniques and previews promising investigational MRI techniques for assessing complications of kidney grafts.

Association of physical activity, sedentary behavior, diet quality with adiposity: a longitudinal analysis in children categorized by baseline weight status.

BACKGROUND/OBJECTIVES: Childhood obesity rates have increased in recent years. The effectiveness of future public health interventions to reduce childhood obesity will be enhanced by a better understanding of behavioral factors that influence adiposity in children as they transition from childhood to adolescence. The purpose of this study was to examine whether initial weight status modifies the longitudinal associations of physical activity, sedentary behavior, and diet quality with changes in adiposity over time. SUBJECTS/METHODS: A total of 658 children (45% boys) were stratified into 3 groups based on 5th grade BMI percentiles ( < 85th, 85-95th, > 95th) and followed from 5th grade to 6th and/or 7th grade. Study variables, including fat-mass-index (FMI), moderate-to-vigorous physical activity (MVPA), diet quality, and sedentary behavior, were measured at 5th, 6th, and/or 7th grades. Separate growth curve models were conducted within each weight status group to examine the associations between MVPA, sedentary behavior, diet quality and adiposity, operationalized as FMI. All models controlled for sex, maturity offset, race, and parent education. RESULTS: Of the 658 children, 53% were classified with normal weight at baseline, 18% with overweight, and 29% with obesity. Associations between MVPA, sedentary behavior, diet quality and FMI varied within each weight status group. MVPA was negatively associated with adiposity (FMI) for all weight status groups. Diet quality and sedentary behavior were associated with adiposity only in children with obesity at baseline; neither diet quality nor sedentary behavior was associated with FMI for those with overweight. CONCLUSIONS: MVPA was negatively associated with adiposity (FMI) in all weight status groups, suggesting that MVPA may protect against higher adiposity. Sedentary behavior and diet quality were associated with adiposity only in children with obesity at baseline; neither sedentary behavior nor diet quality was associated with FMI for children with overweight.

Differential sensitivities to blood pressure variations in internal carotid and intracranial arteries: a numerical approach to stroke prediction.

Stroke remains a global health concern, necessitating early prediction for effective management. Atherosclerosis-induced internal carotid and intra cranial stenosis contributes significantly to stroke risk. This study explores the relationship between blood pressure and stroke prediction, focusing on internal carotid artery (ICA) branches: middle cerebral artery (MCA), anterior cerebral artery (ACA), and their role in hemodynamics. Computational fluid dynamics (CFD) informed by the Windkessel model were employed to simulate patient-specific ICA models with introduced stenosis. Central to our investigation is the impact of stenosis on blood pressure, flow velocity, and flow rate across these branches, incorporating Fractional Flow Reserve (FFR) analysis. Results highlight differential sensitivities to blood pressure variations, with M1 branch showing high sensitivity, ACA moderate, and M2 minimal. Comparing blood pressure fluctuations between ICA and MCA revealed heightened sensitivity to potential reverse flow compared to ICA and ACA comparisons, emphasizing MCA's role. Blood flow adjustments due to stenosis demonstrated intricate compensatory mechanisms. FFR emerged as a robust predictor of stenosis severity, particularly in the M2 branch. In conclusion, this study provides comprehensive insights into hemodynamic complexities within major intracranial arteries, elucidating the significance of blood pressure variations, flow attributes, and FFR in stenosis contexts. Subject-specific data integration enhances model reliability, aiding stroke risk assessment and advancing cerebrovascular disease understanding.

Compromised Muscle Properties in a Severe Hypophosphatasia Murine Model.

Hypophosphatasia (HPP) is a rare metabolic bone disorder characterized by low levels of tissue non-specific alkaline phosphatase (TNAP) that causes under-mineralization of the bone, leading to bone deformity and fractures. In addition, patients often present with chronic muscle pain, reduced muscle strength, and an altered gait. In this work, we explored dynamic muscle function in a homozygous TNAP knockout mouse model of severe juvenile onset HPP. We found a reduction in skeletal muscle size and impairment in a range of isolated muscle contractile properties. Using histological methods, we found that the structure of HPP muscles was similar to healthy muscles in fiber size, actin and myosin structures, as well as the α-tubulin and mitochondria networks. However, HPP mice had significantly fewer embryonic and type I fibers than wild type mice, and fewer metabolically active NADH+ muscle fibers. We then used oxygen respirometry to evaluate mitochondrial function and found that complex I and complex II leak respiration were reduced in HPP mice, but that there was no disruption in efficiency of electron transport in complex I or complex II. In summary, the severe HPP mouse model recapitulates the muscle strength impairment phenotypes observed in human patients. Further exploration of the role of alkaline phosphatase in skeletal muscle could provide insight into mechanisms of muscle weakness in HPP.

Impacto de un Heart Team en pacientes con estenosis aórtica candidatos a reemplazo percutáneo / Impact of a Heart Team in patients with aortic stenosis who are candidates for transcatheter aortic valve replacement

RESUMEN La difusión del reemplazo valvular aórtico percutáneo (TAVI) en la estenosis aórtica (EAo) generó la creación de un Heart Team (HT), para elegir el mejor tratamiento. Existen pocos reportes sobre su utilidad. Objetivos: analizar los resultados del tratamiento de los pacientes con EAo evaluados por un HT durante 10 años Material y métodos: Inclusión consecutiva de todos los pacientes con EAo candidatos a TAVI entre enero del 2012 y julio del 2021 para seleccionar el mejor tratamiento, incluyendo además Cirugía de reemplazo valvular aórtico (CRVA) y Tratamiento médico conservador (TMC). Resultados: De 841 pacientes, se asignaron a TAVI 455 (53%), CRVA 213 (24%) y TMC 183 (23%). El porcentaje asignado a TAVI aumentó con el tiempo de 48 a 62% (p < 0,05). Los pacientes que fueron a TAVI, con respecto a los enviados a CRVA, eran mayores (86 ± 7 vs 83 ± 7 años), con mayor EUROSCORE II (6,2, IC95% 5,7-6,6 vs 5,6, IC95% 4,4-6,5) y más frágiles (1,62 ± 1 vs 0,91 ± 1), en todos los casos p <0,01. La sobrevida actuarial (IC 95%) a 1 y a 2 años fue, para TAVI 88% (84-91%) y 82% (77-86%), para CRVA 83% (76-88%) y 78% (70-84%) y para TMC 70% (60-87%) y 59% (48-68%) respectivamente (p <0,001). Conclusiones: Durante los primeros 10 años de establecido un Heart Team para la toma de decisiones en EAo, se asignaron a TAVI aproximadamente la mitad y el resto se asignó por mitades a cirugía u observación. La sobrevida de los pacientes intervenidos fue similar a 2 años y mayor que la de los no intervenidos.

ABSTRACT As transcatheter aortic valve implantation (TAVI) for aortic stenosis (AS) became widespread, the need for a Heart Team (HT) arose to choose the best treatment. There are few reports regarding its usefulness. Objectives: To analyze treatment outcomes in patients with AS evaluated by a HT for 10 years. Methods: Consecutive enrollment of all patients with AS who were candidates for TAVI between January 2012 and July 2021 to choose the best treatment, including surgical aortic valve replacement (SAVR) and conservative medical management (CMM). Results: Out of 841 patients, 455 were assigned to TAVI (53%), 213 to SAVR (24%), and 183 to CMM (23%). The percentage assigned to TAVI has increased from 48% to 62% over time (p <0.05). Patients who underwent TAVI versus those who underwent SAVR were older (86 ± 7 vs. 83 ± 7 years), had a higher EUROSCORE II (6.2, 95% CI 5.7-6.6 vs. 5.6; 95% CI 4.4-6.5) and were frailer (1.62 ± 1 vs. 0.91 ± 1), in all cases p <0.01. Actuarial survival (95% CI) at 1 and 2 years was 88% (84-91%) and 82% (77-86%) for TAVI, 83% (76-88%) and 78% (70-84%) for SAVR, and 70% (60-87%) and 59% (48-68%) for CMM, respectively (p <0.001). Conclusions: For the first 10 years after a Heart Team was established for AS decision-making, approximately half of the patients were assigned to TAVI, and the rest were equally assigned in halves to either surgery or observation. Survival for patients who received interventions was similar at 2 years and higher than in those who did not.

Understanding Commitment of Local Food Banks, Faith-Based Organizations, and Schools to Provide Nongovernment Food Programs.

Background: Nongovernment food assistance is typically provided to families by faith-based organizations, schools, and food banks. Community organizations appear to be strongly committed to these programs, but little is known about the basis for this commitment. Objectives: The aim of this study was to examine the values and identities of community organizations to understand the reasons for their commitment to providing nongovernment food assistance. Methods: Thirty-three in-depth interviews were conducted with 36 leaders at faith-based organizations (19 participants), schools (14 participants), and a local food bank (3 participants) in South Carolina. Observations were made, and informational documents (e.g., flyers and pamphlets) were reviewed. Thematic coding using the constant comparative method was guided by the policy concepts of organizational perspectives, values, and identities. Results: Nongovernment food programs offered participants volunteering opportunities to become involved with community organizations, which in turn increased financial support for the sustainability of these programs. School participants regarded themselves as a mechanism through which food programs were provided because of their commitment to students and believed they have limited capacity to make proposals to influence the food programs. Seeking to improve the well-being of the community by ending hunger was not the primary value on which organizations focused; instead, it was the process of fulfilling other values (e.g., forming or maintaining relationships within the community), maintaining identity, and appealing to their participants that strengthened their commitment to nongovernment food programs. Conclusion: Nongovernment programs are meant to be a solution to food insecurity complementary to government programs. Commitment to nongovernment programs fulfills organizational identities, wants, and assumptions, but a consequence of commitment to food programs, derived from fulfilling other values, is that the roots of hunger in a community become obscured and alternative solutions are ignored or rejected.

Evaluation of the reproducibility of responses to nasal allergen challenge and effects of inhaled nasal corticosteroids.

BACKGROUND: Similar immune responses in the nasal and bronchial mucosa implies that nasal allergen challenge (NAC) is a suitable early phase experimental model for drug development targeting allergic rhinitis (AR) and asthma. We assessed NAC reproducibility and the effects of intranasal corticosteroids (INCS) on symptoms, physiology, and inflammatory mediators. METHODS: 20 participants with mild atopic asthma and AR underwent three single blinded nasal challenges each separated by three weeks (NCT03431961). Cohort A (n = 10) underwent a control saline challenge, followed by two allergen challenges. Cohort B (n = 10) underwent a NAC with no treatment intervention, followed by NAC with 14 days pre-treatment with saline nasal spray (placebo), then NAC with 14 days pre-treatment with INCS (220 µg triamcinolone acetonide twice daily). Nasosorption, nasal lavage, blood samples, forced expiratory volume 1 (FEV1), total nasal symptom score (TNSS), peak nasal inspiratory flow (PNIF) were collected up to 24 h after NAC. Total and active tryptase were measured as early-phase allergy biomarkers (≤30 min) and IL-13 and eosinophil cell counts as late-phase allergy biomarkers (3-7 h) in serum and nasal samples. Period-period reproducibility was assessed by intraclass correlation coefficients (ICC), and sample size estimates were performed using effect sizes measured after INCS. RESULTS: NAC significantly induced acute increases in nasosorption tryptase and TNSS and reduced PNIF, and induced late increases in nasosorption IL-13 with sustained reductions in PNIF. Reproducibility across NACs varied for symptoms and biomarkers, with total tryptase 5 min post NAC having the highest reproducibility (ICC = 0.91). Treatment with INCS inhibited NAC-induced IL-13 while blunting changes in TNSS and PNIF. For a similar crossover study, 7 participants per treatment arm are needed to detect treatment effects comparable to INCS for TNSS. CONCLUSION: NAC-induced biomarkers and symptoms are reproducible and responsive to INCS. NAC is suitable for assessing pharmacodynamic activity and proof of mechanism for drugs targeting allergic inflammation.

Gene Polymorphisms of Epithelial Cell-Derived Alarmins and Their Effects on Protein Levels and Disease Severity in Patients with COVID-19.

BACKGROUND: The immune response in COVID-19 is characterized by the release of alarmin cytokines, which play crucial roles in immune activation and inflammation. The interplay between these cytokines and genetic variations may influence disease severity and outcomes, while sex differences might further contribute to variations in the immune response. METHODS: We measured the levels of alarmin cytokines in a cohort of COVID-19 and non-COVID-19 patients using a sensitive Meso Scale Discovery system. Additionally, we conducted an SNP analysis to identify genetic variations within the IL-33 and TSLP genes. The association between these genetic variations, cytokine production, and COVID-19 severity was examined. RESULTS: Our findings revealed elevated levels of IL-33 and IL-25 in COVID-19-positive patients compared to COVID-19-negative patients (p < 0.05), indicating their potential as therapeutic targets for disease modulation. Moreover, a minor allele within the IL-33 gene (rs3939286) was found to be associated with a protective effect against severe COVID-19 (p < 0.05), and minor alleles of the TSLP gene (rs2289276 and rs13806933) were found to significantly reduce TSLP protein levels in serum (p < 0.05). Sex-specific effects of TSLP and IL-33 SNPs were observed, suggesting a potential influence of sex hormones and genetic variations on the regulation of cytokine production. CONCLUSION: The present study highlights the importance of alarmin cytokines and genetic variations in COVID-19 severity, providing valuable insights into personalized treatment approaches. Our results suggest that targeting alarmin cytokines may offer potential therapeutic benefits in managing COVID-19. Furthermore, the sex-specific effects of genetic variations emphasize the need to consider individual genetic profiles and sex differences when designing targeted interventions.