Single-Cell Profiling Reveals Immune Aberrations in Progressive Idiopathic Pulmonary Fibrosis.

RATIONALE: Changes in peripheral blood cell populations have been observed but not detailed at single-cell resolution in idiopathic pulmonary fibrosis (IPF). OBJECTIVES: To provide an atlas of the changes in the peripheral immune system in stable and progressive IPF. METHODS: Peripheral blood mononuclear cells (PBMCs) from IPF patients and controls were profiled using 10x Chromium 5' single-cell RNA sequencing (scRNA-seq). Flow cytometry was used for validation. Protein concentrations of Regulatory T-cells (Tregs) and Monocytes chemoattractants were measured in plasma and lung homogenates from patients and controls. MEASUREMENTS AND MAIN RESULTS: Thirty-eight PBMC samples from 25 patients with IPF and 13 matched controls yielded 149,564 cells that segregated into 23 subpopulations. Classical monocytes were increased in progressive and stable IPF compared to controls (32.1%, 25.2%, 17.9%, respectively, p<0.05). Total lymphocytes were decreased in IPF vs controls, and in progressive vs stable IPF (52.6% vs 62.6%, p=0.035). Tregs were increased in progressive vs stable IPF (1.8% vs 1.1% of all PBMC, p=0.007), although not different than controls, and may be associated with decreased survival (P=0.009 in Kaplan-Meier analysis; P=0.069 after adjusting for age, sex, and baseline FVC). Flow cytometry analysis confirmed this finding in an independent cohort of IPF patients. Fraction of Tregs out of all T cells was also increased in two cohorts of lung scRNA-seq. CCL22 and CCL18, ligands for CCR4 and CCR8 Treg chemotaxis receptors, were increased in IPF. CONCLUSIONS: The single-cell atlas of the peripheral immune system in IPF, reveals an outcome-predictive increase in classical monocytes and Tregs, as well as evidence for a lung-blood immune recruitment axis involving CCL7 (for classical monocytes) and CCL18/CCL22 (for Tregs).

Percutaneous closure of incomplete surgical left atrial appendage ligation: success begins with the decision to try.

The authors present a case of percutaneous closure of an incomplete surgical left atrial appendage (LAA) ligation with a new device LAmbre (Lifetech ScientificCo Ltd).

An Approach to Diversifying the Selection of a Guideline Panel-The Process Utilized for the Updated Adult Critical Care Ultrasound Guidelines.

OBJECTIVES: Clinical practice guidelines are essential for promoting evidence-based healthcare. While diversification of panel members can reduce disparities in care, processes for panel selection lack transparency. We aim to share our approach in forming a diverse expert panel for the updated Adult Critical Care Ultrasound Guidelines. DESIGN: This process evaluation aims to understand whether the implementation of a transparent and intentional approach to guideline panel selection would result in the creation of a diverse expert guideline panel. SETTING: This study was conducted in the setting of creating a guideline panel for the updated Adult Critical Care Ultrasound Guidelines. PATIENTS: Understanding that family/patient advocacy in guideline creations can promote the impact of a clinical practice guideline, patient representation on the expert panel was prioritized. INTERVENTIONS: Interventions included creation of a clear definition of expertise, an open invitation to the Society of Critical Care Medicine membership to apply for the panel, additional panel nomination by guideline leadership, voluntary disclosure of pre-identified diversity criteria by potential candidates, and independent review of applications including diversity criteria. This resulted in an overall score per candidate per reviewer and an open forum for discussion and final consensus. MEASUREMENTS AND MAIN RESULTS: The variables of diversity were collected and analyzed after panel selection. These were compared with historical data on panel composition. The final guideline panel comprised of 33 panelists from six countries: 45% women and 79% historically excluded people and groups. The panel has representation from nonphysician professionals and patients advocates. Of the healthcare professionals, there is representation from early, mid, and late career stages. CONCLUSIONS: Our intentional and transparent approach resulted in a panel with improved gender parity and robust diversity along ethnic, racial, and professional lines. We hope it can serve as a starting point as we strive to become a more inclusive and diverse discipline that creates globally representative guidelines.

Atrial secondary tricuspid regurgitation: pathophysiology, definition, diagnosis, and treatment.

Atrial secondary tricuspid regurgitation (A-STR) is a distinct phenotype of secondary tricuspid regurgitation with predominant dilation of the right atrium and normal right and left ventricular function. Atrial secondary tricuspid regurgitation occurs most commonly in elderly women with atrial fibrillation and in heart failure with preserved ejection fraction in sinus rhythm. In A-STR, the main mechanism of leaflet malcoaptation is related to the presence of a significant dilation of the tricuspid annulus secondary to right atrial enlargement. In addition, there is an insufficient adaptive growth of tricuspid valve leaflets that become unable to cover the enlarged annular area. As opposed to the ventricular phenotype, in A-STR, the tricuspid valve leaflet tethering is typically trivial. The A-STR phenotype accounts for 10%-15% of clinically relevant tricuspid regurgitation and has better outcomes compared with the more prevalent ventricular phenotype. Recent data suggest that patients with A-STR may benefit from more aggressive rhythm control and timely valve interventions. However, little is mentioned in current guidelines on how to identify, evaluate, and manage these patients due to the lack of consistent evidence and variable definitions of this entity in recent investigations. This interdisciplinary expert opinion document focusing on A-STR is intended to help physicians understand this complex and rapidly evolving topic by reviewing its distinct pathophysiology, diagnosis, and multi-modality imaging characteristics. It first defines A-STR by proposing specific quantitative criteria for defining the atrial phenotype and for discriminating it from the ventricular phenotype, in order to facilitate standardization and consistency in research.

Essential Point-of-Care Ultrasound Insights for 2024.

To assess point-of-care ultrasound (POCUS) in 2024, we should start by defining its expanded scope and integration into general and specialty practice. Clinicians should abide by the evolving evidence for POCUS utilization and patient outcomes different from mortality and morbidity, especially as there are notable advancements in handheld ultrasound technology with a clear shift from capability to portability. To reduce diagnostic errors, POCUS practitioners need a holistic framework that accounts for known and new applications. Defining the POCUS scope of practices, proper training, and innovation, like artificial intelligence, can play a bigger role in mitigating diagnostic errors as we move forward.

Deep learning prediction of hospital readmissions for asthma and COPD.

QUESTION: Severe asthma and COPD exacerbations requiring hospitalization are linked to increased disease morbidity and healthcare costs. We sought to identify Electronic Health Record (EHR) features of severe asthma and COPD exacerbations and evaluate the performance of four machine learning (ML) and one deep learning (DL) model in predicting readmissions using EHR data. STUDY DESIGN AND METHODS: Observational study between September 30, 2012, and December 31, 2017, of patients hospitalized with asthma and COPD exacerbations. RESULTS: This study included 5,794 patients, 1,893 with asthma and 3,901 with COPD. Patients with asthma were predominantly female (n = 1288 [68%]), 35% were Black (n = 669), and 25% (n = 479) were Hispanic. Black (44 vs. 33%, p = 0.01) and Hispanic patients (30 vs. 24%, p = 0.02) were more likely to be readmitted for asthma. Similarly, patients with COPD readmissions included a large percentage of Blacks (18 vs. 10%, p < 0.01) and Hispanics (8 vs. 5%, p < 0.01). To identify patients at high risk of readmission index hospitalization data of a subset of 2,682 patients, 777 with asthma and 1,905 with COPD, was analyzed with four ML models, and one DL model. We found that multilayer perceptron, the DL method, had the best sensitivity and specificity compared to the four ML methods implemented in the same dataset. INTERPRETATION: Multilayer perceptron, a deep learning method, had the best performance in predicting asthma and COPD readmissions, demonstrating that EHR and deep learning integration can improve high-risk patient detection.

Foreign Body Ingestion by a Psychiatric Patient Requiring an Appendectomy: A Case Report.

In the surgical field, the correct approach to the psychiatric patient represents a medical challenge, given the special considerations to be taken in the individualization of their diagnosis and treatment. We present an uncommon case of a 29-year-old patient with associated psychiatric pathology who presented to the emergency room after the introduction of two foreign bodies into the nasal cavity. After the endoscopic removal of one of the foreign bodies, the X-ray follow-up shows a second foreign body into the esophagus, which progressed to the vermiform appendix, causing the classical clinical signs of acute appendicitis as a complication. The importance of considering that events treated by the otorhinolaryngology area may have complications for urgent management by the general surgery service is denoted in this article.

Critical Care Echocardiography-A Driven Approach to Undifferentiated Shock.

The clinical approach to undifferentiated shock in critically ill patients should be revised to use modern, point-of-care tools that are readily available. With the increasing availability of 2-dimensional ultrasonography and advanced Doppler capabilities, a quick, simplified, and integrated stepwise approach to shock using critical care echocardiography is proposed. Evidence supports the feasibility and usefulness of critical care echo-cardiography in enhancing diagnostic accuracy for shock, but there is a lack of systematic application of the technology in patients with undifferentiated shock. The proposed approach begins with the use of noninvasive ultrasonography with pulsed-wave Doppler capability to determine the flow state by measuring the velocity time integral of the left ventricular outflow tract. This narrative review explores the use left ventricular outflow tract velocity time integral, velocity time integral variation, limited visceral organ Doppler, and lung ultrasonography as a systematic approach for patients with undifferentiated shock.

Recovery of Lung Function After 149 Days on Extracorporeal Membrane Oxygenation for COVID-19.

This report highlights survival and the patient's perspective after prolonged venovenous extracorporeal membrane oxygenation (ECMO) for COVID-19-related respiratory failure. A 36-year-old man with COVID-19 presented with fever, anosmia, and hypoxia. After respiratory deterioration necessitating intubation and lung-protective ventilation, he was referred for ECMO. After 3 days of conventional venovenous ECMO, he required multiple creative cannulation configurations. Adequate sedation and recurrent bradycardia were persistent challenges. After 149 consecutive days of ECMO, he recovered native lung function and was weaned from mechanical ventilation. This represents the longest-duration ECMO support in a survivor of COVID-19 yet reported. Necessary strategies included unconventional cannulation and flexible anticoagulation.

Major Publications in the Critical Care Pharmacotherapy Literature: 2022.

OBJECTIVES: A number of trials related to critical care pharmacotherapy were published in 2022. We aimed to summarize the most influential publications related to the pharmacotherapeutic care of critically ill patients in 2022. DATA SOURCES: PubMed/Medical Literature Analysis and Retrieval System Online and the Clinical Pharmacy and Pharmacology Pharmacotherapy Literature Update. STUDY SELECTION: Randomized controlled trials, prospective studies, or systematic review/meta-analyses of adult critically ill patients assessing a pharmacotherapeutic intervention and reporting clinical endpoints published between January 1, 2022, and December 31, 2022, were included in this article. DATA EXTRACTION: Articles from a systematic search and the Clinical Pharmacy and Pharmacology Pharmacotherapy Literature Update were included and stratified into clinical domains based upon consistent themes. Consensus was obtained on the most influential publication within each clinical domain utilizing an a priori defined three-round modified Delphi process with the following considerations: 1) overall contribution to scientific knowledge and 2) novelty to the literature. DATA SYNTHESIS: The systematic search and Clinical Pharmacy and Pharmacology Pharmacotherapy Literature Update yielded a total of 704 articles, of which 660 were excluded. The remaining 44 articles were stratified into the following clinical domains: emergency/neurology, cardiovascular, gastroenterology/fluids/nutrition, hematology, infectious diseases/immunomodulation, and endocrine/metabolic. The final article selected from each clinical domain was summarized following a three-round modified Delphi process and included three randomized controlled trials and three systematic review/meta-analyses. Article topics summarized included dexmedetomidine versus other sedatives during mechanical ventilation, beta-blocker treatment in the critically ill, restriction of IV fluids in septic shock, venous thromboembolism prophylaxis in critically ill adults, duration of antibiotic therapy for Pseudomonas aeruginosa ventilator-associated pneumonia, and low-dose methylprednisolone treatment in severe community-acquired pneumonia. CONCLUSIONS: This concise review provides a perspective on articles published in 2022 that are relevant to the pharmacotherapeutic care of critically ill patients and their potential impact on clinical practice.

Dataset for the study of the effect of anticoagulation in the incidence of stroke and other outcomes in patients with left ventricular thrombus.

The optimal duration of anticoagulation in patients with left ventricular thrombus (LVT) is unknown. The data package herein presented contains the information used to assess the effect of duration of anticoagulation in the incidence of stroke in patients with left ventricular thrombus (LVT) in a tertiary hospital. In order to collect the required data, all transthoracic echocardiography studies at our institution from January 1st 2014 to December 31st 2021 with LVT were retrieved using dedicated software (Phillips Intellispace Cardiovascular; Koninklijke Phillips N.V., 2004-2020). Second, a dataset was designed ad hoc for this study in which the recruited data for the predefined objectives were obtained from electronic medical records. These data included clinical and demographic information including treatment choices (vitamin K antagonists [VKA] versus direct oral anticoagulants [DOAC]), duration of treatment, reason for interruption of treatment, occurrence of stroke, acute myocardial infarction, bleeding events, thrombus resolution, recurrence, and death. Retrieved data were stored in an excel sheet for analysis using the statistical package STATA (StataCorp v. 15.0, College station, TX). This methodology allows the reuse of these data for further analysis, in the context of the present study and also for future recruitment of additional patients from other institutions to increase statistical power.

Shared genetic architecture of blood eosinophil counts and asthma in UK Biobank.

Rationale: Asthma is a complex, heterogeneous disease strongly associated with type 2 inflammation, and blood eosinophil counts guide therapeutic interventions in moderate and severe asthma. Eosinophils are leukocytes involved in type 2 immune responses. Despite these critical associations between asthma and blood eosinophil counts, the shared genetic architecture of these two traits remains unknown. The objective of the present study was to characterise the genetic architecture of blood eosinophil counts and asthma in the UK Biobank. Methods: We performed genome-wide association studies (GWAS) of doctor-diagnosed asthma, blood eosinophil, neutrophil, lymphocyte and monocyte counts in the UK Biobank. Genetic correlation analysis was performed on GWAS results and validated in the Trans-National Asthma Genetic Consortium (TAGC) study of asthma. Results: GWAS of doctor-diagnosed asthma and blood eosinophil counts in the UK Biobank identified 585 and 3429 significant variants, respectively. STAT6, a transcription factor involved in interleukin-4 signalling, was a key shared pathway between asthma and blood eosinophil counts. Genetic correlation analysis demonstrated a positive correlation between doctor-diagnosed asthma and blood eosinophil counts (r=0.38±0.10, correlation±se; p=4.7×10-11). As a validation of this association, we found a similar correlation between TAGC and blood eosinophil counts in the UK Biobank (0.37±0.08, correlation±se; p=1.2×10-6). Conclusions: These findings define the shared genetic architecture between blood eosinophil counts and asthma risk in subjects of European ancestry and point to a genetic link to the STAT6 signalling pathway in these two traits.

Single-cell profiling reveals immune aberrations in progressive idiopathic pulmonary fibrosis.

Rationale: Changes in peripheral blood cell populations have been observed but not detailed at single-cell resolution in idiopathic pulmonary fibrosis (IPF). Objectives: To provide an atlas of the changes in the peripheral immune system in stable and progressive IPF. Methods: Peripheral blood mononuclear cells (PBMCs) from IPF patients and controls were profiled using 10x Chromium 5' single-cell RNA sequencing (scRNA-seq). Flow cytometry was used for validation. Protein concentrations of Regulatory T-cells (Tregs) and Monocytes chemoattractants were measured in plasma and lung homogenates from patients and controls. Measurements and Main Results: Thirty-eight PBMC samples from 25 patients with IPF and 13 matched controls yielded 149,564 cells that segregated into 23 subpopulations, corresponding to all expected peripheral blood cell populations. Classical monocytes were increased in progressive and stable IPF compared to controls (32.1%, 25.2%, 17.9%, respectively, p<0.05). Total lymphocytes were decreased in IPF vs controls, and in progressive vs stable IPF (52.6% vs 62.6%, p=0.035). Tregs were increased in progressive IPF (1.8% vs 1.1%, p=0.007), and were associated with decreased survival (P=0.009 in Kaplan-Meier analysis). Flow cytometry analysis confirmed this finding in an independent cohort of IPF patients. Tregs were also increased in two cohorts of lung scRNA-seq. CCL22 and CCL18, ligands for CCR4 and CCR8 Treg chemotaxis receptors, were increased in IPF. Conclusions: The single-cell atlas of the peripheral immune system in IPF, reveals an outcome-predictive increase in classical monocytes and Tregs, as well as evidence for a lung-blood immune recruitment axis involving CCL7 (for classical monocytes) and CCL18/CCL22 (for Tregs).

A ring-like accretion structure in M87 connecting its black hole and jet.

The nearby radio galaxy M87 is a prime target for studying black hole accretion and jet formation1,2. Event Horizon Telescope observations of M87 in 2017, at a wavelength of 1.3 mm, revealed a ring-like structure, which was interpreted as gravitationally lensed emission around a central black hole3. Here we report images of M87 obtained in 2018, at a wavelength of 3.5 mm, showing that the compact radio core is spatially resolved. High-resolution imaging shows a ring-like structure of [Formula: see text] Schwarzschild radii in diameter, approximately 50% larger than that seen at 1.3 mm. The outer edge at 3.5 mm is also larger than that at 1.3 mm. This larger and thicker ring indicates a substantial contribution from the accretion flow with absorption effects, in addition to the gravitationally lensed ring-like emission. The images show that the edge-brightened jet connects to the accretion flow of the black hole. Close to the black hole, the emission profile of the jet-launching region is wider than the expected profile of a black-hole-driven jet, suggesting the possible presence of a wind associated with the accretion flow.

Forensic age estimation: comparison and validation of the Iscan method in 3D reconstructions using a surface scanner in a Spanish population.

When investigating a death, post-mortem identification provides with results of great legal and humanitarian significance. The effectiveness of the methods used to estimate age depends on the reference population, considering variables such as sex and ancestry. The aim of this study was to validate the Iscan method to estimate age in a Spanish forensic population, comparing the estimates obtained in dry bones and 3D reconstructions created with a surface scanner. We carried out a cross-sectional study on 109 autopsied corpses (67% male), scanning the sternal end of the right fourth rib in a 3D mesh, using an EinScan-Pro® surface scanner (precision: 0.05 mm). Two observers estimated the phases in dry bones and 3D images according to the Iscan method and to the sex of the subject. The mean age was 57.73 years (SD = 19.12 years;18-93 years). The intra-observer agreement was almost perfect in bones (κ = 0.877-0.960) and 3D images (κ = 0.954), while the inter-observer agreement was almost perfect in bones (κ = 0.813) and substantial in 3D images (κ = 0.727). The correlation with the Iscan phases was very strong in bones (Rho = 0.794-0.820; p < 0.001) and strong in 3D images (Rho = 0.690-0.691; p < 0.001). Both sex-adjusted linear regression models were significant (dry bones: R2 = 0.65; SEE = ± 11.264 years; 3D images: R2 = 0.50; SEE = ± 13.537 years) from phase 4 onwards. An overestimation of age was observed in the first phases, and an underestimation in the later ones. Virtual analysis using a surface scanner in the fourth rib is a valid means of estimating age. However, the error values and confidence intervals were considerable, so the joint use of different methods and anatomical sites is recommended.

Co-Training for Unsupervised Domain Adaptation of Semantic Segmentation Models.

Semantic image segmentation is a core task for autonomous driving, which is performed by deep models. Since training these models draws to a curse of human-based image labeling, the use of synthetic images with automatically generated labels together with unlabeled real-world images is a promising alternative. This implies addressing an unsupervised domain adaptation (UDA) problem. In this paper, we propose a new co-training procedure for synth-to-real UDA of semantic segmentation models. It performs iterations where the (unlabeled) real-world training images are labeled by intermediate deep models trained with both the (labeled) synthetic images and the real-world ones labeled in previous iterations. More specifically, a self-training stage provides two domain-adapted models and a model collaboration loop allows the mutual improvement of these two models. The final semantic segmentation labels (pseudo-labels) for the real-world images are provided by these two models. The overall procedure treats the deep models as black boxes and drives their collaboration at the level of pseudo-labeled target images, i.e., neither modifying loss functions is required, nor explicit feature alignment. We test our proposal on standard synthetic and real-world datasets for onboard semantic segmentation. Our procedure shows improvements ranging from approximately 13 to 31 mIoU points over baselines.