Cardiovascular Subphenotypes in Acute Respiratory Distress Syndrome.

OBJECTIVES: To use clustering methods on transthoracic echocardiography (TTE) findings and hemodynamic parameters to characterize circulatory failure subphenotypes and potentially elucidate underlying mechanisms in patients with acute respiratory distress syndrome (ARDS) and to describe their association with mortality compared with current definitions of right ventricular dysfunction (RVD). DESIGN: Retrospective, single-center cohort study. SETTING: University Hospital ICU, Birmingham, United Kingdom. PATIENTS: ICU patients that received TTE within 7 days of ARDS onset between April 2016 and December 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Latent class analysis (LCA) of TTE/hemodynamic parameters was performed in 801 patients, 62 years old (interquartile range, 50-72 yr old), 63% male, and 40% 90-day mortality rate. Four cardiovascular subphenotypes were identified: class 1 (43%; mostly normal left and right ventricular [LV/RV] function), class 2 (24%; mostly dilated RV with preserved systolic function), class 3 (13%, mostly dilated RV with impaired systolic function), and class 4 (21%; mostly high cardiac output, with hyperdynamic LV function). The four subphenotypes differed in their characteristics and outcomes, with 90-day mortality rates of 19%, 40%, 78%, and 59% in classes 1-4, respectively ( p < 0.0001). Following multivariable logistic regression analysis, class 3 had the highest odds ratio (OR) for mortality (OR, 6.9; 95% CI, 4.0-11.8) compared with other RVD definitions. Different three-variable models had high diagnostic accuracy in identifying each of these latent subphenotypes. CONCLUSIONS: LCA of TTE parameters identified four cardiovascular subphenotypes in ARDS that more closely aligned with circulatory failure mechanisms and mortality than current RVD definitions.

Right Ventricular Dysfunction and Its Association With Mortality in Coronavirus Disease 2019 Acute Respiratory Distress Syndrome.

OBJECTIVES: To assess whether right ventricular dilation or systolic impairment is associated with mortality and/or disease severity in invasively ventilated patients with coronavirus disease 2019 acute respiratory distress syndrome. DESIGN: Retrospective cohort study. SETTING: Single-center U.K. ICU. PATIENTS: Patients with coronavirus disease 2019 acute respiratory distress syndrome undergoing invasive mechanical ventilation that received a transthoracic echocardiogram between March and December 2020. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Right ventricular dilation was defined as right ventricular:left ventricular end-diastolic area greater than 0.6, right ventricular systolic impairment as fractional area change less than 35%, or tricuspid annular plane systolic excursion less than 17 mm. One hundred seventy-two patients were included, 59 years old (interquartile range, 49-67), with mostly moderate acute respiratory distress syndrome (n = 101; 59%). Ninety-day mortality was 41% (n = 70): 49% in patients with right ventricular dilation, 53% in right ventricular systolic impairment, and 72% in right ventricular dilation with systolic impairment. The right ventricular dilation with systolic impairment phenotype was independently associated with mortality (odds ratio, 3.11 [95% CI, 1.15-7.60]), but either disease state alone was not. Right ventricular fractional area change correlated with Pao2:Fio2 ratio, Paco2, chest radiograph opacification, and dynamic compliance, whereas right ventricular:left ventricle end-diastolic area correlated negatively with urine output. CONCLUSIONS: Right ventricular systolic impairment correlated with pulmonary pathophysiology, whereas right ventricular dilation correlated with renal dysfunction. Right ventricular dilation with systolic impairment was the only right ventricular phenotype that was independently associated with mortality.

Revealing transparency gaps in publicly available COVID-19 datasets used for medical artificial intelligence development-a systematic review.

During the COVID-19 pandemic, artificial intelligence (AI) models were created to address health-care resource constraints. Previous research shows that health-care datasets often have limitations, leading to biased AI technologies. This systematic review assessed datasets used for AI development during the pandemic, identifying several deficiencies. Datasets were identified by screening articles from MEDLINE and using Google Dataset Search. 192 datasets were analysed for metadata completeness, composition, data accessibility, and ethical considerations. Findings revealed substantial gaps: only 48% of datasets documented individuals' country of origin, 43% reported age, and under 25% included sex, gender, race, or ethnicity. Information on data labelling, ethical review, or consent was frequently missing. Many datasets reused data with inadequate traceability. Notably, historical paediatric chest x-rays appeared in some datasets without acknowledgment. These deficiencies highlight the need for better data quality and transparent documentation to lessen the risk that biased AI models are developed in future health emergencies.

The value of standards for health datasets in artificial intelligence-based applications.

Artificial intelligence as a medical device is increasingly being applied to healthcare for diagnosis, risk stratification and resource allocation. However, a growing body of evidence has highlighted the risk of algorithmic bias, which may perpetuate existing health inequity. This problem arises in part because of systemic inequalities in dataset curation, unequal opportunity to participate in research and inequalities of access. This study aims to explore existing standards, frameworks and best practices for ensuring adequate data diversity in health datasets. Exploring the body of existing literature and expert views is an important step towards the development of consensus-based guidelines. The study comprises two parts: a systematic review of existing standards, frameworks and best practices for healthcare datasets; and a survey and thematic analysis of stakeholder views of bias, health equity and best practices for artificial intelligence as a medical device. We found that the need for dataset diversity was well described in literature, and experts generally favored the development of a robust set of guidelines, but there were mixed views about how these could be implemented practically. The outputs of this study will be used to inform the development of standards for transparency of data diversity in health datasets (the STANDING Together initiative).

Intrathecal diamorphine for perioperative analgesia during colorectal surgery: a cross-sectional survey of current UK practice.

OBJECTIVES: To describe current UK clinical practice around the use of intrathecal diamorphine as analgesia for major elective laparoscopic colorectal surgery. DESIGN: Online self-administered survey. SETTING: Acute public hospitals in the UK (National Health Service - NHS) . PARTICIPANTS: Consultant anaesthetists involved in colorectal surgery lists. MAIN OUTCOME MEASURES: Rate of intrathecal opioids used by anaesthetists for elective laparoscopic colorectal procedures; minimum, most common and maximum doses of intrathecal diamorphine used, timing of administration of intrathecal injection, and relationship between the number of patients anaesthetised for laparoscopic colorectal resections per month by each anaesthetist, and the doses of intrathecal diamorphine they administer. RESULTS: In total, 479 responses were received. Of these, 399 (83%) use intrathecal opioid routinely: 351/399 (88%) use diamorphine, 35 (8.8%) use morphine, 8 (2%) use fentanyl, and 7 (1.3%) use other drugs. The median intrathecal diamorphine dose most commonly administered by anaesthetists was 500 µg (IQR 400-750 [(range 200-1500])). The median of the maximum dose administered by anaesthetists was 600 µg (IQR 500-1000 [(range 200-2000])). Greater intrathecal diamorphine dosing was positively associated with higher number of cases per month (rho=0.113, pp=0.033). CONCLUSIONS: Intrathecal diamorphine is widely used by UK anaesthetists for patients undergoing major elective laparoscopic colorectal surgery. However, there is little consensus regarding optimal dosing. Therefore, high-quality randomised dose-response trials are needed to investigate the relationship between doses of intrathecal diamorphine and patient outcomes.

Skill decay following Basic Life Support training: a systematic review protocol.

INTRODUCTION: Survival from out of hospital cardiac arrest (OHCA) is lower in the UK than in several developed nations. Bystander cardiopulmonary resuscitation (CPR) is associated with increased rates of survival to hospital discharge following OHCA, prompting the introduction of several initiatives by the UK government to increase rates of bystander CPR, including the inclusion of Basic Life Support (BLS) teaching within the English national curriculum. While there is clear benefit in this, increasing evidence suggests poor retention of skills following BLS teaching. The aim of this systematic review is to summarise the literature regarding skill decay following BLS training, reporting particularly the time period over which this occurs, and which components of would-be rescuers' performance of the BLS algorithm are most affected. METHODS AND ANALYSIS: A search will be conducted to identify studies in which individuals have received BLS training and received subsequent assessment of their skills at a later date. A search strategy comprising relevant Medical Subject Headings (MeSH) terms and keywords has been devised with assistance from an experienced librarian. Relevant databases will be searched with titles, abstract and full-text review conducted independently by two reviewers. Data will be extracted from included studies by two reviewers, with meta-analysis conducted if the appropriate preconditions (such as limited heterogeneity) are met. ETHIC AND DISSEMINATION: No formal ethical approval is required for this systematic review. Results will be disseminated in the form of manuscript submission to a relevant journal and presentation at relevant meetings. To maximise the public's access to this review's findings, any scientific report will be accompanied by a lay summary posted via social media channels, and a press release disseminated to national and international news agencies. PROSPERO REGISTRATION NUMBER: CRD42021237233.

Thoracic Injury in Patients Injured by Explosions on the Battlefield and in Terrorist Incidents.

Thoracic injury is common on the battlefield and in terrorist attacks, occurring in 10% to 70% of patients depending on the type of weapons used. Typical injuries seen include bullet, blast, and fragment injuries to the thorax, which are often associated with injuries to other parts of the body. Initial treatment prehospital and in the ED is carried out according to the principles of Tactical Combat Casualty Care or other standard trauma management systems. Immediately life-threatening problems including catastrophic hemorrhage are dealt with rapidly, and early consideration is given to CT scanning or rapid surgical intervention where appropriate. All patients should be given lung-protective ventilation. Treatment of these patients in the critical care unit is complicated by the severity of associated injuries and by features specific to combat trauma including blast lung injury, a high incidence of delirium, unusual infections such as colonization with multidrug-resistant Acinetobacter baumannii complex, and sometimes invasive fungal infections. A minority of patients with blast lung injury in published series have been successfully treated with prolonged respiratory support with high-frequency oscillatory ventilation and extracorporeal membrane oxygenation. The role of newer treatment options such as resuscitative endovascular balloon occlusion of the aorta is not yet known. In this article we review the relatively sparse literature on this group of patients and provide practical advice based on the literature and our institution's extensive experience of managing battlefield casualties.

Characterisation and outcomes of ARDS secondary to pneumonia in patients with and without SARS-CoV-2: a single-centre experience.

INTRODUCTION: Acute respiratory distress syndrome (ARDS) is the major cause of mortality in patients with SARS-CoV-2 pneumonia. It appears that development of 'cytokine storm' in patients with SARS-CoV-2 pneumonia precipitates progression to ARDS. However, severity scores on admission do not predict severity or mortality in patients with SARS-CoV-2 pneumonia. Our objective was to determine whether patients with SARS-CoV-2 ARDS are clinically distinct, therefore requiring alternative management strategies, compared with other patients with ARDS. We report a single-centre retrospective study comparing the characteristics and outcomes of patients with ARDS with and without SARS-CoV-2. METHODS: Two intensive care unit (ICU) cohorts of patients at the Queen Elizabeth Hospital Birmingham were analysed: SARS-CoV-2 patients admitted between 11 March and 21 April 2020 and all patients with community-acquired pneumonia (CAP) from bacterial or viral infection who developed ARDS between 1 January 2017 and 1 November 2019. All data were routinely collected on the hospital's electronic patient records. RESULTS: A greater proportion of SARS-CoV-2 patients were from an Asian ethnic group (p=0.002). SARS-CoV-2 patients had lower circulating leucocytes, neutrophils and monocytes (p<0.0001), but higher CRP (p=0.016) on ICU admission. SARS-CoV-2 patients required a longer duration of mechanical ventilation (p=0.01), but had lower vasopressor requirements (p=0.016). DISCUSSION: The clinical syndromes and respiratory mechanics of SARS-CoV-2 and CAP-ARDS are broadly similar. However, SARS-CoV-2 patients initially have a lower requirement for vasopressor support, fewer circulating leukocytes and require prolonged ventilation support. Further studies are required to determine whether the dysregulated inflammation observed in SARS-CoV-2 ARDS may contribute to the increased duration of respiratory failure.

BST2/Tetherin Overexpression Modulates Morbillivirus Glycoprotein Production to Inhibit Cell-Cell Fusion.

The measles virus (MeV), a member of the genus Morbillivirus, is an established pathogen of humans. A key feature of morbilliviruses is their ability to spread by virus-cell and cell-cell fusion. The latter process, which leads to syncytia formation in vitro and in vivo, is driven by the viral fusion (F) and haemagglutinin (H) glycoproteins. In this study, we demonstrate that MeV glycoproteins are sensitive to inhibition by bone marrow stromal antigen 2 (BST2/Tetherin/CD317) proteins. BST2 overexpression causes a large reduction in MeV syncytia expansion. Using quantitative cell-cell fusion assays, immunolabeling, and biochemistry we further demonstrate that ectopically expressed BST2 directly inhibits MeV cell-cell fusion. This restriction is mediated by the targeting of the MeV H glycoprotein, but not other MeV proteins. Using truncation mutants, we further establish that the C-terminal glycosyl-phosphatidylinositol (GPI) anchor of BST2 is required for the restriction of MeV replication in vitro and cell-cell fusion. By extending our study to the ruminant morbillivirus peste des petits ruminants virus (PPRV) and its natural host, sheep, we also confirm this is a broad and cross-species specific phenotype.