A Comparison of Long-Term Outcomes in Patients Managed With Venovenous Extracorporeal Membrane Oxygenation in the First and Second Waves of the COVID-19 Pandemic in the United Kingdom.

OBJECTIVES: Early studies of venovenous extracorporeal membrane oxygenation (ECMO) in COVID-19 have revealed similar outcomes to historical cohorts. Changes in the disease and treatments have led to differences in the patients supported on venovenous ECMO in the first and second waves. We aimed to compare these two groups in both the acute and follow-up phase. DESIGN: Retrospective single-center cohort study comparing mortality at censoring date (November 30, 2021) and decannulation, patient characteristics, complications and lung function and quality of life (QOL-by European Quality of Life 5 Dimensions 3 Level Version) at first follow-up in patients supported on venovenous ECMO between wave 1 and wave 2 of the COVID-19 pandemic. SETTING: Critical care department of a severe acute respiratory failure service. PATIENTS: Patients supported on ECMO for COVID-19 between wave 1 (March 17, 2020, to August 31, 2020) and wave 2 (January 9, 2020, to May 25, 2021). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One hundred twenty-three patients were included in our analysis. Survival at censoring date (χ 2 , 6.35; p = 0.012) and decannulation (90.4% vs 70.0%; p < 0.001) was significantly lower in the second wave, while duration of ECMO run was longer (12.0 d [18.0-30.0 d] vs 29.5 d [15.5-58.3 d]; p = 0.005). Wave 2 patients had longer application of noninvasive ventilation (NIV) prior to ECMO and a higher frequency of barotrauma. Patient age and NIV use were independently associated with increased mortality (odds ratio 1.07 [1.01-1.14]; p = 0.025 and 3.37 [1.12-12.60]; p = 0.043, respectively). QOL and lung function apart from transfer coefficient of carbon monoxide corrected for hemoglobin was similar at follow-up across the waves. CONCLUSIONS: Most patients with COVID-19 supported on ECMO in both waves survived in the short and longer term. At follow-up patients had similar lung function and QOL across the two waves. This suggests that ECMO has an ongoing role in the management of a carefully selected group of patients with COVID-19.

Deficient retinoid-driven angiogenesis may contribute to failure of adult human lung regeneration in emphysema.

BACKGROUND: Molecular pathways that regulate alveolar development and adult repair represent potential therapeutic targets for emphysema. Signalling via retinoic acid (RA), derived from vitamin A, is required for mammalian alveologenesis, and exogenous RA can induce alveolar regeneration in rodents. Little is known about RA signalling in the human lung and its potential role in lung disease. OBJECTIVES: To examine regulation of human alveolar epithelial and endothelial repair by RA, and characterise RA signalling in human emphysema. METHODS: The role of RA signalling in alveolar epithelial repair was investigated with a scratch assay using an alveolar cell line (A549) and primary human alveolar type 2 (AT2) cells from resected lung, and the role in angiogenesis using a tube formation assay with human lung microvascular endothelial cells (HLMVEC). Localisation of RA synthetic (RALDH-1) and degrading (cytochrome P450 subfamily 26 A1 (CYP26A1)) enzymes in human lung was determined by immunofluorescence. Regulation of RA pathway components was investigated in emphysematous and control human lung tissue by quantitative real-time PCR and Western analysis. RESULTS: RA stimulated HLMVEC angiogenesis in vitro; this was partially reproduced with a RAR-α agonist. RA induced mRNA expression of vascular endothelial growth factor A (VEGFA) and VEGFR2. RA did not modulate AT2 repair. CYP26A1 protein was identified in human lung microvasculature, whereas RALDH-1 partially co-localised with vimentin-positive fibroblasts. CYP26A1 mRNA and protein were increased in emphysema. CONCLUSIONS: RA regulates lung microvascular angiogenesis; the endothelium produces CYP26A1 which is increased in emphysema, possibly leading to reduced RA availability. These data highlight a role for RA in maintenance of the human pulmonary microvascular endothelium.

High prevalence of malignancy in HIV-positive patients with mediastinal lymphadenopathy: a study in the era of antiretroviral therapy.

BACKGROUND AND OBJECTIVE: Mediastinal lymphadenopathy (MLN) in human immunodeficiency virus (HIV) infection has a wide spectrum of aetiologies with different prognoses and treatments. The decision to pursue a histopathological diagnosis represents a clinical challenge as patients present with non-specific symptoms. This study aimed to determine the aetiology and predictive factors of MLN in a cohort of HIV-infected patients in the combination antiretroviral therapy (cART) era. METHODS: Single-centre retrospective cohort study of 217 consecutive HIV-infected patients who underwent computed tomography (CT) of the chest between January 2004 and December 2009. Fifty-two patients were identified to have MLN (>10 mm in short axis). CT images were re-reviewed by an independent radiologist blinded to the clinical information. Final diagnoses of MLN were obtained from clinical records. Multivariate analysis was performed to identify predictors of aetiology of MLN. RESULTS: Seventeen patients (33%) had a diagnosis of malignancy. Consolidation on CT was associated with a reduced likelihood of malignancy odds ratio (OR) 0.03 (95% confidence interval 0.002-0.422), and larger lymph nodes were associated with an increase in the odds of malignancy (OR 2.89; 95% confidence interval 1.24-6.71). CD4 count was found not to be a predictor of aetiology of MLN. CONCLUSIONS: In the era of combination cART, opportunistic infections and malignancy remain to be the frequent causes of MLN in HIV-positive patients, but the prevalence of non-HIV related malignancy has increased compared with previous studies. Although certain findings are predictors of non-malignant disease, pathological diagnosis of MLN in HIV-positive patients should be pursued whenever possible.

Epidemiological drivers of transmissibility and severity of SARS-CoV-2 in England.

As the SARS-CoV-2 pandemic progressed, distinct variants emerged and dominated in England. These variants, Wildtype, Alpha, Delta, and Omicron were characterized by variations in transmissibility and severity. We used a robust mathematical model and Bayesian inference framework to analyse epidemiological surveillance data from England. We quantified the impact of non-pharmaceutical interventions (NPIs), therapeutics, and vaccination on virus transmission and severity. Each successive variant had a higher intrinsic transmissibility. Omicron (BA.1) had the highest basic reproduction number at 8.3 (95% credible interval (CrI) 7.7-8.8). Varying levels of NPIs were crucial in controlling virus transmission until population immunity accumulated. Immune escape properties of Omicron decreased effective levels of immunity in the population by a third. Furthermore, in contrast to previous studies, we found Alpha had the highest basic infection fatality ratio (2.9%, 95% CrI 2.7-3.2), followed by Delta (2.2%, 95% CrI 2.0-2.4), Wildtype (1.2%, 95% CrI 1.1-1.2), and Omicron (0.7%, 95% CrI 0.6-0.8). Our findings highlight the importance of continued surveillance. Long-term strategies for monitoring and maintaining effective immunity against SARS-CoV-2 are critical to inform the role of NPIs to effectively manage future variants with potentially higher intrinsic transmissibility and severe outcomes.

Taxine alkaloid poisoning successfully supported with venoarterial extracorporeal membrane oxygenation: a case report.

BACKGROUND: Ingestion of the berries of the European yew tree can result in fatal cardiac arrhythmias. CASE SUMMARY: A 53-year-old female presented to our emergency department following ingestion of ∼200 European yew tree berries. At presentation, she was in cardiogenic shock due to a mixture of tachy- and bradyarrhythmias including ventricular tachycardia, atrial fibrillation with slow ventricular response and prolonged ventricular conduction, and periods of asystole. She was referred to a specialist cardiac centre and promptly established on mechanical circulatory support with venoarterial extracorporeal membrane oxygenation (V-A ECMO) by a retrieval team. Following resolution of her arrhythmias, she was weaned from V-A ECMO after 4 days of support and was discharged home with full neurological recovery on Day 12. DISCUSSION: Poisoning can lead to acute reversible but potentially fatal cardiogenic shock. We believe that access to prompt initiation of V-A ECMO was key to this patient's survival.

Symptomatic, biochemical and radiographic recovery in patients with COVID-19.

BACKGROUND: The symptoms, radiography, biochemistry and healthcare utilisation of patients with COVID-19 following discharge from hospital have not been well described. METHODS: Retrospective analysis of 401 adult patients attending a clinic following an index hospital admission or emergency department attendance with COVID-19. Regression models were used to assess the association between characteristics and persistent abnormal chest radiographs or breathlessness. RESULTS: 75.1% of patients were symptomatic at a median of 53 days post discharge and 72 days after symptom onset and chest radiographs were abnormal in 47.4%. Symptoms and radiographic abnormalities were similar in PCR-positive and PCR-negative patients. Severity of COVID-19 was significantly associated with persistent radiographic abnormalities and breathlessness. 18.5% of patients had unscheduled healthcare visits in the 30 days post discharge. CONCLUSIONS: Patients with COVID-19 experience persistent symptoms and abnormal blood biomarkers with a gradual resolution of radiological abnormalities over time. These findings can inform patients and clinicians about expected recovery times and plan services for follow-up of patients with COVID-19.

Early signs of right ventricular systolic and diastolic dysfunction in acute severe respiratory failure: the importance of diastolic restrictive pattern.

BACKGROUND: The incidence and pathophysiology of right ventricular failure in patients with severe respiratory insufficiency has been largely investigated. However, there is a lack of early signs suggesting right ventricular systolic and diastolic dysfunction prior to acute cor pulmonale development. METHODS: We conducted a retrospective analytical cohort study of patients for acute respiratory distress syndrome undertaking an echocardiography during admission in the cardiothoracic intensive care unit. Patients were divided according to treatment: conventional protective ventilation (38 patients, 38%); interventional lung assist (23 patients, 23%); veno-venous extracorporeal membrane oxygenation (37 patients, 37%). Systolic and diastolic function was studied assessing, respectively: right ventricular systolic longitudinal function (tricuspid annular plane systolic excursion) and systolic contraction duration (tricuspid annular plane systolic excursion length); right ventricular diastolic filling time and right ventricular diastolic restrictive pattern (presence of pulmonary valve presystolic ejection wave). Correlation between the respiratory mechanics and systo-diastolic parameters were analysed. RESULTS: In 98 patients studied, systolic dysfunction (tricuspid annular plane systolic excursion <16 mm) was present in 33.6% while diastolic restrictive pattern was present in 64%. A negative correlation was found between tricuspid annular plane systolic excursion and tricuspid annular plane systolic excursion length (P<0.0001; r -0.42). Tricuspid annular plane systolic excursion and tricuspid annular plane systolic excursion length correlated with right ventricular diastolic filling time (P<0.001; r -0.39). Pulmonary valve presystolic ejection wave was associated with tricuspid annular plane systolic excursion (P<0.0001), tricuspid annular plane systolic excursion length (P<0.0001), right ventricular diastolic filling time (P<0.0001), positive end-expiratory pressure (P<0.0001) and peak inspiratory pressure (P<0.0001). CONCLUSION: Diastolic restrictive pattern is present in a remarkable percentage of patients with respiratory distress syndrome. Bedside echocardiography allows a mechanistic evaluation of systolic and diastolic interaction of the right ventricle.

Imaging the lung: the old ways and the new.

Our understanding of lung biology can be greatly enhanced by studying embryonic and postnatal lung development, and the perturbations which occur during disease. Imaging techniques provide a unique insight into these processes. A wide variety of imaging techniques have been used to study the lungs at various stages of development and disease, ranging from histological stains to more novel techniques such as single plane illumination microscopy (SPIM), intravital microscopy (IVM), and micro-computed tomography (micro-CT). Each of these tools can be used to elicit different information about the lungs and each has its own unique advantages and disadvantages for pulmonary research. In this review we assess some of the most commonly-used and novel imaging techniques available for lung research today.