Routine Metagenomics Service for ICU Patients with Respiratory Infection.

Respiratory metagenomics (RMg) needs evaluation in a pilot service setting to determine utility and inform implementation into routine clinical practice. Feasibility, performance, and clinical impacts on antimicrobial prescribing and infection control were recorded during a pilot RMg service. RMg was performed on 128 samples from 87 patients with suspected lower respiratory tract infection (LRTI) on two general and one specialist respiratory ICUs at Guy's and St Thomas' NHS Foundation Trust, London.

COVID-19-associated pulmonary aspergillosis in mechanically ventilated patients: a prospective, multicentre UK study.

Background: Invasive pulmonary aspergillosis is a complication of severe COVID-19, with regional variation in reported incidence and mortality. We describe the incidence, risk factors and mortality associated with COVID-19-associated pulmonary aspergillosis (CAPA) in a prospective, multicentre UK cohort.

Methods: From March 2020 to March 2021, 266 mechanically ventilated adults with COVID-19 were enrolled across 5 UK hospital intensive care units (ICUs).

Urinary catecholamine excretion, cardiovascular variability, and outcomes in tetanus.

Severe tetanus is characterized by muscle spasm and cardiovascular system disturbance. The pathophysiology of muscle spasm is relatively well understood and involves inhibition of central inhibitory synapses by tetanus toxin. That of cardiovascular disturbance is less clear, but is believed to relate to disinhibition of the autonomic nervous system.

A randomised trial of anti-GM-CSF otilimab in severe COVID-19 pneumonia (OSCAR).

Background: Granulocyte-macrophage colony-stimulating factor (GM-CSF) and dysregulated myeloid cell responses are implicated in the pathophysiology and severity of COVID-19.

Methods: In this randomised, sequential, multicentre, placebo-controlled, double-blind study, adults aged 18-79 years (Part 1) or ≥70 years (Part 2) with severe COVID-19, respiratory failure and systemic inflammation (elevated C-reactive protein/ferritin) received a single intravenous infusion of otilimab 90 mg (human anti-GM-CSF monoclonal antibody) plus standard care (NCT04376684). The primary outcome was the proportion of patients alive and free of respiratory failure at Day 28.

A multisite evaluation of antifungal use in critical care: implications for antifungal stewardship.

Background: ICUs are settings of high antifungal consumption. There are few data on prescribing practices in ICUs to guide antifungal stewardship implementation in this setting.

Methods: An antifungal therapy (AFT) service evaluation (15 May-19 November 2019) across ICUs at three London hospitals, evaluating consumption, prescribing rationale, post-prescription review, de-escalation and final invasive fungal infection (IFI) diagnostic classification.

Fatal COVID-19 outcomes are associated with an antibody response targeting epitopes shared with endemic coronaviruses.

The role of immune responses to previously seen endemic coronavirus epitopes in severe acute respiratory coronavirus 2 (SARS-CoV-2) infection and disease progression has not yet been determined. Here, we show that a key characteristic of fatal outcomes with coronavirus disease 2019 (COVID-19) is that the immune response to the SARS-CoV-2 spike protein is enriched for antibodies directed against epitopes shared with endemic beta-coronaviruses and has a lower proportion of antibodies targeting the more protective variable regions of the spike. The magnitude of antibody responses to the SARS-CoV-2 full-length spike protein, its domains and subunits, and the SARS-CoV-2 nucleocapsid also correlated strongly with responses to the endemic beta-coronavirus spike proteins in individuals admitted to an intensive care unit (ICU) with fatal COVID-19 outcomes, but not in individuals with nonfatal outcomes.

Identification of immune correlates of fatal outcomes in critically ill COVID-19 patients.

Prior studies have demonstrated that immunologic dysfunction underpins severe illness in COVID-19 patients, but have lacked an in-depth analysis of the immunologic drivers of death in the most critically ill patients. We performed immunophenotyping of viral antigen-specific and unconventional T cell responses, neutralizing antibodies, and serum proteins in critically ill patients with SARS-CoV-2 infection, using influenza infection, SARS-CoV-2-convalescent health care workers, and healthy adults as controls. We identify mucosal-associated invariant T (MAIT) cell activation as an independent and significant predictor of death in COVID-19 (HR = 5.

Effectiveness of Continuous Endotracheal Cuff Pressure Control for the Prevention of Ventilator-Associated Respiratory Infections: An Open-Label Randomized, Controlled Trial.

Background: An endotracheal tube cuff pressure between 20 and 30 cmH2O is recommended to prevent ventilator-associated respiratory infection (VARI). We aimed to evaluate whether continuous cuff pressure control (CPC) was associated with reduced VARI incidence compared with intermittent CPC.

Methods: We conducted a multicenter open-label randomized controlled trial in intensive care unit (ICU) patients within 24 hours of intubation in Vietnam.

Development and evaluation of a nanopore 16S rRNA gene sequencing service for same day targeted treatment of bacterial respiratory infection in the intensive care unit.

Objectives: Assess the feasibility and impact of nanopore-based 16S rRNA gene sequencing (Np16S) service on antibiotic treatment for acute severe pneumonia on the intensive care unit (ICU).

Methods: Speciation and sequencing accuracy of Np16S on isolates with bioinformatics pipeline optimisation, followed by technical evaluation including quality checks and clinical-reporting criteria analysing stored respiratory samples using single-sample flow cells. Pilot service comparing Np16S results with all routine respiratory tests and impact on same-day antimicrobial prescribing.

A survey on the practices and capabilities in the management of respiratory failure in South East England.

Introduction: The variability of acute respiratory distress syndrome management may affect the referral practice to severe respiratory failure centres. We described the management of acute respiratory distress syndrome in our catchment area.

Methods: An electronic survey was administered to 42 intensive care units in South-East England.

Serial measurement of pancreatic stone protein for the early detection of sepsis in intensive care unit patients: a prospective multicentric study.

Background: The early recognition and management of sepsis improves outcomes. Biomarkers may help in identifying earlier sub-clinical signs of sepsis. We explored the potential of serial measurements of C-reactive protein (CRP), procalcitonin (PCT) and pancreatic stone protein (PSP) for the early recognition of sepsis in patients hospitalized in the intensive care unit (ICU).

A case of broncho-cutaneous fistula secondary to tuberculosis successfully managed with awake veno-venous extracorporeal membrane oxygenation.

A broncho-cutaneous fistula (BCF) is a communicating tract between the bronchus and the cutaneous surface of the thoracic wall and can be the primary presenting sign of several disease processes. It has been associated with positive pressure ventilation (PPV), post pneumonectomy, thoracostomy tubes, perforating chest trauma, neoplasia and chronic empyema. We report a case of a 45-year-old immunocompetent man presenting with severe hypercapnic respiratory failure secondary to a BCF as a result of tuberculosis (TB)-related empyema necessitans.

Cloth Lanyards as a Source of Intermittent Transmission of Candida auris on an ICU.

Objectives: Candida auris has been implicated in ICU outbreaks worldwide and is notable for being difficult to identify and treat, its resilience in the environment, and significant patient mortality associated with invasive disease. Here, we describe a small C. auris outbreak and how it was terminated.

Timing of Tracheostomy for Prolonged Respiratory Wean in Critically Ill Coronavirus Disease 2019 Patients: A Machine Learning Approach.

Objectives: To propose the optimal timing to consider tracheostomy insertion for weaning of mechanically ventilated patients recovering from coronavirus disease 2019 pneumonia. We investigated the relationship between duration of mechanical ventilation prior to tracheostomy insertion and in-hospital mortality. In addition, we present a machine learning approach to facilitate decision-making.

Tracheostomy, ventilatory wean, and decannulation in COVID-19 patients.

Purpose: COVID-19 patients requiring mechanical ventilation can overwhelm existing bed capacity. We aimed to better understand the factors that influence the trajectory of tracheostomy care in this population to facilitate capacity planning and improve outcomes.

Methods: We conducted an observational cohort study of patients in a high-volume centre in the worst-affected region of the UK including all patients that underwent tracheostomy for COVID-19 pneumonitis ventilatory wean from 1st March 2020 to 10th May 2020.

Restrictive Transfusion Practice in Adults Receiving Venovenous Extracorporeal Membrane Oxygenation: A Single-Center Experience.

Objectives: Restrictive transfusion policies have been adopted in critical care, although these have not included patients receiving extracorporeal membrane oxygenation. We aimed to assess survival outcomes, adverse events related to RBC transfusion, and cost implications following a change from a "liberal" to a "restrictive" RBC transfusion practice in patients receiving extracorporeal membrane oxygenation.

Design: Retrospective observational study.