Metagenomics in the Diagnosis of Pneumonia: Protocol for a Systematic Review.

BACKGROUND: Causative pathogens are currently identified in only a minority of pneumonia cases, which affects antimicrobial stewardship. Metagenomic next-generation sequencing (mNGS) has potential to enhance pathogen detection due to its sensitivity and broad applicability. However, while studies have shown improved sensitivity compared with conventional microbiological methods for pneumonia diagnosis, it remains unclear whether this can translate into clinical benefit. Most existing studies focus on patients who are ventilated, readily allowing for analysis of bronchoalveolar lavage fluid (BALF). The impact of sample type on the use of metagenomic analysis remains poorly defined. Similarly, previous studies rarely differentiate between the types of pneumonia involved-community-acquired pneumonia (CAP), hospital-acquired pneumonia (HAP), or ventilator-associated pneumonia (VAP)-which have different clinical profiles. OBJECTIVE: This study aims to determine the clinical use of mNGS in CAP, HAP, and VAP, compared with traditional microbiological methods. METHODS: We aim to review all studies (excluding case reports of a series of fewer than 10 people) of adult patients with suspected or confirmed pneumonia that compare metagenomic analysis with traditional microbiology techniques, including culture, antigen-based testing, and polymerase chain reaction-based assays. Relevant studies will be identified through systematic searches of the Embase, MEDLINE, Scopus, and Cochrane CENTRAL databases. Screening of titles, abstracts, and subsequent review of eligible full texts will be done by 2 separate reviewers (SQ and 1 of AL, CJ, or CH), with a third clinician (ES) providing adjudication in case of disagreement. Our focus is on the clinical use of metagenomics for patients with CAP, HAP, and VAP. Data extracted will focus on clinically important outcomes-pathogen positivity rate, laboratory turnaround time, impact on clinical decision-making, length of stay, and 30-day mortality. Subgroup analyses will be performed based on the type of pneumonia (CAP, HAP, or VAP) and sample type used. The risk of bias will be assessed using the QUADAS-2 tool for diagnostic accuracy studies. Outcome data will be combined in a random-effects meta-analysis, and where this is not possible, a narrative synthesis will be undertaken. RESULTS: The searches were completed with the assistance of a medical librarian on January 13, 2024, returning 5750 records. Screening and data extraction are anticipated to be completed by September 2024. CONCLUSIONS: Despite significant promise, the impact of metagenomic analysis on clinical pathways remains unclear. Furthermore, it is unclear whether the use of this technique will alter depending on whether the pneumonia is a CAP, HAP, or VAP or the sample type that is collected. This systematic review will assess the current evidence base to support the benefit of clinical outcomes for metagenomic analysis, depending on the setting of pneumonia diagnosis or specimen type used. It will identify areas where further research is needed to advance this methodology into routine care. TRIAL REGISTRATION: PROSPERO CRD42023488096; https://tinyurl.com/3suy7cma. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/57334.

What Is the Accuracy of Clinical Staging for Stage III-Single-station N2 NSCLC? A Multi-Centre UK Study.

Introduction: Single-station N2 (ssN2) versus multi-station N2 has been used as a selection criterion for treatment recommendations between surgical versus non-surgical multimodality treatment in stage III-N2 NSCLC. We hypothesized that clinical staging would be susceptible to upstaging on pathologic staging and, therefore, challenge this practice. Methods: A retrospective study of prospectively collected routine clinical data for patients with stage III-N2 NSCLC that had completed computed tomography (CT), positron emission tomography (PET), and staging endobronchial ultrasound (EBUS) and had been confirmed clinical stage III-ssN2 at multidisciplinary team discussion and went on to complete surgical resection as the first treatment to provide pathologic staging. The study was completed in two cohorts (A) across a single cancer alliance in England (Greater Manchester) January 1, 2015 to December 31, 2018 and (B) across five United Kingdom centers to validate the findings in part A January 1, 2016 to December 31, 2020. Results: A total of 115 patients met the inclusion criteria across cohort A (56 patients) and cohort B (59 patients) across 15 United Kingdom hospitals. The proportion of cases in which clinical stage III-ssN2 was upstaged to pathologic stage III-multi-station N2 was 34% (19 of 56) in cohort A, 32% in cohort B (19 of 59), and 33% across the combined study cohort (38 of 115). Most patients had a single radiologically abnormal lymph node on CT and PET (88%, 105 of 115). In the majority, the reasons for missed N2 disease on staging EBUS were due to inaccessible (stations 5, 6, 8, 9) N2 nodes at EBUS (34%, 13 of 38) and accessible lymph nodes not sampled during staging EBUS as not meeting sampling threshold (40%, 15 of 38) rather than false-negative sampling during EBUS (26%, 10 of 38). Conclusions: During multidisciplinary team discussions, clinicians must be aware that one-third of patients with stage III-ssN2 on the basis of CT, PET, and staging EBUS do not truly have ssN2 and this questions the use of this criterion to define treatment recommendations.

ERS International Congress 2023: highlights from the Respiratory Intensive Care Assembly.

Early career members of Assembly 2 (Respiratory Intensive Care) attended the 2023 European Respiratory Society International Congress in Milan, Italy. The conference covered acute and chronic respiratory failure. Sessions of interest to our assembly members and to those interested in respiratory critical care are summarised in this article and include the latest updates in respiratory intensive care, in particular acute respiratory distress syndrome and mechanical ventilation.

Utility of severity assessment tools in COVID-19 pneumonia: a multicentre observational study.

BACKGROUND: Severity scores in pneumonia and sepsis are being applied to SARS-CoV-2 infection. We aimed to assess whether these severity scores are accurate predictors of early adverse outcomes in COVID-19. METHODS: We conducted a multicentre observational study of hospitalised SARS-CoV-2 infection. We assessed risk scores (CURB65, qSOFA, Lac-CURB65, MuLBSTA and NEWS2) in relation to admission to intensive care or death within 7 days of admission, defined as early severe adverse events (ESAE). The 4C Mortality Score was also assessed in a sub-cohort of patients. FINDINGS: In 2,387 participants, the overall mortality was 18%. In all scores examined, increasing score was associated with increased risk of ESAE. Area under the curve (AUC) to predict ESAE for CURB65, qSOFA, Lac-CURB65, MuLBSTA and NEWS2 were 0.61, 0.62, 0.59, 0.59 and 0.68, respectively. AUC to predict ESAE was 0.60 with ISARIC 4C Mortality Score. CONCLUSION: None of the scores examined accurately predicted ESAE in SARS-CoV-2 infection. Non-validated scores should not be used to inform clinical decision making in COVID-19.

European Respiratory Society International Congress 2018: highlights from Assembly 2 on respiratory intensive care.

The respiratory intensive care Assembly of the European Respiratory Society is proud to present a summary of several important sessions held at the International Congress in Paris in 2018. For the highly esteemed reader who may have missed the Congress, a concise review was written on three topics: the state-of-the-art session on respiratory critical care, hot topics in weaning and the best abstracts in noninvasive ventilation.

Are they high on steroids? Tailored interventions help improve screening for steroid-induced hyperglycaemia in hospitalised patients.

Steroid-induced hyperglycaemia (SIH) is a common adverse effect in patients both with and without diabetes. This project aimed to improve the screening and diagnosis of SIH by improving the knowledge of healthcare professionals who contribute to the management of SIH in hospitalised patients. Monitoring and diagnosis of SIH were measured in areas of high steroid use in our hospital from May 2016 to January 2017. Several interventions were implemented to improve knowledge and screening for SIH including a staff education programme for nurses, healthcare assistants and doctors. The Trust guidelines for SIH management were updated based on feedback from staff. The changes to the guideline included shortening the document from 14 to 4 pages, incorporating a flowchart summarising the management of SIH and publishing the guideline on the Trust intranet. A questionnaire based on the recommendations of the Joint British Diabetes Societies for SIH was used to assess the change in knowledge pre-intervention and post-intervention. Results showed an increase in junior doctors' knowledge of this topic. Although there was an initial improvement in screening for SIH, this returned to near baseline by the end of the study. This study highlights that screening for SIH can be improved by increasing the knowledge of healthcare staff. However, there is a need for ongoing interventions to sustain this change.