Surgical and Pathological Results Following Neoadjuvant Nivolumab and Platinum-Based Chemotherapy for Locally Advanced Resectable NSCLC: A Multicentre Real-World Series From England.

Background: To evaluate the real-world surgical and pathological outcomes following neoadjuvant nivolumab in combination with chemotherapy in a multicentre national cohort of patients.

Methods: Retrospective analysis on consecutive patients treated in three tertiary referral hospitals in UK with neoadjuvant chemotherapy and immunotherapy (nivolumab) for stage II-IIIB nonsmall cell lung cancer (March 2023-May 2024). Surgical and pathological outcomes were assessed.

Preoperative smoking cessation interventions: a systematic review and meta-analysis.

Background: Smoking is the leading single cause of preventable death in England and also increases the risk of postoperative complications. The preoperative period is a potential opportunity to introduce smoking cessation interventions to smokers to reduce the risk of postoperative complications. A systematic search was conducted to find all studies that investigated the effectiveness of preoperative smoking cessation interventions.

Management of benign airway stenosis-predictors of tracheal resection.

Background: Benign airway stenoses are complex disorders that present with progressive dyspnoea, stridor, and significant respiratory distress. These conditions have a high recurrence rate and despite the plethora of endoscopic and open techniques available for treatment, the outcomes are variable. Our primary was to determine the pre-operative factors associated with an increased hazard of cricotracheal resection (CTR)/tracheal resection (TR) and reconstruction in cases of benign subglottic and tracheal strictures.

Role of vitamin D supplementation in modifying outcomes after surgery: a systematic review of randomised controlled trials.

Background: There is increasing evidence to suggest vitamin D plays a role in immune and vascular function; hence, it may be of biological and clinical relevance for patients undergoing major surgery. With a greater number of randomised studies being conducted evaluating the impact of vitamin D supplementation on surgical patients, it is an opportune time to conduct further analysis of the impact of vitamin D on surgical outcomes.

Methods: MEDLINE, EMBASE and the Cochrane Trials Register were interrogated up to December 2023 to identify randomised controlled trials of vitamin D supplementation in surgery.

Comparison of video assisted thoracoscopic surgery and thoracotomy for treatment of pleural infection stage II and III: a literature review.

Background And Objective: Pleural infection is associated with significant mortality and morbidity worldwide, with a steadily increasing incidence. We sought to investigate whether video-assisted thoracic surgery (VATS) or thoracotomy provides the best outcomes in the treatment of stage II and III pleural infection as indications remain controversial.

Methods: Systematic review of relevant articles from the PubMed database.

Deep immune B and plasma cell repertoire in non-small cell lung cancer.

Introduction: B cells, which have long been thought to be minor players in the development of anti-tumor responses, have been implicated as key players in lung cancer pathogenesis and response to checkpoint blockade in patients with lung cancer. Enrichment of late-stage plasma and memory cells in the tumor microenvironment has been shown in lung cancer, with the plasma cell repertoire existing on a functional spectrum with suppressive phenotypes correlating with outcome. B cell dynamics may be influenced by the inflammatory microenvironment observed in smokers and between LUAD and LUSC.

Impaired alveolar macrophage 11β-hydroxysteroid dehydrogenase type 1 reductase activity contributes to increased pulmonary inflammation and mortality in sepsis-related ARDS.

Background: Acute Respiratory Distress Syndrome (ARDS) is a devastating pulmonary inflammatory disorder, commonly precipitated by sepsis. Glucocorticoids are immunomodulatory steroids that can suppress inflammation. Their anti-inflammatory properties within tissues are influenced by their pre-receptor metabolism and amplification from inactive precursors by 11β-hydroxysteroid dehydrogenase type-1 (HSD-1).

The evolution of lung cancer and impact of subclonal selection in TRACERx.

Lung cancer is the leading cause of cancer-associated mortality worldwide. Here we analysed 1,644 tumour regions sampled at surgery or during follow-up from the first 421 patients with non-small cell lung cancer prospectively enrolled into the TRACERx study. This project aims to decipher lung cancer evolution and address the primary study endpoint: determining the relationship between intratumour heterogeneity and clinical outcome.

The evolution of non-small cell lung cancer metastases in TRACERx.

Metastatic disease is responsible for the majority of cancer-related deaths. We report the longitudinal evolutionary analysis of 126 non-small cell lung cancer (NSCLC) tumours from 421 prospectively recruited patients in TRACERx who developed metastatic disease, compared with a control cohort of 144 non-metastatic tumours. In 25% of cases, metastases diverged early, before the last clonal sweep in the primary tumour, and early divergence was enriched for patients who were smokers at the time of initial diagnosis.

Lung cancer resection in patients with underlying usual interstitial pneumonia: a meta-analysis.

Objective: Patients with lung cancer with underlying idiopathic pulmonary fibrosis and usual interstitial pneumonia (UIP) pattern on CT represent a very high-risk group in terms of postoperative UIP acute exacerbations (AEs) and in-hospital mortality. We sought to investigate the outcomes in these patients.

Methods: We carried out a meta-analysis, searching four international databases from 1 January 1947 to 27 April 2022, for studies in any language reporting on the acute postoperative outcomes of patients with lung cancer undergoing surgical resection with underlying UIP (the primary outcome).

Does the time to diagnosis and treatment influence outcome in adults with pleural infections.

Objective: To investigate the effect of early diagnosis and intervention in adult patients with complicated parapneumonic pleural effusion or pleural empyema and the impact on outcomes.

Methods: A systematic review based on a literature search of the PubMed database was performed.

Results: Eleven eligible studies were included; nine observational studies and two randomised controlled trials totalling a study population of 10,717 patients.

Impact of video-assisted thoracoscopic lobectomy versus open lobectomy for lung cancer on recovery assessed using self-reported physical function: VIOLET RCT.

Background: Lung cancer is the leading cause of cancer death. Surgery remains the main method of managing early-stage disease. Minimal-access video-assisted thoracoscopic surgery results in less tissue trauma than open surgery; however, it is not known if it improves patient outcomes.

Feasibility study of a randomised controlled trial of preoperative and postoperative nutritional supplementation in major lung surgery.

Objectives: Malnutrition and weight loss are important risk factors for complications after lung surgery. However, it is uncertain whether modifying or optimising perioperative nutritional state with oral supplements results in a reduction in malnutrition, complications or quality of life.

Design: A randomised, open label, controlled feasibility study was conducted to assess the feasibility of carrying out a large multicentre randomised trial of nutritional intervention.

Intrapleural fibrinolysis and DNase versus video-assisted thoracic surgery (VATS) for the treatment of pleural empyema (FIVERVATS): protocol for a randomised, controlled trial - surgery as first-line treatment.

Introduction: Pleural empyema is a frequent disease with a high morbidity and mortality. Current standard treatment includes antibiotics and thoracic ultrasound (TUS)-guided pigtail drainage. Simultaneously with drainage, an intrapleural fibrinolyticum can be given.

Video-Assisted Thoracoscopic or Open Lobectomy in Early-Stage Lung Cancer.

BACKGROUND: There is limited randomized evidence on the comparative outcomes of early-stage lung cancer resection by video-assisted thoracoscopic surgery (VATS) versus open resection. METHODS: We conducted a parallel-group multicenter randomized trial that recruited participants with known or suspected early-stage lung cancer and randomly assigned them to open or VATS resection of their lesions. The primary outcome was physical function at 5 weeks as a measure of recovery using the European Organisation for Research and Treatment of Cancer core health-related quality of life questionnaire (QLQ-C30) (scores range from 0 to 100, with higher scores indicating better function; the clinical minimally important difference for improvement is 5 points).

A highly predictive autoantibody-based biomarker panel for prognosis in early-stage NSCLC with potential therapeutic implications.

Background: Lung cancer is the leading cause of cancer-related death worldwide. Surgical resection remains the definitive curative treatment for early-stage disease offering an overall 5-year survival rate of 62%. Despite careful case selection, a significant proportion of early-stage cancers relapse aggressively within the first year post-operatively.

Assessment of Alveolar Macrophage Dysfunction Using an Model of Acute Respiratory Distress Syndrome.

Impaired alveolar macrophage (AM) efferocytosis may contribute to acute respiratory distress syndrome (ARDS) pathogenesis; however, studies are limited by the difficulty in obtaining primary AMs from patients with ARDS. Our objective was to determine whether an model of ARDS can recapitulate the same AM functional defect observed and be used to further investigate pathophysiological mechanisms. AMs were isolated from the lung tissue of patients undergoing lobectomy and then treated with pooled bronchoalveolar lavage (BAL) fluid previously collected from patients with ARDS.

Acute respiratory distress syndrome is associated with impaired alveolar macrophage efferocytosis.

https://bit.ly/2Q7REdM

Cigarette smoke exposure and alveolar macrophages: mechanisms for lung disease.

Cigarette smoking is the leading cause of preventable death worldwide. It causes chronic lung disease and predisposes individuals to acute lung injury and pulmonary infection. Alveolar macrophages are sentinel cells strategically positioned in the interface between the airway lumen and the alveolar spaces.

Ex vivo modelling of PD-1/PD-L1 immune checkpoint blockade under acute, chronic, and exhaustion-like conditions of T-cell stimulation.

Blockade of PD-1/PD-L1 interactions is proving an exciting, durable therapeutic modality in a range of cancers whereby T cells are released from checkpoint inhibition to revive their inherent anti-tumour activity. Here we have studied various ways to model ex vivo T cell function in order to compare the impact of the clinically utilised anti-PD-1 antibody, pembrolizumab (Keytruda) on the activation of human T cells: focussing on the release of pro-inflammatory IFNγ and anti-inflammatory IL-10 to assess functionality. Firstly, we investigated the actions of pembrolizumab in an acute model of T-cell activation with either immature or mature allogeneic dendritic cells (DCs); pembrolizumab enhanced IFNγ and IL-10 release from purified CD4+ T-cells in the majority of donors with a bias towards pro-inflammatory cytokine release.