Mast cell activation disrupts interactions between endothelial cells and pericytes during early life allergic asthma.

Allergic asthma generally starts during early life and is linked to substantial tissue remodeling and lung dysfunction. Although angiogenesis is a feature of the disrupted airway, the impact of allergic asthma on the pulmonary microcirculation during early life is unknown. Here, using quantitative imaging in precision-cut lung slices (PCLSs), we report that exposure of neonatal mice to house dust mite (HDM) extract disrupts endothelial cell/pericyte interactions in adventitial areas. Central to the blood vessel structure, the loss of pericyte coverage was driven by mast cell (MC) proteases, such as tryptase, that can induce pericyte retraction and loss of the critical adhesion molecule N-cadherin. Furthermore, spatial transcriptomics of pediatric asthmatic endobronchial biopsies suggests intense vascular stress and remodeling linked with increased expression of MC activation pathways in regions enriched in blood vessels. These data provide previously unappreciated insights into the pathophysiology of allergic asthma with potential long-term vascular defects.

Maintaining safe lung cancer surgery during the COVID-19 pandemic in a global city.

BACKGROUND: SARS-CoV-2 has challenged health service provision worldwide. This work evaluates safe surgical pathways and standard operating procedures implemented in the high volume, global city of London during the first wave of SARS-CoV-2 infection. We also assess the safety of minimally invasive surgery(MIS) for anatomical lung resection. METHODS: This multicentre cohort study was conducted across all London thoracic surgical units, covering a catchment area of approximately 14.8 Million. A Pan-London Collaborative was created for data sharing and dissemination of protocols. All patients undergoing anatomical lung resection 1st March-1st June 2020 were included. Primary outcomes were SARS-CoV-2 infection, access to minimally invasive surgery, post-operative complication, length of intensive care and hospital stay (LOS), and death during follow up. FINDINGS: 352 patients underwent anatomical lung resection with a median age of 69 (IQR: 35-86) years. Self-isolation and pre-operative screening were implemented following the UK national lockdown. Pre-operative SARS-CoV-2 swabs were performed in 63.1% and CT imaging in 54.8%. 61.7% of cases were performed minimally invasively (MIS), compared to 59.9% pre pandemic. Median LOS was 6 days with a 30-day survival of 98.3% (comparable to a median LOS of 6 days and 30-day survival of 98.4% pre-pandemic). Significant complications developed in 7.3% of patients (Clavien-Dindo Grade 3-4) and 12 there were re-admissions(3.4%). Seven patients(2.0%) were diagnosed with SARS-CoV-2 infection, two of whom died (28.5%). INTERPRETATION: SARS-CoV-2 infection significantly increases morbidity and mortality in patients undergoing elective anatomical pulmonary resection. However, surgery can be safely undertaken via open and MIS approaches at the peak of a viral pandemic if precautionary measures are implemented. High volume surgery should continue during further viral peaks to minimise health service burden and potential harm to cancer patients. FUNDING: This work did not receive funding.

Retrospective Observational Study into the Early Causes of Death Following Surgery for NSCLC.

INTRODUCTION: Respiratory failure has historically been the major cause of mortality after elective lung resections. With improved intubation using fiber-optic scopes, better preoperative respiratory risk assessment, more advanced anesthetic single lung ventilation, and minimally invasive surgical technique, this may have changed. Our objective was to assess the main causes of mortality over the past 10 years in patients undergoing elective lung surgery in a major UK center. MATERIALS AND METHODS: A retrospective unit data search was made for all deaths during the 10-year period between January 2007 and December 2016 inclusive. All inpatient deaths within 30 days of an elective anatomical lung resection for lung malignancies were included. RESULTS: Three-thousand three-hundred sixteen lung resections for malignancy were performed in the 10-year period. There were 44 (1.3%) deaths during this period, 27 (61.4%) after open lobectomies, 8 (18.2%) after video-assisted thoracoscopic surgery lobectomies, 5 (11.4%) after sleeve lobectomies, and 4 (9%) after pneumonectomies. Causes of death included 24 (54.5%) respiratory failure, 10 (22.7%) ischemic bowel, 4 (9%) coronary events, 2 (4.5%) strokes, 2 (4.5%) on table hemorrhage, 1 (2.3%) massive pulmonary embolus, and 1 (2.3%) postoperative hemorrhage. CONCLUSION: Although respiratory failure is still a major cause of mortality in the postoperative patient, bowel ischemia has been found to be the second greatest cause of death. This study highlights the need to identify those at risk of this fatal complication during preoperative assessment and their postoperative management.

Increasing frequency of non-smoking lung cancer: Presentation of patients with early disease to a tertiary institution in the UK.

BACKGROUND: Never-smokers with lung cancer often present late as there are no established aetiological risk factors. The aim of the study is to define the frequency over time and characterise clinical features of never-smokers presenting sufficiently early to determine if it is possible to identify patients at risk. METHODS: We retrospectively analysed data from a prospectively collected database of patients who underwent surgery. The frequency was defined as number of never-smokers versus current and ex-smokers by year. Clinical features at presentation were collated as frequency. RESULTS: A total of 2170 patients underwent resection for lung cancer from March 2008 to November 2014. The annual frequency of developing lung cancer in never-smokers increased from 13% to 28%, attributable to an absolute increase in numbers and not simply a change in the ratio of never-smokers to current and ex-smokers. A total of 436 (20%) patients were never-smokers. The mean age was 60 (16 SD) years and 67% were female. Presenting features were non-specific consisting of cough in 34%, chest infections in 18% and haemoptysis in 11%. A total of 14% were detected on incidental chest film, 30% on computed tomography, 7% on positron-emission tomography/computed tomography and 1% on MRI. CONCLUSIONS: We observed more than a double of the annual frequency of never-smokers in the last 7 years. Patients present with non-specific symptoms and majority were detected on incidental imaging, a modality that is likely to play an increasingly important role for early detection in this cohort that does not have any observable clinical risk factors.

An Unusual Case of Needle Embolus Presenting With Delayed Spontaneous Pneumothorax.

We report the case of a 39-year-old man presenting with an acute right-sided traumatic pneumothorax secondary to migration of a hypodermic needle fractured during intravenous drug use. We discuss the unusual passage of this foreign body from the left groin to the right ventricular wall and into the mediastinum, ultimately presenting with a right pneumothorax 1 year later.

Selection for adjuvant chemotherapy in completely resected stage I non-small cell lung cancer: external validation of a Chinese prognostic risk model.

BACKGROUND: The ability to sub-stratify survival within stage I is an important consideration as it is assumed that survival is heterogeneous within this sub-group. Liang et al. recently published a nomogram to predict post-operative survival in patients undergoing lung cancer surgery. The aim of our study is external validation of their published nomogram in a British cohort focusing on stages IA and IB to determine applicability in selection of adjuvant chemotherapy within stage I. METHODS: Patient variables were extracted and the score individually calculated. Receiver operative characteristics curve (ROC) was calculated and compared with the original derivation cohort and the discriminatory ability was further quantified using survival plots by splitting our (external) validation cohort into three tertiles and Kaplan Meier plots were constructed and individual curves tested using Cox regression analysis on Stata 13 and R 3.1.2 respectively. RESULTS: A total of 1,238 patients were included for analysis. For all patients from stage IA to IIB the mean (SD) score was 9.95 (4.2). The ROC score comparing patients who died versus those that remained alive was 0.62 (95% CI: 0.58 to 0.67). When divided into prognostic score tertiles, survival discrimination remained evident for the entire cohort, as well as those for stage IA and IB alone. The P value comparing survival between the middle and highest score with baseline (low score) was P=0.031 and P=0.034 respectively. CONCLUSIONS: Our results of external validation suggested lower survival discrimination than reported by the original group; however discrimination between survival remained evident for stage I.

The association between surgical volume, survival and quality of care.

Improving surgical outcomes is important to the thoracic surgical community and operative mortality is often used as a benchmark to gauge the quality of lung resection. In lung cancer surgery, increasing hospital volume is associated with better survival although the categorisation of procedure volume is arbitrary. When US and UK data are scrutinised, the association holds true for increasingly higher volumes up to 150 resection per year and more. The reason may be due to better infrastructure, better-staffed units, more resources and wider specialist and technology-based services in higher volume centers. For individual surgeon volume, reports are not consistent. However, studies suggest that surgeon sub-specialty is an important consideration. The results of general thoracic surgeons and cardiac surgeons are reported to be better than general surgeons for lung resection surgery, and the effects of specialty training was also associated with an increase in the number of patients undergoing lung resection. We conclude that the current evidence strongly supports the association between increasing hospital volume with lower mortality and improved long-term survival following lung resection. Whilst the data presented supports centralization of lung cancer surgery in high volume hospitals, patient choice and the threshold of quality of improvement required to overcome travel and closure of local services need to be considered.