Antibiotic pharmacokinetics in infected pleural effusions.

Pleural infection is usually treated with empirical broad-spectrum antibiotics, but limited data exist on their penetrance into the infected pleural space. We performed a pharmacokinetic study analysing the concentration of five intravenous antibiotics across 146 separate time points in 35 patients (amoxicillin, metronidazole, piperacillin-tazobactam, clindamycin and cotrimoxazole). All antibiotics tested, apart from co-trimoxazole, reach pleural fluid levels equivalent to levels within the blood and well above the relevant minimum inhibitory concentrations. The results demonstrate that concerns about the penetration of commonly used antibiotics, apart from co-trimoxazole, into the infected pleural space are unfounded.

Application of ultrasound-guided medical thoracoscopy in patients with small amounts or without pleural effusion.

BACKGROUND: Pleural disease is a common clinical condition, and some patients present with a small amount of pleural effusion or no pleural effusion. It is difficult to diagnose such patients in clinical practice. Medical thoracoscopy is the gold standard for the diagnosis of pleural effusion with unknown origin, and guidelines recommend that pneumothorax should be induced in such patients before medical thoracoscopy examination. However, the process of inducing pneumothorax is tedious and has many complications. Our study was conducted to clarify the value of thoracic ultrasound combined with medical thoracoscopy in patients with small amounts or without pleural effusion to simplify the process of medical thoracoscopy examination. METHODS: In this retrospective study, we included patients who were assigned to complete medical thoracoscopy. Successful completion of medical thoracoscopy in patients was regarded as letting the endoscope get into the pleural cavity and completion of the biopsy. Finally, we analyzed the value of preoperative ultrasound in patients without or with small amounts of pleural effusion. RESULTS: Seventy-two patients were finally included in the study. Among them, 68 patients who underwent ultrasound positioning of the access site successfully completed the examination and four patients failed the examination. Fifty-one cases showed no fluid sonolucent area at the access site, of which 48 cases had pleural sliding signs at the access site, and 47 patients successfully completed the examination; 3 cases without pleural sliding signs at the access site failed to complete thoracoscopy. In 21 cases, the fluid sonolucent area was selected as the access site, and all of them successfully completed thoracoscopy. CONCLUSION: Medical thoracoscopy is one of the methods to confirm the diagnosis in patients with pleural disease with small amounts or without pleural effusion. The application of thoracic ultrasound before medical thoracoscopy can be used for the selection of the access site. It is possible to replace pneumothorax induction before medical thoracoscopy.

The association between frailty and survival in patients with pleural disease: a retrospective cohort study.

BACKGROUND: There are currently no data on the relationship between frailty and mortality in pleural disease. Understanding the relationship between frailty and outcomes is increasingly important for clinicians to guide decisions regarding investigation and management. This study aims to explore the relationship between all-cause mortality and frailty status in patients with pleural disease. METHODS: In this retrospective analysis of a prospectively collected observational cohort study, outpatients presenting to the pleural service at a tertiary centre in Bristol, UK with a radiologically confirmed, undiagnosed pleural effusion underwent comprehensive assessment and were assigned a final diagnosis at 12 months. The modified frailty index (mFI) was calculated and participants classified as frail (mFI ≥ 0.4) or not frail (mFI ≤ 0.2). RESULTS: 676 participants were included from 3rd March 2008 to 29th December 2020. The median time to mortality was 490 days (IQR 161-1595). A positive association was found between 12-month mortality and frailty (aHR = 1.72, 95% CI 1.02-2.76, p = 0.025) and age ≥ 80 (aHR = 1.80, 95% CI 1.24-2.62, p = 0.002). Subgroup analyses found a stronger association between 12-month mortality and frailty in benign disease (aHR = 4.36, 95% CI 2.17-8.77, p < 0.0001) than in all pleural disease. Malignancy irrespective of frailty status was associated with an increase in all-cause mortality (aHR = 10.40, 95% CI 6.01-18.01, p < 0.0001). CONCLUSION: This is the first study evaluating the relationship between frailty and outcomes in pleural disease. Our data demonstrates a strong association between frailty and 12-month mortality in this cohort. A malignant diagnosis is an independent predictor of 12-month mortality, irrespective of frailty status. Frailty was also strongly associated with 12-month mortality in patients with a benign underlying cause for their pleural disease. This has clinical relevance for pleural physicians; evaluating patients' frailty status and its impact on mortality can guide clinicians in assessing suitability for invasive investigation and management. TRIAL REGISTRATION: This study is registered with the Health Research Authority (REC reference 08/H0102/11) and the NIHR Portfolio (Study ID 8960).

Patient perspectives on the use of indwelling pleural catheters in malignant pleural effusions.

BACKGROUND: Indwelling pleural catheters are an effective treatment option for patients with malignant pleural effusions. Despite their popularity, there remains a paucity of data on the patient experience and key patient-centred outcomes. OBJECTIVE: To investigate the experience of patients receiving an indwelling pleural catheter to better inform and identify potential areas for improvement in care. METHODS: This was a multicentre survey study at three academic, tertiary-care centres in Canada. Patients with a diagnosis of malignant pleural effusion who had an indwelling pleural catheter inserted were included. An adapted questionnaire specific to indwelling pleural catheters was used with responses recorded on a 4-point Likert scale. Patients completed the questionnaire in-person or by phone at 2-week and 3-month follow-up appointments. RESULTS: A total of 105 patients were enrolled in the study with 84 patients included in the final analysis. At the 2-week follow-up, patient-reported improvements in dyspnoea and quality of life from indwelling pleural catheter were high at 93% and 87%, respectively. The predominant issues identified were discomfort at time of insertion (58%), itching (49%), difficulty with sleeping (39%), discomfort with home drainage (36%) and the pleural catheter reminding patients of their disease (63%). Avoiding hospitalisation for the management of dyspnoea was important to 95% of patients. Findings were similar at 3 months. CONCLUSIONS: Indwelling pleural catheters are an effective intervention to directly improve dyspnoea and quality of life but have important disadvantages for some; clinicians and patients should be aware of these when making an informed decision regarding treatment.

Diagnostic sensitivity of pleural fluid cytology in malignant pleural effusions: systematic review and meta-analysis.

BACKGROUND: Pleural fluid cytology is an important diagnostic test used for the investigation of pleural effusions. There is considerable variability in the reported sensitivity for the diagnosis of malignant pleural effusions (MPE) in the literature. OBJECTIVE: The purpose of this review is to determine the diagnostic sensitivity of pleural fluid cytology for MPE, both overall and by tumour type, to better inform the decision-making process when investigating pleural effusions. DATA SOURCES: A literature search of EMBASE and MEDLINE was performed by four reviewers. Articles satisfying inclusion criteria were evaluated for bias using the QUADAS-2 tool. DATA EXTRACTION: For quantitative analysis, we performed a metaanalysis using a binary random-effects model to determine pooled sensitivity. Subgroup analysis was performed based on primary cancer site and meta-regression by year of publication. SYNTHESIS: Thirty-six studies with 6057 patients with MPE were included in the meta-analysis. The overall diagnostic sensitivity of pleural fluid cytology for MPE was 58.2% (95% CI 52.5% to 63.9%; range 20.5%-86.0%). There was substantial heterogeneity present among studies (I2 95.5%). For primary thoracic malignancies, sensitivity was highest in lung adenocarcinoma (83.6%; 95% CI 77.7% to 89.6%) and lowest in lung squamous cell carcinoma (24.2%; 95% CI 17.0% to 31.5%) and mesothelioma (28.9%; 95% CI 16.2% to 41.5%). For malignancies with extrathoracic origin, sensitivity was high for ovarian cancer (85.2%; 95% CI 74.2% to 96.1%) and modest for breast cancer (65.3%; 95% CI 49.8% to 80.8%). CONCLUSIONS: Pleural fluid cytology has an overall sensitivity of 58.2% for the diagnosis of MPE. Clinicians should be aware of the high variability in diagnostic sensitivity by primary tumour type as well as the potential reasons for false-negative cytology results.PROSPERO registration numberCRD42021231473.

Differentiation of malignant from benign pleural effusions based on artificial intelligence.

INTRODUCTION: This study aimed to construct artificial intelligence models based on thoracic CT images to perform segmentation and classification of benign pleural effusion (BPE) and malignant pleural effusion (MPE). METHODS: A total of 918 patients with pleural effusion were initially included, with 607 randomly selected cases used as the training cohort and the other 311 as the internal testing cohort; another independent external testing cohort with 362 cases was used. We developed a pleural effusion segmentation model (M1) by combining 3D spatially weighted U-Net with 2D classical U-Net. Then, a classification model (M2) was built to identify BPE and MPE using a CT volume and its 3D pleural effusion mask as inputs. RESULTS: The average Dice similarity coefficient, Jaccard coefficient, precision, sensitivity, Hausdorff distance 95% (HD95) and average surface distance indicators in M1 were 87.6±5.0%, 82.2±6.2%, 99.0±1.0%, 83.0±6.6%, 6.9±3.8 and 1.6±1.1, respectively, which were better than those of the 3D U-Net and 3D spatially weighted U-Net. Regarding M2, the area under the receiver operating characteristic curve, sensitivity and specificity obtained with volume concat masks as input were 0.842 (95% CI 0.801 to 0.878), 89.4% (95% CI 84.4% to 93.2%) and 65.1% (95% CI 57.3% to 72.3%) in the external testing cohort. These performance metrics were significantly improved compared with those for the other input patterns. CONCLUSIONS: We applied a deep learning model to the segmentation of pleural effusions, and the model showed encouraging performance in the differential diagnosis of BPE and MPE.

Cytoreductive surgery with hyperthermic intrathoracic chemotherapy for malignant pleural mesothelioma: a systematic review.

INTRODUCTION: Cytoreductive surgery has been used a part of multimodality treatment in patients with malignant pleural mesothelioma (MPM). The residual microscopic disease that remains will lead to disease progression in the majority of patients. Delivery of hyperthermic intrathoracic chemotherapy at the time of surgery has been used to address this microscopic disease, however it's effect and place in the multimodality treatment sphere is unknown. The aim of this systematic review was to assess the effect of surgery and hyperthermic intrathoracic chemotherapy in patients with MPM on overall survival and disease-free interval. METHODS: Ovid MEDLINE, Embase, Web of Science and the Cochrane Database of Systematic Reviews were searched from database inception through to June 2021. Studies reporting overall survival and/or disease-free interval in patients with MPM undergoing cytoreductive surgery with hyperthermic intrathoracic chemotherapy were considered. Study quality was assessed using the Newcastle-Ottawa Scale. A narrative review was performed. RESULTS: Fifteen studies were eligible for inclusion comprising 598 patients. Surgery with hyperthermic intrathoracic chemotherapy was associated with a median overall survival and disease-free interval ranging from 11 to 75 months and 7.2 to 57 months, respectively. These appeared to be superior to patients not receiving hyperthermic intrathoracic chemotherapy (overall survival: 5-36 months and disease-free interval: 12.1-21 months). A higher dose of hyperthermic intrathoracic chemotherapy was associated with an improvement in overall survival compared with a lower dose: 18-31 months versus 6-18 months, respectively. The most common morbidity was atrial fibrillation followed by renal complications. CONCLUSION: Surgery with hyperthermic intrathoracic chemotherapy offers a safe and effective therapy with an improvement in disease-free interval and overall survival, particularly when hyperthermic intrathoracic chemotherapy is administered at a higher dose. PROSPERO REGISTRATION NUMBER: CRD42019129002.

Additional Up-Front Thoracic Ultrasound in the Workup of Patients with Unilateral Pleural Effusion: A Prospective Observational Pilot Study.

BACKGROUND: In patients with pleural effusion, specific ultrasound characteristics are associated with pleural malignancy. OBJECTIVES: This study aimed to evaluate the added value of an additional, up-front, systematic thoracic ultrasound (TUS) to standard imaging in patients with unilateral pleural effusion of unknown cause in a clinical setting. METHODS: In a prospective observational pilot study, patients referred for workup and thoracentesis of a unilateral pleural effusion received up-front TUS following a set protocol in addition to available imaging and US guiding the thoracentesis or diagnostic puncture. The primary outcome was the proportion of cases where systematic TUS changed the planned diagnostic workup. Follow-up took place 26 weeks after inclusion. RESULTS: From February to December 2020, 55 patients were included. Thirty-six (65%) patients had other chest imaging available before TUS. Twenty-one (38%) were diagnosed with malignant pleural effusion. Three patients (5%) had clinically relevant changes in the diagnostic workup after additional systematic TUS. CONCLUSIONS: Additional up-front, systematic TUS had limited clinically relevant effect on the planned diagnostic workup in patients with unilateral pleural effusion in a setting where chest CT scans often are available at referral.

Conditional diagnostic accuracy according to inflammation status and age for diagnosing tuberculous effusion.

BACKGROUND: Tuberculous effusion varies from lymphocyte-dominant to neutrophilic effusion according to inflammation status. The criteria of adenosine deaminase (ADA) and lymphocyte/neutrophil (L/N) ratio have yet not been evaluated across different disease conditions. METHODS: Patients who conducted pleural fluid analysis from 2009 to 2019 at Asan Medical Center were included. Criteria (ADA of 50 and L/N ratio of 0.75) were evaluated by quantile subgroups according to age, C-reactive protein (CRP), white blood cell (WBC), and lactate dehydrogenase (LD) by the Monte Carlo simulation method to diagnose tuberculosis. The model for the ADA and L/N ratio was evaluated by AUROC. RESULTS: Among the 2,918 reviewed cases, 2034 were included with 229 (11.26%) tuberculosis cases. The mean baseline ADA AUROC was 0.88 across all patients. Increased CRP and WBC showed high proportions of neutrophilic tuberculous effusion, with low sensitivity of approximately 45% and 33% in the fifth WBC and CRP groups, respectively. The AUROC of the models decreased with the increase in WBC and CRP groups (ADA model: 0.69 [the top quantile WBC group], 0.74 [the top quantile CRP group]). The AUROC of the models did not show a trend according to the increase in LD and age. CONCLUSION: Inflammatory status affects the diagnostic metrics for tuberculous effusion due to the progression of tuberculous effusion. Clinicians should consider the low accuracy of tuberculous effusion criteria in high-inflammatory conditions when diagnosing tuberculosis.

Establishing a Multidisciplinary Team-Based Pleural Service in the Era of Financial Austerity: The Role of the Thoracic Surgeon.

Medical thoracoscopy/pleuroscopy has become, after bronchoscopy, the second most commonly utilized endoscopic procedure in interventional pulmonology. Due to their common origin, medical thoracoscopy/pleuroscopy and video-assisted thoracic surgery (VATS) are quite similar procedures technically. In contrast to the prevailing attitude that it should predominantly be performed by interventional pulmonologists, we believe that, like all hybrid-in-nature techniques, it should be implemented as part of a combined specialist care service/team. Herewith, we describe our attempt to establish a multidisciplinary pleural disease program during a difficult economic period for our country, comprising thoracic surgeons, pulmonologists and anesthesiologists, all of whom brought in their experience, expertise and resources to establish and develop the service resulting in a hybridization of the technique, with, as reported, quite favorable results.

Combining clinical, radiological and genetic approaches to pneumothorax management.

Familial spontaneous pneumothorax (FSP) accounts for 10% of primary spontaneous pneumothoraces. Appropriate investigation of FSP enables early diagnosis of serious monogenic diseases and the practice of precision medicine. Here, we show that a pneumothorax genetics multidisciplinary team (MDT) can efficiently diagnose a range of syndromic causes of FSP. A sizeable group (73.6%) of clinically unclassifiable FSPs remains. Using whole genome sequencing we demonstrate that most of these cases are not known monogenic disorders. Therefore, clinico-radiological assessment by an MDT has high sensitivity for currently known clinically important monogenic causes of FSP, which has relevance for the design of efficient pneumothorax services.

Fully automated volumetric measurement of malignant pleural mesothelioma by deep learning AI: validation and comparison with modified RECIST response criteria.

BACKGROUND: In malignant pleural mesothelioma (MPM), complex tumour morphology results in inconsistent radiological response assessment. Promising volumetric methods require automation to be practical. We developed a fully automated Convolutional Neural Network (CNN) for this purpose, performed blinded validation and compared CNN and human response classification and survival prediction in patients treated with chemotherapy. METHODS: In a multicentre retrospective cohort study; 183 CT datasets were split into training and internal validation (123 datasets (80 fully annotated); 108 patients; 1 centre) and external validation (60 datasets (all fully annotated); 30 patients; 3 centres). Detailed manual annotations were used to train the CNN, which used two-dimensional U-Net architecture. CNN performance was evaluated using correlation, Bland-Altman and Dice agreement. Volumetric response/progression were defined as ≤30%/≥20% change and compared with modified Response Evaluation Criteria In Solid Tumours (mRECIST) by Cohen's kappa. Survival was assessed using Kaplan-Meier methodology. RESULTS: Human and artificial intelligence (AI) volumes were strongly correlated (validation set r=0.851, p<0.0001). Agreement was strong (validation set mean bias +31 cm3 (p=0.182), 95% limits 345 to +407 cm3). Infrequent AI segmentation errors (4/60 validation cases) were associated with fissural tumour, contralateral pleural thickening and adjacent atelectasis. Human and AI volumetric responses agreed in 20/30 (67%) validation cases κ=0.439 (0.178 to 0.700). AI and mRECIST agreed in 16/30 (55%) validation cases κ=0.284 (0.026 to 0.543). Higher baseline tumour volume was associated with shorter survival. CONCLUSION: We have developed and validated the first fully automated CNN for volumetric MPM segmentation. CNN performance may be further improved by enriching future training sets with morphologically challenging features. Volumetric response thresholds require further calibration in future studies.

Review of the British Thoracic Society Winter Meeting 2021, 24-26 November 2021.

The Winter Meeting of the British Thoracic Society (BTS) is a platform for the latest clinical and scientific research in respiratory medicine. This review summarises the key symposia and presentations from the BTS Winter Meeting 2021 held online due to the COVID-19 pandemic.

Prevalence and clinical outcomes of pleural effusion in COVID-19 patients: A systematic review and meta-analysis.

Observational studies indicate that pleural effusion has an association with risk and the clinical prognosis of COVID-19 disease; however, the available literature on this area is inconsistent. The objective of this systematic review and meta-analysis is to evaluate the correlation between COVID-19 disease and pleural effusion. A rigorous literature search was conducted using multiple databases. All eligible observational studies were included from around the globe. The pooled prevalence and associated 95% confidence interval (CI) were calculated using the random effect model. Mantel-Haenszel odds ratios were produced to report overall effect size using random effect models for severity and mortality outcomes. Funnel plots, Egger regression tests, and Begg-Mazumdar's rank correlation test were used to appraise publication bias. Data from 23 studies including 6234 COVID-19 patients was obtained. The overall prevalence of pleural effusion in COVID-19 patients was 9.55% (95% CI, I2 = 92%). Our findings also indicated that the presence of pleural effusions associated with increased risk of severity of disease(OR = 5.08, 95% CI 3.14-8.22, I2 = 77.4%) and mortality due to illness(OR = 4.53, 95% CI 2.16-9.49, I2 = 66%) compared with patients without pleural effusion. Sensitivity analyses illustrated a similar effect size while decreasing the heterogeneity. No significant publication bias was evident in the meta-analysis. The presence of pleural effusion can assist as a prognostic factor to evaluate the risk of worse outcomes in COVID-19 patients hence, it is recommended that hospitalized COVID-19 patients with pleural effusion should be managed on an early basis.

Retrospective review comparing intrapleural fibrinolytic therapy (alteplase) and surgical intervention in complex pleural effusion.

BACKGROUND: Intrapleural fibrinolytic therapy (IPFT) is one of the treatment options for complex pleural effusion. In this study, the IPFT agent used was alteplase, a tissue plasminogen activator (t-PA). This study aims to determine the difference in the outcome of patients with complex pleural effusion between IPFT and surgery in terms of radiological improvement, inflammatory parameters, length of stay, and post-intervention complications. METHODS: A retrospective review of patients with complex pleural effusion treated at Universiti Kebangsaan Malaysia Medical Center from January 2012 to August 2020 was performed. Patient demographics, chest imaging, drainage chart, inflammatory parameters, length of hospital stay, and post-intervention and outcome were analyzed. RESULTS: Fifty-eight patients were identified (surgical intervention, n = 18; 31% and IPFT, n = 40, 69%). The mean age was 51.7 ± 18.2 years. Indication for surgical intervention was pleural infection (n = 18; 100%), and MPE (n = 0). Indications for IPFT was pleural infection (n = 30; 75%) and MPE (n = 10; 25%). The dosages of t-PA were one to five doses of 2-50 mg. The baseline chest radiograph in the IPFT group was worse than in the surgical intervention group. (119.96 ± 56.05 vs. 78.19 ± 55.6; p = 0.029) At week 1, the radiological success rate for IPFT and surgical intervention were 27% and 20%, respectively, and at weeks 4-8, the success rate was 56% and 80% respectively. IPFT was associated with lesser complications; fever (17.5%), chest pain (10%), and non-life-threatening bleeding (5%). CONCLUSION: IPFT was comparable to surgery in radiological outcome, inflammatory parameters, and length of stay with lesser reported complications.

Epidemiology and prognostic factors of pleural empyema.

BACKGROUND: Infection of the pleural cavity invariably leads to hospitalisation, and a fatal outcome is not uncommon. Our aim was to study the epidemiology of pleural empyema on a nationwide basis in the whole population and in three subgroups of patients, namely post-lung resection, associated cancer and those with no surgery and no cancer. METHODS: Data from patients aged ≥18 years hospitalised with a diagnosis of pleural infection in France between January 2013 and December 2017 were retrieved from the medical-administrative national hospitalisation database and retrospectively analysed. Mortality, length of stay and costs were assessed. RESULTS: There were 25 512 hospitalisations for pleural empyema. The annual rate was 7.15 cases per 100 000 habitants in 2013 and increased to 7.75 cases per 100 000 inhabitants in 2017. The mean age of patients was 62.4±15.6 years and 71.7% were men. Post-lung resection, associated cancer and no surgery-no cancer cases accounted for 9.8%, 30.1% and 60.1% of patients, respectively. These groups were significantly different in terms of clinical characteristics, mortality and risk factors for length of stay, costs and mortality. Mortality was 17.1% in the whole population, 29.5% in the associated cancer group, 17.7% in the post-lung resection group and 10.7% in the no surgery-no cancer group. In the whole population, age, presence of fistula, higher Charlson Comorbidity Index (>3), alcohol abuse, arterial hypertension, hyperlipidaemia, atheroma, atrial fibrillation, performance status >3 and three subgroups of pleural empyema independently predicted mortality. CONCLUSIONS: Empyema is increasing in incidence. Factors associated with mortality are recent lung resection and associated diagnosis of cancer.

Use of preclinical models for malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) is an aggressive cancer most commonly caused by prior exposure to asbestos. Median survival is 12-18 months, since surgery is ineffective and chemotherapy offers minimal benefit. Preclinical models that faithfully recapitulate the genomic and histopathological features of cancer are critical for the development of new treatments. The most commonly used models of MPM are two-dimensional cell lines established from primary tumours or pleural fluid. While these have provided some important insights into MPM biology, these cell models have significant limitations. In order to address some of these limitations, spheroids and microfluidic chips have more recently been used to investigate the role of the three-dimensional environment in MPM. Efforts have also been made to develop animal models of MPM, including asbestos-induced murine tumour models, MPM-prone genetically modified mice and patient-derived xenografts. Here, we discuss the available in vitro and in vivo models of MPM and highlight their strengths and limitations. We discuss how newer technologies, such as the tumour-derived organoids, might allow us to address the limitations of existing models and aid in the identification of effective treatments for this challenging-to-treat disease.

Pleural recurrence after transthoracic needle lung biopsy in stage I lung cancer: a systematic review and individual patient-level meta-analysis.

INTRODUCTION: Conflicting results exist regarding whether preoperative transthoracic biopsy increases the risk of pleural recurrence in early lung cancer. We conducted a systematic, patient-level meta-analysis to evaluate the risk of pleural recurrence in stage I lung cancer after percutaneous transthoracic lung biopsy. METHODS: A systematic search of OVID-MEDLINE, Embase and the Cochrane Database of Systematic Reviews was performed through October 2018. Eligible studies were original articles on the risk of pleural recurrence in stage I lung cancer after transthoracic biopsy. We contacted the corresponding authors of eligible studies to obtain individual patient-level data. We used the Fine-Gray model for time to recurrence and lung cancer-specific survival and a Cox proportional hazards model for overall survival. RESULTS: We analysed 2394 individual patient data from 6 out of 10 eligible studies. Compared with other diagnostic procedures, transthoracic biopsy was associated with a higher risk for ipsilateral pleural recurrence, which manifested solely (subdistribution HR (sHR), 2.58; 95% CI 1.15 to 5.78) and concomitantly with other metastases (sHR 1.99; 95% CI 1.14 to 3.48). In the analysis of secondary outcomes considering a significant interaction between diagnostic procedures and age groups, reductions of time to recurrence (sHR, 2.01; 95% CI 1.11 to 3.64), lung cancer-specific survival (sHR 2.53; 95% CI 1.06 to 6.05) and overall survival (HR 2.08; 95% CI 1.12 to 3.87) were observed in patients younger than 55 years, whereas such associations were not observed in other age groups. DISCUSSION: Preoperative transthoracic lung biopsy was associated with increased pleural recurrence in stage I lung cancer and reduced survival in patients younger than 55 years.

Lessons from Pharmacovigilance: Pulmonary Immune-Related Adverse Events After Immune Checkpoint Inhibitor Therapy.

PURPOSE: To characterize pulmonary toxicities associated with the use of novel immune checkpoint inhibitors METHODS: Adverse event reports from immune checkpoint inhibitors targeting PD-1/L1 and CTLA-4 were captured from the W.H.O pharmacovigilance database (VigiBase) up until Dec. 31st 2019 and were analyzed to evaluate for measures of association between the use of immune checkpoint inhibitors and pulmonary toxicities. Disproportionality analysis using both frequentist and Bayesian approaches were used to detect signals between pulmonary immune-related adverse events and the use of these agents. RESULTS: A total of 9202 adverse pulmonary immune checkpoint inhibitor-related events were captured up until 2019. Adverse pulmonary events were compromised of 1305 airway, 18 alveolar, 5491 interstitial, 898 pleural, 560 vascular and 939 non-specific pulmonary events. We found a common association between all immune checkpoint inhibitors studied and pneumonitis, interstitial lung disease, pulmonary embolism and respiratory failure. We also noted other associations between immune checkpoint inhibitors, however not as uniformly across agents. Most of these immune-related adverse drug reactions were noted to be severe and accounted for a significant source of mortality in the reported cases. CONCLUSION: Immune checkpoint inhibitors are associated with a spectrum of inflammatory pulmonary toxicities. The breadth of pulmonary complications and prevalence may be underappreciated with the use of these agents.

Patient-derived malignant pleural mesothelioma cell cultures: a tool to advance biomarker-driven treatments.

Malignant pleural mesothelioma (MPM) is an aggressive cancer, associated with poor prognosis. We assessed the feasibility of patient-derived cell cultures to serve as an ex vivo model of MPM. Patient-derived MPM cell cultures (n=16) exhibited stemness features and reflected intratumour and interpatient heterogeneity. A subset of the cells were subjected to high-throughput drug screening and coculture assays with cancer-specific cytotoxic T cells and showed diverse responses. Some of the biphasic MPM cells were capable of processing and presenting the neoantigen SSX-2 endogenously. In conclusion, patient-derived MPM cell cultures are a promising and faithful ex vivo model of MPM.