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INTRODUCTION: Persistent air leak (PAL) is associated with prolonged hospitalization, high morbidity and increased treatment costs. Conservative treatment consists of observation, chest tube drainage, and pleurodesis. Guidelines recommend surgical evaluation if air leak does not respond after 3-5 days. One-way endobronchial valves (EBV) have been proposed as a treatment option for patients with PAL in which surgical treatment is not feasible, high risk or has failed. We aimed to provide a comprehensive overview of reported EBV use for PAL and issue best practice recommendations based on multicenter experience. METHODS: We conducted a retrospective observational case-series study at four different European academic hospitals and provided best practice recommendations based on our experience. A systematic literature review was performed to summarize the current knowledge on EBV in PAL. RESULTS: We enrolled 66 patients, male (66.7%), median age 59.5 years. The most common underlying lung disease was chronic obstructive pulmonary disease (39.4%) and lung cancer (33.3%). The median time between pneumothorax and valve placement was 24.5 days (interquartile range: 14.0-54.3). Air leak resolved in 40/66 patients (60.6%) within 30 days after EBV treatment. Concerning safety outcome, no procedure-related mortality was reported and complication rate was low (6.1%). Five patients (7.6%) died in the first 30 days after intervention. CONCLUSION: EBV placement is a treatment option in patients with PAL. In this multicenter case-series of high-risk patients not eligible for lung surgery, we show that EBV placement resulted in air leak resolution in 6 out of 10 patients with a low complication rate. Considering the minimally invasive nature of EBV to treat PAL as opposed to surgery, further research should investigate if EBV treatment should be expanded in low to intermediate risk PAL patients.
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BACKGROUND: The combination of pembrolizumab, an anti-PD-1 antibody, and lenvatinib, an antiangiogenic multikinase inhibitor, shows synergistic activity in preclinical and clinical studies in solid tumours. We assessed the clinical activity of this combination therapy in patients with pleural mesothelioma who progressed after platinum-pemetrexed chemotherapy. METHODS: In this single-arm, single-centre, phase 2 study, done at the Netherlands Cancer Institute in Amsterdam, The Netherlands, eligible patients (aged ≥18 years) with pleural mesothelioma with an Eastern Cooperative Oncology Group performance status of 0-1, progression after chemotherapy (no previous immunotherapy), and measurable disease according to the modified Response Evaluation Criteria In Solid Tumours (mRECIST) for mesothelioma version 1.1. Patients received 200 mg intravenous pembrolizumab once every 3 weeks plus 20 mg oral lenvatinib once per day for up to 2 years or until disease progression, development of unacceptable toxicity, or withdrawal of consent. The primary endpoint was objective response rate identified by a local investigator according to mRECIST version 1.1. This trial is registered with ClinicalTrials.gov, NCT04287829, and is recruiting for the second cohort. FINDINGS: Between March 5, 2021, and Jan 31, 2022, 42 patients were screened, of whom 38 were included in the primary endpoint and safety analyses (median age 71 years [IQR 65-75], 33 [87%] male and five [13%] female) . At data cutoff (Jan 31, 2023), with a median follow-up of 17·7 months (IQR 13·8-19·4), 22 (58%; 95% CI 41-74) of 38 patients had an objective response. The independent review showed an objective response in 17 (45%; 95% CI 29-62) of 38 patients. Serious treatment-related adverse events occurred in ten (26%) patients, including one treatment-related death due to myocardial infarction. The most common treatment-related grade 3 or worse adverse events were hypertension (eight patients [21%]) and anorexia and lymphopenia (both four patients [11%]). In 29 (76%) of 38 patients, at least one dose reduction or discontinuation of lenvatinib was required. INTERPRETATION: Pembrolizumab plus lenvatinib showed promising anti-tumour activity in patients with pleural mesothelioma with considerable toxicity, similar to that in previous studies. Available evidence from the literature suggests a high starting dose of lenvatinib for optimal anti-tumour activity. This, however, demands a high standard of supportive care. The combination therapy of pembrolizumab and lenvatinib warrants further investigation in pleural mesothelioma. FUNDING: Merck Sharp & Dohme.
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Antineoplásicos Imunológicos , Mesotelioma Maligno , Mesotelioma , Neoplasias Pleurais , Humanos , Masculino , Feminino , Adolescente , Adulto , Idoso , Antineoplásicos Imunológicos/efeitos adversos , Mesotelioma Maligno/tratamento farmacológico , Mesotelioma/patologia , Neoplasias Pleurais/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversosRESUMO
RATIONALE: Autofluorescence bronchoscopy (AFB) and computed tomography (CT) enable lung cancer (LC) detection at the early (pre-)invasive stage. However, LC risk in patients with preinvasive endobronchial lesions is unclear. OBJECTIVES: To assess LC incidence and identify potential risk determinants in patients with preinvasive lesions. METHODS: In our tertiary care referral center, 164 subjects with preinvasive lesions were monitored up to 12.5 years by repeated AFB and CT. Occurrence of LC was monitored. Clinical management depended on histological grade, with cancer patients receiving standard care. Potential risk determinants (smoking status, baseline histology, cancer history, and chronic obstructive pulmonary disease [COPD] status) were evaluated in relation to cancer occurrence, event-free survival (EFS), and overall survival (OS). MEASUREMENTS AND MAIN RESULTS: During surveillance (median of 30 mo, range 4-152) of 164 subjects with preinvasive lesions (80 high grade and 84 low grade at inclusion), 61 LCs were detected in 55 subjects (median time to event 16.5 mo). Twenty-three LCs (38%) were detected by CT, and 38 (62%) were detected by AFB. More cancers (36 of 61; 59%) developed from separate, rather than initial lesional sites. Subjects with high-grade lesions were more likely to be diagnosed with LC at the same or another site in the lungs than those with low-grade lesions (P = 0.03). Independent risk determinants for OS were previous curatively treated cancer and COPD (P ≤ 0.05). CONCLUSIONS: Presence of preinvasive lesions, especially high-grade lesions, may serve as LC risk markers. LCs occur both at preinvasive lesion sites and elsewhere in the bronchial epithelium or lung parenchyma. Prospective validation of biomarkers and randomized intervention studies are needed to determine optimal management strategies.
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Broncoscopia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/epidemiologia , Tomografia Computadorizada por Raios X , Comorbidade , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Incidência , Pulmão/diagnóstico por imagem , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Reprodutibilidade dos Testes , Fatores de Risco , Fumar/epidemiologiaRESUMO
Introduction: Tracheobronchial amyloidosis is a rare idiopathic disorder characterised by extracellular deposition of misfolded protein fibrils in the tracheobronchial tree. It presents with nonspecific symptoms. Deciding on the best treatment approach can be challenging due to the lack of a treatment guideline. We undertook a review to assess the therapeutic options for tracheobronchial amyloidosis and to highlight gaps within the existing evidence. Methods: We performed a literature search from 1 January 1990 until 1 March 2022 to identify relevant literature regarding patient characteristics, symptoms, management and prognosis for patients with tracheobronchial amyloidosis. Results: 77 studies consisting of 300 patients were included. We found a great heterogeneity in the management of tracheobronchial amyloidosis patients. Although a fifth of the reported patients were managed with a wait-and-see approach, many different treatments were used as a single intervention, or multiple treatments were combined. An interesting finding is the slightly higher percentage of patients with Sjögren syndrome (n=5, 1.7%) and tracheobronchial amyloidosis compared to the normal population (0.5-1.0%). Conclusions: There is a great heterogeneity in the management of tracheobronchial amyloidosis patients. The treatment is still based on expert opinion due to the lack of a treatment guideline. Various treatment approaches include a wait-and-see approach, external beam radiotherapy, therapeutic bronchoscopy, immunosuppressive treatment and surgery.
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PURPOSE: Pleural plaques (PPs) are morphologic manifestations of long-term asbestos exposure. The relationship between PP and lung function is not well understood, whereas the time-consuming nature of PP delineation to obtain volume impedes research. To automate the laborious task of delineation, we aimed to develop automatic artificial intelligence (AI)-driven segmentation of PP. Moreover, we aimed to explore the relationship between pleural plaque volume (PPV) and pulmonary function tests. MATERIALS AND METHODS: Radiologists manually delineated PPs retrospectively in computed tomography (CT) images of patients with occupational exposure to asbestos (May 2014 to November 2019). We trained an AI model with a no-new-UNet architecture. The Dice Similarity Coefficient quantified the overlap between AI and radiologists. The Spearman correlation coefficient ( r ) was used for the correlation between PPV and pulmonary function test metrics. When recorded, these were vital capacity (VC), forced vital capacity (FVC), and diffusing capacity for carbon monoxide (DLCO). RESULTS: We trained the AI system on 422 CT scans in 5 folds, each time with a different fold (n = 84 to 85) as a test set. On these independent test sets combined, the correlation between the predicted volumes and the ground truth was r = 0.90, and the median overlap was 0.71 Dice Similarity Coefficient. We found weak to moderate correlations with PPV for VC (n = 80, r = -0.40) and FVC (n = 82, r = -0.38), but no correlation for DLCO (n = 84, r = -0.09). When the cohort was split on the median PPV, we observed statistically significantly lower VC ( P = 0.001) and FVC ( P = 0.04) values for the higher PPV patients, but not for DLCO ( P = 0.19). CONCLUSION: We successfully developed an AI algorithm to automatically segment PP in CT images to enable fast volume extraction. Moreover, we have observed that PPV is associated with loss in VC and FVC.
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The ideal airway stent is still not available. Indications for 3D stents currently are limited to rare cases. Therefore, further research is required to investigate whether personalised airway stents will perform better than conventional stents. https://bit.ly/3GLjPa4.
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Subcutaneous emphysema, pneumothorax and pneumomediastinum are well-known complications of invasive ventilation in patients with acute hypoxemic respiratory failure. We determined the incidences of air leaks that were visible on available chest images in a cohort of critically ill patients with acute hypoxemic respiratory failure due to coronavirus disease of 2019 (COVID-19) in a single-center cohort in the Netherlands. A total of 712 chest images from 154 patients were re-evaluated by a multidisciplinary team of independent assessors; there was a median of three (2-5) chest radiographs and a median of one (1-2) chest CT scans per patient. The incidences of subcutaneous emphysema, pneumothoraxes and pneumomediastinum present in 13 patients (8.4%) were 4.5%, 4.5%, and 3.9%. The median first day of the presence of an air leak was 18 (2-21) days after arrival in the ICU and 18 (9-22)days after the start of invasive ventilation. We conclude that the incidence of air leaks was high in this cohort of COVID-19 patients, but it was fairly comparable with what was previously reported in patients with acute hypoxemic respiratory failure in the pre-COVID-19 era.
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INTRODUCTION: High flow nasal cannula (HFNC) reduces the need for intubation in patients with hypoxaemic acute respiratory failure (ARF), but its added value in patients with severe coronavirus disease 2019 (COVID-19) and a do-not-intubate (DNI) order is unknown. We aimed to assess (variables associated with) survival in these patients. MATERIALS AND METHODS: We described a multicentre retrospective observational cohort study in five hospitals in the Netherlands and assessed the survival in COVID-19 patients with severe acute respiratory failure and a DNI order who were treated with high flow nasal cannula. We also studied variables associated with survival. RESULTS AND DISCUSSION: One-third of patients survived after 30 days. Survival was 43.9% in the subgroup of patients with a good WHO performance status and only 16.1% in patients with a poor WHO performance status. Patients who were admitted to the hospital for a longer period prior to HFNC initiation were less likely to survive. HFNC resulted in an increase in ROX values, reflective of improved oxygenation and/or decreased respiratory rate. CONCLUSION: Our data suggest that a trial of HFNC could be considered to increase chances of survival in patients with ARF due to COVID-19 pneumonitis and a DNI order, especially in those with a good WHO performance status.
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COVID-19 , Ventilação não Invasiva , Síndrome do Desconforto Respiratório , Insuficiência Respiratória , Humanos , Cânula , COVID-19/complicações , COVID-19/terapia , Estudos Retrospectivos , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/terapia , Análise de Sobrevida , Síndrome do Desconforto Respiratório/terapia , OxigenoterapiaRESUMO
INTRODUCTION: Pre-invasive squamous lesions of the central airways can progress into invasive lung cancers. Identifying these high-risk patients could enable detection of invasive lung cancers at an early stage. In this study, we investigated the value of 18 F-fluorodeoxyglucose (18 F-FDG) positron emission tomography (PET) scans in predicting progression in patients with pre-invasive squamous endobronchial lesions. METHODS: In this retrospective study, patients with pre-invasive endobronchial lesions, who underwent an 18 F-FDG PET scan at the VU University Medical Center Amsterdam, between January 2000 and December 2016, were included. Autofluorescence bronchoscopy (AFB) was used for tissue sampling and was repeated every 3 months. The minimum and median follow-up was 3 and 46.5 months. Study endpoints were the occurrence of biopsy proven invasive carcinoma, time-to-progression and overall survival (OS). RESULTS: A total number of 40 of 225 patients met the inclusion criteria of which 17 (42.5%) patients had a positive baseline 18 F-FDG PET scan. A total of 13 of 17 (76.5%) developed invasive lung carcinoma during follow-up, with a median time to progression of 5.0 months (range, 3.0-25.0). In 23 (57.5%) patients with a negative 18 F-FDG PET scan at baseline, 6 (26%) developed lung cancer, with a median time to progression of 34.0 months (range, 14.0-42.0 months, p < 0.002). With a median OS of 56.0 months (range, 9.0-60.0 months) versus 49.0 months (range, 6.0-60.0 months) (p = 0.876) for the 18 F-FDG PET positive and negative groups, respectively. CONCLUSIONS: Patients with pre-invasive endobronchial squamous lesions and a positive baseline 18 F-FDG PET scan were at high-risk for developing lung carcinoma, highlighting that this patient group requires early radical treatment.
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Carcinoma de Células Escamosas , Neoplasias Pulmonares , Humanos , Fluordesoxiglucose F18 , Estudos Retrospectivos , Tomografia por Emissão de Pósitrons , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/patologiaRESUMO
Introduction: Diffuse alveolar haemorrhage (DAH) is a potentially life-threatening disease, characterized by diffuse accumulation of red blood cells within the alveoli. It can be caused by a variety of disorders. In case DAH results in severe respiratory failure, veno-venous extracorporeal membrane oxygenation (VV-ECMO) can be required. Since VV-ECMO coincides with the need for anticoagulation therapy, this results in a major clinical challenge in DAH patients with hemoptysis. Case presentation: We report a patient case with severe DAH-induced acute respiratory failure and hemoptysis in need for VV-ECMO complicated by life-threatening membrane oxygenator thrombosis. The DAH-induced hemoptysis was successfully treated with local bronchoscopic recombinant factor VIIa (rFVIIa), allowing systemic anticoagulation to prevent further membrane oxygenator thrombosis. Neither systemic clinical side effects nor differences in the serum coagulation markers occurred after applying recombinant factor VIIa (rFVIIa) treatment endobronchially. Conclusion: This is, to our knowledge, the first case that reports the use of rFVIIa in a patient with DAH due to vasculitis and in need for VV-ECMO complicated by membrane oxygenator thrombosis.
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BACKGROUND: The "buffalo chest" is a condition in which a simultaneous bilateral pneumothorax occurs due to a communication of both pleural cavities caused by an iatrogenic or idiopathic fenestration of the mediastinum. This rare condition is known by many clinicians because of a particular anecdote which stated that Native Americans could kill a North American bison with a single arrow in the chest by creating a simultaneous bilateral pneumothorax, due to the animal's peculiar anatomy in which there is one contiguous pleural space due to an incomplete mediastinum. RESEARCH QUESTION: What evidence is there for the existence of buffalo chest? STUDY DESIGN AND METHODS: The term "buffalo chest" and its anecdote were first mentioned in a ''personal communication'' by a veterinarian in the Annals of Surgery in 1984. A mixed method research was performed on buffalo chest and its etiology. A total of 47 cases of buffalo chest were identified in humans. RESULTS: This study found that all authors were referring to the article from 1984 or to each other. Evidence was found for interpleural communications in other mammal species, but no literature on the anatomy of the mediastinum of the bison was found. The main reason for this research was fact-checking the origin of the anecdote and search for evidence for the existence of buffalo chest. Autopsies were performed on eight bison, and four indeed were found to have had interpleural communications. INTERPRETATION: We hypothesize that humans can also have interpleural fenestrations, which can be diagnosed when a pneumothorax occurs.