Lymphocyte Depleting and Modulating Therapies for Chronic Lung Allograft Dysfunction.

Chronic lung rejection, also called chronic lung allograft dysfunction (CLAD), remains the major hurdle limiting long-term survival after lung transplantation, and limited therapeutic options are available to slow the progressive decline in lung function. Most interventions are only temporarily effective in stabilizing the loss of or modestly improving lung function, with disease progression resuming over time in the majority of patients. Therefore, identification of effective treatments that prevent the onset or halt progression of CLAD is urgently needed. As a key effector cell in its pathophysiology, lymphocytes have been considered a therapeutic target in CLAD. The aim of this review is to evaluate the use and efficacy of lymphocyte depleting and immunomodulating therapies in progressive CLAD beyond usual maintenance immunosuppressive strategies. Modalities used include anti-thymocyte globulin, alemtuzumab, methotrexate, cyclophosphamide, total lymphoid irradiation, and extracorporeal photopheresis, and to explore possible future strategies. When considering both efficacy and risk of side effects, extracorporeal photopheresis, anti-thymocyte globulin and total lymphoid irradiation appear to offer the best treatment options currently available for progressive CLAD patients. SIGNIFICANCE STATEMENT: Effective treatments to prevent the onset and progression of chronic lung rejection after lung transplantation are still a major shortcoming. Based on existing data to date, considering both efficacy and risk of side effects, extracorporeal photopheresis, anti-thymocyte globulin, and total lymphoid irradiation are currently the most viable second-line treatment options. However, it is important to note that interpretation of most results is hampered by the lack of randomized controlled trials.

Role of C1q-binding anti-HLA antibodies as a predictor of lung allograft outcome.

Presence of anti-human leukocyte antigen donor-specific antibodies (DSAs) is associated with poor outcome after lung transplantation. Currently, DSAs are detected using the Luminex technique, which may be overly sensitive. The new C1q assay allows for the exclusive detection of complement (C1q)-binding antibodies, involved in antibody-mediated rejection. We investigated whether early detection of complement-binding DSAs is associated with chronic lung allograft dysfunction (CLAD) and survival.From 2009 to 2012, lung transplant recipients from three transplantation centres were screened for the presence of DSA and their complement-binding capacity during the 6-12 months post-transplantation in a stable condition.The analysis included 168 patients. The 3-year rates of freedom from CLAD and graft survival were lower for patients with complement-binding DSAs (33.6% and 53.7%, respectively), as compared with patients with non-complement-binding DSAs (61.9% and 77.4%, respectively) and patients without DSA (70% and 84.9%, respectively) (p<0.001 and p=0.001, respectively). Detection of complement-binding DSA was associated with a risk of graft loss that was nearly tripled after adjustment for clinical, functional, histological and immunological factors (hazard ratio 2.98, 95% CI 1.33-6.66; p=0.008).Assessment of the C1q-binding capacity of DSA appears to be useful in identifying stable lung transplant recipients at high risk of lung allograft loss.

Pharmacological management of IPF.

Idiopathic pulmonary fibrosis (IPF) is a deadly disease with a median survival of approximately three years in historical cohorts. Despite increased knowledge of disease pathophysiology and selection of more targeted therapy, main clinical trials yielded negative results. However, two agents, pirfenidone and nintedanib, were recently shown to be effective in IPF and received marketing authorization worldwide. Both drugs significantly reduce functional decline and disease progression with an acceptable safety profile. Yet, none of these drugs actually improves or even stabilizes the disease or the symptoms perceived by the patient. Several other treatments and combinations are currently tested, and many more are ready for clinical trials. Their completion is critical for achieving the ultimate goal of curing patients with IPF.

Investigation of Lung Involvement in Connective Tissue Disorders.

Lung involvement in connective tissue disorders (CTDs) may present as pleomorphic since any lung compartment may be involved such as airways, exocrine secretory and alveolar epithelia, interstitial lung structure, pulmonary vasculature and pleura as well as, in specific disorders, several tissues of the thoracoabdominal ventilator pump. Any combination of the above anatomic structures may be involved concomitantly although some specific combinations may include a determinant of rheumatic disorders. The diagnosis of a specific CTD requires the fulfilment of clearly defined clinical and laboratory criteria including in most cases positivity for autoantibodies, mostly specific serologic combinations. In this setting, serologic investigation targets mainly, although not exclusively, the detection of antinuclear antibodies. A specific serologic positivity or a combination of autoantibodies constitutes not only a diagnostic criterion for a specific CTD, but may also characterize the pattern of respiratory manifestation in a determinant rheumatic disorder. Therefore, the investigation of lung involvement in CTDs requires adequate skills in the ambit of a multidisciplinary approach and an extended spectrum of diagnostic tools and modalities able to detect both early clinical clues and serologic conversion as well as any pathophysiologic alteration that regards the complexity of respiratory functional status. Although many patients with CTDs suffer from a 'vicious' combination of lung involvement, lung drug toxicity and infections related to the above two as well as to the 'mater' disease, for space reasons this review will focus on the established lung manifestations that regard the 7 major CTDs.

Forkhead Box F1 represses cell growth and inhibits COL1 and ARPC2 expression in lung fibroblasts in vitro.

Aberrant expression of master phenotype regulators or alterations in their downstream pathways in lung fibroblasts may play a central role in idiopathic pulmonary fibrosis (IPF). Interrogating IPF fibroblast transcriptome datasets, we identified Forkhead Box F1 (FOXF1), a DNA-binding protein required for lung development, as a candidate actor in IPF. Thus we determined FOXF1 expression levels in fibroblasts cultured from normal or IPF lungs in vitro, and explored FOXF1 functions in these cells using transient and stable loss-of-function and gain-of-function models. FOXF1 mRNA and protein were expressed at higher levels in IPF fibroblasts compared with normal fibroblasts (mRNA: +44%, protein: +77%). Immunohistochemistry showed FOXF1 expression in nuclei of bronchial smooth muscle cells, endothelial cells, and lung fibroblasts including fibroblastic foci of IPF lungs. In normal lung fibroblasts, FOXF1 repressed cell growth and expression of collagen-1 (COL1) and actin-related protein 2/3 complex, subunit 2 (ARPC2). ARPC2 knockdown inhibited cell growth and COL1 expression, consistent with FOXF1 acting in part through ARPC2 repression. In IPF fibroblasts, COL1 and ARPC2 repression by FOXF1 was blunted, and FOXF1 did not repress growth. FOXF1 expression was induced by the antifibrotic mediator prostaglandin E2 and repressed by the profibrotic cytokine transforming growth factor-ß1 in both normal and IPF lung fibroblasts. Ex vivo, FOXF1 knockdown conferred CCL-210 lung fibroblasts the ability to implant in uninjured mouse lungs. In conclusion, FOXF1 functions and regulation were consistent with participation in antifibrotic pathways. Alterations of pathways downstream of FOXF1 may participate to fibrogenesis in IPF fibroblasts.

Outcomes of listing for lung and heart-lung transplantation in pulmonary hypertension: comparative experience in France and the UK.

Background: Lung or heart-lung transplantation (LT/HLT) for severe pulmonary hypertension (PH) as the primary disease indication carries a high risk of waiting list mortality and post-transplant complications. France and the UK both have coordinated PH patient services but with different referral pathways for accessing LT services. Methods: We conducted a comparative analysis of adult PH patients listed for LT/HLT in the UK and France. Results: We included 211 PH patients in France (2006-2018) and 170 in the UK (2010-2019). Cumulative incidence of transplant, delisting and waiting list death within 3 years were 81%, 4% and 11% in France versus 58%, 10% and 15% in the UK (p<0.001 for transplant and delisting; p=0.1 for death). Median non-priority waiting time was 45 days in France versus 165 days in the UK (p<0.001). High-priority listing occurred in 54% and 51% of transplanted patients respectively in France and the UK (p=0.8). Factors associated with achieving transplantation related to recipients' height, male sex, clinical severity and priority listing status. 1-year post-transplant survival was 78% in France and 72% in the UK (p= 0.04). Conclusion: Access to transplantation for PH patients is better in France than in the UK where more patients were delisted due to clinical deterioration because of longer waiting time. High rates of priority listing occurred in both countries. Survival for those achieving transplantation was slightly better in France. Ensuring optimal outcomes after transplant listing for PH patients is challenging and may involve early listing of higher risk patients, increasing donor lung utilisation and improving allocation rules for these specific patients.

["Wellness Bubbles" for caregivers, a way to improve the quality of life at work]. / Les "Bulles de bien-être" pour les soignants, une piste pour améliorer la qualité de vie au travail.

Improving the well-being at work of caregivers is a major challenge for our healthcare system. Both global and local solutions must be proposed. At the Marie-Lannelongue hospital, located in the Paris region, a structure dedicated to the well-being of caregivers at work, the "Bubble", has been set up. How does it work and what are its beneficial effects? How have the professionals received it? Is it an example to follow? These are some of the questions that a survey has enabled us to answer.

Molecular monitoring of lung allograft health: is it ready for routine clinical use?

Maintenance of long-term lung allograft health in lung transplant recipients (LTRs) requires a fine balancing act between providing sufficient immunosuppression to reduce the risk of rejection whilst at the same time not over-immunosuppressing individuals and exposing them to the myriad of immunosuppressant drug side-effects that can cause morbidity and mortality. At present, lung transplant physicians only have limited and rather blunt tools available to assist them with this task. Although therapeutic drug monitoring provides clinically useful information about single time point and longitudinal exposure of LTRs to immunosuppressants, it lacks precision in determining the functional level of immunosuppression that an individual is experiencing. There is a significant gap in our ability to monitor lung allograft health and therefore tailor optimal personalised immunosuppression regimens. Molecular diagnostics performed on blood, bronchoalveolar lavage or lung tissue that can detect early signs of subclinical allograft injury, differentiate rejection from infection or distinguish cellular from humoral rejection could offer clinicians powerful tools in protecting lung allograft health. In this review, we look at the current evidence behind molecular monitoring in lung transplantation and ask if it is ready for routine clinical use. Although donor-derived cell-free DNA and tissue transcriptomics appear to be the techniques with the most immediate clinical potential, more robust data are required on their performance and additional clinical value beyond standard of care.

Outcomes of extended resection for locally advanced thymic malignancies.

BACKGROUND: Thymic malignancies are rare tumors about which data are limited. Our objective here was to evaluate the outcomes and risk factors for complications and death in patients who underwent extended surgery to remove thymic malignancies. METHODS: We retrospectively included patients who underwent extended resection of locally advanced, nonmetastatic thymic malignancies at our institution. Patients were deemed eligible for resection by a multidisciplinary team. During surgery, priority was given to achieving complete resection rather than to sparing organs. RESULTS: The 108 patients had a mean age of 53 ± 15 years (range, 9-83); among them, 91 had thymoma, 12 thymic carcinoma, and 5 neuroendocrine tumor. The Masaoka stage was III or higher in 86 patients; examination of operative specimens resulted in downstaging of 22 patients. Tumor-free resection margins were achieved in 98 patients. Overall 5- and 10-year survival rates were 80% and 68%, respectively. Myasthenia gravis, present in 36 patients, was the only independent significant risk factor for major postoperative complications. Age older than 70 years, thymic carcinoma or neuroendocrine tumor, pT3 or pT4 stage, and R1 or R2 resection margins independently predicted death. The number of resected structures was not associated with survival. Thymic carcinoma or neuroendocrine tumor was independently associated with shorter disease-free survival. CONCLUSION: In an expert center, extended resection targeting complete resection rather than organ preservation provided good outcomes in patients with locally advanced thymic malignancies. The risk/benefit ratio of surgery should be assessed with special care in patients who are elderly or have myasthenia gravis.

A Patient-Centered Model of Fast-Track Lung Cancer Diagnosis.

INTRODUCTION: Despite the increasing importance of digital resources in modern life over the past decades, little is known about the impact of internet-based solutions on patient's health. We aimed to study the potential benefit of a digital platform helping patients to deal with abnormal chest CT scan revealing possible lung cancer. METHODS: We set up a fast-track lung cancer diagnosis pathway through a secure online platform. Patient-generated information combined with online review of their imaging enables preplanning of further investigations ahead of clinical assessment. We compared outcomes of "self-referred" patients (patient group), who directly fill out the online questionnaire, to general practitioner-driven patients (GP group), who were referred by their GP. RESULTS: From June 2021 to June 2022, we included 125 patients (61% males, median age 67 years, IQR 56.9-72.5): 41% in the patient group and 59% in the GP group. No difference was found between groups in terms of time from contact to first appointment (median 5 days in both groups, P = .6), percentage of pathways including prebooked tests (94% vs. 92%, P = .6), number of scheduled invasive procedures (median 1, IQR 1-2 vs. 2, IQR 1-2, P = .4) and in final cancer diagnosis (76% vs. 78%, P = .4). CONCLUSION: A lung cancer diagnosis pathway directly accessible by patients through a secure online platform was feasible and as efficient as the usual general practitioner pathway. It demonstrated the benefit of leaning on new digital tools in order to answer to the new challenges of a patient-centered health care system.

Immune-related generalised oedema - A new category of adverse events with immune checkpoint inhibitors.

BACKGROUND: Generalised oedema was occasionally reported associated with immune checkpoint inhibitors (ICPIs). The purpose of this study is to investigate immune-related generalised oedema (ir-GE) drug related to ICPI, through frequency, clinical and pathological characteristics, and patient's outcome. PATIENTS AND METHODS: Objectives of the study were to report on ir-GE associated with ICPI to define frequency, associated signs and symptoms, pathological characteristics, severity, and response to corticosteroids. To be included in the study, adult patients had to have ir-GE related to ICPI with certain or likely link, without any other known causes of generalised oedema. The study design was observational, over the period 2014-2020, from pharmacovigilance databases in France, including the prospective Registre des Effets Indésirables Sévères des Anticorps Monoclonaux Immunomodulateurs en Cancérologie (REISAMIC) registry. Calculation of the frequency of ir-GE was restricted to the prospective REISAMIC registry. RESULTS: Over 6633 screened patients, 20 had ir-GE confirmed drug related to ICPI. Based on the prospective REISAMIC registry, the frequency of ir-GE was 0.19% of ICPI-treated patients (3 cases out of 1598 screened patients). The 20 patients with ir-GE had a median (range) age of 62 (26-81) years, most frequent tumour types were melanoma (n = 9; 45%) and lung cancer (n = 6; 30%). The most frequent localisations of oedema were peripheral (n = 17; 85%), pleural (n = 13; 65%), and peritoneal (n = 10; 50%). Polyserositis was observed in 11 (55%) patients. The median (range) weight gain per patient was 9 (2-30) kg. Associated signs and symptoms met criteria for capillary leak syndrome (n = 4; 20%), sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) (n = 3; 15%), or subcutaneous autoimmune syndrome (n = 2; 10%). Corticosteroids were administered to 15 patients; of them, 10 (67%) improved clinically after corticosteroids. Based on CTCAEV5.0, the highest severity of ir-GE was grade ≥4 in 11 (55%) patients and four (20%) patients died due to ir-GE. CONCLUSIONS: Generalised immune system-related oedema is a new category of adverse event with immune checkpoint inhibitors and is often associated with a life-threatening condition. The pathophysiology may in some cases be related to endothelial dysfunctions, such as SOS/VOD or capillary leak syndrome.

Feasibility and long-term outcomes of surgery for primary thoracic synovial sarcoma.

OBJECTIVES: Primary thoracic synovial sarcoma (SS) is a rare, high-grade, malignancy. Involvement of vital organs is frequent and may decrease the benefits of surgical resection. We reviewed our practice at a highly experienced thoracic-surgery centre to assess early- and long-term outcomes after surgery. METHODS: We conducted a retrospective, observational, single-centre study of patients undergoing curative-intent surgery for primary thoracic SS between 1 January 2000 and 31 January 2021 as part of a multidisciplinary management. We assessed demographics, medical history, histopathology and follow-up information. RESULTS: We enrolled 20 patients (13 males) with a median age of 40 years old and a median tumour size of 11 cm. Neoadjuvant chemotherapy was administered to 13 patients. Surgery consisted in extrapleural pneumonectomy (n = 7), extrapleural lobectomy (n = 5), chest wall resection (n = 4) or tumour resection (n = 4). R0 resection was achieved in 16 (80%) patients. Adjuvant therapy was given to 13 patients. 6 patients developed postoperative complications. The median hospital stay was 11.5 days. Overall survival at 2 and 5 years was 51% and 22%, respectively; median overall survival was 25 months and median disease-free survival was 8.5 months. Relapses occurred in 15 patients. By univariate analysis, incomplete resection was the only significant predictor of survival (P = 0.01). CONCLUSIONS: Primary thoracic SS is an aggressive disease. Surgery included in a multimodal treatment may contribute to achieving a good outcome, providing that an R0 resection is obtained. Given the considerable technical challenges of surgery, patient selection and referral to an experienced centre are crucial to minimize morbidity and mortality.

Sarcoid-like Granulomatosis Associated with Immune Checkpoint Inhibitors in Melanoma.

We aimed to review the clinical and biological presentation of granulomatosis associated with immune-checkpoint inhibitors (ICI) in patients with melanoma and to explore its association with classical sarcoidosis as well as with cancer response to ICI. To this end, a retrospective study on 18 melanoma patients with histologically proven ICI-induced granulomatosis over a 12-year period in a single center, as well as on 67 similar cases reported in the literature, was conducted. Results indicate ICI-induced granulomatosis is an early side effect (median time to onset: 2 months). Its clinical presentation, with predominant (90%) thoracic involvement, histopathological appearance and supposed underlying biology (involving the mTOR pathway in immune cells, Th17 polarization and TReg dysfunction) are indistinguishable from those of sarcoidosis. Moreover, it appears to be associated with ICI benefit (>65% objective response rate). Evolution is generally favorable, and symptomatic steroid treatment and/or ICI discontinuation are rarely necessary. ICI-associated granulomatosis is critical to explore for several reasons. Practically, it is essential to differentiate it from cancer progression. Secondly, this "experimental" sarcoidosis brings new elements that may help to address sarcoidosis origin and pathophysiology. Its association with ICI efficacy must be confirmed on a larger scale but could have significant impacts on patient management and biomarker definition.

Epidemiological Study to Assess the Prevalence of Lung Cancer in patients with smoking-associated atherosclerotic cardiovascular diseases: PREVALUNG study protocol.

INTRODUCTION: Eligibility criteria definition for a lung cancer screening (LCS) is an unmet need. We hypothesised that patients with a history of atheromatous cardiovascular disease (ACVD) associated with tobacco consumption are at risk of lung cancer (LC). The main objective is to assess LC prevalence among patients with ACVD and history of tobacco consumption by using low-dose chest CT scan. Secondary objectives include the evaluation LCS in this population and the constitution of a biological biobank to stratify risk of LC. METHODS AND ANALYSIS: We are performing a monocentric 'single-centre' prospective study among patients followed up in adult cardiovascular programmes of vascular surgery, cardiology and cardiac surgery recruited from 18 November 2019 to 18 May 2021. The inclusion criteria are (1) age 45-75 years old, (2) history of ACVD and (3) history of daily tobacco consumption for 10 years prior to onset of ACVD. Exclusion criteria are symptoms of LC, existing follow-up for pulmonary nodule, fibrosis, pulmonary hypertension, resting dyspnoea and active pulmonary infectious disease. We targeted the inclusion of 500 patients. After inclusion (V0), patients are scheduled for a low-dose chest CT and blood and faeces harvesting within 7 months (V1). Each patient is scheduled for a follow-up by telephonic visits at month 3 (V2), month 6 (V3) and month 12 (V4) after V1. Each patient is followed up until 1 year after V1 (14 February 2023). We measure LC prevalence and quantify the National Lung Screening Trial and Dutch-Belgian Randomized Lung Cancer Screening Trial (NELSON) trial eligibility criteria, radiation, positive screening, false positivity, rate of localised LC diagnosis, quality of life with the Short Form 12 (SF-12) and anxiety with the Spielberger State-Trait Anxiety Inventory A and B (STAI-YA and STAI-YB, respectively), smoking cessation and onset of cardiovascular and oncological events within 1 year of follow-up. A case-control study nested in the cohort is performed to identify clinical or biological candidate biomarkers of LC. ETHICS AND DISSEMINATION: The study was approved according the French Jardé law; the study is referenced at the French 'Agence Nationale de Sécurité du Médicament et des Produits de Santé' (reference ID RCB: 2019-A00262-55) and registered on clinicaltrial.gov. The results of the study will be presented after the closure of the follow-up scheduled on 14 February 2023 and disseminated through peer-reviewed journals and national and international conferences. TRIAL REGISTRATION NUMBER: NCT03976804.

Risk stratification in patients with pulmonary arterial hypertension at the time of listing for lung transplantation.

BACKGROUND: It is unknown whether pulmonary arterial hypertension (PAH) risk stratification instruments could be helpful to support the decision to list a patient for lung transplantation (LT). Our aim was to evaluate contemporary risk assessment tools in a cohort of PAH patients listed for LT. METHODS: Consecutive PAH patients (without pulmonary veno-occlusive disease or unrepaired congenital heart disease) listed for LT at the French Pulmonary Hypertension Reference Center between January 2006 and December 2018 were included. At the time of listing, risk stratification was assessed using the ESC/ERS criteria, the REVEAL Lite 2 score and the COMPERA 2.0 method. The primary end point was overall survival after LT listing. Secondary outcome measures were mortality on waiting list and posttransplant survival. RESULTS: One hundred and two patients were enrolled (mean age 38 ± 13 years, 69% females). Overall survival after listing was 72%, 58% and 46% at 1, 3 and 5 years respectively. Survival after LT listing was lower in "high-risk" patients according to the ESC/ERS criteria (p = 0.0001) and the REVEAL Lite 2 score (p = 0.04). The COMPERA 2.0 method discriminated post-listing survival of patients at high-risk, intermediate-high and intermediate-low risk (p = 0.04). The proportion of patients requiring urgent transplantation and extracorporeal life support as a bridge to transplantation was higher in the "high-risk" patients. Posttransplant survival was significantly lower in "high-risk" patients according to the ESC/ERS criteria (p = 0.0004). CONCLUSIONS: High-risk PAH patients at the time of LT listing have poor outcomes, suggesting that LT should be considered earlier in the course of PAH remaining refractory to triple combination therapy with a parenteral prostacyclin.

Long-term outcomes after chest wall resection and repair with titanium bars and sternal plates.

Objectives: En-bloc complete resection remains the treatment of choice for localized chest wall (CW) tumors. Titanium bars reconstruction demonstrated encouraging results with satisfactory early outcomes. However, long-term outcomes remain under-reported. The purpose of this study is to evaluate long-term outcomes after CW resection and repair with titanium devices. Methods: From June 2012 to December 2018, we retrospectively reviewed all patients with CW tumors who underwent surgical resection and repair using titanium. Long-term outcomes were assessed. Results: We identified 87 patients who underwent CW tumor resections and titanium reconstruction. Sixty-eight patients were included in the study (excluding benign tumors, Pancoast tumors, palliative surgeries, or clavicle reconstruction). There were 29 sarcomas, 20 isolated CW metastases, eight lung cancers, four breast cancers, three thymic malignancies, two sarcomatoid mesothelioma, and one desmoid tumor. Complete resection was achieved in 64 patients (94%), while R1 resection in four patients (6%). Resection involved one rib in two patients, two ribs in thirteen, three ribs in eighteen, four ribs in nine, five ribs in two, seven ribs in one, partial sternum in fifteen, and full sternum in sixteen patients. No patient experienced flail chest. The 1-year, 3-year, and 5-year overall survival rates and disease-free survivals were 82.3%, 61.4%,57.3%, and 67.6%,57.3%,52.6%, respectively. Surgical site infection occurred in 18% (n = 12) of cases. Eleven of twelve patients had an early infection (<1 year), which required material removal in six patients. Asymptomatic connector unsealing occurred in 6% (n = 4), with only one re-intervention. Titanium allergy has never been reported. Chronic chest pain (lasting more than 3 months after surgery, with daily use of pain killer) was reported in 24% of patients. Conclusion: CW resections with titanium reconstruction are associated with long-term survivors. Titanium devices were safe, reliable, and achieved satisfactory oncological results with low morbidity and implant-related complication rates.

Complete Remission After Immunotherapy-Induced Abdominal Tuberculosis in a Patient With Advanced NSCLC Treated With Pembrolizumab: A Case Report.

The use of immune checkpoint inhibitors (ICIs) has drastically transformed the therapeutic landscape in lung cancer. Special focus has been put on immune-related toxicity; however, infections can also seem during ICI treatment. Although rare, tuberculosis (TB) has been increasingly identified after ICIs, and it seems that the programmed cell death protein 1 and programmed death-ligand 1 pathway is directly involved in its pathophysiology. Here, we describe the case of a patient with advanced NSCLC who developed abdominal TB after 32 months of pembrolizumab and who remains in tumor remission 10 months after discontinuation of this drug. Routine screening for latent TB before ICI treatment is advised, with closer collaboration between infectious disease specialists and oncologists.

Diagnosis Yield and Safety of Surgical Biopsy in Interstitial Lung Diseases: A Prospective Study.

BACKGROUND: Surgical lung biopsy is essential in the diagnostic algorithm of interstitial lung disease (ILD) of unknown cause. Safety concerns have been recently reiterated. This study prospectively assessed the yield of diagnosis and safety of video-assisted thoracoscopic surgical lung biopsy (VATS-LB) for ILD diagnosis. METHODS: This prospective study, conducted in 6 ILD-referral Paris hospitals, included 103 patients with ILD. VATS-LB was proposed after initial multidisciplinary discussion. A final diagnosis was made after the procedure, during a second multidisciplinary discussion. The main outcome was to determine the final diagnoses and their proportion after VATS-LB. Other outcomes were the percentage of change in diagnosis and treatment propositions after VATS-LB and adverse events during 3 months after the operation, postoperative pulmonary function, quality of life, and pain. RESULTS: A definite diagnosis was reached in 87 patients (84.4%), and 16 remained unclassifiable (15.6%). After VATS-LB, the hypothesized diagnosis changed in 65 patients (63.1%) and treatment changed in 41 patients (39.8%). One patient died of acute exacerbation. In-hospital complications were predicted by a shorter preoperative 6-minute walking test distance and by forced vital capacity lower than 77%. Postoperative quality of life was not modified at 3 months, whereas forced vital capacity decreased slightly. Postoperative neuropathic pain was revealed in 5% of patients at 1 month and in 2% at 3 months. CONCLUSIONS: VATS-LB dramatically changed preoperative hypothetical diagnoses and treatment in ILD of unknown cause, with good patient survival in ILD referral centers.

Our current understanding of and approach to the management of lung cancer with pulmonary hypertension.

INTRODUCTION: Lung cancer is a frequent pathology for which the best curative treatment is pulmonary resection. Pulmonary arterial hypertension is a rare disease but pulmonary hypertension associated with parenchymal disease or left heart disease is frequently observed in these patients. The diagnosis of pulmonary hypertension before lung resection makes the perioperative management of these patients more difficult and sometimes leads to rejecting patients for surgery. AREAS COVERED: We performed a review of literature on PubMed on Pulmonary hypertension associated lung resection, preoperative assessment of lung resection and perioperative management of PH patients, including guidelines and clinical trials.In this review, we summarize the current state of knowledge regarding the pre and perioperative management of patients with suspected or confirmed PH who can benefit from surgical treatment of lung cancer. EXPERT OPINION: Management of PH patients before lung resection should include a very careful workup including at least right heart catheterization with evaluation of the targeted PH treatment in an expert center and evaluation of other comorbidities. Perioperative management must be carried out in a specialized center.