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Background: Pulmonary alveolar proteinosis (PAP) is a rare syndrome caused by several distinct diseases leading to progressive dyspnoea, hypoxemia, risk of respiratory failure and early death due to accumulation of proteinaceous material in the lungs. Diagnostic strategies may include computed tomography (CT) of the lungs, bronchoalveolar lavage, evaluation of antibodies against granulocyte macrophage colony stimulating factor (GM-CSF), genetic testing, and, eventually, lung biopsy. The management options are focused at removing the proteinaceous material by whole lung lavage (WLL), augmentation therapy with GM-CSF, rituximab, plasmapheresis, and lung transplantation. The presented diagnostic and management guideline aim to provide guidance to physicians managing patients with PAP., Methods: A European Respiratory Society Task Force committee composed of clinicians, methodologists, and patients with experience in PAP developed recommendations in accordance with the ERS Handbook for Clinical Practice Guidelines and the GRADE (Grading of Recommendations, Assessment, Development and Evaluations) approach. This included a systematic review of the literature and application of the GRADE approach to assess the certainty of the evidence and strength of recommendations. The committee formulated five PICO (Patients, Intervention, Comparison, Outcomes) questions, and two narrative questions to develop specific evidence-based recommendations., Results: The Task Force committee developed recommendations for five PICOs. These included management of PAP with WLL, GM-CSF augmentation therapy, rituximab, plasmapheresis, and lung transplantation. Also, the committee made recommendations regarding the use of GM-CSF antibody testing, diagnostic bronchoalveolar lavage (BAL) and biopsy based on narrative questions.In addition to the recommendations, the committee provided information on the hierarchy of diagnostic interventions and therapy., Conclusions: The diagnosis of PAP is based on CT and BAL cytology or lung histology, whereas diagnosis of specific PAP-causing diseases requires GM-CSF antibody testing or genetic analysis. There are several therapies including WLL and augmentation therapy with GM-CSF available to treat PAP, but supporting evidence is still limited., (Copyright ©The authors 2024. For reproduction rights and permissions contact permissions@ersnet.org.)

Purpose: Cranial irradiation can lead to long-term neurological complications, in particular memory disorders. The aim of this prospective study is to evaluate the impact of irradiation of benign skull base tumours located near the hippocampi on autobiographical memory., Patients and Methods: From 2016 to 2019, patients with cavernous sinus meningioma or pituitary adenoma treated with normofractionated irradiation were included. Patients underwent full neuropsychological assessment at baseline, 1year and 2years post-treatment. Neuropsychological tests were converted to Z-Score for comparability., Results: Twelve of the 19 patients included had a complete neuropsychological evaluation at 2years and were analysed. On the "TEMPau" test, no significant difference in autobiographical memory was found at 2years, regardless of the period of autobiographical memory. The mean hippocampal dose had no impact on the variation in autobiographical memory. There was no significant cognitive impairment in the other domains assessed, such as attention, anterograde memory, working memory and executive functions. Autobiographical memory was independent of these other cognitive domains, which justifies its specific study., Conclusion: Radiotherapy to the skull base for a benign pathology does not lead to significant cognitive impairment. Longer follow-up would be needed to confirm these results., (Copyright © 2024. Published by Elsevier Masson SAS.)

Locally recurrent nasopharyngeal carcinoma (NPC) presents substantial challenges in clinical management. Although postoperative re-irradiation (re-RT) has been acknowledged as a potential treatment option, standardized guidelines and consensus regarding the use of re-RT in this context are lacking. This article provides a comprehensive review and summary of international recommendations on postoperative management for potentially resectable locally recurrent NPC, with a special focus on postoperative re-RT. A thorough search was conducted to identify relevant studies on postoperative re-RT for locally recurrent NPC. Controversial issues, including resectability criteria, margin assessment, indications for postoperative re-RT, and the optimal dose and method of re-RT, were addressed through a Delphi consensus process. The consensus recommendations emphasize the need for a clearer and broader definition of resectability, highlighting the importance of achieving clear surgical margins, preferably through an en bloc approach with frozen section margin assessment. Furthermore, these guidelines suggest considering re-RT for patients with positive or close margins. Optimal postoperative re-RT doses typically range around 60 Gy, and hyperfractionation has shown promise in reducing toxicity. These guidelines aim to assist clinicians in making evidence-based decisions and improving patient outcomes in the management of potentially resectable locally recurrent NPC. By addressing key areas of controversy and providing recommendations on resectability, margin assessment, and re-RT parameters, these guidelines serve as a valuable resource for clinical experts involved in the treatment of locally recurrent NPC., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Rare cancers constitute less than 10% of head and neck cancers and lack sufficient evidence for standardized care. The French Rare Head and Neck Cancer Expert Network (REFCOR) as established a national database to collect data on these rare cancers. This study aims to describe patient and tumour characteristics in this database., Methods: Prospective data collection was conducted across multiple centers. Survival analyses were performed using Kaplan Meier method and Log Rank test. Odds ratios were used for comparing proportions., Results: A total of 7208 patients were included over a period of 10 years. The most frequent histologies were: Not Otherwise Specified (NOS) adenocarcinoma 13 %, adenoid cystic carcinoma 12 %, squamous cell carcinoma of rare locations 10 %, mucoepidermoid carcinoma 9 %, intestinal-type adenocarcinoma (8 %). Tumours were located in sinonasal area (38 %); salivary glands (32 %); oral cavity / oropharynx / nasopharynx (16 %); larynx / hypopharynx (3 %); ears (1 %); others (3 %). Tumours were predominantly classified as T4 (23 %), N0 (54 %), and M0 (62 %). Primary treatment approach involved tumour resection (78 %) and / or radiotherapy (63 %). Patients with salivary gland cancers exhibited better 5-year overall survival (OS) rates (p < 0.05), and lower recurrence rates compared to patients with sinonasal, laryngeal/ hypopharyngeal cancers. No significant differences were observed in the other comparisons. Acinar cell carcinoma demonstrated the best OS while mucous melanoma had the poorest prognosis., Conclusion: Melanoma, carcinoma NOS, and sinonasal undifferenciated carcinoma still have poor prognoses. Efforts are being made, including training and guidelines, to expand network coverage (REFCOR, EURACAN), improve data collection and contribute to personalized therapies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Articular manifestations should be screened before and during anti-IL-5/5R biologic treatment in severe asthma. Rigorous multidisciplinary team discussion should be carried out to assess the risk-benefit balance of withholding effective treatment. https://bit.ly/3vfPn4k., Competing Interests: Conflict of interest: C. Dupin reports consulting fees from AstraZeneca, Sanofi and GSK; lecture honoraria from AstraZeneca, GSK, Sanofi, Novartis, Chiesi, OPA Pratique, Pneumoscoop and La Lettre du Pneumologue; and travel support from AstraZeneca, Sanofi, Novartis, Chiesi and GSK; all outside the submitted work. Conflict of interest: L. Guilleminault reports grants from AstraZeneca; consulting fees from Bayer, MSD, AstraZeneca, GSK, Novartis, Sanofi and Chiesi; lecture honoraria from MSD, AstraZeneca, GSK, Novartis, Sanofi and Chiesi; payment for expert testimony from Bayer, MSD and Sanofi; and travel support from MSD, AstraZeneca, GSK, Novartis and Sanofi; all outside the submitted work. Conflict of interest: G. Devouassoux reports lecture or consulting fees from GSK, Menarini, ALK, AstraZeneca, Novartis, Chiesi and Sanofi; payment for expert testimony from GSK, AstraZeneca, Sanofi and Chiesi; and travel support from AstraZeneca, GSK, Sanofi, Novartis, Chiesi; all outside the submitted work. Conflict of interest: M. Le Brun reports grants from GSK, AstenSante and Novartis; lecture honoraria from GSK and La Revue du Praticien; and travel support from Asten Santé and Novartis; all outside the submitted work. Conflict of interest: G. Mourin reports lecture honoraria from AstraZeneca and GSK; and travel support from AstraZeneca, Sanofi, Menarini and GSK; all outside the submitted work. Conflict of interest: P. Bonniaud reports grants from AstraZeneca; lecture honoraria from Sanofi and AstraZeneca; travel support from AstraZeneca, Novartis and Sanofi; advisory board participation from AstraZeneca, Novartis, Sanofi and GSK; all outside the submitted work. Conflict of interest: E. Ebstein reports consulting fees from Abbvie, Novartis and BMS; lecture honoraria from UCB and Galapagos; and travel support from UCB and Novartis; all outside the submitted work. Conflict of interest: C. Taillé reports grants from GSK; consulting fees from AstraZeneca, GSK and Sanofi; lecture honoraria from AstraZeneca, GSK, Sanofi, Novartis, Stallergenes and Chiesi; and travel support from AstraZeneca and GSK; all outside the submitted work. Conflict of interest: S. Valéry, M. Merveilleau, M. Russier, J. Pradelli, P-A. Juge all have nothing to disclose., (Copyright ©The authors 2024.)

Background: Benralizumab is effective in the treatment of eosinophilic asthma and is being investigated for the treatment of other eosinophil-associated diseases. Reports on the use of benralizumab for the treatment of eosinophilic granulomatosis with polyangiitis (EGPA) are limited to case reports and small case series., Methods: We conducted a multicentre, retrospective study including EGPA patients treated with off-label benralizumab. The primary endpoint was the rate of complete response defined as no disease activity (Birmingham Vasculitis Activity Score=0) and a prednisone dose ≤4 mg/day. Partial response was defined as no disease activity and a prednisone dose ≥4 mg/day., Results: Sixty-eight patients were included, including 31 (46%) who had previously received mepolizumab. The use of benralizumab was warranted by uncontrolled asthma in 54 (81%), persistent ear, nose and throat (ENT) manifestations in 27 (40%) and persistent glucocorticoids (GCs) use in 48 (74%) patients. Median (IQR) follow-up after starting benralizumab was 23 (9-34) months. Thirty-three patients (49%) achieved a complete response, 24 (36%) achieved a partial response and 10 (15%) did not respond. Among the 57 patients who initially responded, 10 (18%) eventually required further line treatments. GCs were discontinued in 23 patients (38%). Prior mepolizumab use was associated with a higher rate of primary failure (26.7% vs 5.4%, p=0.034) and less frequent GCs discontinuation (14.8% vs 55.9%, p=0.001). Vasculitis flares occurred in 7 patients (11%) and were associated with histological evidence of vasculitis and/or antineutrophil cytoplasmic antibodies positivity at benralizumab initiation (p=0.004)., Conclusions: Benralizumab appears to be an effective treatment for refractory asthma or ENT manifestations in EGPA and allows GC-sparing. However, its efficacy was lower after prior failure of mepolizumab., Competing Interests: Competing interests: The authors declare no financial support. MG reports personal fees from GlaxoSmithKline and AstraZeneca outside the submitted work. CT reports personal fees from AstraZeneca, Sanofi, GlaxoSmithKline, Chiesi and Novartis outside the submitted work. CDupin reports personal fees from AstraZeneca and GlaxoSmithKline outside the submitted work. HY reports personal fees from GlaxoSmithKline outside the submitted work. Other authors has nothing to disclose., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Sinonasal undifferentiated carcinoma (SNUC) is a rare and aggressive disease requiring multimodal treatment, and multiple new entities once included in the spectrum of SNUC, such as SWI/SNF-deficient carcinomas, are emerging. We aimed to provide new data regarding the role of chemotherapy and surgery and the prognostic factors of disease-free survival., Methods: This study was based on data from the REFCOR database and included patients with SNUC treated with curative intent from 2007 to 2021 across 22 centres in France., Results: A total of 80 patients were included in the analysis. Among the entire cohort, the 5-year disease-free survival (DFS) and overall survival (OS) rates were 58% and 63%, respectively. Of 100% of the patients treated with irradiation, 29% underwent surgery, 56% neoadjuvant chemotherapy (82% had either a partial or a complete response) and 76% chemoradiotherapy. No treatment modality was associated with a better OS or DFS, including surgery (p = 0.34). There was a trend for a better DFS for the patients treated with chemotherapy (neoadjuvant or concomitant, p = 0.062). Overall survival at 3 years was 58% for SWI/SNF deficient group and 86% for non deficient group (p = 0.14). The locoregional relapse rate without distant metastases was 21% in the exclusive radiotherapy group and 26% in the surgery group. Grade 3 or higher toxicities concerned 9%, 32% and 29% of patients for surgery, radiotherapy and chemotherapy respectively., Conclusion: In the management of localised SNUC among all patients treated with irradiation, surgery yielded no benefit, whereas the addition of chemotherapy tended to improve disease-free survival., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Amaury Daste: Consulting or Advisory Role: Merck, MSD, BMS; Travel, Accommodations, Expenses: BMS, Merck., (© 2023 Published by Elsevier Ltd.)

Background: Predictors of ICU-acquired pulmonary aspergillosis (IPA) are not well-established in critically ill patients with ventilator-associated pneumonia (VAP), making IPA commonly misdiagnosed and anti-fungal therapy delayed. We aimed to develop a clinical score for prediction of IPA among patients with VAP., Methods: Mechanically ventilated patients who developed VAP in 4 ICUs in Bretagne, Western France, were included. The score was constructed in a learning cohort, based on predictors of IPA in logistic regression model, and validated in a validation cohort., Results: Among 1636 mechanically ventilated patients, 215 developed VAP but only 39 developed IPA (4 possible and 35 probable/putative) (18%). Most cases (31/39) were documented through a positive broncho-alveolar sample culture. Independent predictors of IPA were immunodepression (including onco-hematological disorder, immunomodulatory treatment, solid organ transplant, neutropenia < 0.5G/L and high-dose steroids ≥ 1 mg/kg/day of prednisolone equivalent) (p = 0.001; score = 1 point) and lymphocyte count at admission < 0.8 G/L (p = 0.019; score = 1 point). Operational values of the predictive score in the learning/validation cohort were 50%/52% sensitivity and 90%/87% specificity, respectively, for high PiPa score (score = 2) and 94%/91% sensitivity and 44%/46% specificity, respectively, for moderate PiPa score (score = 1). Finally, the AUC for the prediction of IPA was 0.783 in the learning cohort and 0.770 in the validation cohort., Conclusions: We evaluated a clinical score with good predictive value which may help to predict IPA in patient with VAP. External validation will be needed to confirm our preliminary findings., (© 2023. The Author(s).)

Opinion Statement: Since total neoadjuvant treatment achieves almost 30% pathologic complete response, organ preservation has been increasingly debated for good responders after neoadjuvant treatment for patients diagnosed with rectal cancer. Two organ preservation strategies are available: a watch and wait strategy and a local excision strategy including patients with a near clinical complete response. A major issue is the selection of patients according to the initial tumor staging or the response assessment. Despite modern imaging improvement, identifying complete response remains challenging. A better selection could be possible by radiomics analyses, exploiting numerous image features to feed data characterization algorithms. The subsequent step is to include baseline and/or pre-therapeutic MRI, PET-CT, and CT radiomics added to the patients' clinicopathological data, inside machine learning (ML) prediction models, with predictive or prognostic purposes. These models could be further improved by the addition of new biomarkers such as circulating tumor biomarkers, molecular profiling, or pathological immune biomarkers., (© 2023. The Author(s).)

Purpose: Although the proportion of immunocompromised patients admitted to the ICU is increasing, data regarding specific management, including acquired infection (ICU-AI) prophylaxis, in this setting are lacking. We aim to investigate the effect of multiple-site decontamination regimens (MSD) in immunocompromised patients., Methods: We conducted a prospective pre-/post-observational study in 2 ICUs in Bretagne, western France. Adults who required mechanical ventilation for 24 h or more were eligible. During the study period, MSD was implemented in participating ICUs in addition to standard care. It consists of the administration of topical antibiotics (gentamicin, colistin sulfate, and amphotericin B), four times daily in the oropharynx and the gastric tube, 4% chlorhexidine bodywash once daily, and a 5-day nasal mupirocin course., Results: Overall, 295 immunocompromised patients were available for analysis (151 in the post-implementation group vs 143 in the pre-implementation group). Solid organ cancer was present in 77/295 patients while immunomodulatory treatments were noticed in 135/295. They were 35 ICU-AI in 29/143 patients in the standard-care group as compared with 10 ICU-AI in 9/151 patients in the post-implementation group (p < 0.001). In a multivariable Poisson regression model, MSD was independently associated with a decreased incidence of ICU-AI (incidence rate ratio = 0.39; 95%CI [0.20-0.87] p = 0.008). There were 35/143 deaths in the standard-care group as compared with 22/151 in the post-implementation group (p = 0.046), this difference remained in a multivariable Cox model (HR = 0.58; 95CI [0.34-0.95] p = 0.048)., Conclusion: In conclusion, MSD appeared to be associated with improved outcomes in critically ill immunocompromised patients., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

This is the first case of a 37-year-old female patient carrier of a heterozygous NKX2.1 mutation associated with RA-ILD with a histological pattern of LIP. This case illustrates the wide panel of ILD subtypes associated with NKX2.1 mutations. https://bit.ly/3F49OTS., Competing Interests: Conflict of interest: P. Le Guen has nothing to disclose. Conflict of interest: R. Borie has received grants and personal fees from Roche and Boehringer Ingelheim, and personal fees from Savara, outside the submitted work. Conflict of interest: M. Legendre has nothing to disclose. Conflict of interest: C. Dupin has served on an advisory board for, and received a congress invitation and a speaker fee from AstraZeneca; received speaker fees and congress invitations from Boehringer Ingelheim, Chiesi and Novartis; served as a study investigator for, and received a speaker fee and a congress invitation from GSK; served as an advisory board member and received a congress invitation from Sanofi; and received a congress invitation from Roche, all outside the submitted work. Conflict of interest: L. Dunogeant has nothing to disclose. Conflict of interest: S. Ottaviani has nothing to disclose. Conflict of interest: M-P. Debray has received personal fees and nonfinancial support from Boehringer Ingelheim, and nonfinancial support from Roche, outside the submitted work. Conflict of interest: A. Cazes has received personal fees from Roche, Boehringer and AstraZeneca, outside the submitted work. Conflict of interest: P. Dieudé has nothing to disclose. Conflict of interest: C. Kannengiesser has nothing to disclose. Conflict of interest: B. Crestani has received speaker honoraria and support for a congress from AstraZeneca; received grants, speaker honoraria and support for congresses from Boehringer Ingelheim and Roche; received speaker honoraria, honoraria to consultancy and support for a congress from Sanofi; served on an advisory board for Genzyme; and served on an advisory board and received support for a congress from BMS, all outside the submitted work., (Copyright ©The authors 2023.)

Background: Acinic cell carcinomas (AciCCs) are malignant tumours of the salivary glands. The aim of this work was to analyse data from the national REFCOR multicenter cohort (i) to investigate the prognostic factors influencing survival outcomes in AciCC, (ii) to assess the impact on survival of postoperative radiotherapy (RT) in patients treated for AciCC without high-grade transformation and (iii) to explore the prognostic impact of prophylactic neck dissection (ND) in patients treated for AciCC of the major salivary glands., Patients and Methods: Data from all the patients treated for salivary AciCC between 2009 and 2020 were extracted from the REFCOR database. Survival outcomes and prognostic factors influencing Disease-Free Survival (DFS) and Overall Survival (OS) were investigated using univariate and multivariate analyses. Propensity score matching was used to assess the impact of postoperative RT and prophylactic ND on DFS., Results: A total of 187 patients were included. After a median follow-up of 53 months, their 5-year OS and DFS rates were 92.8% and 76.2%, respectively. In multivariate analysis, male sex, older age, higher T and N status, and high grade were independently associated with a worse DFS. In the subpopulation analysed after propensity score matching, patients with cN0 AciCC without high-grade transformation who were treated by surgery and RT did not have an improved DFS compared to patients who were treated by surgery alone (hazard ratio (HR) = 0.87, p = 0.8). Factors associated with nodal invasion were T3-T4 status and intermediate/high histological grade. After propensity score matching, prophylactic ND was associated with a trend toward a better DFS (HR = 0.46, p = 0.16)., Conclusions: These results suggest that (i) long-term follow-up (>5 years) should be considered in patients with AciCC, (ii) treatment by surgery alone could be an option in selected cN0 patients with AciCC without high-grade transformation and (iii) prophylactic ND may be considered preferentially in patients with T3-T4 status and/or intermediate/high histological grade., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Survivors of severe-to-critical coronavirus disease 2019 (COVID-19) may have functional impairment, radiological sequelae and persistent symptoms requiring prolonged follow-up. This pragmatic study aimed to describe their clinical follow-up and determine their respiratory recovery trajectories, and the factors that could influence them and their health-related quality of life., Methods: Adults hospitalised for severe-to-critical COVID-19 were evaluated at 3 months and up to 12 months post-hospital discharge in this prospective, multicentre, cohort study., Results: Among 485 enrolled participants, 293 (60%) were reassessed at 6 months and 163 (35%) at 12 months; 89 (51%) and 47 (27%) of the 173 participants initially managed with standard oxygen were reassessed at 6 and 12 months, respectively. At 3 months, 34%, 70% and 56% of the participants had a restrictive lung defect, impaired diffusing capacity of the lung for carbon monoxide ( D LCO ) and significant radiological sequelae, respectively. During extended follow-up, both D LCO and forced vital capacity percentage predicted increased by means of +4 points at 6 months and +6 points at 12 months. Sex, body mass index, chronic respiratory disease, immunosuppression, pneumonia extent or corticosteroid use during acute COVID-19 and prolonged invasive mechanical ventilation (IMV) were associated with D LCO at 3 months, but not its trajectory thereafter. Among 475 (98%) patients with at least one chest computed tomography scan during follow-up, 196 (41%) had significant sequelae on their last images., Conclusions: Although pulmonary function and radiological abnormalities improved up to 1 year post-acute COVID-19, high percentages of severe-to-critical disease survivors, including a notable proportion of those managed with standard oxygen, had significant lung sequelae and residual symptoms justifying prolonged follow-up., Competing Interests: Conflict of interest: F. Schlemmer reports support for the present manuscript from Fondation du Souffle, consulting fees from Pfizer, lecture honoraria from Gilead, and travel support from Chiesi, GSK, Elivie, Boerhinger Ingelheim, Gilead and Roche, outside the submitted work. P. Le Guen reports support for attending ATS 2022 from Unimed, outside the submitted work. M. Roumila reports grants from Vivisol and AstraZeneca, outside the submitted work. T. Gille reports lecture honoraria from Boehringer Ingelheim and Roche/Genetech, and travel support from Oxyvie, LVL Medical and Vitalaire, outside the submitted work. L. Sésé reports consulting fees from AstraZeneca, lecture honoraria from Boehringer Ingelheim and Roche-Genentech, and travel support from Novartis and Sanofi Aventis, outside the submitted work. Y. Uzunhan reports personal fees from Boehringer Ingelheim, grants and non-financial support from Oxyvie, and personal fees from Roche, outside the submitted work. M. Patout reports grants from Fisher & Paykel, ResMed and Asten Santé, consulting fees from Philips Respironics, ResMed, Asten Santé and GSK, lecture honoraria from Philips Respironics, Asten Santé, ResMed, Air Liquide Medical, SOS Oxygène, Antadir, Chiesi and Jazz Pharmaceutical, travel support from Asten Santé, advisory board participation from ResMed, Philips Respironics and Asten Santé, stock/stock options from Kernel Biomedical, and receipt of equipment/materials from Philips Respironics, ResMed and Fisher & Paykel, outside the submitted work. M. Zysman reports grants from AVAD and INSERM U1045, lecture honoraria from CSL Behring, GSK, Boehringer Ingelheim and AstraZeneca, and travel support Chiesi and AstraZeneca, outside the submitted work. S. Habib reports lecture honoraria from GSK and AstraZeneca, travel support from GSK and Novartis, and advisory board participation with Pfizer, Novartis and Sanofi. C. Jung reports grants from Danone and Menarini, lecture honoraria from Adare and Nestle, and a leadership role and stock/stock options from Biofoodie, outside the submitted work. All other authors have nothing to disclose., (Copyright ©The authors 2023.)

Introduction: Decontamination regimen decreases acquired infection (ICU-AI) incidence but has remained controversial, mostly because it contains a course of intravenous antibiotic. Multiple-site decontamination (MSD), which does not include systemic antibiotics, has been less widely studied but is associated with lower risks of ventilator-associated pneumonia (VAP), bloodstream infection (BSI) and multidrug resistant micro-organism (MDRO) acquisition. We aimed to confirm these favorable outcomes., Methods: A prospective pre/post-observational study was conducted in 5 ICUs in western France. Among them, 4 implemented MSD, whereas the fifth applied standard care (SC) throughout the study period. Patients who required intubation were eligible for study and divided into two groups: the MSD group if they were admitted to an ICU that already implemented MSD, or the SC group. The primary objective was to measure ICU-AI incidence., Results: Close to 1400 (1346) patients were available for analysis (334 in the MSD and 1012 patients in the SC group). In a multivariable Poisson regression model, MSD was independently associated with decreased incidence of ICU-AI (IRR = 0.33; 95 %CI [0.18-0.60] p < 0.001). Non-parsimonious propensity-score matching resulted in 334 patient-pairs with well-balanced baseline characteristics. There was a lower incidence of ICU-AI(6.3 % vs 20.7 % p < 0.001), VAP (3.6 % vs 16.2 % p < 0.001) and BSI (3.0 % vs 7.2 % p = 0.029) in the MSD group as compared with the SC group. Five (1.5 %) and 11 (3.3 %) patients respectively acquired MDRO (p = 0.206)., Conclusion: MSD is associated with decreased risk of ICU-AI, VAP and BSI, with no increase in MDRO acquisition., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Background: Invasive fungal infections acquired in the intensive care unit (AFI) are life-threating complications of critical illness. However, there is no consensus on antifungal prophylaxis in this setting. Multiple site decontamination is a well-studied prophylaxis against bacterial and fungal infections. Data on the effect of decontamination regimens on AFI are lacking. We hypothesised that multiple site decontamination could decrease the rate of AFI in mechanically ventilated patients., Methods: We conducted a pre/post observational study in 2 ICUs, on adult patients who required mechanical ventilation for >24 h. During the study period, multiple-site decontamination was added to standard of care. It consists of amphotericin B four times daily in the oropharynx and the gastric tube along with topical antibiotics, chlorhexidine body wash and nasal mupirocin., Results: In 870 patients, there were 27 AFI in 26 patients. Aspergillosis accounted for 20/143 of ventilator-associated pneumonia and candidemia for 7/75 of ICU-acquired bloodstream infections. There were 3/308 (1%) patients with AFI in the decontamination group and 23/562 (4%) in the standard-care group ( p  = 0.011). In a propensity-score matched analysis, there were 3/308 (1%) and 16/308 (5%) AFI in the decontamination group and the standard-care group respectively ( p  = 0.004) (3/308 vs 11/308 ventilator-associated pulmonary aspergillosis, respectively [ p  = 0.055] and 0/308 vs 6/308 candidemia, respectively [ p  = 0.037])., Conclusion: Acquired fungal infection is a rare event, but accounts for a large proportion of ICU-acquired infections. Our study showed a preventive effect of decontamination against acquired fungal infection, especially candidemia.Take home messageAcquired fungal infection (AFI) incidence is close to 4% in mechanically ventilated patients without antifungal prophylaxis (3% for pulmonary aspergillosis and 1% for candidemia).Aspergillosis accounts for 14% of ventilator-associated pneumonia and candidemia for 9% of acquired bloodstream infections.Immunocompromised patients, those infected with SARS-COV 2 or influenza virus, males and patients admitted during the fall season are at higher risk of AFI.Mechanically ventilated patients receiving multiple site decontamination (MSD) have a lower risk of AFI.

Aim: The goal of this study was to compare success rates of a regenerative limb salvage approach (rLS) using dehydrated human chorion amnion membrane (dHACM) to traditional flap-based limb salvage (fLS). Materials & methods: This prospective RTC enrolled patients presenting with complex extremity wounds over a 3-year period. Primary outcomes included success of primary reconstruction, persistence of exposed structures, time to definitive closure, and time to weight bearing. Results: Patients meeting inclusion criteria were randomized to fLS (n = 14) or rLS (n = 25). The primary reconstructive method was successful for 85.7% of fLS subjects and 80% of rLS subjects (p = 1.00). Conclusion: This trial provides strong evidence that rLS is an effective option in the setting of complex extremity wounds, with success rates comparable to traditional flaps. Clinical Trial Registration : NCT03521258 (ClinicalTrials.gov).

Background: Biological therapies have revolutionized the treatment of severe asthma with type 2 inflammation. Although such treatments are very effective in reducing exacerbation and the dose of oral steroids, little is known about the persistence of symptoms in severe asthma patients treated with biologics., Purpose: We aim to describe asthma control and healthcare consumption of severe asthma patients treated with biologics., Design: The Second Souffle study is a real-life prospective observational study endorsed by the Clinical Research Initiative in Severe Asthma: a Lever for Innovation & Science Network., Methods: Adults with a confirmed diagnosis of severe asthma for at least 12 months' duration were enrolled in the study. A self-administered questionnaire including the Asthma Control Questionnaire (ACQ), Asthma Quality of Life Questionnaire (AQLQ) and a compliance evaluation test was given to the patients. Healthcare consumption within 12 months prior to enrolment was documented. In patients receiving biologics, doctors indicated whether the patients were biologic responders or non-responders., Results: The characteristics of 431 patients with severe asthma were analysed. Among them, 409 patients (94.9%) presented asthma with type 2 inflammation (T2 high) profile, and 297 (72.6%) patients with a T2 high phenotype were treated with a biologic. Physicians estimated that 88.2% of patients receiving biologics were responders. However, asthma control was only achieved in 25.3% of those patients (ACQ > 0.75). A high proportion of patients (77.8%) identified as responders to biologics were not controlled according to the ACQ score. About 50% of patients continue to use oral corticosteroids either daily (25.2%) or more than three times a year for at least three consecutive days (25.6%). Gastro-oesophageal Reflux Disease (GERD) and Obstructive Sleep Apnoea syndrome (OSA) were identified as independent factors associated with uncontrolled asthma., Conclusion: Although a high proportion of severe asthma patients respond to biologics, only 25.3% have controlled asthma. GERD and OSA are independent factors of uncontrolled asthma.

Purpose: The objective was to assess the local oncological outcomes of endoscopic versus external surgical treatment of sinonasal intestinal-type adenocarcinomas (ITAC) and the factors of recurrence., Methods: a retrospective non-randomized case-control multicenter study was carried out, including 452 untreated sinonasal ITACs recruited from 10 tertiary referral centers. The tumors were re-classified according to the UICC 2017 (pT). Survival curves were obtained using the Kaplan-Meier method. Univariate analysis was done with the log-rank test. Multivariate analysis was performed with a Cox model adjusted for age, T stage, and radiotherapy. A binary logistic regression compared surgical complications and performed two supplementary analyses on positive margins., Results: We compared 195 and 257 patients operated by the external and endoscopic approach, respectively. The mean follow-up was 59.2 ± 48.7 months. Post-operative margins were invaded in 30.6 versus 18.9% of patients, respectively (p = 0.007). The overall recurrence rate was 33.8 versus 24.6%, respectively (p = 0.034). There was a significant difference in favor of the endoscopic approach regarding local recurrence-free survival thanks to better surgical margins in univariate and multivariate analysis (Odd Ratio = 2.01 (1.2-3.36) p = 0.0087). The complication rate (Odds Ratio = 3.4 (1.79-6.32) p < 0.001) was significantly lower in the endoscopic group. The histological positivity of signet-ring cells shows a statistically significant difference in recurrence-free survival (p = 0.0028)., Conclusion: the oncological control of ITAC is better through the endoscopic approach, with negative margins and the absence of signet-ring-cells, two independent factors of recurrence., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Colorectal cancer (CRC) is the third most frequent cancer worldwide, accounts for about 10% of the total cancer cases, and ranks as the second cause of death by cancer. CRC is more prevalent in developed countries in close causal relation with occidental diets. Due to anatomy, the diet has a strong impact on CRC. High contents in meat are acknowledged risk factors whereas a diet rich in fruits and vegetables is an established CRC protective factor. Fruits and vegetables contain numerous Bioactive Food Components (BFCs), physiologically active food compounds, beneficial on health. Preventive and therapeutic benefits of BFCs in cancer have increasingly been reported over the past 20 years. BFCs show both chemopreventive and anti-tumor properties in CRC but more interestingly, abundant research describes BFCs as enhancers of conventional cancer treatments. Despite these promising results, their clinical transferability is slowed down by bioavailability interrogations and their poorly understood hormetic effect. In this review, we would like to reposition BFCs as well-fitted for applications in CRC. We provide a synthetic overview of trustworthy BFC applications in CRC, with a special highlight on combinatory approaches and conventional cancer treatment potentiation strategies.

Introduction: The aim of the study was to confirm the diagnostic accuracy of a second FDG-PET/CT following neoadjuvant or induction chemotherapy (NAIC) prior to radical cystectomy for patients with localized muscle-invasive bladder cancer (MIBC)., Methods: Retrospective review of 62 consecutive patients with MIBC, that had a first FDG-PET/CT between April 2016 and September 2021. Patients then underwent NAIC, followed by a second FDG-PET/CT and radical cystectomy. Patients with no hypermetabolism in the bladder and lymph nodes on the second FDG-PET/CT were considered metabolic complete responders, while patients with no evidence of residual disease on histopathology were considered pathologic complete responders. The accuracy of the second FDG-PET/CT to distinguish complete responders from patients with residual disease was calculated, with histopathology as gold standard., Results: Of 62 patients, 1 was lost to follow-up, 5 died before radical cystectomy, 5 had delay >2 months between the second FDG-PET/CT and radical cystectomy, and 6 did not undergo radical cystectomy and instead underwent alternative treatment. The study cohort comprised 45 patients, 39 males and 6 females, with an age of 66 ± 6 years. In comparison to histopathology, FDG-PET/CT provided (i) sensitivity of 95% and specificity of 42%, for the overall disease; (ii) sensitivity of 100% and specificity of 36%, for the primary tumor only; and (iii) sensitivity of 97% and specificity of 30%, for the lymph nodes only., Conclusion: FDG-PET/CT has over 95% sensitivity for distinguishing complete responders from patients with residual disease. Thus, FDG-PET/CT can be used for early response evaluation following NAIC to identify patients that did not completely respond to chemotherapy and may require alternative treatment pathways., (© 2023 S. Karger AG, Basel.)

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., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Introduction: The first line of treatment for nonfunctioning pituitary adenoma (NFPA) is surgery. Adjuvant radiotherapy or surveillance and new treatment (second surgical operation or salvage radiotherapy) in case of recurrence are options discussed at the multidisciplinary tumor board. The purpose of this study was to evaluate the therapeutic outcome for each option., Methods: The records of 256 patients followed with NFPA between 2007 and 2018 were retrospectively reviewed. Mean age at initial surgery was 55 years [18-86]. Post-operative MRI found a residual tumor in 87% of patients. Mean follow-up was 12.1 years [0.8-42.7]., Results: After initial surgery, 40 patients had adjuvant radiotherapy. At 5, 10 and 15 years progression-free survival (PFS) was significantly different after surgery alone (77%, 58% and 40%) compared to surgery and adjuvant radiotherapy (84%, 78% and 78%) (HR = 0.24 [0-0.53] p < 0.0005). Overall, after first, second or third surgical operation, 69 patients had adjuvant radiotherapy and 41 salvage radiotherapy. Five-year PFS was similar for adjuvant (90%) and salvage radiotherapy (97%) (p = 0.62). After a second surgical operation, 62% and 71% of patients were irradiated after 2 and 5 years respectively. The risk of corticotropic and thyrotropic deficiency rates were 38% and 59% after second or third surgical operation and 40% and 73% after radiotherapy. Brain tumors occurred in 4 patients: 1 meningioma present at initial surgery, and after radiotherapy, 1 neurinoma which appeared at 5 years, 1 glioblastoma at 13 years and 1 meningioma at 20 years., Conclusion: Among patients treated by surgery for NFPA, a "wait-and-see" attitude should be an option since adjuvant radiotherapy is not superior to salvage radiotherapy. However, in case of recurrence or progression, the authors recommended delivery of salvage radiotherapy to avoid a second surgical operation., (© 2022. The Author(s).)

Stereotactic radiotherapy and radiosurgery allow delivery of high irradiation doses in a limited volume. These techniques are specially adapted to brain and nervous pathologies. Indication are not only cancers and tumors but also non tumor tissues such as arteriovenous malformations. In some case purpose of stereotactic radiotherapy is solely functional, for example for trigeminal neuralgia. We detail the questions that raise treatment of these non-tumor pathologies. These pathologies imply a multidisciplinary approach that associate radiation oncologists, neuro-radiologist and neurosurgeons., (Copyright © 2022 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Management of oropharyngeal cancer depends on several factors. Immediate surgery or radiotherapy may be considered. If the patient is operable, the choice depends on the extent of the disease, the contributing factors, and the expected functional results. For HPV-positive cancers, studies show comparable efficacy between surgery and radiotherapy. For early-stage cancers, unimodal treatment should be preferred. For HPV-negative cancers, the results of retrospective and observational studies are in favor of surgery. These studies have some limitations. In observational and/or retrospective studies, reclassification biases and the applicability of propensity scores weaken the validity of studies showing differences in management. Tumor and patient comparability are others majors interpretation biases. It is precipitate to conclude that surgery is superior for HPV-negative oropharyngeal cancers. Toxicity, therefore, becomes a criterion of choice for treatment. Unimodal management by surgery allows limited toxicity for the early stages. Surgery has less impact on salivation. Radiotherapy is rather less deleterious for swallowing in the early stages. For the advanced stages of HPV-induced tumors, the non-superiority of surgery should lead to the choice of radiochemotherapy. For oropharyngeal cancers, the possible benefit of surgery in HPV-negative oropharyngeal cancers must be confirmed in randomized studies. For the early stages of oropharyngeal cancer with unimodal treatment, management could be decided by shared decision making., (Copyright © 2022 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Objectives: To identify the factors related to the presence of occult metastases before salvage total laryngectomy (STL) in rcN0 patients and to propose an algorithm to identify patients who do not require neck dissection (ND)., Patients and Methods: This multicentric retrospective study included five centers with recruitment from 2008 to 2018. Inclusion criteria were: i) having been treated for laryngeal squamous cell carcinoma in first intention by radiotherapy (either alone or potentiated or preceded by induction chemotherapy), ii) having received STL with or without ND, iii) having an rcN0 neck at the time of STL., Results: 120 patients met the inclusion criteria. The overall rate of occult metastases was 9.1 %. The rate was significantly higher in patients with an initial positive cN+ lymph node status (p < 0.005) and in advanced stages with rcT3-T4 lesions at recurrence (p < 0.005). Patients with occult metastases recurred earlier than those without (p = 0.002). The overall survival of patients was the same with or without ND (p = 0.16). There were significantly more healing complications requiring revision surgery in the group with ND than in the group without (p = 0.048)., Conclusion: ND does not confer a net survival benefit and is associated with significant complications. Patients without initial lymph node metastases who are rcT1-T2 at recurrence or rcT3-T4 with a recurrence period of more than 12 months could benefit from STL without ND. This decisional algorithm, which needs to be validated, would help avoid 58 % of ND procedures and their proven morbidity., Discipline: Head and neck surgery., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Genetic studies of familial forms of interstitial lung disease (ILD) have led to the discovery of telomere-related gene (TRG) mutations (TERT, TERC, RTEL1, PARN, DKC1, TINF2, NAF1, NOP10, NHP2, ACD, ZCCH8) in approximately 30% of familial ILD forms. ILD patients with TRG mutation are also subject to extra-pulmonary (immune-hematological, hepatic and/or mucosal-cutaneous) manifestations. TRG mutations may be associated not only with idiopathic pulmonary fibrosis (IPF), but also with non-IPF ILDs, including idiopathic and secondary ILDs, such as hypersensitivity pneumonitis (HP). The presence of TRG mutation may also be associated with an accelerated decline of forced vital capacity (FVC) or poorer prognosis after lung transplantation, notwithstanding which, usual ILD treatments may be proposed. Lastly, patients and their relatives are called upon to reduce their exposure to environmental lung toxicity, and are likely to derive benefit from specific genetic counseling and pre-symptomatic genetic testing., (Copyright © 2022 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

Background: Diagnosis of interstitial lung disease is based on the analysis of clinical, biological, radiological, and pathological findings during a multidisciplinary discussion (MDD). When a definitive diagnosis is not possible, guidelines recommend obtaining lung samples through surgical lung biopsy (SLB). We sought to determine morbidity, mortality, diagnostic yield, and therapeutic impact of SLB in the management of patients with interstitial lung disease., Methods: We retrospectively analyzed morbidity, mortality, diagnostic yield, and therapeutic changes after SLB for interstitial lung disease performed electively from January 2015 to May 2019 in a reference center. Each case was reviewed during 2 MDDs, first without and then with the result of the SLB., Results: The study group included 73 patients (56% male, age 66 [interquartile range (IQR), 57-70] years, forced vital capacity 79% [IQR, 69%-91%], diffusing capacity of the lungs for carbon monoxide 52% [IQR, 46%-63%]). Median postoperative hospital length of stay was 2 (IQR, 0-11) days. Thirteen (17%) patients experienced at least 1 complication, including pain at 1 month (n = 8) and residual pneumothorax (n = 6). No serious complication or postoperative death was noticed. After the first retrospective MDD, the working diagnosis was idiopathic nonspecific interstitial pneumonia in 20 (27%), idiopathic pulmonary fibrosis in 18 (25%), fibrotic hypersensitivity pneumonitis in 15 (21%), unclassifiable interstitial lung disease in 5 (7%), and other diagnosis in 15 (21%) patients. After SLB and second retrospective MDD, the final diagnosis was modified in 35 (48%) patients and led to therapeutic changes in 33 (45%) patients., Conclusions: SLB is associated with no serious complication or death and notably changes the diagnosis and treatment of interstitial lung disease., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Radiosensitization of glioblastoma is a major ambition to increase the survival of this incurable cancer. The 5-aminolevulinic acid (5-ALA) is metabolized by the heme biosynthesis pathway. 5-ALA overload leads to the accumulation of the intermediate fluorescent metabolite protoporphyrin IX (PpIX) with a radiosensitization potential, never tested in a relevant model of glioblastoma. We used a patient-derived tumor cell line grafted orthotopically to create a brain tumor model. We evaluated tumor growth and tumor burden after different regimens of encephalic multifractionated radiation therapy with or without 5-ALA. A fractionation scheme of 5 × 2 Gy three times a week resulted in intermediate survival [48-62 days] compared to 0 Gy (15-24 days), 3 × 2 Gy (41-47 days) and, 5 × 3 Gy (73-83 days). Survival was correlated to tumor growth. Tumor growth and survival were similar after 5 × 2 Gy irradiations, regardless of 5-ALA treatment (RT group (53-67 days), RT+5-ALA group (40-74 days), HR = 1.57, p = 0.24). Spheroid growth and survival were diminished by radiotherapy in vitro, unchanged by 5-ALA pre-treatment, confirming the in vivo results. The analysis of two additional stem-like patient-derived cell lines confirmed the absence of radiosensitization by 5-ALA. Our study shows for the first time that in a preclinical tumor model relevant to human glioblastoma, treated as in clinical routine, 5-ALA administration, although leading to important accumulation of PpIX, does not potentiate radiotherapy.

Purpose: Endoscopic endonasal surgery (EES) is becoming a standard for most malignant sinonasal tumours. Margin analysis after piecemeal resection is complex and optimally relies on accurate histosurgical mapping. Postoperative radiotherapy may be adapted based on margin assessment mapping to reduce the dose to some sinonasal subvolumes. We assessed the use of histosurgical mapping by radiation oncologists (RO)., Material and Methods: A French practice survey was performed across 29 ENT expert RO (2 did not answer) regarding integration of information on EES, as well as quality of operative and pathology reportsto refine radiotherapy planning after EES. This was assessed through an electronic questionnaire., Results: EES was ubiquitously performed in France. Operative and pathology reports yielded accurate description of EES samples according to 66.7% of interviewed RO. Accuracy of margin assessment was however insufficient according to more than 40.0% of RO. Additional margins/biopsies of the operative bed were available in 55.2% (16/29) of the centres. In the absence of additional margins, quality of resection after EES was considered as microscopically incomplete in 48.3% or dubious in 48.3% of RO. As performed, histosurgical mapping allowed radiotherapy dose and volumes adaptation according to 26.3% of RO only., Conclusions: Standardized histosurgical mapping with margin and additional margin analysis could be more systematic. Advantages of accurate EES reporting could be dose painting radiotherapy to further decrease morbidity in sinonasal tumours., (Copyright © 2021 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

On 13 May 2020, a COVID-19 cluster was detected in a French processing plant. Infected workers were described. The associations between the SARS-CoV-2 infection and the socio-demographic and occupational characteristics were assessed in order to implement risk management measures targeting workers at increased risk of contamination. Workers were tested by RT-PCR from samples taken during screening campaigns. Workers who tested positive were isolated and their contacts were quarantined. Workers were described and associations with the SARS-CoV-2 infection were assessed through risk ratios using multivariable Poisson regression. Of the 1347 workers, 87.5% were tested: 140 cases were identified; 4 were hospitalised, including 2 admitted to intensive care. In the company, the cluster remained limited to deboning and cutting activities. The attack rate was 11.9% in the company, reaching 16.6% in the cutting department. Being an employee of a subcontractor significantly increased the risk of infection by 2.98 [1.81-4.99]. In the cutting department, an association with virus infection was found for a group of non-French speaking workers from the same Eastern European country (RR = 2.67 [1.76-4.05]). They shared accommodation or carpooled more frequently than the other cases. The outbreak investigation revealed a significantly increased risk of SARS-CoV-2 infection for workers of subcontractors and some foreign-born workers. There are many such populations in meat processing plants; the observed associations and the ways in which these workers are contaminated need to be confirmed by further work. Prevention campaigns should now target these workers. Environmental risk factors in the workplace setting remain to be clarified., (© 2021. The Author(s).)

Purpose: Management of head and neck cancers of unknown primary (HNCUP) combines neck dissection (ND) and radiotherapy, with or without chemotherapy. The prognostic value of ND has hardly been studied in HNCUP., Methods: A retrospective multicentric study assessed the impact of ND extent (adenectomy, selective ND, radical/radical-modified ND) on nodal relapse, progression-free survival (PFS) or survival, taking into account nodal stage., Results: 53 patients (16.5%) had no ND, 33 (10.2%) had lymphadenectomy, 116 (36.0%) underwent selective ND and 120 underwent radical/radical-modified ND (37.3%), 15 of which received radical ND (4.7%). With a 34-month median follow-up, the 3-year incidence of nodal relapse was 12.5% and progression-free survival (PFS) 69.1%. In multivariate analysis after adjusting for nodal stage, the risk of nodal relapse or progression was reduced with lymphadenectomy, selective or radical/modified ND, but survival rates were similar. Patients undergoing lymphadenectomy or ND had a better PFS and lowered nodal relapse incidence in the N1 + N2a group, but the improvement was not significant for the N2b or N2 + N3c patients. Severe toxicity rates exceeded 40% with radical ND., Conclusion: In HNCUP, ND improves PFS, regardless of nodal stage. The magnitude of the benefit of ND does not appear to depend on ND extent and decreases with a more advanced nodal stage.

Clinical and laboratory predictors of COVID-19 severity are now well described and combined to propose mortality or severity scores. However, they all necessitate saturable equipment such as scanners, or procedures difficult to implement such as blood gas measures. To provide an easy and fast COVID-19 severity risk score upon hospital admission, and keeping in mind the above limits, we sought for a scoring system needing limited invasive data such as a simple blood test and co-morbidity assessment by anamnesis. A retrospective study of 303 patients (203 from Bordeaux University hospital and an external independent cohort of 100 patients from Paris Pitié-Salpêtrière hospital) collected clinical and biochemical parameters at admission. Using stepwise model selection by Akaike Information Criterion (AIC), we built the severity score Covichem. Among 26 tested variables, 7: obesity, cardiovascular conditions, plasma sodium, albumin, ferritin, LDH and CK were the independent predictors of severity used in Covichem (accuracy 0.87, AUROC 0.91). Accuracy was 0.92 in the external validation cohort (89% sensitivity and 95% specificity). Covichem score could be useful as a rapid, costless and easy to implement severity assessment tool during acute COVID-19 pandemic waves., Competing Interests: The authors have declared that no competing interests exist.

Extracellular vesicles (EVs) are produced by healthy tissues and tumor cells and are released in various bodily fluids, including blood. They are limited by bilayer phospholipidic membranes, and they carry a rich content in biomolecules. Their release cleanses the cells of their waste or serves as functional local and distant cell-cell communication and molecular exchange particles. This rich and heterogeneous content has been given intense attention in cancer physiopathology because EVs support cancer control and progression. Because of their specific active cargo, they are being evaluated as carriers of liquid biopsy biomarkers. Compared to soluble circulating biomarkers, their complexity might provide rich information on tumor and metastases status. Thanks to the acquired genomic changes commonly observed in oncogenic processes, double-stranded DNA (dsDNA) in EVs might be the latest most promising biomarker of tumor presence and complexity. This review will focus on the recent knowledge on the DNA inclusion in vesicles, the technical aspects of EV-DNA detection and quantification, and the use of EV-DNA as a clinical biomarker., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Amintas, Vendrely, Dupin, Buscail, Laurent, Bournet, Merlio, Bedel, Moreau-Gaudry, Boutin, Dabernat and Buscail.)

Introduction: Interstitial lung diseases (ILDs) can be caused by mutations in the SFTPA1 and SFTPA2 genes, which encode the surfactant protein (SP) complex SP-A. Only 11 SFTPA1 or SFTPA2 mutations have so far been reported worldwide, of which five have been functionally assessed. In the framework of ILD molecular diagnosis, we identified 14 independent patients with pathogenic SFTPA1 or SFTPA2 mutations. The present study aimed to functionally assess the 11 different mutations identified and to accurately describe the disease phenotype of the patients and their affected relatives., Methods: The consequences of the 11 SFTPA1 or SFTPA2 mutations were analysed both in vitro , by studying the production and secretion of the corresponding mutated proteins and ex vivo , by analysing SP-A expression in lung tissue samples. The associated disease phenotypes were documented., Results: For the 11 identified mutations, protein production was preserved but secretion was abolished. The expression pattern of lung SP-A available in six patients was altered and the family history reported ILD and/or lung adenocarcinoma in 13 out of 14 families (93%). Among the 28 SFTPA1 or SFTPA2 mutation carriers, the mean age at ILD onset was 45 years (range 0.6-65 years) and 48% underwent lung transplantation (mean age 51 years). Seven carriers were asymptomatic., Discussion: This study, which expands the molecular and clinical spectrum of SP-A disorders, shows that pathogenic SFTPA1 or SFTPA2 mutations share similar consequences for SP-A secretion in cell models and in lung tissue immunostaining, whereas they are associated with a highly variable phenotypic expression of disease, ranging from severe forms requiring lung transplantation to incomplete penetrance., Competing Interests: Conflict of interest: M. Legendre has nothing to disclose. Conflict of interest: A. Butt has nothing to disclose. Conflict of interest: R. Borie reports grants and personal fees from Boehringer Ingelheim and Roche, and personal fees from Savapharma, outside the submitted work. Conflict of interest: M-P. Debray has nothing to disclose. Conflict of interest: D. Bouvry has nothing to disclose. Conflict of interest: E. Filhol-Blin has nothing to disclose. Conflict of interest: T. Desroziers has nothing to disclose. Conflict of interest: V. Nau has nothing to disclose. Conflict of interest: B. Copin has nothing to disclose. Conflict of interest: F. Dastot Le Moal has nothing to disclose. Conflict of interest: M. Héry has nothing to disclose. Conflict of interest: P. Duquesnoy has nothing to disclose. Conflict of interest: N. Allou has nothing to disclose. Conflict of interest: A. Bergeron has nothing to disclose. Conflict of interest: J. Bermudez has nothing to disclose. Conflict of interest: A. Cazes has been invited to national and international meetings, and/or has received grants and/or personal fees for various activities from Boehringer Ingelheim and Roche, outside the submitted work. Conflict of interest: A-L. Chene has nothing to disclose. Conflict of interest: V. Cottin reports personal fees for lectures and advisory board work and non-financial support for meeting attendance from Actelion; grants, personal fees for lectures and advisory board work, and non-financial support for meeting attendance from Boehringer Ingelheim; personal fees for advisory board and data monitoring committee work from Bayer/MSD and Galapagos; personal fees for lectures and advisory board work from Novartis; personal fees for lectures, consultancy, data monitoring committee and steering committee work, and non-financial support for meeting attendance from Roche/Promedior; personal fees for lectures from Sanofi and AstraZeneca; personal fees for data monitoring committee work from Celgene and Galecto; and personal fees for advisory board work from Shionogi, outside the submitted work. Conflict of interest: B. Crestani has nothing to disclose. Conflict of interest: J-C. Dalphin has nothing to disclose. Conflict of interest: C. Dombret has nothing to disclose. Conflict of interest: B. Doray has nothing to disclose. Conflict of interest: C. Dupin reports personal fees for lectures and advisory board work, and non-financial support and meeting invitations from AstraZeneca; personal fees for lectures, non-financial support and meeting invitations from Boehringer and Novartis; personal fees for research and lectures, and non-financial support and meeting invitations from GSK; personal fees for lectures and meeting invitations from Chiesi; personal fees for lectures and advisory board work, and non-financial support from Sanofi; and personal fees, non-financial support and meeting invitations from Roche, outside the submitted work. Conflict of interest: V. Giraud has nothing to disclose. Conflict of interest: A. Gondouin has nothing to disclose. Conflict of interest: L. Gouya has nothing to disclose. Conflict of interest: D. Israël-Biet has nothing to disclose. Conflict of interest: C. Kannengiesser has nothing to disclose. Conflict of interest: A. Le Borgne has nothing to disclose. Conflict of interest: S. Leroy has nothing to disclose. Conflict of interest: E. Longchampt has nothing to disclose. Conflict of interest: G. Lorillon has nothing to disclose. Conflict of interest: H. Nunes has nothing to disclose. Conflict of interest: C. Picard has nothing to disclose. Conflict of interest: M. Reynaud-Gaubert has nothing to disclose. Conflict of interest: J. Traclet has nothing to disclose. Conflict of interest: P. de Vuyst has nothing to disclose. Conflict of interest: A. Coulomb L'Hermine has nothing to disclose. Conflict of interest: A. Clement has nothing to disclose. Conflict of interest: S. Amselem has nothing to disclose. Conflict of interest: N. Nathan reports a 2018 AstraZeneca Mobility Grant from Société de pneumologie pédiatrique et d'allergologie (France), outside the submitted work., (Copyright ©ERS 2020.)

To increase the knowledge about S. capitis in the neonatal setting, we conducted a nationwide 3-month survey in 38 neonatal intensive care units (NICUs) covering 56.6% of French NICU beds. We demonstrated 14.2% of S. capitis BSI (S.capBSI) among nosocomial BSIs. S.capBSI incidence rate was 0.59 per 1000 patient-days. A total of 55.0% of the S.capBSIs were late onset catheter-related BSIs. The S. capitis strains infected preterm babies (median gestational age 26 weeks, median birth weight 855 g). They were resistant to methicillin and aminoglycosides and belonged to the NRCS-A clone. Evolution was favorable in all but one case, following vancomycin treatment.

This article discusses a selection of the scientific presentations in the field of interstitial lung diseases (ILDs) that took place at the 2019 European Respiratory Society International Congress in Madrid, Spain. There were sessions from all four groups within Assembly 12: group 12.01 "Idiopathic interstitial pneumonias", group 12.02 "ILDs/diffuse parenchymal lung diseases (DPLDs) of known origin", group 12.03 "Sarcoidosis and other granulomatous ILDs/DPLDs" and group 12.04 "Rare ILDs/DPLDs". The presented studies brought cutting-edge developments on several aspects of these conditions, including pathogenesis, diagnosis and treatment. As many of the ILDs are individually rare, the sharing of experiences and new data that occur during the Congress are very important for physicians interested in ILDs and ILD patients alike., Competing Interests: Conflict of interest: C. Dupin reports grants from AstraZeneca, GSK and Sanofi, personal fees and non-financial support from AstraZeneca, Chiesi, GSK, Roche and Sanofi, non-financial support from Boehringer, and personal fees from Novartis, all outside the submitted work. Conflict of interest: V. Fernandes has nothing to disclose. Conflict of interest: F. Hernandez-Gonzales has nothing to disclose. Conflict of interest: S.E. Torrisi has nothing to disclose. Conflict of interest: T.M. Alfaro has nothing to disclose. Conflict of interest: M. Kreuter reports grants and personal fees from Boehringer and Roche, and personal fees from Galapagos, outside the submitted work. Conflict of interest: M.S. Wijsenbeek reports grants from Boehringer Ingelheim and Hoffman la Roche, and other support from Boehringer Ingelheim, Hoffman la Roche, Galapagos and Respivant, all paid to her institution and all outside the submitted work. Conflict of interest: E.A. Renzoni reports lecture and advisory board fees from Roche and Boehringer Ingelheim, outside the submitted work. Conflict of interest: E. Bargagli has nothing to disclose. Conflict of interest: H. Nunes reports consultancy and research support fees from Roche/Genentech and Boehringer Ingelheim, personal fees for serving as an expert for a clinical end-point committee from Galapagos, and other support for serving as an investigator on clinical trials from Sanofi, Gilead, Novartis and Galecto Biotech AB, and for service as a board expert on a clinical trial from Actelion Pharmaceuticals, during the conduct of the study. Conflict of interest: P. Spagnolo reports grants, personal fees and non-financial support from Roche, PPM Services and Boehringer Ingelheim, and personal fees from Red X Pharma, Galapagos and Chiesi, all outside the submitted work; additionally, his wife is an employee of Novartis. Conflict of interest: F. Bonella reports grants, personal fees and non-financial support from Boehringer Ingelheim, Roche and Galapagos, and grants and personal fees from Savara, outside the submitted work. Conflict of interest: M. Molina-Molina reports grants and personal fees from Roche, Boehringer Ingelheim and Esteve-Teijin, and personal fees from Chiesi and Pfizer, outside the submitted work. Conflict of interest: K. Antoniou has nothing to disclose. Conflict of interest: V. Poletti has nothing to disclose., (Copyright ©ERS 2020.)

Background: Dupilumab is a monoclonal anti-IL-4Rα antibody developed for the treatment of severe asthma (SA). An early access programme for dupilumab was opened in France in SA patients experiencing unacceptable steroids side-effects and/or life-threatening exacerbations., Objective: To assess changes in asthma control between baseline and 12 months of treatment., Methods: Multi-centre (n = 13) retrospective real-life cohort study. This study is registered on ClinicalTrials.gov (NCT04022447)., Results: Overall, 64 patients with SA (median age 51, interquartile range [44-61]; 53% females) received dupilumab as add-on therapy to maximal standard of care; and 76% were on oral daily steroids at baseline. After 12 months, median asthma control test score improved from 14 [7-16] to 22 [17-24] (P < .001); median forced expiratory volume in 1 seconds increased from 58% [47-75] to 68% [58-88] (P = .001); and daily prednisone dose was reduced from 20 [10-30] to 5 [0-7] mg/d (P < .001). Annual exacerbations decreased from 4 [2-7] to 1 [0-2] (P < .001). Hypereosinophilia ≥1500/mm 3 was observed at least once during follow-up in 16 patients (25%), persisting after 6 months in 8 (14%) of them. Increase in blood eosinophil count did not modify the clinical response during the study period. Injection-site reaction was the most common side effect (14%). Three deaths were observed, none related to treatment by investigators., Conclusion & Clinical Relevance: In this first real-life cohort study of predominantly steroid-dependent SA, dupilumab significantly improved asthma control and lung function and reduced oral steroids use and exacerbations rate. Despite limitations due to the retrospective study, these results are consistent with controlled trials efficacy data. Further studies are required to assess the clinical significance and long-term prognosis of sustained dupilumab-induced hypereosinophilia., (© 2020 John Wiley & Sons Ltd.)

French regulations about research ethics are based on the so-called Jardé law, which defines researches involving human beings. Researches involving human beings require the submission of research protocols to a committee for protection of persons with a precise list of documents to submit for a favourable opinion. This law describes different categories of researches and determines the ethical procedures to apply before setting up a research protocol. This issue of categorisation is central and must be taken into account by researchers from the beginning of the research process. Researches considered as not involving human beings also require a set of ethical precautions focused on patients' information and the collection of their non-opposition (due to the application of the General Data Protection Regulation adopted by the European Parliament). Thus, many regulations exist and they require a real work for researchers to meet these requirements in research ethics. This article aims to summarise French regulations. Selected examples are specifically taken into the field of radiation oncology research., (Copyright © 2020 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

At least 10% of patients with pulmonary fibrosis, whether idiopathic or secondary, present heritable pulmonary fibrosis suspected on familial aggregation of pulmonary fibrosis, specific syndromes or early age of diagnosis. Approximately 30% of those patients have an identified mutation mostly in telomere related genes (TRG) more rarely in surfactant homeostasis or other genes. TRG mutation may be associated with hematological and hepatic diseases that may worsen after lung transplantation requiring a specific care and adapted immunosuppression. Surfactant genes mutations are usually associated with ground-glass opacities and cysts on CT scan and may improve with steroids, hydroxychloroquine or azithromycin. Moreover relatives should benefit from a genetic analysis associated with a clinical evaluation according to the gene involved. Genetics of pulmonary fibrosis raise specific problems from diagnosis, therapy or genetic counseling varying from one gene to another., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Introduction: Trichoadenoma is a very rare follicular tumour with a remarkable histopathological appearance. In this article we present a series of 12 cases of trichoadenoma, as well as the anatomoclinical and dermatoscopic findings in a typical case. We discuss these findings in the light of an extensive literature research., Patients and Methods: We collated 12 cases of trichoadenoma of indisputable diagnosis made at the dermatopathology laboratory of the Dermatological Clinic of the University Hospitals of Strasbourg over a 30-year period (1989-2018)., Results: The 12 cases comprised 7 women and 5 men, of average age 58.9 years, the majority having lesions on the cephalic extremity followed by the buttocks and thighs. Histopathological examination, which was similar in all 12 cases, showed multiple epidermal cysts containing an eosinophil lamellar keratin with a stratified wall without any visible hair, located in the superficial and mid dermis and appearing to be stacked on top of one another. In immunohistochemistry, broad spectrum keratin markers were still positive, the follicular marker Ber-EP4 weakly expressed and PHLDA1 was negative. For the case examined using polarized-light dermatoscopy, small rounded white-yellow areas were observed corresponding to cystic structures surrounded by irregular linear vessels., Discussion: Trichoadenoma is a rare tumour seen in middle-aged adults of mean age 45 years, and has no sexual predominance. It is asymptomatic, slow-growing, variable in colour, measures less than one centimeter and is most often located on the face or buttocks. In terms of histology, the juxtaposition of multiple small cystic structures suggests a follicular origin. Differential diagnosis is made with trichoblastomas, which always intensely express PHLDA1 and/or Ber-EP4, desmoplastic trichoepithelioma, which consists of multiple much thinner spans in a highly fibrous stroma with clearly visible arborescent vessels over a white-yellow ivory background at dermatoscopy, microcystic carcinoma, which has a deeper extension, and plaque milium, in which the cysts are larger., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)