Real-World efficacy and safety of combination nivolumab plus ipilimumab for Untreated, Unresectable, pleural Mesothelioma: The Meso-Immune (GFPC 04-2021) trial.

BACKGROUND: First-line standard-of-care for unresectable, pleural mesothelioma (PM) changed with the phase 3 CheckMate 743 study results, showing that nivolumab plus ipilimumab (Nivo + Ipi) significantly extended overall survival (OS) versus platinum + pemetrexed chemotherapy for PM (median OS 18.1 versus 14.1 months; hazard ratio: 0.74; p = 0.002). Efficacy and safety data in real-world (rw) settings are needed to confirm these results. METHODS: This French multicenter, retrospective cohort study was undertaken to assess the outcomes of treatment-naïve PM patients given Nivo + Ipi via an early-access program (EAP). The primary objective was investigator-assessed real world -progression-free survival (PFS). The secondary objectives were the combination's -overall survival (OS) and safety. RESULTS: From 1 April 2021 to 15 Feb 2022, the analysis included 201 of the 305 EAP-enrolled patients treated in 63 centers (79.6 % men; median age: 75 years; 91.8 % Eastern Cooperative Oncology Group performance status (ECOG-PS) 0/1; 74.5 % epithelioid histology). With median (95 % CI) follow-up for all patients of 18.4 (17.7-19.2) months, -PFS and OS were 6.3 (5.3-7.5) and 18.9 (17.6-not reached (NR)) months, with 1-year OS at 66.4 % (60.1-73.3 %). Median OS and 1-year survival rates were 21.0 (18.7-NR) and 70.8 % (63.9 %-780.6 %), and 14.1 (10.9-21.0) months and 54.9 % (42.8 %-70.4 %) for epithelioid and non-epithelioid PM subgroups, respectively. PFS was equal between the two subgroups. Grade 3-4 adverse events occurred in 23.3 % of patients and three deaths were treatment-related. CONCLUSIONS: For this unselected PM population, efficacy and safety outcomes compared favorably with CheckMate 743 trial results.

Implementation and use of the Safewards model in healthcare services: A scoping review.

Safewards is a multi-intervention mental health nursing model of practice improvement aimed at preventing and reducing conflict and containment. The use of Safewards has now extended beyond mental health settings. Implementation of Safewards has been reported to be challenging and therefore requires an evidence-informed and structured approach. This review's objectives were to: (i) Comprehensively map approaches used to implement Safewards interventions; (ii) Characterise the outcomes measured in Safewards implementation studies; and (iii) Identify the facilitators and barriers to Safewards training and its implementation in practice. All quantitative, qualitative and mixed-methods publications of Safewards, the interventions, evaluations, barriers and facilitators from all healthcare services internationally were included. The Joanna Briggs Institute scoping review and Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for Scoping Reviews were used to guide methodology. Data were reported according to the 12 items of the TIDieR. Twenty-seven publications reported the implementation of Safewards. Descriptions were limited for reporting items such as intervention descriptions, materials, resources, specific procedures and processes, modifications made to interventions and delivery of interventions and training. No consistent theoretical implementation framework was reported. Collaboration, leadership, feedback and co-design were strong drivers for staff buy-in, engagement and success for implementation in mental health and acute settings. Transparency, replicability and generalisation require a detailed description of all elements of an intervention being implemented. Without adequate information, only assumptions can be drawn about the clinical governance and process of the implementation and training, and it is difficult to conclude when attempting to replicate the interventions.

Safewards in acute medical/surgical care wards: Capability, Opportunity, Motivation and Behaviour model and Theoretical Domains Framework analysis.

BACKGROUND: Safewards is an evidence-based practice improvement model to minimise conflict in inpatient mental health units. There is limited published research on implementing Safewards in acute medical/surgical care wards. OBJECTIVE: To identify, from nurses' perspectives, barriers, and facilitators to implement four Safewards interventions in acute medical/surgical care wards. METHODS: This article reports qualitative findings from a funded mixed-method evaluation of the Safewards Acute Care Pilot Project. Six focus group interviews comprising 35 nursing staff from four hospitals in Victoria, Australia were completed between April and October 2022. The semi-structured interview guide included questions developed using the Capability, Opportunity, Motivation and Behaviour model. Data was thematically analysed and mapped to a matrix combining Capability, Opportunity, Motivation and Behaviour model and the Theoretical Domains Framework to elucidate barriers and facilitators to implementing four Safewards interventions in acute medical/surgical care wards. RESULTS: Three components in the Capability, Opportunity, Motivation and Behaviour model and three Theoretical Domains Framework domains were identified as barriers to the adoption of Safewards in acute medical/surgical care wards. Specific barriers included physical opportunity challenges related to the environmental context and resources domains. The key themes included time constraints and competing priorities; lack of physical space and infrastructure; and poor patient uptake due to lack of understanding. Gaps emerged as a psychological capability barrier within the Theoretical Domains Framework knowledge domain. Additionally, resistance to practice changes was associated with the motivation component of the Capability, Opportunity, Motivation and Behaviour model. Conversely, six TDF domains were relevant to facilitating the implementation of the Safewards interventions: memory, attention, and decision processes; physical skills; social influences; social/professional role and identity; goals; and beliefs about consequences. Key facilitators included the Safewards interventions serving as reminders to focus on compassionate nursing care; nursing staff possessing the skillset for interventions; peer pressure and mandated change; supportive and passionate leadership; presence of champions to drive momentum; belief in nursing staff ownership and expertise for leading implementation; personal commitment to improve work environments and care quality; and the belief that Safewards would improve ward culture. CONCLUSIONS: Addressing barriers and leveraging facilitators can inform strategies for enhancing staff capability to implement Safewards in acute care wards. Specifically, a tailored, multilayered approach focusing on leadership support, training, resources, patient input, and feedback can promote effective adoption of the Safewards model and adaptation of discrete interventions. TWEETABLE ABSTRACT: Safewards adaptation: Addressing barriers like resources, space, and patient awareness; leveraging peer modelling and leadership strategies for success.

Accelerated subsequent lung cancer after post-operative radiotherapy for breast cancer.

BACKGROUND: Post-operative whole breast radiotherapy for breast cancer (BC) may increase the risk of subsequent lung cancer (LC). The impact of radiotherapy intensification (boost) has not been specifically explored in this context. We investigated the role of radiation modalities on the development of subsequent LC among our patients treated by radiotherapy for localized BC. METHODS: All patients with a diagnosis of LC between 2000 and 2020 with a history of prior localized BC treated by surgery and post-operative radiotherapy were retrospectively reviewed. Primary endpoint was time to first diagnosis of LC after BC treatment with radiotherapy (RT). RESULTS: From 98 patients who developed subsequent LC after primary BC treated with post-operative RT, 38% of patients (n = 37) received an additional RT boost, and 46% (n = 45) received hormonal treatment post radiation. A total of 61% (n = 60) were smokers. With regards to LC characteristics, adenocarcinoma was the most frequent histology (68%, n = 66); 36% (n = 35) harbored at least 1 molecular alteration, 57% (n = 20) of them being amenable to targeted therapy. Median time to first diagnosis of LC was 6 years [1.7-28.4 yrs] in the whole cohort. In the subgroup of patients treated with boost this time was reduced to 4 years [1.8-20.8 years] compared to 8 years for patients without boost [1.7-28.4 yrs] (p = 0.007). Boost, smoking usage, endocrine therapy, and age <50 yrs old at BC radiation remained independent factors associated with shorter time to first diagnosis of LC after BC treatment. DISCUSSION: We report for the first time the potential impact of boost -part of BC radiation treatment- for BC on the risk of subsequent LC. The impact of low dose radiation on lung parenchyma could explain this phenomenon, but the underlying physiopathology is still under investigation. This work highlights the need for clinicians to identify patients at risk of developing faster subsequent thoracic malignancy after BC radiation, for implementing personalized surveillance.

Atezolizumab with or without bevacizumab and platinum-pemetrexed in patients with stage IIIB/IV non-squamous non-small cell lung cancer with EGFR mutation, ALK rearrangement or ROS1 fusion progressing after targeted therapies: A multicentre phase II open-label non-randomised study GFPC 06-2018.

BACKGROUND: Previous reports showed limited efficacy of immune checkpoint inhibitors as single-agent treatment for non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutation or ALK/ROS1 fusion. We aimed at evaluating the efficacy and safety of immune checkpoint inhibitor combined with chemotherapy and bevacizumab (when eligible) in this patient subgroup. METHODS: We conducted a French national open-label multicentre non-randomised non-comparative phase II study in patients with stage IIIB/IV NSCLC, oncogenic addiction (EGFR mutation or ALK/ROS1 fusion), with disease progression after tyrosine kinase inhibitor and no prior chemotherapy. Patients received platinum, pemetrexed, atezolizumab, bevacizumab (PPAB cohort) or, if not eligible to bevacizumab, platinum-pemetrexed-atezolizumab (PPA cohort). The primary end-point was the objective response rate (RECIST v1.1) after 12 weeks, evaluated by blind independent central review. RESULTS: 71 patients were included in PPAB cohort and 78 in PPA cohort (mean age, 60.4/66.1 years; women 69.0%/51.3%; EGFR mutation, 87.3%/89.7%; ALK rearrangement, 12.7%/5.1%; ROS1 fusion, 0%/6.4%, respectively). After 12 weeks, objective response rate was 58.2% (90% confidence interval [CI], 47.4-68.4) in PPAB cohort and 46.5% (90% CI, 36.3-56.9) in PPA cohort. Median progression-free survival and overall survival were 7.3 (95% CI 6.9-9.0) months and 17.2 (95% CI 13.7-NA) months in PPAB cohort and 7.2 (95% CI 5.7-9.2) months and 16.8 (95% CI 13.5-NA) months in PPA cohort, respectively. Grade 3-4 adverse events occurred in 69.1% of patients in PPAB cohort and 51.4% in PPA cohort; Grade 3-4 atezolizumab-related adverse events occurred in 27.9% and 15.3%, respectively. CONCLUSION: Combination approach with atezolizumab with or without bevacizumab and platinum-pemetrexed achieved promising activity in metastatic EGFR-mutated or ALK/ROS1-rearranged NSCLC after tyrosine kinase inhibitor failure, with acceptable safety profile.

Study of the persistence and dynamics of recombinant mCherry-producing Yarrowia lipolytica strains in the mouse intestine using fluorescence imaging.

Yarrowia lipolytica is a dimorphic oleaginous non-conventional yeast widely used as a powerful host for expressing heterologous proteins, as well as a promising source of engineered cell factories for various applications. This microorganism has a documented use in Feed and Food and a GRAS (generally recognized as safe) status. Moreover, in vivo studies demonstrated a beneficial effect of this yeast on animal health. However, despite the focus on Y. lipolytica for the industrial manufacturing of heterologous proteins and for probiotic effects, its potential for oral delivery of recombinant therapeutic proteins has seldom been evaluated in mammals. As the first steps towards this aim, we engineered two Y. lipolytica strains, a dairy strain and a laboratory strain, to produce the model fluorescent protein mCherry. We demonstrated that both Y. lipolytica strains transiently persisted for at least 1 week after four daily oral administrations and they maintained the active expression of mCherry in the mouse intestine. We used confocal microscopy to image individual Y. lipolytica cells of freshly collected intestinal tissues. They were found essentially in the lumen and they were rarely in contact with epithelial cells while transiting through the ileum, caecum and colon of mice. Taken as a whole, our results have shown that fluorescent Y. lipolytica strains constitute novel tools to study the persistence and dynamics of orally administered yeasts which could be used in the future as oral delivery vectors for the secretion of active therapeutic proteins in the gut.

Optimizing the response to mental health deterioration: Nurses experiences of using a Mental Health Observation Response Chart.

Recognizing mental health deterioration remains a challenge for health systems globally, with evidence of suboptimal care for patients with increasing co-morbid psychiatric illness. Mechanisms exist to detect and respond to physical deterioration with the use of Observation Response Charts, monitoring of vital signs and medical emergency teams but registered nurses lack psychiatric nursing skills to care for this patient population. Currently, there are no validated processes in place to recognize and respond to mental health deterioration in general hospital wards. This qualitative descriptive study explores nurses' experiences of using a Mental Health Observation Response Chart that uses signs of distress to track and trigger tiered responses to mental health deterioration on general hospital wards. Thirty-five surgical and rehabilitation nurses participated in focus groups from January to March 2020. All qualitative data were thematically analysed using an inductive approach. Analysis resulted in four themes: clinical relevance, a useful chart, identifying distress, and working with doctors. The clinical relevance of the chart was influenced by the level of nursing experience; patient distress; existing escalation pathways and ward culture. The study findings will inform the establishment of a process for nurses to recognize mental health deterioration that could improve patient outcomes and promote staff safety. Further research is needed to validate specific signs of distress with patients in general hospital wards and to develop findings for the clinical relevance of this approach to detect mental health deterioration and improve patient outcomes.

Long response to immune checkpoint inhibitors in metastatic NSCLC despite EGFR germline mutation. A case report.

First-line therapy in advanced non-small-cell-lung-cancer (NSCLC) is based on chemotherapy except for patients with a tumor proportion score for programmed death ligand 1 (PD-L1) of 50% or greater, pembrolizumab is administrated. However, patients with somatic-EGFR-mutated tumors had usually been excluded from clinical applications of immune checkpoint inhibitors (ICIs). Germline-EGFR-mutated-patients are known to not respond to EGFR-Tyrosine-Kinase-inhibitors (TKIs). But what about germline EGFR mutations and response to ICIs? Herein, we describe the case of a long response to ICIs treatment in a complex metastatic NSCLC with co-occuring EGFR germline and KRAS somatic mutations, high PD-L1 score and a smoking history.

A Unique Enhancement of Propionibacterium freudenreichii's Ability to Remove Pb(II) from Aqueous Solution by Tween 80 Treatment.

Microbial agents have promise for the bioremediation of Pb(II)-polluted environments and wastewater, the biodecontamination of foods, and the alleviation of toxicity in living organisms. The dairy bacterium Propionibacterium freudenreichii is poorly able to remove Pb(II) from aqueous solution at 25 ppm, ranging from 0 to 10% of initial concentration. Here, we report on an original strong enhancement of this activity (ranging from 75% to 93%, p < 0.01) following the addition of a polysorbate detergent (Tween® 80) during or either shortly after the growth of a P. freudenreichii culture. We evaluated the optimal Tween® 80 concentration for pretreatment conditions, documented the role of other detergents, and explored the possible mechanisms involved. Our results reveal a novel, environmentally friendly, low-cost pretreatment procedure for enhancing the selective removal of lead from water by probiotic-documented bacteria.

Comprehensive Genome Profiling in Patients With Metastatic Non-Small Cell Lung Cancer: The Precision Medicine Phase II Randomized SAFIR02-Lung/IFCT 1301 Trial.

PURPOSE: Targeted therapies (TT) and immune checkpoint blockers (ICB) have revolutionized the approach to non-small cell lung cancer (NSCLC) treatment in the era of precision medicine. Their impact as switch maintenance therapy based on molecular characterization is unknown. PATIENTS AND METHODS: SAFIR02-Lung/IFCT 1301 was an open-label, randomized, phase II trial, involving 33 centers in France. We investigated eight TT (substudy-1) and one ICB (substudy-2), compared with standard-of-care as a maintenance strategy in patients with advanced EGFR, ALK wild-type (wt) NSCLC without progression after first-line chemotherapy, based on high-throughput genome analysis. The primary outcome was progression-free survival (PFS). RESULTS: Among the 175 patients randomized in substudy-1, 116 received TT (selumetinib, vistusertib, capivasertib, AZD4547, AZD8931, vandetanib, olaparib, savolitinib) and 59 standard-of-care. Median PFS was 2.7 months [95% confidence interval (CI), 1.6-2.9] with TT versus 2.7 months (1.6-4.1) with standard-of-care (HR, 0.97; 95% CI, 0.7-1.36; P = 0.87). There were no significant differences in PFS within any molecular subgroup. In substudy-2, 183 patients were randomized, 121 received durvalumab and 62 standard-of-care. Median PFS was 3.0 months (2.3-4.4) with durvalumab versus 3.0 months (2.0-5.1) with standard-of-care (HR, 0.86; 95% CI, 0.62-1.20; P = 0.38). Preplanned subgroup analysis showed an enhanced benefit with durvalumab in patients with PD-L1 tumor proportion score (TPS) ≥1%, (n = 29; HR, 0.29; 95% CI, 0.11-0.75) as compared with PD-L1 <1% (n = 31; HR, 0.71; 95% CI, 0.31-1.60; Pinteraction = 0.036). CONCLUSIONS: Molecular profiling can feasibly be implemented to guide treatment choice for the maintenance strategy in EGFR/ALK wt NSCLC; in this study it did not lead to substantial treatment benefits beyond durvalumab for PD-L1 ≥ 1 patients.

Brief Report on Teleconsultation in Lung Cancer: Toward a Semiotic Paradigm Shift?

Introduction: Telehealth is taking an increasingly important part of medicine. This practice change is being accelerated by the pandemic linked to coronavirus disease 2019. Oncology is a medical specialty for which this paradigm shift is particularly relevant. Methods: We developed a survey aiming at evaluating the use of teleconsultation by physicians managing patients with lung cancer in France. The survey was available online from December 15, 2020, to February 10, 2021. Results: Answers were obtained from 142 clinicians (73.9% pneumologists, 18.3% medical oncologists, and 7.7% with another specialty), 129 (90.8%) of whom had already performed teleconsultation. Among those, 123 (95.3%) started after the coronavirus disease 2019 pandemic. In addition, 72.9% had a moderate usage of this tool (<10 teleconsultations/mo). The frequency of clinicians never using teleconsultation was higher in private practices (p = 0.029). The two clinical situations for which teleconsultation was frequently used were visits during treatment without imaging assessment (53.5%) and post-treatment surveillance (80.3%). Depending on the type of treatment received, the frequency of teleconsultation was variable. Lung cancer subtype also affected the clinician's practice. Indeed, 47.2% never proposed this tool for SCLC. Teleconsultation was considered to be of no contribution, a moderate contribution, a significant contribution, or a revolution of the clinical practice for 14.1%, 66.2%, 10.6%, and 2.1% of the respondents, respectively. The participants expected to decrease, stabilize, or increase their teleconsultation activity in 18.3%, 52.8%, and 23.2% of the cases, respectively. Conclusions: Most thoracic oncologists in France are using teleconsultation, mostly as an additional tool that should not replace the doctor-patient in-person relationship.

Nationwide Real-Life Safety and Treatment Exposure Data on Durvalumab After Concurrent Chemoradiotherapy in Unresectable Stage III, Locally Advanced, Non-small Cell Lung Cancer: Analysis of Patients Enrolled in the French Early Access Program.

PURPOSE: Consolidation immunotherapy with the PD-L1 inhibitor durvalumab following concurrent chemoradiotherapy (cCRT) has shown a significant survival improvement and is now a standard of care in patients with unresectable stage III or non-operable non-small cell lung cancer (NSCLC). METHODS: In this early access program cohort, demographic, disease characteristics and safety data were collected for 576 patients from 188 centers, who received durvalumab 10 mg/kg intravenous infusion every 2 weeks, until disease progression or unacceptable toxicity or for a maximum of 12 months following cCRT. Durvalumab exposure data were available for 402 patients. RESULTS: Overall, 576 patients were included, 72.9% were men, median age 64.0 years, 52.3% had a stage IIIB disease. PD-L1 status captured in 445 (77%) patients was positive (48.1%), negative (32.6%), unknown (19.3%). At the end of cCRT, adverse events (AEs) all grade ≤ 2, were reported in 22.7% of patients, mainly esophagitis (6.3%). The main reasons of discontinuation were completion of the planned 12 months of consolidation treatment (42.1% patients), disease progression (28.6%) and adverse events (19.5%). Treatment completion was similar in PDL-1 positive and PDL-1 negative patients groups. 20.7% patients had a SAE drug reaction and 17.7% stopped treatment mainly due to SAE. ADR rate and early treatment discontinuation were higher in patients > 70 years old. Death due to AEs occurred in 7 patients, 2 had interstitial lung disease. CONCLUSION: Safety data with durvalumab consolidation after cCRT in a large cohort of patients with stage III NSCLC are reported in this real-life cohort. Consistent data were reported both in the PD-L1 positive and PD-L1 negative NSCLC patients in daily practice.

Screening major trauma patients for prevalence of illicit drugs.

INTRODUCTION: Australasian emergency departments (ED) routinely test patient alcohol levels following major trauma, but assessment for illicit drugs is uncommon. METHODS: A prospective cross-sectional study of major motor-vehicle-related trauma patients attending both adult major trauma centres in Victoria, Australia. All eligible patients had point-of-care saliva testing to determine the prevalence of common illicit drugs. RESULTS: Over 12 months, 1411 patients were screened, 36 refused (2.6%) and 63 were excluded. Of the final 1312 cases included, 173 (13.2%; 95% confidence interval 11.5, 15.1) tested positive to at least one illicit substance, with 133 (76.9%; 69.7, 82.8) positive for meth/amphetamines. One in five had more than one illicit substance detected. Patients testing positive were most frequently in motor vehicles (91.9% vs. 85.6%) and least frequently cyclists (2.3% vs. 4.2%) or pedestrians (5.2% vs. 10.3%), compared to those testing negative. They were younger (mean age 35.4 vs. 43.1 years), more likely to arrive overnight (27.2% vs. 12.1%) or after single vehicle crashes (54.3% vs. 42.3%). Although the initial disposition from ED did not differ, those testing positive were more likely to re-present within 28 days (13.9% vs. 5.4%). DISCUSSION AND CONCLUSIONS: A high prevalence of potentially illicit substances among patients presenting with suspected major trauma supports the need for urgent preventive strategies. The low rate of patient refusal and large numbers screened by ED staff suggests that point-of care testing for illicit substances in major trauma is acceptable and feasible. This study and ongoing surveillance may be used to inform driver education strategies.

Effect of Safewards on reducing conflict and containment and the experiences of staff and consumers: A mixed-methods systematic review.

Safewards is an internationally adopted framework that provides interventions to reduce conflict and containment in healthcare settings. This systematic review evaluated the effect of Safewards on conflict and containment events in inpatient units and the perceptions of staff and consumers. Quantitative, qualitative, and mixed-methods studies were considered for inclusion. Following the Joanna Briggs Institute methodology, two reviewers independently screened, appraised, and extracted data. Qualitative data were synthesized using inductive-thematic analysis. Quantitative and qualitative data were integrated with a convergent-segregated approach and presented in tabular and narrative format. A search of 13 databases and grey literature yielded 14 studies of variable methodological quality. Four studies reported reduced rates of conflict and one study reported reductions that were not statistically significant. Six studies reported reductions in rates of containment, three studies found no statistical significance and one study reported statistically significant reductions at follow-up. Staff and consumers in four studies reported an improved experience of safety. Three themes were developed as follows: (i) therapeutic hold, cohesion, support and the environment, (ii) conflict, containment and the experience of safety, and (iii) the complexities of adapting and embedding change. This review found most staff and consumers reported Safewards improved therapeutic relationships, cohesion, and ward atmosphere. Staff and consumers reported improved ward atmosphere, leading to consumer-centred, recovery-oriented care. Safewards improved the experience of safety from the perspective of staff and consumers when combined with ongoing training, leadership and time for consolidation. While results are promising they should be used cautiously until more robust evidence is established.

Suicide by hanging: A scoping review.

Suicide by hanging is increasing in many countries around the world and whilst efforts are being made to influence the prevention agenda to reduce the incidence, little is known regarding the contributing factors for choosing this method. The purpose of this scoping review is to summate understandings about how the epidemiology and prevention of suicide by hanging is recognised, described, and discussed in the literature, and critically appraise the extent to which the lived-experiences of survivors of suicide attempts are included. A scoping review was conducted implementing the appropriate framework and in accord with the PRIMSA-ScR extension. Three databases (CINAHL, PubMed, and PsycINFO) were searched along with the reference lists of eligible sources in January and February 2021. Thirty-six articles with a primary focus on hanging as a method of suicide and/or its prevention are included in this review, with brief thematic analysis used to summarise the featured studies. Three distinct themes emerging from the literature include: (i) Hanging suicide deaths in the community environment or person's usual place of residence, (ii) Hanging suicide deaths in controlled environments (including police cells, prisons, and inpatient units), and (iii) Medical management of near-lethal hangings. This review highlights the necessity for improving education and policy regarding the controlled environments frequently associated with hanging suicides and the medical management of near-lethal hangings, as well as the ongoing need for policy to guide and govern the responsible media portrayal of known suicides as well as fictional hangings. Finally, this review highlights the necessity for including those with lived-experiences of a suicide attempt by hanging to advance the current prevention agenda.

Novel EWSR1::UBP1 fusion expands the spectrum of spindle cell rhabdomyosarcomas.

Over the last decade, the development of next-generation sequencing techniques has led to the molecular dismantlement of adult and pediatric sarcoma, with the identification of multiple gene fusions associated with specific subtypes and currently integrated into diagnostic classifications. In this report, we describe and discuss the identification of a novel EWSR1-UBP1 gene fusion in an adult patient presenting with multi-metastatic sarcoma. Extensive pathological, transcriptomic, and genomic characterization of this tumor in comparison with a cohort of different subtypes of pediatric and adult sarcoma revealed that this fusion represents a novel variant of spindle cell rhabdomyosarcoma with features of TFCP2-rearranged subfamily.

Surgical or medical strategy for locally-advanced, stage IIIA/B-N2 non-small cell lung cancer: Reproducibility of decision-making at a multidisciplinary tumor board.

BACKGROUND: Stage IIIA/B-N2 is a very heterogeneous group of patients and accounts for one third of NSCLC at diagnosis. The best treatment strategy is established at a Multidisciplinary Tumor Board (MTB): surgical resection with neoadjuvant or adjuvant therapy versus definitive chemoradiation with immune checkpoint inhibitors consolidation. Despite the crucial role of MTBs in this complex setting, limited data is available regarding its performances and the reproducibility of the decision-making. METHODS: Using a large cohort of IIIA/B-N2 NSCLC patients, we described patient's characteristics and treatment strategies established at the initial MTB: with a "surgical strategy" group, for potentially resectable disease, and a "medical strategy" group for non-resectable patients. A third group consisted of patients who were not eligible for surgery after neoadjuvant treatment and switched from the surgical to the medical strategy. We randomly selected 30 cases (10 in each of the 3 groups) for a blinded re-discussion at a fictive MTB and analyzed the reproducibility and factors associated with treatment decision. RESULTS: Ninety-seven IIIA/B-N2 NSCLC patients were enrolled between June 2017 and December 2019. The initial MTB opted for a medical or a surgical strategy in 44% and 56% of patients respectively. We identified histology, tumor size and localization, extent of lymph node involvement and the presence of bulky mediastinal nodes as key decision-making factors. Thirteen patients were not eligible for surgical resection after neoadjuvant therapy and switched for a medical strategy. Overall concordance between the initial decision and the re-discussion was 70%. The kappa correlation coefficient was 0.43. Concordance was higher for patients with limited mediastinal node invasion. Survival did not appear to be impacted by conflicting decisions. CONCLUSIONS: Reproducibility of treatment decision-making for stage IIIA/B-N2 NSCLC patients at a MTB is moderate but does not impact survival.

Adherent-Invasive and Non-Invasive Escherichia coli Isolates Differ in Their Effects on Caenorhabditis elegans' Lifespan.

The adherent-invasive Escherichia coli (AIEC) pathotype has been implicated in the pathogenesis of inflammatory bowel diseases in general and in Crohn's disease (CD) in particular. AIEC strains are primarily characterized by their ability to adhere to and invade intestinal epithelial cells. However, the genetic and phenotypic features of AIEC isolates vary greatly as a function of the strain's clonality, host factors, and the gut microenvironment. It is thus essential to identify the determinants of AIEC pathogenicity and understand their role in intestinal epithelial barrier dysfunction and inflammation. We reasoned that soil nematode Caenorhabditis elegans (a simple but powerful model of host-bacterium interactions) could be used to study the virulence of AIEC vs. non- AIEC E. coli strains. Indeed, we found that the colonization of C. elegans (strain N2) by E. coli impacted survival in a strain-specific manner. Moreover, the AIEC strains' ability to invade cells in vitro was linked to the median lifespan in C. elegans (strain PX627). However, neither the E. coli intrinsic invasiveness (i.e., the fact for an individual strain to be characterized as invasive or not) nor AIEC's virulence levels (i.e., the intensity of invasion, established in % from the infectious inoculum) in intestinal epithelial cells was correlated with C. elegans' lifespan in the killing assay. Nevertheless, AIEC longevity of C. elegans might be a relevant model for screening anti-adhesion drugs and anti-invasive probiotics.

Impact of COVID-19 on the management of patients with thoracic cancers in a tertiary referral center.

INTRODUCTION: Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 has spread worldwide in 2020 leading the World Health Organization to declare a pandemic. Patients with thoracic cancers have been reported at higher risk to develop severe disease, and die from COVID-19. In this setting, clinical practice recommendations for the management of patients were published. We report here how these guidelines were implemented in a routine practice setting. METHODS: We retrospectively collected the characteristics, treatment regimen and modification, as well as COVID-19 status and death for all patients with thoracic malignancies scheduled for an appointment at Institute Curie from March 23rd to April 17th 2020. RESULTS: A total of 339 patients were included. Treatment strategy was modified for a total of 110 (32 %) patients because of COVID-19; these modifications were in accordance with guidelines for 92 % of patients. The majority of dose modifications were related to immune checkpoint inhibitors, for which switch to flat dosing every 4-6 weeks was made. A total of 5 (1.5 %) patients were diagnosed with COVID-19 disease, 1 of whom died from disease complication. CONCLUSION: Our study provides a unique insight in the decision making for patients with thoracic malignancies in the setting of COVID-19 outbreak, showing how guidelines were implemented in the clinic, and what may be optimized in the clinical practice of thoracic oncology in the future.