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Nancy Patricia Caballero-Suárez,1 Vania Barrientos-Casarrubias,1 Ester Gutiérrez-Velilla,1 Lilian Margarita González Avilés,2 Luis Daniel Pérez-López,1,2 Claudia Alvarado-De la Barrera,1 Santiago Ávila-Ríos,1 Janella Mora-Gallegos3 1Centro de Investigación en Enfermedades Infecciosas (CIENI), Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas” (INER), Mexico City, Mexico; 2Programa de Maestría en Psicología, Universidad Nacional Autónoma de México (UNAM), Mexico City, Mexico; 3Programa de Atención a Pacientes y Familiares (PAPyF), Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas” (INER), Mexico City, MexicoCorrespondence: Nancy Patricia Caballero-Suárez, Departamento de Investigación en Enfermedades Infecciosas (CIENI), Instituto Nacional de Enfermedades Respiratorias (INER), Calzada de Tlalpan 4502, Sección XVI, Tlalpan, Mexico City, 14080, Mexico, Tel +52 155 56667985 ext. 169, Email nancy.caballero@cieni.org.mxPurpose: This study aimed to assess the level of anxiety and depression in relatives of critically ill COVID-19 patients admitted to the intensive care unit (ICU), and to perform an exploratory pilot study on the implementation of telephone psychological interventions to reduce the initial levels of anxiety and depression in this population.Patients and Methods: Family members of COVID-19 inpatients at ICU answered GAD-7, PHQ-9 and questions on socio-demographic data. A brief psychological intervention was applied via telephone based on the needs of the participants (with adequate adaptation, with symptoms of anxiety, depression, or both). After intervention, participants completed the Patient Global Impression of Change Scale.Results: A total of 1307 relatives were included (66.5% female), 34% and 29% had anxiety and depressive symptoms, respectively. These symptoms were associated with female gender, unemployment, and being the parent or partner of the patient. After intervention, 57.9% reported felt better, 31.3% a little better and 6.6% much better; and with emotional regulation techniques and psychoeducation, higher percentages of feeling better or much better were reported.Conclusion: Brief interventions to reduce the psychological impact of inpatient family members could be effective but will need to be explored further in future studies.Keywords: pandemic, relatives, mental health, brief psychotherapy

Background: Thoracoscopic talc insufflation (TTI) has been used to obliterate the pleural space and prevent recurrent pleural effusions or pneumothorax. Reports of acute pneumonitis and ARDS after the use of talc raised concern about its safety. Differences in particle size of various talc preparations may explain the variable occurrence of pneumonitis. We sought to determine the incidence of lung injury after TTI over a 13-year period at our institution.Methods: Patients who underwent TTI between January 1994 and July 2007 were identified from a prospectively maintained logbook. The talc used was commercially available sterile talc (Sclerosol). The hospital course was reviewed in detail, and all cases of respiratory insufficiency were examined with regard to onset, suspected cause, and outcome. Talc-related lung injury was defined as the presence of new infiltrates on chest radiograph and increased oxygen requirements, with no other identifiable trigger than talc exposure.Results: A total of 138 patients underwent 142 TTIs for recurrent pleural effusions or spontaneous pneumothorax. TTI was performed most frequently for malignant pleural effusions (75.5% of effusions). The median dose of talc was 6 g (range, 2-8 g). Dyspnea with increased oxygen requirements developed within 72 h postprocedure for 12 patients. Four patients (2.8%) had talc-related lung injury, and talc exposure may have contributed to the respiratory deterioration in four additional patients.Conclusions: We report the occurrence of lung injury after TTI using the only talc approved by the US Food and Drug Administration. These results reinforce previous concerns regarding the talc used for pleurodesis in North America. [ABSTRACT FROM AUTHOR]

This paper addresses the role of conversational memory in Embodied Conversational Agents (ECAs). It describes an investigation into developing such a memory architecture and integrating it into an ECA. ECAs are virtual agents whose purpose is to engage in conversations with human users, typically through natural language speech. While several works in the literature seek to produce viable ECA dialog architectures, only a few authors have addressed the episodic memory architectures in conversational agents and their role in enhancing their intelligence. In this work, we propose, implement, and test a unified episodic memory architecture for ECAs. We describe a process that determines the prevalent contexts in the conversations obtained from the interactions. The process presented demonstrates the use of multiple techniques to extract and store relevant snippets from long conversations, most of whose contents are unremarkable and need not be remembered. The mechanisms used to store, retrieve, and recall episodes from previous conversations are presented and discussed. Finally, we test our episodic memory architecture to assess its effectiveness. The results indicate moderate success in some aspects of the memory-enhanced ECAs, as well as some work still to be done in other aspects.

This article describes and evaluates an approach to create and/or improve tactical agents through direct human interaction in real time through a force-feedback haptic device. This concept takes advantage of a force-feedback joystick to enhance motor skill and decision-making transfer from the human to the agent in real time. Haptic devices have been shown to have high bandwidth and sensitivity. Experiments are described for this new approach, named Instructional Learning. It is used both as a way to build agents from scratch as well as to improve and/or correct agents built through other means. The approach is evaluated through experiments that involve three applications of increasing complexity – chasing a fleer (Chaser), shepherding a flock of sheep into a pen (Sheep), and driving a virtual automobile (Car) through a simulated road network. The results indicate that in some instances, instructional learning can successfully create agents under some circumstances. However, instructional learning failed to build and/or improve agents in other instances. The Instructional Learning approach, the experiments, and their results are described and extensively discussed.

This article describes research to build an embodied conversational agent (ECA) as an interface to a question-and-answer (Q/A) system about a National Science Foundation (NSF) program. We call this ECA the LifeLike Avatar, and it can interact with its users in spoken natural language to answer general as well as specific questions about specific topics. In an idealized case, the LifeLike Avatar could conceivably provide a user with a level of interaction such that he or she would not be certain as to whether he or she is talking to the actual person via video teleconference. This could be considered a (vastly) extended version of the seminal Turing test. Although passing such a test is still far off, our work moves the science in that direction. The Uncanny Valley notwithstanding, applications of such lifelike interfaces could include those where specific instructors/caregivers could be represented as stand-ins for the actual person in situations where personal representation is important. Possible areas that come to mind that might benefit from these lifelike ECAs include health-care support for elderly/disabled patients in extended home care, education/training, and knowledge preservation. Another more personal application would be to posthumously preserve elements of the persona of a loved one by family members. We apply this approach to a Q/A system for knowledge preservation and dissemination, where the specific individual who had this knowledge was to retire from the US National Science Foundation. The system is described in detail, and evaluations were performed to determine how well the system was perceived by users.

Background: Severe post tracheostomy (PT) and post intubation (PI) tracheal stenosis is an uncommon clinical entity that often requires interventional bronchoscopy before surgery is considered. We present our experience with severe PI and PT stenosis in regards to patient characteristics, possible risk factors, and therapy. Methods: We conducted a retrospective chart review of 31 patients with PI and PT stenosis treated at Lahey Clinic over the past 8 years. Demographic characteristics, body mass index, comorbidities, stenosis type and site, procedures performed and local treatments applied were recorded. Results: The most common profile of a patient with tracheal stenosis in our series was a female (75%), obese (66%) patient with a history of diabetes mellitus (35.4%), hypertension (51.6%), and cardiovascular disease (45.1%), who was a current smoker (38.7%). Eleven patients (PI group) had only oro-tracheal intubation (5.2 days of intubation) and developed web-like stenosis at the cuff site. Twenty patients (PT group) had undergone tracheostomy (54.5 days of intubation) and in 17 (85%) of them the stenosis appeared around the tracheal stoma. There was an average of 2.4 procedures performed per patient. Rigid bronchoscopy with Nd:YAG laser and dilatation (mechanical or balloon) were the preferred methods used. Only 1(3.2%) patient was sent to surgery for re-stenosis after multiple interventional bronchoscopy treatments. Conclusion: We have identified putative risk factors for the development of PI and PT stenosis. Differences in lesions characteristics and stenosis site were noted in our two patient groups. All patients underwent interventional bronchoscopy procedures as the first-line, and frequently the only treatment approach. [ABSTRACT FROM AUTHOR]

Background: Endobronchial ultrasound-guided transbronchial aspiration (EBUS-TBNA) has become the standard for initial lung cancer diagnosis and staging. Previous guidelines have generally focused on the "when" and "how" of EBUS-TBNA; however, little guidance is available on handling and processing specimens during and after acquisition to help optimize both diagnostic yield and tissue integrity for ancillary studies. This document examines the available literature on EBUS-TBNA specimen processing and handling., Study Design and Methods: Rigorous methodology was applied to provide a trustworthy evidence-based guideline and expert panel report. Panelists developed key clinical questions utilizing the Population, Intervention, Comparator, and Outcome (PICO) format, addressing specific topics in EBUS-TBNA specimen processing. MEDLINE (via PubMed) and the Cochrane Library were systematically searched to identify relevant literature, supplemented by manual searches. References were screened for inclusion with document evaluation tools to assess the quality of included studies, extract meaningful data, and grade the level of evidence to support each recommendation or suggestion., Results: Our systematic review and critical analysis of the literature of the 9 PICO questions related to handling and processing EBUS-TBNA specimens resulted in 9 evidence-based statements., Interpretation: Evidence of the handling and processing of EBUS-TBNA specimens varies in strength but is satisfactory in some areas to guide clinicians in certain aspects of specimen handling. Additional research in many aspects of specimen handling and processing is needed to help improve our knowledge base., Competing Interests: Financial/Nonfinancial Disclosures Panelists’ conflicts of interest are detailed in e-Appendix 2., (Copyright © 2024 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Objective: To determine whether targeted sampling (TS), which omits biopsy of triple- normal lymph nodes (LNs) on positron emission tomography, computed tomography, and endobronchial ultrasound (EBUS), is noninferior to systematic sampling (SS) of mediastinal LNs during EBUS for staging of patients with early-stage non-small cell lung cancer (NSCLC)., Methods: Patients who are clinical nodal (cN)0-N1 with suspected NSCLC eligible for EBUS based on positron emission tomography/computed tomography were enrolled in this prospective, multicenter trial. During EBUS, all patients underwent TS and then crossed over to SS, whereby at least 3 mediastinal LN stations (4R, 4L, 7) were routinely sampled. Gold standard of comparison was pathologic results. Based on the previous feasibility trial, a noninferiority margin of 6% was established for difference in missed nodal metastasis (MNM) incidence between TS and SS. The McNemar test on paired proportions was used to determine MNM incidence for each sampling method. Analysis was per-protocol using a level of significance of P < .05., Results: Between November 2020 and April 2022, 91 patients were enrolled at 6 high-volume Canadian tertiary care centers. A total of 256 LNs underwent TS and SS. Incidence of MNM was 0.78% in SS and 2.34% in TS, with an absolute difference of 1.56% (95% confidence interval, -0.003% to 4.1%; P = .13). This falls within the noninferiority margin. A total of 6/256 LNs from 4 patients who were not sampled by TS were found to be malignant when sampled by SS., Conclusions: In high-volume thoracic endosonography centers, TS is not inferior to SS in nodal staging of early-stage NSCLC. This results in change of clinical management for a minority of patients., Competing Interests: Conflict of Interest Statement Dr Turner serves on an advisory board and has received speaker honoraria from Astra Zeneca. Dr Yasufuku has received unrestricted grants from Olympus Medical Systems for continuing medical education. Dr Hanna serves on an advisory board for AstraZeneca, data safety committee for Roche/Genentech, and speaker’s bureau for Minogue Medical. Dr Nayak has received speaker honoraria from Merck and Co. All other authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (Copyright © 2023 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Central airway obstruction (CAO), seen in a variety of malignant and non-malignant airway disorders, is associated with a poor prognosis. The management of CAO is dependent on provider training and local resources, which may make the clinical approach and outcomes highly variable. We reviewed the current literature and provided evidence-based recommendations for the management of CAO., Methods: A multidisciplinary expert panel developed key questions using the PICO (Patient, Intervention, Comparator, and Outcomes) format and conducted a systematic literature search using MEDLINE (PubMed) and the Cochrane Library. The panel screened references for inclusion and used vetted evaluation tools to assess the quality of included studies and extract data, and graded the level of evidence supporting each recommendation. A modified Delphi technique was used to reach consensus on recommendations., Results: A total of 9,688 abstracts were reviewed, 150 full-text articles were assessed, and 31 studies were included in the analysis. One good practice statement and 10 graded recommendations were developed. The overall certainty of evidence was very low., Conclusions: Therapeutic bronchoscopy can improve the symptoms, quality of life, and survival of patients with malignant and non-malignant CAO. Multi-modality therapeutic options, including rigid bronchoscopy with general anesthesia, tumor/tissue debridement, ablation, dilation, and stent placement, should be utilized when appropriate. Therapeutic options and outcomes are dependent on the underlying etiology of CAO. A multidisciplinary approach and shared decision-making with the patient are strongly encouraged., Competing Interests: Financial/Nonfinancial Disclosures The COI statement is provided in e-Appendix 1., (Copyright © 2024 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: Small chest drains are used in many centers as the default drainage strategy for various pleural effusions. This can lead to drain overuse, which may be harmful. This study aimed to reduce chest drain overuse., Methods: We studied consecutive pleural procedures performed in the radiology department before (August 1, 2015, to July 31, 2016) and after intervention (September 1, 2019, to January 31, 2020). Chest drains were deemed indicated or not based on criteria established by a local interdisciplinary work group. The intervention consisted of a pleural drainage order set embedded in electronic medical records. It included indications for chest drain insertion, prespecified drain sizes for each indication, fluid analyses, and postprocedure radiography orders. Overall chest drain use and proportion of nonindicated drains were the outcomes of interest., Results: We reviewed a total of 288 procedures (pre-intervention) and 155 procedures (post-intervention) (thoracentesis and drains). Order-set implementation led to a reduction in drain use (86.5% vs 54.8% of all procedures, P < .001) and reduction in drain insertions in the absence of an indication (from 45.4% to 29.4% of drains, P = .01). The need for repeat procedures did not increase after order-set implementation (22.0% pre vs 17.7% post, P = .40). Complication rates and length of hospital stay did not differ significantly after the intervention. More pleural infections were treated with drain sizes of 12Fr and greater (31 vs 70%, P < .001) after order-set deployment, and direct procedural costs were reduced by 27 CAN$ per procedure., Conclusion: Implementation of a pleural drainage order-set reduced chest drain use, improved procedure selection according to clinical needs, and reduced direct procedural costs. In institutions where small chest drains are used as the default drainage strategy for pleural effusions, this order set can reduce chest drain overuse., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Incidental pulmonary nodules (IPN) are common radiologic findings, yet management of IPNs is inconsistent across Canada. This study aims to improve IPN management based on multidisciplinary expert consensus and provides recommendations to overcome patient and system-level barriers. Methods: A modified Delphi consensus technique was conducted. Multidisciplinary experts with extensive experience in lung nodule management in Canada were recruited to participate in the panel. A survey was administered in 3 rounds, using a 5-point Likert scale to determine the level of agreement (1 = extremely agree, 5 = extremely disagree). Results: Eleven experts agreed to participate in the panel; 10 completed all 3 rounds. Consensus was achieved for 183/217 (84.3%) statements. Panellists agreed that radiology reports should include a standardized summary of findings and follow-up recommendations for all nodule sizes (ie, <6, 6-8, and >8 mm). There was strong consensus regarding the importance of an automated system for patient follow-up and that leadership support for organizational change at the administrative level is of utmost importance in improving IPN management. There was no consensus on the need for standardized national referral pathways, development of new guidelines, or establishing a uniform picture archiving and communication system. Conclusion: Canadian IPN experts agree that improved IPN management should include standardized radiology reporting of IPNs, standardized and automated follow-up of patients with IPNs, guideline adherence and implementation, and leadership support for organizational change. Future research should focus on the implementation and long-term effectiveness of these recommendations in clinical practice., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: G.C.D., S.L., M.C.T., C.F., C.D., S.S., J.H., J.T., A.V.G., J.S., and D.M. received unrestricted support for meetings, planning and data collection, manuscript writing and editing, participating in the Delphi panel, and consulting fees from AstraZeneca. G.C.D. received research funding from MaRS/Merck & Co., Inc. and from Pfizer Inc.; honoraria from Merck & Co., Inc. and GSK Medical; and has received grants outside the submitted work paid directly to Queen’s University from the Ontario Lung Association and Ontario Thoracic Society. G.C.D. serves as the Canadian Thoracic Society Choosing Wisely Canada Working Group chair. J.S. received consulting fees from AstraZeneca to support the conduction of this study and was an employee of Amaris Consulting at the time of this study. D.G. and P.M. received consulting fees from AstraZeneca to support the conduction of this study and are employees of Amaris Consulting. The authors have no other conflicts of interest to declare.

Candida auris is an emerging multidrug-resistant and opportunistic pathogenic yeast. Whole-genome sequencing analysis has defined five major clades, each from a distinct geographic region. The current study aimed to examine the genome of the C. auris 20-1498 strain, which is the first isolate of this fungus identified in Mexico. Based on whole-genome sequencing, the draft genome was found to contain 70 contigs. It had a total genome size of 12.86 Mbp, an N50 value of 1.6 Mbp, and an average guanine-cytosine (GC) content of 45.5%. Genome annotation revealed a total of 5432 genes encoding 5515 proteins. According to the genomic analysis, the C. auris 20-1498 strain belongs to clade IV (containing strains endemic to South America). Of the two genes ( ERG11 and FKS1 ) associated with drug resistance in C. auris , a mutation was detected in K143R, a gene located in a mutation hotspot of ERG11 (lanosterol 14-α-demethylase), an antifungal drug target. The focus on whole-genome sequencing and the identification of mutations linked to the drug resistance of fungi could lead to the discovery of new therapeutic targets and new antifungal compounds.

Background: Advanced diagnostic bronchoscopy targeting the lung periphery has developed at an accelerated pace over the last two decades, whereas evidence to support introduction of innovative technologies has been variable and deficient. A major gap relates to variable reporting of diagnostic yield, in addition to limited comparative studies. Objectives: To develop a research framework to standardize the evaluation of advanced diagnostic bronchoscopy techniques for peripheral lung lesions. Specifically, we aimed for consensus on a robust definition of diagnostic yield, and we propose potential study designs at various stages of technology development. Methods: Panel members were selected for their diverse expertise. Workgroup meetings were conducted in virtual or hybrid format. The cochairs subsequently developed summary statements, with voting proceeding according to a modified Delphi process. The statement was cosponsored by the American Thoracic Society and the American College of Chest Physicians. Results: Consensus was reached on 15 statements on the definition of diagnostic outcomes and study designs. A strict definition of diagnostic yield should be used, and studies should be reported according to the STARD (Standards for Reporting Diagnostic Accuracy Studies) guidelines. Clinical or radiographic follow-up may be incorporated into the reference standard definition but should not be used to calculate diagnostic yield from the procedural encounter. Methodologically robust comparative studies, with incorporation of patient-reported outcomes, are needed to adequately assess and validate minimally invasive diagnostic technologies targeting the lung periphery. Conclusions: This American Thoracic Society/American College of Chest Physicians statement aims to provide a research framework that allows greater standardization of device validation efforts through clearly defined diagnostic outcomes and robust study designs. High-quality studies, both industry and publicly funded, can support subsequent health economic analyses and guide implementation decisions in various healthcare settings.

Background: Whether Inuit in Canada experience disparities in lung cancer survival remains unknown. When requiring investigation and treatment for lung cancer, all residents of Nunavik, the Inuit homeland in Quebec, are sent to the McGill University Health Centre (MUHC), in Montréal. We sought to compare survival among patients with lung cancer at the MUHC, who were residents of Nunavik and Montréal, Quebec, respectively., Methods: We conducted a retrospective cohort study. Using lung cancer registry data, we identified Nunavik residents with histologically confirmed lung cancer diagnosed between 2005 and 2017. We aimed to match 2 Montréal residents to each Nunavik resident on sex, age, calendar year of diagnosis, and histology (non-small cell lung cancer v. small cell lung cancer). We reviewed medical records for data on additional patient characteristics and treatment, and obtained vital status from a provincial registry. We compared survival using Kaplan-Meier analysis and Cox proportional hazards regression., Results: We included 95 residents of Nunavik and 185 residents of Montréal. For non-small cell lung cancer, median survival times were 321 (95% confidence interval [CI] 184-626) days for Nunavik ( n = 71) and 720 (95% CI 536-1208) days for Montréal residents ( n = 141). For small cell lung cancer, median survival times were 190 (95% CI 159-308) days for Nunavik ( n = 24) and 270 (95% CI 194-766) days for Montréal residents ( n = 44). Adjusting for matching variables, stage, performance status, and comorbidity, Nunavik residents had a higher hazard of death (hazard ratio 1.68, 95% CI 1.17-2.41)., Interpretation: Nunavik residents experience disparities in survival after lung cancer diagnosis. Although studies in other Inuit Nunangat regions are needed, our findings point to an urgent need to ensure that interventions aimed at improving lung cancer survival, including lung cancer screening, are accessible to Inuit Nunangat residents., Competing Interests: Competing interests: Sarah MacIsaac reports fellowship training grants from Janssen Pharmaceuticals and Boehringer Ingelheim, payment or honoraria from Boehringer Ingelheim, participation on a board for Boehringer Ingelheim, and a role on a Canadian Thoracic Society equity, diversity, and inclusion committee. Nathalie Boulanger is director of professional services, Ungava Tulattavik Health Centre. Nicole Ezer reports grants from Canadian Institutes of Health Research (CIHR), MUHC (McGill University Health Centre) Foundation, and Fonds de recherche du Québec – Santé; consulting fees from the GSK Advisory Board for chronic obstructive pulmonary disease (COPD); speaker fees for AstraZeneca family practice clinic teaching on COPD; speaker fees for GSK family practice clinic teaching on spirometry; and advisor roles on a Ministère de la Santé et des Services sociaux committee on lung cancer screening and Institut national d’excellence en santé et services sociaux committee on lung cancer screening. Anne Gonzalez reports a grant from Lung Cancer Canada, and is chair of the Lung Cancer Section, Thoracic Oncology, and Chest Procedures Network, American College of Chest Physicians. Scott Owen reports consulting fees for being on the advisory boards of AstraZeneca, Bristol Myers Squibb (BMS), Roche, Novocure, and Takeda. Carmela Pepe reports advisory board membership and speaker honoraria from AstraZeneca and Merck, speaker honoraria from BMS, and advisory board membership from Takeda. Jonathan Spicer reports grants to his institution from BMS, Merck, AstraZeneca, Roche, Protalix Biotherapeutics, and CLS Therapeutics, and payments from AstraZeneca, Merck, BMS, Roche, Amgen, Pfizer, Xenetic Biosciences, Protalix Biotherapeutics, BMS, and Eisai. Shirley White-Dupuis receives honoraria from the Research Institute of the McGill University Health Centre for expertise and guidance on lung health research projects as a member of Puvaqatsianirmut, and is chair of the board of directors of the Nunavik Regional Board of Health and Social Services. Larry Watt receives honoraria from the Research Institute of the McGill University Health Centre for expertise and guidance on lung health research as a member of Puvaqatsianirmut, and is also executive director of Ungava Tulattavik Health Centre. Minnie Grey is former executive director of Nunavik Regional Board and Health Social Services. Faiz Ahmad Khan reports grants from CIHR, World Health Organization, Fonds de recherche du Québec – Nature et technologies, National Research Council of Canada, and Observatoire international sur les impacts sociétaux de l’IA et du numérique, funded by the Fonds de recherche du Québec. No other competing interests were declared., (© 2024 CMA Impact Inc. or its licensors.)

Background: Programmed cell death ligand-1 (PD-L1) expression on tumor cells, evaluated by immunohistochemistry, guides the use of immunotherapy in advanced non-small cell lung cancer (NSCLC)., Research Question: What is the sensitivity and specificity of PD-L1 testing performed in cytologic vs paired histologic specimens in patients with NSCLC?, Study Design and Methods: The MEDLINE, Embase, Web of Science, and Cochrane Library databases were searched through June 1, 2021. The primary outcome was pooled sensitivity and specificity of PD-L1 testing performed on cytologic specimens compared with the reference standard of histologic specimens, analyzed at the PD-L1 expression cutoffs (tumor proportion score) ≥ 1% and ≥ 50%. Pooled sensitivity and specificity, and associated 95% CIs, were estimated using bivariate generalized linear mixed models., Results: Twenty-six articles were included, encompassing a total of 1,064 pairs of histology specimens and cytology cell blocks, and 267 pairs of histology specimens and direct smears. Among these, 946 paired specimens were acquired without interval treatment between the collection of histology and cytology samples. The pooled sensitivity and specificity of cytology specimens compared with paired histology specimens at the PD-L1 expression cutoff ≥ 1% were 0.84 (95% CI, 0.77-0.89) and 0.88 (95% CI, 0.82-0.93), respectively, whereas the pooled sensitivity and specificity at cutoff ≥ 50% were 0.78 (95% CI, 0.69-0.86) and 0.94 (95% CI, 0.91-0.96), respectively. When only paired specimens acquired without interval treatment were considered, the pooled sensitivity and specificity of cytology specimens at PD-L1 expression cutoff ≥ 1% were 0.84 (95% CI, 0.76-0.90) and 0.89 (95% CI, 0.82-0.94), respectively, whereas the pooled sensitivity and specificity at cutoff ≥ 50% were 0.80 (95% CI, 0.71-0.89) and 0.94 (95% CI, 0.91-0.96), respectively., Interpretation: Cytologic specimens provide an accurate assessment of PD-L1 expression in most patients with NSCLC, at both ≥ 1% and ≥ 50% cutoffs, when compared with histologic specimens., Trial Registration: PROSPERO; No.: CRD42020153279; URL: https://www.crd.york.ac.uk/prospero/., Competing Interests: Financial/Nonfinancial Disclosures None declared., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Arranging semiconducting nanocrystals into ordered superstructures is a promising platform to study fundamental light-matter interactions and develop programmable optical metamaterials. We investigated how the geometrical arrangement of CdS nanocrystals in hierarchical assemblies affects chiroptical properties. To create these structures, we controlled the evaporation of a colloidal CdS nanocrystal solution between two parallel plates. We combined in situ microscopy and computational modeling to establish a formation mechanism involving the shear-induced alignment of nanocrystal fibers and the subsequent mechanical relaxation of the stretched fibers to form Raman noodle-type band textures. The high linear anisotropy in these films shares many similarities with cholesteric liquid crystals. The films deposited on top and bottom surfaces exhibit opposite chirality. The mechanistic insights from this study are consequential to enable future advances in the design and fabrication of programmable optical metamaterials for further development of polarization-based optics toward applications in sensing, hyperspectral imaging, and quantum information technology.

Objective: Obstructive sleep apnea (OSA) is a common sleep disorder in people with traumatic brain injury (TBI). Although sleep disturbances have been associated with an increased risk of suicide compared with the general population, the relationship between OSA and suicide risk after TBI is not well documented. In this study, we hypothesized that OSA diagnosis would predict suicide risk in veterans with TBI., Setting: Five Veterans Affairs (VA) Polytrauma Rehabilitation Centers., Participants: Participants were drawn from the VA TBI Model Systems study, with follow-up interviews at year 1 ( n = 392), year 2 ( n = 444), year 5 ( n = 498), or year 10 ( n = 252) post-TBI (7.8%-14.5% follow-up attrition)., Design: This was a retrospective analysis from observational data using logistic regression with repeated measurements. Suicide ideation and suicide attempts were examined as outcomes at each follow-up to evaluate the relationship between OSA and suicide risk after adjusting for other risk factors determined a priori via literature review., Main Measures: Suicidal ideation (Patient Health Questionnaire-9 item 9), suicide attempt during the past year (self-reported), and OSA diagnosis (self-reported)., Results: Contrary to study hypotheses, OSA diagnosis had no statistically significant association with suicide ideation or attempt after accounting for known predictors. However, greater depression symptoms, headache severity, and pre-TBI suicidal ideation and attempts predicted suicide risk at follow-up after accounting for other predictors., Conclusions: Results of this study did not support a relationship between OSA and suicide risk, possibly due to methodological limitations of OSA measurement. Future research on this topic should include objective measures of OSA severity and OSA treatment including adherence. Although suicide is a low base rate occurrence, the impact is disastrous and further research is needed to mitigate suicide risk., Competing Interests: The authors declare no conflicts of interests., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Diagnostic testing is fundamental to medicine. However, studies of diagnostic testing in respiratory medicine vary significantly in terms of their methodology, definitions, and reporting of results. This has led to often conflicting or ambiguous results. To address this issue, a group of 20 respiratory journal editors worked to develop reporting standards for studies of diagnostic testing based on a rigorous methodology to guide authors, peer reviewers, and researchers when conducting studies of diagnostic testing in respiratory medicine. Four key areas are covered, including defining the reference standard of truth, measures of dichotomous test performance when used for dichotomous outcomes, measures of multichotomous test performance for dichotomous outcomes, and what constitutes a useful definition of diagnostic yield. The importance of using contingency tables for reporting results is addressed with examples from the literature. A practical checklist is provided as well for reporting studies of diagnostic testing., Competing Interests: Disclosure: D.E.O.: Research grant Intuitive Surgical, UpToDate author; prior ABIM test writing committee pulmonary medicine. D.F.K.: consulting fees from NOAH Medical, Boston Scientific and I am an Associate Editor for UpToDate. The remaining authors declare no conflict of interest or other disclosures., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Malignant pleural effusions (MPEs) are common and associated with a poor prognosis. Yet, many patients face suboptimal management characterized by repeated, nondefinitive therapeutic procedures and potentially avoidable hospital admissions., Methods: We conducted a retrospective comparison of patients who underwent a definitive palliative intervention for MPE (indwelling pleural catheter or pleurodesis) at our center, before and after the implementation of a pleural care program. Targeted interventions included staff education, establishment of formal pleural drainage policies, a pleural clinic with weekday walk-in capacity, and a rapid access pathway for oncology patients. Outcomes assessed were the proportion of emergency room (ER) presentations, hospitalizations, number of nondefinitive pleural procedures, and time-to-definitive palliative procedure., Results: A total of 144 patients were included: 69 in the preintervention group and 75 in the postintervention group. Although there was no difference in the proportion of ER presentations before and after interventions (43.5% vs. 38.7%, P =0.56), hospital admissions declined significantly (47.8% vs. 24.0%, P =0.003). The proportion of patients undergoing chest drain insertion decreased significantly (46.4% vs. 13.3%, P <0.001), with a stable low number of nondefinitive procedures per patient (1.6±1.1 vs. 1.3±0.9, P =0.32). A 7-day decrease in median time from presentation-to-definitive palliative procedure ( P =0.05) was observed., Conclusion: A targeted pleural care program improved MPE palliation through reduction in hospitalizations and chest drain use, and shorter time-to-definitive palliation, despite failing to reduce ER presentations., Competing Interests: Disclosure: S.B. reports educational grant from Olympus America Inc. B.S. reports funding from Novartis, Takeda, Bristol Myers Squibb, AstraZeneca, and Pfzier for consultation and speaker bureau activities. The remaining authors have no conflict of interest or other disclosures., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Individuals released from prisons to community supervision often experience unstable housing, unemployment, substance misuse, mental ill-health, and lack of support systems contributing to high rates of recidivism. Occupational therapy practitioners have distinct value in promoting engagement in new habits and routines to support "occupation," or development of daily living skills to support community reentry., Objective: We developed an occupational therapy (OT) program within a Department of Corrections (DOC) Community Supervision Center in the Midwest United States. The purpose of this study was to determine feasibility and efficacy of an OT program for community reentry., Methods: The program was piloted with a sample of five justice-involved men who received OT interventions. Pre- and post-test assessments included a behavioral health interview, demographic survey, five Patient-Reported Outcomes Measurement Information System (PROMIS) assessments, the Vulnerability Index-Service Prioritization Decision Assistance Tool (VI-SPDAT) and Activity Card Sort-Advancing Inclusive Assessment. Descriptive analyses were performed to determine goal attainment and compare pre- and post-test scores over time and to a reference population (PROMIS). Staff of the DOC were also interviewed to assess perceived feasibility and efficacy of this pilot., Results: Significant health changes were reported in participant self-efficacy, managing emotions, anxiety, and sleep disturbances (1 > SD). Moderate changes were seen in reduced feelings of social isolation (0.5 > 1SD)., Conclusion: It was feasible to implement an OT program with tailored reentry interventions based on unique needs of criminal justice involved individuals. Initial findings suggest OT offers health promotion benefits to reduce risk of recidivism and prepare individuals for community reentry following incarceration.

Competing Interests: Disclosure: There is no conflict of interest or other disclosures.

The field of diagnostic bronchoscopy has developed at an accelerated pace. Certain limitations have plagued the evaluation of advanced bronchoscopy techniques, including the use of inconsistently defined measures of diagnostic accuracy, and confusion around the definition of "diagnostic yield." This methodological review outlines standard measures of diagnostic accuracy and highlights how these differ from "diagnostic yield." We draw examples from the interventional bronchoscopy literature to illustrate key concepts and potential pitfalls., Competing Interests: Disclosure: There is no conflict of interest or other disclosures., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Smoking cessation integration within lung cancer screening programs is challenging. Currently, phone counselling is available across Canada for individuals referred by healthcare workers and by self-referral. We compared quit rates after phone counselling interventions between participants who self-refer, those referred by healthcare workers, and those referred by a lung cancer screening program., Methods: This is a retrospective cohort study of participants referred to provincial smoking cessation quit line in contemporaneous cohorts: self-referred participants, healthcare worker referred, and those referred by a lung cancer screening program if they were still actively smoking at the time of first contact. Baseline, covariates (sociodemographic information, smoking history, and history of mental health disorder) and quit intentions (stage of change, readiness for change, previous use of quit programs, and previous quit attempts) were compared among the three cohorts. Our primary outcome was defined as self-reported 30-day abstinence rates at 6 months. Multivariable logistic regression was used to identify whether group assignment was associated with higher quit rates., Results: Participants referred by a lung cancer screening program had low quit rates (12%, 95% CI: 5-19) at six months despite the use of phone counselling. Compared to patients who were self-referred to the smoking cessation phone helpline, individuals referred by a lung cancer screening program were much less likely to quit (adjusted OR 0.37; 95% CI: 0.17-0.8), whereas those referred by healthcare workers were twice as likely to quit (adjusted OR 2.16 (1.3-3.58)) even after adjustment for differences in smoking intensity and quit intentions., Conclusions: Phone counselling alone has very limited benefit in a lung cancer screening program. Participants differ significantly from those who are otherwise referred by healthcare workers. This study underlines the importance of a dedicated and personalized tobacco treatment program within every lung cancer screening program. The program should incorporate best practices and encourage treatment regardless of readiness to quit., Competing Interests: NE works as a consultant for the Programme Quebecois de Cancerologie lung cancer screening demonstration project. All other authors declare that they have no conflicts of interest., (Copyright © 2022 Ankita Ghatak et al.)

Inactivating mutations in SMARCA4 and concurrent epigenetic silencing of SMARCA2 characterize subsets of ovarian and lung cancers. Concomitant loss of these key subunits of SWI/SNF chromatin remodeling complexes in both cancers is associated with chemotherapy resistance and poor prognosis. Here, we discover that SMARCA4/2 loss inhibits chemotherapy-induced apoptosis through disrupting intracellular organelle calcium ion (Ca 2+ ) release in these cancers. By restricting chromatin accessibility to ITPR3, encoding Ca 2+ channel IP3R3, SMARCA4/2 deficiency causes reduced IP3R3 expression leading to impaired Ca 2+ transfer from the endoplasmic reticulum to mitochondria required for apoptosis induction. Reactivation of SMARCA2 by a histone deacetylase inhibitor rescues IP3R3 expression and enhances cisplatin response in SMARCA4/2-deficient cancer cells both in vitro and in vivo. Our findings elucidate the contribution of SMARCA4/2 to Ca 2+ -dependent apoptosis induction, which may be exploited to enhance chemotherapy response in SMARCA4/2-deficient cancers., (© 2021. The Author(s).)

Background: Anatomic variations in the hepatic venous system are the least understood aspect of hepatic anatomy. The variations are diverse, and data are lacking with respect to the population of Spain and methods of detection. The objective was to examine morphological patterns of variations in hepatic venous vascularization using cadaveric dissections vs. radiological imaging, and to analyze the findings with respect to Spain and to published studies., Methods: Thirty-one livers were anatomically dissected and analyzed for their hepatic venous anatomy and then compared to the venous anatomy of livers examined in 216 CT scans from 119 men and 97 women, ranging between 27 and 89 years of age. Statistical analysis was done using the Chi squared and Fisher homogeneity tests., Results: The hepatic portal vein showed morphological variations in cadavers vs. CT of 67.3% vs. 67.6% (p-I), 29% vs. 12.2% (p-II), 0% vs. 14.6% (p-III), 0% vs. 14.6% (p-IV), 3.2% vs. 0.5% (p-V) and 6.5% vs. 1.9% (p-VI), respectively in cadavers vs. CT. Hepatic vein pattern variation were found in 64.5% vs. 50.7% (h-I), 32.2% vs. 31.5% (h-II), 0% vs. 2.3% (h-III), 0% vs. 4.7% (h-IV), respectively in dissections vs. CT). In Accessory Hepatic Veins the frequency in pattern variation was 64.5% vs. 18.8% (a-2.1), 29.0% vs. 8.0% (a-2.2), 58.1% vs. 11.3% (a-2.3), 9.7% vs. 0.9% (a-2.4), 67.7% vs. 16.9% (a-2.5), 9.7% vs. 4.2% (a-2.6) and 0% vs. 0.5% (a-2.7), respectively, in cadavers vs. CT. CT showed in 27.2% no accessory hepatic veins. Sex was not a factor influencing patterns of variation., Conclusion: Anatomical variants of the hepatic portal vein, the hepatic vein and accessory hepatic veins are very diverse and show greater variability in the specimens compared to those detected with radiological images, finding a wider spectrum of variations as it allows the clinician to have a more precise definition of the vasculature. A higher precision in the definition of anatomical variations is warranted for surgical planning in liver resection and transplantation., (Copyright © 2021 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Background: Programmed death-ligand 1 (PD-L1) testing is feasible in most specimens acquired using endobronchial ultrasound-guided needle aspiration (EBUS-TBNA)., Research Question: Are the outcomes of patients with advanced non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICI) on the basis of PD-L1 expression in EBUS-TBNA samples significantly different from those of patients who are treated on the basis of PD-L1 expression in histological samples?, Study Design and Methods: Patients treated with pembrolizumab or nivolumab between June 2016 and 2019 were included. Patient characteristics, PD-L1 expression, line of treatment, response (Response Evaluation Criteria in Solid Tumors [RECIST] criteria), and vital status (May 14, 2020) were recorded. Progression-free survival (PFS) and overall survival (OS) were assessed, and hazard ratios (HR) estimated., Results: A total of 145 patients were treated with pembrolizumab or nivolumab on the basis of PD-L1 expression in EBUS-TBNA (31.7%) or histological (68.3%) samples. Most had metastatic disease, with a predominance of adenocarcinomas (64.1%). First-line pembrolizumab was administered to 61 patients with tumor proportion score ≥50% in EBUS-TBNA (n = 16) or histology samples (n = 45). Median OS and PFS of patients who received first-line pembrolizumab on the basis of PD-L1 results in EBUS-TBNA vs histology samples were not significantly different (OS 25.8 months vs not reached, respectively; HR, 0.82 [95% CI, 0.34-1.95], P = .651). Similarly, the median OS and PFS of patients who received subsequent lines of treatment on the basis of PD-L1 results in EBUS-TBNA vs histological samples were not significantly different (including after adjustment for PD-L1 expression)., Interpretation: These findings suggest that PD-L1 results in EBUS-TBNA samples can guide ICI therapy, with treatment outcomes being comparable to those of patients in whom PD-L1 expression was assessed in histological specimens., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Hypothesis: Fluorocarbon gases introduced above monolayers of phospholipids at the air/water interface were recently found to promote the adsorption of diverse molecular compounds, with potential application in drug-loaded microbubble design. Quantitative determination of the fluorocarbon present in the monolayers is strongly needed for the development of such applications. We hypothesized that neutron reflectometry (NR) and ellipsometry experiments would allow quantification of the fluorocarbon trapped in the monolayers., Experiments: We report the first quantitative determination of the extents of adsorption of perfluorohexane (F-hexane) on different phospholipid monolayers with respect to both their phase and isotopic form. To this aim, we applied an approach based on co-modeling the data obtained from NR and ellipsometry., Findings: We found that F-hexane adsorbs strongly in monolayers of dipalmitoylphosphatidylcholine (DPPC) when they are both in the liquid expanded (LE) and liquid condensed (LC) phases, but to different extents according to the isotopic form of the phospholipid. Kinetic resolution of the interfacial composition from data on both isotopic contrasts (assuming chemical identicality) was therefore not possible using NR alone, so an alternative NR/ellipsometry co-modeling treatment was applied to data from each isotopic contrast. F-hexane adsorbs more abundantly on monolayers of hydrogenous DPPC than chain-deuterated DPPC when they are in the LE phase, whilst the opposite was observed when they monolayers are in the LC phase. The extents of adsorption of F-hexane in monolayers of dimyristoylphosphatidylcholine (DMPC, LE phase) and distearoylphosphatidylcholine (DSPC, LC phase) concurs with the strong dependence of those with phospholipids of different isotopic contrasts according to the monolayer phase. This new methodology can lead to advances in the novel characterization of fluorocarbons interacting with phospholipid monolayers of relevance to applications such as in the shells of fluorocarbon-stabilized medically-oriented microbubbles., 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 © 2021 Elsevier Inc. All rights reserved.)

Objective: For the diagnosis of COVID-19, the yield of nasopharyngeal (NP) swabs is unclear, and bronchoalveolar lavage (BAL) is obtained to confirm the diagnosis. We assessed the utilisation of bronchoscopy for COVID-19 diagnosis in a multicenter study and compared the diagnostic yield of BAL versus NP swabs., Methods: This retrospective study included all patients who were admitted with clinical presentation concerning for COVID-19 and underwent BAL from 1 March to 31 July 2020 at four tertiary care centres in North America. We also compared concordance of BAL with NP swabs for diagnosis of COVID-19 infection., Results: Fifty-three patients, with clinical suspicion for COVID-19 and admitted for respiratory failure, underwent bronchoscopy to collect BAL for SARS-CoV-2 testing. During the same period, 2039 bronchoscopies were performed on patients not infected with COVID-19. Of 42 patients with NP swabs and BAL collected within ≤7 days, 1 was NP swab negative but positive by BAL for SARS-CoV-2 (n=1/42 (2.4%)). Across a wide array of testing platforms, the overall agreement between NP swabs and BAL results was 97.6% (95% CI: 93.0% to 100%) with Cohen's k of 0.90 (95% CI: 0.69 to 1.00). The sensitivity, specificity, positive and negative predictive values of NP swabs compared with BAL were 83.3% (95% CI: 53.5% to 100%), 100%, 100% and 97.3% (95% CI: 92.1% to 100%), respectively., Conclusions: BAL was used infrequently to assess COVID-19 in busy institutions. NP swabs have a high concordance with BAL for COVID-19 testing, but negative NP swabs should be confirmed with BAL when clinical suspicion is high., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Quality gaps exist in the diagnostic evaluation of lung cancer patients. The initial CT chest guides the workup of patients with suspected lung cancer. We sought to determine how frequently CT reports provided guideline-concordant recommendations with regard to additional imaging studies and/or invasive diagnostic procedures . Methods . This was a retrospective study. The records of patients referred for investigation of suspected lung cancer between January 1, 2015, and June 30, 2016, were reviewed. Patients with confirmed lung cancer, for whom CT scan images and reports were available, are included. CT reports were reviewed, with attention to additional imaging studies and/or invasive diagnostic procedures suggested. These recommendations were examined against current guidelines for lung cancer diagnosis and staging, based on suspected disease stage., Results: One hundred forty-six patients are included in the analysis. Most patients were diagnosed with non-small-cell lung cancer (NSCLC), and 63% had advanced disease (stages III and IV). Only 12% of CT reports contained guideline-concordant recommendations for additional imaging studies, with PET scan suggested in only 6% of reports. Potential invasive diagnostic procedures were suggested in one fifth of CT reports, and only 58% of these recommendations were in keeping with current guidelines. In particular, transthoracic needle aspiration (TTNA) was suggested in 26% of patients despite advanced stage disease., Conclusion: Guideline-concordant recommendations for investigation of suspected lung cancer are rarely available on CT reports. This is true with respect to both imaging studies and invasive diagnostic procedures. Incorporation of more evidence-based suggestions may reduce quality gaps in lung cancer diagnosis and staging., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Andrew Weinstock et al.)

A 58-year-old woman was diagnosed with severe endometriosis and had multiple gastrointestinal tract complications for many years. Candida auris and C. parapsilosis were isolated from the bloodstream. Identification of C. auris was confirmed by amplification and sequencing of the internal transcriber spacer and the D1/D2 domain of the large rRNA gene subunit. Antifungal susceptibility was tested in both isolates using the Clinical Laboratory Standards Institute protocol M27-A3/S4. The patient evolved favorably with systemic antifungal therapy consisting of caspofungin and liposomal amphotericin B.

The treatment of advanced lung cancer has become increasingly personalized over the past decade as a result of the improved understanding of tumor molecular biology and anti-tumor immunity. An adequate tumor sample is central to targetable mutation analysis, and immunologic profiling. The majority of lung cancer patients currently present at an advanced disease stage, so that diagnosis and staging are largely based on small biopsy and cytology specimens. Flexible bronchoscopy techniques play a prominent role in the acquisition of these diagnostic specimens. This narrative review summarizes the available evidence with regards to the role of various conventional and advanced flexible bronchoscopy techniques in acquiring sufficient tissue for mutation analysis and programmed death-ligand 1 (PD-L1) testing., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure forms (available at http://dx.doi.org/10.21037/jtd-19-4119). The series “Novel Diagnostic Techniques for Lung Cancer” was commissioned by the editorial office without any funding or sponsorship. SB reports non-financial support from Olympus America Inc., outside the submitted work. Dr. AVG reports grant support from the Rossy Cancer Network. The other authors have no other conflicts of interest to declare., (2020 Journal of Thoracic Disease. All rights reserved.)

Background: Inhaled corticosteroids (ICS) are suggested for potential chemoprevention of lung cancer. Several observational studies in patients with chronic obstructive pulmonary disease (COPD) reported inconsistent results, either significant reductions in lung cancer incidence with ICS use or no effect. We assessed this association, using an approach that avoided biases affecting some of the studies., Methods: A cohort of patients with COPD, new users of long-acting bronchodilators over 2000-2014, was formed using the Quebec healthcare databases, and followed until 2015 for a first diagnosis of lung cancer. A 1-year delay after cohort entry was used to avoid protopathic bias and a 1-year latency period was included after the initiation of ICS use. A time-dependent Cox regression model was used to estimate the hazard ratio (HR) of lung cancer associated with ICS exposure, adjusted for covariates., Results: The cohort involved 63 276 subjects, including 63% receiving ICS, with 3743 lung cancers occurring during a mean follow-up of 5 years. The adjusted HR of lung cancer associated with any ICS exposure was 1.01 (95% CI 0.94-1.08), relative to no ICS use. The HR with longer time (>4 years) since ICS initiation was 0.92 (95% CI 0.83-1.03), while with higher mean daily ICS dose (>1000 μg fluticasone equivalents) was 1.36 (95% CI 1.03-1.81)., Conclusions: Inhaled corticosteroid use is not associated with a reduction in lung cancer incidence in patients with COPD. Observational studies reporting such reduction may have been affected by time-related biases and the inclusion of patients with asthma. The proposition of a randomised trial warrants some caution., Competing Interests: Conflict of interest: S. Suissa reports grants and personal fees for advisory board work and lectures from Boehringer Ingelheim and Novartis, personal fees for lectures from AstraZeneca, outside the submitted work. Conflict of interest: S. Dell'Aniello has nothing to disclose. Conflict of interest: A.V. Gonzalez has nothing to disclose. Conflict of interest: P. Ernst has nothing to disclose., (Copyright ©ERS 2020.)

The PD-L1 (CD274) immune-checkpoint ligand is often upregulated in cancers to inhibit T cells and elicit immunosuppression. Independent of this activity, PD-L1 has recently been shown to also exert a cancer cell-intrinsic function promoting tumorigenesis. Here, we establish this tumor-intrinsic role of PD-L1 in triple-negative breast cancer (TNBC) and non-small cell lung cancer (NSCLC). Using FACS-assisted shRNA screens, we identified the cell-surface adhesion receptor CD44 as a key positive regulator of PD-L1 expression in these cancers. Mechanistically, CD44 activated PD-L1 transcription in part through its cleaved intracytoplasmic domain (ICD), which bound to a regulatory region of the PD-L1 locus containing a consensus CD44-ICD binding site. Supporting this genetic interaction, CD44 positively correlated with PD-L1 expression at the mRNA and protein levels in primary tumor samples of TNBC and NSCLC patients. These data provide a novel basis for CD44 as a critical therapeutic target to suppress PD-L1 tumor-intrinsic function. SIGNIFICANCE: CD44 is a potential target to suppress PD-L1 function in TNBC. This finding has the potential to open a new area of therapy for TNBC., (©2019 American Association for Cancer Research.)

Aims: The need to find new antimicrobial agents to cope with this phenomenon increases., Background: Infection diseases are illness caused by different microorganisms, such as bacteria, among those caused by resistant bacteria are associated with greater morbidity, mortality and cost of the treatment than those caused by sensitive bacteria of the same species., Objective: Need to find new antimicrobial agents to cope with this phenomenon increases., Methods: This work carried out the study of biological activities of Cissus incisa, taking account its traditional use. Three extracts were prepared from the leaves of this plant: hexane, chloroform methanol (1:1) and aqueous. Their antibacterial and antitubercular activities were evaluated using microdilution and alamar blue assays; respectively., Results: The chloroform/methanol extract (1:1) was the most active of the three tested extracts for antimicrobial activity. In this way, the extract exhibits a broad spectrum of antimicrobial activity, against the Gram positive and Gram negative bacteria tested, with MIC values between 125 to 500 μg/mL., Conclusion: This research contributes both to the knowledge of the Mexican flora, as well as the discovery of potential antibacterial agents derivate from plants., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Rationale: Immunotherapy has become an integral part of management in patients with advanced non-small cell lung cancer (NSCLC). Programmed death ligand 1 (PD-L1) expression in at least 50% of tumor cells on histologic samples has been correlated with improved efficacy of the immune checkpoint inhibitor pembrolizumab. A limited number of studies have examined the suitability of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) specimens for assessment of PD-L1 status., Objective: We sought to examine the feasibility and results of PD-L1 testing performed on EBUS-TBNA samples acquired for the diagnosis and staging of NSCLC., Materials and Methods: Patients were identified from a prospectively maintained pathology database. Baseline characteristics were tabulated. Hematoxylin and eosin slides were reviewed to categorize cellularity between <100, 100 to 500, and >500 viable tumor cells. Samples were tested using Dako's PD-L1 IHC 22C3 pharmDx kit, with a minimum of 100 viable tumor cells. For patients in whom additional tissue samples were available, the results of PD-L1 testing were compared., Results: PD-L1 testing was attempted on 120 EBUS-TBNA samples. The most common NSCLC subtype was adenocarcinoma (78%). Seventy-six specimens (63%) had a cellularity >500 tumor cells. Among 110 of 120 (92%) patients with an adequate endobronchial ultrasound (EBUS) sample, 53 of 110 (48.2%) had high PD-L1 expression, defined as a Tumor Proportion Score ≥50%. EBUS PD-L1 results were concordant with an available histologic sample in 14 of 18 patients (78%), with no false-negative results., Conclusion: PD-L1 testing was feasible in the majority of EBUS-TBNA samples acquired for the diagnosis and staging of NSCLC. Comparison of EBUS results with histologic samples revealed moderate concordance, with no false-negative results.

Precipitation reactions under flow in confined media are relevant to the control of pathological biomineralization, processes affecting aquifers, and challenges in the petroleum industry. Here we show that for a simple geometry, such conditions create macroscopic structures including helices, tubes, lamellae, slugs, and disordered patterns. All structures emerge when salt solution is slowly injected into thin capillaries filled with hydroxide solution. For the helices, the pitch is proportional to the pump rate revealing a constant period of 0.63 s. Different morphologies of the insoluble metal hydroxide can co-exist causing random transitions along the capillary. On average, 15 % of the final system contains residual hydroxide solution. While mechanically stable for flow speeds above 25 mm min -1 , structures collapse and sediment for slower injection speeds. Some of the observed features share similarities with precipitate tubes in chemical gardens and the dynamics of liquid-liquid pipe flow., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Stroke is a leading cause of death and disability. Tissue plasminogen activator (tPA) improves the clinical outcome when administered properly; however, the most important factor to receive tPA is time. The main reason for late hospital arrival is a considerable delay in onset-to-alarm time (OAT), comprising more than 50% of the onset-to-door time., Aims: To identify the factors associated with a delay in OAT and evaluate its contribution to onset-to-door time in ischemic stroke patients., Methods: Prospective cohort of stroke patients admitted to the UANL University Hospital. OAT was defined as the time from identification of stroke symptoms to the decision to seek medical attention., Results: A total of 189 patients were included. Mean age was 61 ± 13 years, 62% were men. One-hundred and one patients had a short OAT, but only 20.9% arrived during the first 3 hours after stroke onset. Being employed (P = 0032; odds ratio [OR] 2.784, 95% confidence interval [CI] 1.091-7.104), attributing symptoms to stroke (P = 0016; OR 3.348, 95% CI 1.254-8.936), and perceiving stroke symptoms as severe (P = 0031;OR 2.428, 95% CI 1.083-5.445) were associated with a shorter OAT., Conclusions: OAT consumes a considerable amount of the onset-to-door time. It is necessary to increase stroke knowledge and emphasize the severity of stroke, regardless of the severity of its clinical manifestations to reduce the prehospital delay, especially in countries with limited access to treatment with an extended time frame., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Tumor suppressor SMARCA4 (BRG1), a key SWI/SNF chromatin remodeling gene, is frequently inactivated in cancers and is not directly druggable. We recently uncovered that SMARCA4 loss in an ovarian cancer subtype causes cyclin D1 deficiency leading to susceptibility to CDK4/6 inhibition. Here, we show that this vulnerability is conserved in non-small cell lung cancer (NSCLC), where SMARCA4 loss also results in reduced cyclin D1 expression and selective sensitivity to CDK4/6 inhibitors. In addition, SMARCA2, another SWI/SNF subunit lost in a subset of NSCLCs, also regulates cyclin D1 and drug response when SMARCA4 is absent. Mechanistically, SMARCA4/2 loss reduces cyclin D1 expression by a combination of restricting CCND1 chromatin accessibility and suppressing c-Jun, a transcription activator of CCND1. Furthermore, SMARCA4 loss is synthetic lethal with CDK4/6 inhibition both in vitro and in vivo, suggesting that FDA-approved CDK4/6 inhibitors could be effective to treat this significant subgroup of NSCLCs.