Learning from the early careers of master clinicians.

Background: Master clinicians are recognized as multidimensional experts in clinical medicine. Studying their formative clinical activities could generate insights to guide medical trainees and early career clinicians.

Objectives: To investigate which early career activities were adopted more commonly by master clinicians than their matched peers and to characterize master clinicians' early career activities across institutions and specialties.

Pleural fluid microbiota as a biomarker for malignancy and prognosis.

Malignant pleural effusions (MPE) complicate malignancies and portend worse outcomes. MPE is comprised of various components, including immune cells, cancer cells, and cell-free DNA/RNA. There have been investigations into using these components to diagnose and prognosticate MPE.

Immunotherapy for mesothelioma: Moving beyond single immune check point inhibition.

Malignant pleural mesothelioma (MPM) is an aggressive neoplasm with low survival rates. Platinum-based chemotherapy has represented the cornerstone of treatment for over a decade, prompting the investigation of new therapeutic strategies both in the early stage of the disease and in the advanced setting. The advent of immune check-point inhibitors (ICIs) has recently revamped the enthusiasm for using immunotherapy also in MPM.

Osler Centenary Papers: Would Sir William Osler be a role model for medical trainees and physicians today?

If Sir William Osler were alive and practising as one of our contemporary colleagues, would he be viewed as a role model by medical trainees and other physicians? Recently published literature has sought to define clinical excellence; this characterisation of physician performance establishes a context in which role models in medicine can be appraised. Building on this framework, we present rich anecdotes and quotes from Sir William Osler himself, his colleagues, and his students to consider whether Osler would have been regarded as a role model for clinical excellence today. This paper illustrates convincingly that William Osler indeed personified clinical excellence and would have been appreciated as a consummate role model if he were alive and on a medical school's faculty today.

Tumor-draining lymph nodes demonstrate a suppressive immunophenotype in patients with non-small cell lung cancer assessed by endobronchial ultrasound-guided transbronchial needle aspiration: A pilot study.

Objectives: Tumor draining lymph nodes (TDLN) are key sites of early immunoediting in patients with non-small cell lung cancer (NSCLC) and play an important role in generating anti-tumor immunity. Immune suppression in the tumor microenvironment has prognostic implications and may predict therapeutic response. T cell composition of draining lymph nodes may reflect an immunophenotype with similar prognostic potential which could be measured during standard-of-care bronchoscopic assessment.

Intrapleural immunotherapy: An update on emerging treatment strategies for pleural malignancy.

Objectives: Malignant pleural mesothelioma and malignant pleural effusions are a major therapeutic challenge, and are associated with impairment in quality of life and increased mortality. Advances in systemic therapies of malignant pleural mesothelioma have demonstrated limited clinical benefit and there is ongoing interest in intrapleural immunotherapies which have been demonstrated to be well tolerated overall with variable clinical responses. We have reviewed the literature to provide a comprehensive summary of novel intrapleural immunotherapeutic paradigms, including oncolytic virus therapy, gene-mediated cytotoxic immunotherapy, direct cytokine-mediated immunotherapies, innate immunomodulators and adoptive transfer of intrapleural chimeric antigen receptor T-cell therapy.

An Inquiry Into the Early Careers of Master Clinicians.

Background: Residents and fellows often seek to emulate master clinician role models; however, the activities these expert clinical faculty pursued early in their careers are not known.

Objective: We studied the early career clinical experiences and learning behaviors of peer-defined master academic clinicians.

Methods: We performed a retrospective, qualitative interview study of 17 members of the University of California, San Francisco, Department of Medicine Council of Master Clinicians.

Airway Microbiota Is Associated with Upregulation of the PI3K Pathway in Lung Cancer.

Rationale: In lung cancer, upregulation of the PI3K (phosphoinositide 3-kinase) pathway is an early event that contributes to cell proliferation, survival, and tissue invasion. Upregulation of this pathway was recently described as associated with enrichment of the lower airways with bacteria identified as oral commensals.

Objectives: We hypothesize that host-microbe interactions in the lower airways of subjects with lung cancer affect known cancer pathways.

Local Immunotherapy of Cancer: Innovative Approaches to Harnessing Tumor-Specific Immune Responses.

Modern cancer immunotherapies represent a major shift in paradigm with respect to how we understand innate and adaptive responses to malignancy. Successful tumors co-opt normal immunosurveillance mechanisms by potent interactions between the tumor and local draining lymph nodes. Tumor cells mediate a complex and dynamic immunoediting procedure that results in increased vascular efflux into the draining lymphatics, an immunosuppressive microenvironment rich in regulatory T-lymphocytes, dysfunctional antigen presentation, and downregulation of normal effector lymphocyte responses.

Intracavitary Therapeutics for Pleural Malignancies.

Pleural malignancies remain a serious therapeutic challenge, and are frequently refractory to standard treatment; however, they have the advantage of occurring in an enclosed cavity readily accessible for examination, biopsy, and serial sampling. Novel therapeutics can be administered via intracavitary delivery to maximize efficacy by targeting the site of involvement and potentially mitigating the adverse effects of systemic therapies. The easy accessibility of the pleural space lends itself well to repeated sampling and analysis to determine efficacy and toxicity of a given treatment paradigm.

Medical thoracoscopy and its evolving role in the diagnosis and treatment of pleural disease.

Establishing the etiology of exudative pleural effusions in the setting of an unrevealing pleural fluid analysis often requires biopsies from the parietal pleura. While closed pleural biopsy (CPB) has been a popular minimally-invasive approach, it has a poor diagnostic yield, barring a diagnosis of tuberculous pleurisy. Medical thoracoscopy (MT) is a minimally-invasive ambulatory procedure performed under local anesthesia or moderate sedation which allows for direct visualization of biopsy targets as well as simultaneous therapeutic interventions, including chemical pleurodesis and indwelling tunneled pleural catheter (ITPC) placement.