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Aside from stressors that each of us experience directly, we also share the stress of the people around us. Such empathic stress exists on psychological and physiological levels, including subjective, sympathetic, parasympathetic and endocrine activation. The objective of this review is to offer an overview of methodology over the past fifteen years of empathic stress research and derive practical considerations for future research endeavors in the field. We used a keyword search strategy in the databases Web of Science, PsycInfo and PubMed to find empathic stress studies published until December 2023, and included 17 studies into our review. The reviewed laboratory studies provide initial yet consistent evidence for the existence of empathic stress across different populations, in intimate and stranger dyads, with direct and virtual contact, across multiple levels of the stress system, and based on diverse statistical analysis methods. We discuss all findings and derive practical considerations for future empathic stress research. The diversity of methods established provides a solid foundation upon which future studies can expand., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Despite combined anticoagulation therapy consisting of a vitamin K antagonist and an antiplatelet agent, thromboembolic complications often occur in patients with a left ventricular assist device (LVAD). In addition, bleeding events are also common. Resistance to antiplatelet drugs is a well-known phenomenon; however, the utilization of laboratory chemistry testing for the presence of such resistance, and then switching therapy, is controversial., Methods: We tested 132 patients with LVAD (HeartWare n = 57, HeartMate II n = 22, HeartMate 3 n = 53) on acetylsalicylic acid (ASA) therapy for resistance and followed them for a maximum of 7 years regarding pump thrombosis. Light transmission aggregometry (LTA) and impedance aggregometry (IPA) were performed for testing platelet function., Results: We could show that patients with ASA resistance displayed an increased risk of pump thrombosis, regardless of the test used (LTA: OR = 6.20, CI [1.86-20.64], p = 0.003; IPA: OR = 12.14, CI [3.00-49.07], p < 0.001). In patients with a HeartMate 3, we could not detect any pump thrombosis associated with aspirin resistance. Furthermore, there was no significant difference in bleeding events between patients with ASA resistance and ASA responders., Conclusion: Laboratory testing of ASA resistance seems to be a good tool to detect an increased risk of pump thrombosis, at least for patients with a HeartWare or HeartMate II. The extent to which these thromboses can be prevented with a change of medication has to be investigated in further studies. No pump thrombosis was detected in patients with a HeartMate 3, and the question should be asked as to what constellation of underlying and concomitant diseases must be present to justify ASA therapy for these patients., (© 2024 The Authors. Artificial Organs published by International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

Lobectomy has been the standard treatment for stage I lung cancer in healthy patients, largely based on a randomized trial published in 1995. Nevertheless, research has continued regarding the role of sublobar resection. Three additional randomized trials addressing resection extent in healthy patients have recently been published. These 4 trials involve differences in design, eligibility, interventions, and intraoperative processes. Patients were ineligible if intraoperative assessment demonstrated stage > IA or inadequate resection margins. All trials consistently show no differences in perioperative morbidity, mortality, and postoperative changes in lung function between sublobar resection and lobectomy-consistent with other nonrandomized evidence. Long-term outcomes are generally encouraging of lesser resection, but some inconsistencies are apparent. The 2 larger recent trials demonstrated no overall survival difference while the others suggested better survival after lobectomy versus sublobar resection. Recurrence-free survival was found to be the same after lobectomy versus sublobar resection in 3 trials, despite higher locoregional recurrences after sublobar resection. The low 5-year recurrence-free survival (64%, regardless of resection extent) in 1 recent trial highlights the need for further optimization. Thus, there is high-level evidence that sublobar resection is a reasonable alternative to lobectomy in healthy patients. However, variability in long-term results suggests that aspects of patients, tumors and interventions need to be better understood. Therefore, we propose to apply sublobar resection cautiously; especially because there are no short-term benefits. Sublobar resection requires careful attention to intraoperative details (nodes, margins), and may be best suited for less aggressive (eg, ground glass, slow growing) tumors., Competing Interests: Disclosure GA Woodard discloses research grants from the American Cancer Society, International Lung Cancer Foundation Young Investigator Award, and Yale Lung Cancer SPORE Career Enhancement Program; also AstraZeneca Advisory board consulting fees – all of these activities are unrelated to this work. All other authors (Frank Detterbeck, Sora Ely, Brooks Udelsman, Justin Blasberg, Daniel Boffa, Andrew Dhanasopon, Vincent Mase) have nothing to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Abstract: The coronavirus disease 2019 (COVID-19) pandemic disrupted health care systems, including implementation of lung cancer screening programs. The impact and recovery from this disruption on screening processes is not well appreciated. Herein, the radiology database of a Northeast tertiary health care network was reviewed before and during the pandemic (2013-2022). In the 3 months before the pandemic, an average of 77.3 lung cancer screening with computed tomography scans (LCS-CT) were performed per month. The average dropped to 23.3 between April and June of 2020, whereas COVID-19 hospitalizations peaked at 1604. By July, average hospitalizations dropped to 50, and LCS-CTs rose to >110 per month for the remaining year. LCS-CTs did not decline during COVID-19 surges in December of 2021 and 2022. The LCS-CT performance grew by 4.5% in 2020, 69.6% in 2021, and 27.0% in 2022, exceeding projected growth by 722 examinations. This resiliency indicates a potentially smaller impact of COVID-19 on lung cancer diagnoses than initially feared., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Interactions between immune and tumor cells are critical to determining cancer progression and response. In addition, preclinical prediction of immune-related drug efficacy is limited by interspecies differences between human and mouse, as well as inter-person germline and somatic variation. To address these gaps, we developed an autologous system that models the tumor microenvironment (TME) from individual patients with solid tumors., Method: With patient-derived bone marrow hematopoietic stem and progenitor cells (HSPCs), we engrafted a patient's hematopoietic system in MISTRG6 mice, followed by transfer of patient-derived xenograft (PDX) tissue, providing a fully genetically matched model to recapitulate the individual's TME. We used this system to prospectively study tumor-immune interactions in patients with solid tumor., Results: Autologous PDX mice generated innate and adaptive immune populations; these cells populated the TME; and tumors from autologously engrafted mice grew larger than tumors from non-engrafted littermate controls. Single-cell transcriptomics revealed a prominent vascular endothelial growth factor A (VEGFA) signature in TME myeloid cells, and inhibition of human VEGF-A abrogated enhanced growth., Conclusions: Humanization of the interleukin 6 locus in MISTRG6 mice enhances HSPC engraftment, making it feasible to model tumor-immune interactions in an autologous manner from a bedside bone marrow aspirate. The TME from these autologous tumors display hallmarks of the human TME including innate and adaptive immune activation and provide a platform for preclinical drug testing., Competing Interests: Competing interests: HHMI lab heads have previously granted a non-exclusive CC BY 4.0 license to the public and a sublicensable license to HHMI in their research articles. Pursuant to those licenses, the author-accepted manuscript of this article can be made freely available under a CC BY 4.0 license immediately upon publication. RF is an advisor to GlaxoSmithKline, EvolveImmune, and Ventus Therapeutics., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Purpose: To assess whether the effectiveness of thermal ablation (TA) and stereotactic body radiotherapy (SBRT) as initial treatments for stage I lung cancer varies depending on the histological subtype., Materials and Methods: The 2004-2016 National Cancer Database was queried for patients with American Joint Committee on Cancer stage I lung cancer treated with TA or SBRT. Patients <18 years, those treated with surgery or chemotherapy, or those with unknown survival and follow-up were excluded. TA and SBRT patients were 1:5 propensity score matched separately for each histological subtype to adjust for confounders. Overall survival (OS) was assessed using Cox models., Results: A total of 28,425 patients were included (SBRT, n = 27,478; TA, n = 947). TA was more likely to be used in Caucasian patients, those with more comorbidities and smaller neuroendocrine tumors (NETs) of the lower lobe, and those whose treatment had taken place in the northeastern United States. After propensity score matching, a cohort with 4,085 SBRT and 817 TA patients with balanced confounders was obtained. In this cohort, OS for TA and SBRT was comparable (hazard ratio = 1.07; 95% confidence interval,0.98-1.18; P = .13), although it varied by histological subtypes: higher OS for TA was observed in patients with non-small cell NETs (vs SBRT hazard ratio = 0.48; 95% confidence interval, 0.24-0.95; P = .04). No significant OS differences between TA and SBRT were noted for adenocarcinomas, squamous cell carcinomas, small cell carcinomas, and non-neuroendocrine large cell carcinomas (each, P > .1)., Conclusions: OS following TA and SBRT for stage I lung cancer is comparable for most histological subtypes, except that OS is longer after TA in non-small cell NETs., (Copyright © 2021. Published by Elsevier Inc.)

Minimally invasive surgery for diseases of the chest offsets the morbidity of painful thoracic incisions while allowing for meticulous dissection of major anatomic structures. This benefit translates to improved outcomes and recovery following the surgical management of benign and malignant esophageal pathologic condition, mediastinal tumors, and lung resections. This anatomic region is particularly amenable to a robotic approach given the fixed space and need for complex intracorporeal dissection. As robotic platforms continue to evolve, more complex thoracic surgical interventions will be facilitated, translating to improved outcomes for our patients., Competing Interests: Disclosure Nothing to disclose (G. Schwartz); Intuitive Surgical (M. Sancheti); Intuitive Surgical (J. Blasberg)., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Lung cancer mortality rate can be significantly reduced by up to 20% through routine low-dose computed tomography (LDCT) screening, which, however, has high sensitivity but low specificity, resulting in a high rate of false-positive nodules. Combining PET with CT may provide more accurate diagnosis for indeterminate screening-detected nodules. In this work, we investigated low-dose dynamic 18 F-FDG PET in discrimination between benign and malignant nodules using a virtual clinical trial based on patient study with ground truth. Six patients with initial LDCT screening-detected lung nodules received 90 min single-bed PET scans following a 10 mCi FDG injection. Low-dose static and dynamic images were generated from under-sampled list-mode data at various count levels (100%, 50%, 10%, 5%, and 1%). A virtual clinical trial was performed by adding nodule population variability, measurement noise, and static PET acquisition start time variability to the time activity curves (TACs) of the patient data. We used receiver operating characteristic (ROC) analysis to estimate the classification capability of standardized uptake value (SUV) and net uptake constant K i from their simulated benign and malignant distributions. Various scan durations and start times (t * ) were investigated in dynamic Patlak analysis to optimize simplified acquisition protocols with a population-based input function (PBIF). The area under curve (AUC) of ROC analysis was higher with increased scan duration and earlier t * . Highly similar results were obtained using PBIF to those using image-derived input function (IDIF). The AUC value for K i using optimized t * and scan duration with 10% dose was higher than that for SUV with 100% dose. Our results suggest that dynamic PET with as little as 1 mCi FDG could provide discrimination between benign and malignant lung nodules with higher than 90% sensitivity and specificity for patients similar to the pilot and simulated population in this study, with LDCT screening-detected indeterminate lung nodules.

The landscape of care for early-stage non-small cell lung cancer continues to evolve. While some of the developments do not seem as dramatic as what has occurred in advanced disease in recent years, there is a continuous improvement in our ability to diagnose disease earlier and more accurately. We have an increased understanding of the diversity of early-stage disease and how to better tailor treatments to make them more tolerable without impacting efficacy. The International Association for the Study of Lung Cancer and the Journal of Thoracic Oncology publish this annual update to help readers keep pace with these important developments. Experts in the care of early-stage lung cancer patients have provided focused updates across multiple areas including screening, pathology, staging, surgical techniques and novel technologies, adjuvant therapy, radiotherapy, surveillance, disparities, and quality of life. The source for information includes large academic meetings, the published literature, or novel unpublished data from other international oncology assemblies., (Copyright © 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Membrane transporters P-glycoprotein [P-gp; multidrug resistance 1 (MDR1)], multidrug resistance-associated protein (MRP) 2, and breast cancer resistance protein (BCRP) affect drug absorption and disposition and can also mediate drug-drug interactions leading to safety/toxicity concerns in the clinic. Challenges arise with interpreting cell-based transporter assays when substrates or inhibitors affect more than one actively expressed transporter and when endogenous or residual transporter activity remains following overexpression or knockdown of a given transporter. The objective of this study was to selectively knock out three drug efflux transporter genes (MDR1, MRP2, and BCRP), both individually as well as in combination, in a subclone of Caco-2 cells (C2BBe1) using zinc finger nuclease technology. The wild-type parent and knockout cell lines were tested for transporter function in Transwell bidirectional assays using probe substrates at 5 or 10 μM for 2 hours at 37°C. P-gp substrates digoxin and erythromycin, BCRP substrates estrone 3-sulfate and nitrofurantoin, and MRP2 substrate 5-(and-6)-carboxy-2',7'-dichlorofluorescein each showed a loss of asymmetric transport in the MDR1, BCRP, and MRP2 knockout cell lines, respectively. Furthermore, transporter interactions were deduced for cimetidine, ranitidine, fexofenadine, and colchicine. Compared with the knockout cell lines, standard transporter inhibitors showed substrate-specific variation in reducing the efflux ratios of the test compounds. These data confirm the generation of a panel of stable Caco-2 cell lines with single or double knockout of human efflux transporter genes and a complete loss of specific transport activity. These cell lines may prove useful in clarifying complex drug-transporter interactions without some of the limitations of current chemical or genetic knockdown approaches., (Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.)

A limitation of the traditional Caco-2 cell assay for measuring transporter-mediated efflux of a given substrate is that it is not possible to determine which specific transporter is involved. The methods in this unit describe an approach for generating specific transporter knockout cell lines that can be used to test efflux with any desired substrates. In this approach, human C2BBe1 cells (a subclone of Caco-2 cells) are nucleofected with specific zinc finger nucleases (ZFN), which can be designed to target any gene of interest and generate a double-stranded break. The cell's normal repair mechanisms can then generate targeted deletions (or integrations). A single ZFN can be used to generate a single transporter knockout, or multiple ZFNs can be used to knock out more than one transporter. This unit provides all methods needed to design the required plasmids, generate and identify transporter knockout cell lines, verify their membrane integrity, and test them with functional transport assays., (© 2012 by John Wiley & Sons, Inc.)

Introduction: As CT screening is integrated into non-small cell lung cancer (NSCLC) care, additional parameters are needed to help distinguish cancers from benign nodules. Osteopontin (OPN), a secreted phosphoprotein, has elevated plasma levels in NSCLC. We hypothesize that changes in plasma OPN over time (i.e., OPN velocity [OPNV]) can differentiate NSCLC patients from those without cancer in a CT screening population., Methods: A nested case-control study was conducted within a NSCLC CT screening trial. Incident cancers with serial plasma were matched to controls. OPN was measured by ELISA. Demographic, OPN, and OPNV were compared between cancers and controls using Wilcoxon Signed Rank tests., Results: Ten incident cancers were identified. The pack years distributions were similar, but cancers were older (median of the paired difference: 5.35 years; p=0.002) and their surveillance intervals were shorter (median of the paired difference: -2 months; p=0. 03) than matched controls. Baseline OPN was similar (median of the paired difference: -5.15 ng/ml, p=0.50), but OPNV in the cancers was significantly greater than that of matched controls, (median of the paired difference: 1.06 ng/ml/month, p=0.01). Accuracy rate for prediction of disease status based on OPNV (adjusted for age and surveillance) was 83%., Conclusions: These are early evidence for utility of monitoring plasma OPN during CT screening to assist in identification of NSCLCs.