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Human myiasis is characterized by larval infestation of body tissues or cavities of live individuals. Although most frequently observed in underdeveloped and tropical countries, reports of human myiasis have been encountered throughout the world. Conventional treatment is the mechanical removal of the larvae, one by one, which is painful and embarrassing and repugnant to both health professional and patient. Even though human myiasis is not considered rare, most dental professionals have very little knowledge of the diagnosis and treatment of this pathology. The purpose of this article, therefore, is to report a case of advanced-stage oral myiasis in a 9-year-old patient treated at a health and dentistry clinic. Diagnosis was based on visual observation of Cochliomyia hominivorax larvae, a dipterous fly of the Calliphoridae family, which were between the second and third stages of development. Predisposition factors include lack of information, malnutrition, poor oral hygiene, preexistence of oral lesions, and severe halitosis, which decisively influence the appearance and development of oral myiasis. A brief review of the literature is also included, in which the importance of early clinical diagnosis, myiasis etiology, and possible associations with other pathologies and different types of treatment are discussed. [ABSTRACT FROM AUTHOR]

Background: Treatment strategy for patients with adequately staged cT2N0M0 carcinoma of the thoracic esophagus is currently a subject of debate. This study analyzed the largest series of consecutive cT2N0M0 esophageal cancer patients treated with preoperative chemoradiotherapy.Methods: Data from all patients with cT2N0M0 (assessment included endoscopic ultrasonography and computed tomography of the chest and abdomen) thoracic esophageal cancer who were treated with preoperative chemoradiation between 1997 and 2009 were analyzed. The Cox regression model and Kaplan-Meier plots were used to analyze the data.Results: Data from 49 patients were analyzed. The median follow-up was 28.46 months. Male sex and adenocarcinoma histology predominated. Pathologic complete response was observed 19 (39%) patients. The 10-year actuarial overall survival (OS) for adenocarcinoma patients was >60%. In the univariate analysis for OS, squamous histology (P = .006), smoking (P = .015), and alcohol consumption (P = .032) were found to be associated with poor OS. In the univariate analysis for disease-free survival (DFS), squamous histology (P = .009) and smoking (P = .014) were associated with poor DFS. In the multivariate analysis for OS, smoking was an independent prognosticator (P = .02). In the multivariate analysis for DFS, advanced pathologic stage (P = .05) and lymph node metastases (P = .006) were independent prognosticators. Patients with adenocarcinoma (P = .002) and those with pathologic N0 disease had better OS and DFS. Upward stage migration occurred in only 10% of patients.Conclusions: These data suggest that smoking and alcohol influence the long-term outcome of patients with cT2N0M0 disease. Adenocarcinoma patients treated with trimodality therapy had an excellent actuarial 10-year OS and a high rate of pathologic complete response. Trimodality therapy should be prospectively compared with primary surgery in these patients. [ABSTRACT FROM AUTHOR]

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This article presents a rare case of nodular mucinosis of the breast, typically manifested as a painless subcutaneous mass in young women. We describe the clinical scenario of a 48-year-old woman who previously underwent benign nodule resection in her 20s at the identical site where nodular mucinosis subsequently developed. This recurrence at the previous resection site underscores the unusual nature of the condition and emphasizes the need for continued vigilance in monitoring patients with a history of such lesions., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Sandoval-Mussi et al.)

Background: The presence of lymphovascular invasion (LVI) in early esophageal adenocarcinoma (EAC) is associated with more aggressive disease. Molecular markers associated with LVI are still largely unknown. Using a combination of transcriptomic analysis and validation experiments, we sought to describe markers for LVI and survival., Methods: We performed NanoString expression profiling using RNA from 60 EAC specimens collected from surgery-only cases between 2000 and 2012. Differentially expressed genes (DEGs) were correlated with pathologic characteristics (T and N status and presence of LVI). Kaplan-Meier and Cox regression analyses were used to correlate gene expression with overall survival. Expression of alanyl aminopeptidase, membrane (ANPEP)/CD13 was validated by immunohistochemistry (IHC) in EAC tissue microarray and in EAC cell lines., Results: We identified >20 up-regulated DEGs in tumor samples containing LVI. Multivariable analysis showed depth of invasion and ANPEP/CD13 expression were independently associated with overall survival, whereas nodal status was not. IHC analysis demonstrated overexpression of the ANPEP/CD13 protein in dysplastic Barrett esophagus and EAC tumors. Kaplan-Meier analysis showed that patients with higher RNA expression and strongly positive ANPEP/CD13 membrane IHC-Histoscore staining have shorter survival (P = .002). Down-regulation of ANPEP/CD13 expression by short hairpin RNA vector reduces colony formation, migration, and invasion of FLO-1 EAC cells. Overexpression of CD13 in SKGT4 EAC cells increases colony formation, motility, and invasion in vitro., Conclusions: Elevated expression of ANPEP/CD13 indicates shorter survival of EAC patients and a more invasive phenotype of cancer cells in vitro. Validation in a larger sample group is required to better understand the clinical significance of ANPEP/CD13 and other candidate genes., (Copyright © 2024 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate overall survival and length of stay (LOS) associated with differing management for high output (>1 L over 24 hours) leaks (HOCL) after cancer-related esophagectomy., Background: Although infrequent, chyle leak after esophagectomy is an event that can lead to significant perioperative sequelae. Low-volume leaks appear to respond to nonoperative measures, whereas HOCLs often require invasive therapeutic interventions., Methods: From a prospective single-institution database, we retrospectively reviewed patients treated from 2001 to 2021 who underwent esophagectomy for esophageal cancer. Within that cohort, we focused on a subgroup of patients who manifested a HOCL postoperatively. Clinicopathologic and operative characteristics were collected, including hospital LOS and survival data., Results: A total of 53/2299 patients manifested a HOCL. These were mostly males (77%), with a mean age of 62 years. Of this group, 15 patients received nonoperative management, 15 patients received prompt (<72 hours from diagnosis) interventional management, and 23 received late interventional management. Patients in the late intervention group had longer LOSs compared with early intervention (slope = 9.849, 95% CI: 3.431-16.267). Late intervention (hazard ratio: 4.772, CI: 1.384-16.460) and nonoperative management (hazard ratio: 4.731, CI: 1.294-17.305) were associated with increased mortality compared with early intervention. Patients with early intervention for HOCL had an overall survival similar to patients without chyle leaks in survival analysis., Conclusions: Patients with HOCL should receive early intervention to possibly reverse the prognostic implications of this potentially detrimental complication., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Reconstructing defects after resecting soft-tissue sarcoma (STS) can be challenging. The aim of this retrospective study was to analyze the reconstructive outcomes and identify the potential risk factors in patients undergoing reconstruction after excision of lower-extremity STS., Methods: Patients with lower-extremity STS were included. This database was compiled of patients from a single, large National Cancer Institute-accredited academic hospital. In total, 302 patients were included between January 2016 to January 2022. Univariate and multivariate analyses were performed to calculate odds ratios (ORs) for developing complications for each patient and surgical characteristic., Results: The following factors were independent predictors of any complication: benign pulmonary disease (OR = 4.2; p = 0.02), preoperative radiotherapy (RT; OR = 2.5; p = 0.047), a tumor in the medial thigh (OR = 1.9; p = 0.03), body mass index (BMI) > 30 kg/m 2 (OR = 1.05; p = 0.037), and full-thickness skin graft (OR = 5.4; p = 0.01). In the preoperative RT subgroup, reconstructing a defect via undermining and layered closure alone was an independent predictor of dehiscence (OR = 2.1; p = 0.02) and seroma (OR = 3.1; p = 0.02), whereas pedicled flaps (OR = 0.08; p = 0.001) and free flaps (OR = 0.05; p = 0.001) were independent protectors against any complication., Conclusion: Information derived from this analysis will assist with accurate preoperative patient counseling, which is crucial for informed decision-making and expectation management in lower-extremity STS. BMI and pulmonary function should be optimized to the extent possible to reduce postoperative complications. Patients treated preoperatively with RT should be reconstructed with a pedicled or free flap to optimize recovery., (Copyright © 2023 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Objectives: Disparities in cancer care are omnipresent and originate from a multilevel set of barriers. Our objectives were to describe the likelihood of undergoing surgery for early-stage non-small cell lung cancer at minority-serving hospitals (MSHs), and evaluate the association of race/ethnicity with resection based on MSH status., Methods: A retrospective study using the National Cancer Database (2008-2016) was conducted including patients with clinical stage I non-small cell lung cancer. MSHs were defined as hospitals in the top decile of providing care to Hispanic or African American patients. The primary outcome evaluated was receipt of definitive surgery at MSHs vs non-MSHs. Outcomes related to race/ethnicity stratified by hospital type were also investigated., Results: A total of 142,580 patients were identified from 1192 hospitals (120 MSHs and 1072 non-MSHs). Most patients (85% [n = 121,240]) were non-Hispanic White, followed by African American (9% [n = 12,772]), and Hispanic (3%, [n= 3749]). MSHs cared for 7.4% (n = 10,491) of the patients included. In adjusted analyses, patients treated at MSHs were resected less often than those at non-MSHs (odds ratio, 0.87; 95% CI, 0.76-1.00; P = .0495). African American patients were less likely to receive surgery in the overall analysis (P < .01), and at MSHs specifically (P < .01), compared with non-Hispanic White patients. Hispanic patients had similar rates of resection in the overall analysis (P = .11); however, at MSHs, they underwent surgery more often compared with non-Hispanic White patients (P = .02). Resected patients at MSHs had similar overall survival (median, 91.7 months; 95% CI, 86.6-96.8 months) compared with those resected at non-MSHs (median, 85.7 months; 95% CI, 84.5-86.8 months)., Conclusions: Patients with early-stage non-small cell lung cancer underwent resection less often at MSHs compared with non-MSHs. Disparities related to underutilization of surgery for African American patients continue to persist, regardless of hospital type., (Copyright © 2023 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Purpose: Mastectomy, breast reconstruction (BR) and breast conserving therapy (BCT) are core components of the treatment paradigm for early-stage disease but are differentially associated with significant financial burdens. Given recent price transparency regulations, we sought to characterize rates of disclosure for breast cancer-related surgery, including mastectomy, BCT, and BR (oncoplastic reconstruction, implant, pedicled flap and free flap) and identify associated factors., Methods: For this cross-sectional analysis, cost reports were obtained from the Turquoise Health price transparency platform for all U.S. hospitals meeting national accreditation standards for breast cancer care. The Healthcare Cost Report Information System was used to collect facility-specific data. Addresses were geocoded to identify hospital referral and census regions while data from CMS was also used to identify the geographic practice cost index. We leveraged a Poisson regression model and relevant Medicare billing codes to analyze factors associated with price disclosure and the availability of an OOP price estimator., Results: Of 447 identified hospitals, 221 (49.4%) disclosed prices for mastectomy and 188 42.1%) disclosed prices for both mastectomy and some form of reconstruction including oncoplastic reduction (n = 184, 97.9%), implants (n = 187, 99.5%), pedicled flaps (n = 89, 47.3%), and free flaps (n = 81, 43.1%). Non-profit status and increased market competition were associated with price nondisclosure. 121 hospitals (27.1%) had an out-of-pocket price estimator that included at least one breast surgery., Conclusions: Most eligible hospitals did not disclose prices for breast cancer surgery. Distinct hospital characteristics were associated with price disclosure. Breast cancer patients face persistent difficulty in accessing costs., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Rationale: Pulmonary function testing (PFT) is performed to aid patient selection before surgical resection for non-small cell lung cancer (NSCLC). The interpretation of PFT data relies on normative equations, which vary by race, but the relative strength of association of lung function using race-specific or race-neutral normative equations with postoperative pulmonary complications is unknown. Objectives: To compare the strength of association of lung function, using race-neutral or race-specific equations, with surgical complications after lobectomy for NSCLC. Methods: We studied 3,311 patients who underwent lobectomy for NSCLC and underwent preoperative PFT from 2001 to 2021. We used Global Lung Function Initiative equations to generate race-specific and race-neutral normative equations to calculate percentage predicted forced expiratory volume in 1 second (FEV 1 %). The primary outcome of interest was the occurrence of postoperative pulmonary complications within 30 days of surgery. We used unadjusted and race-adjusted logistic regression models and least absolute shrinkage and selection operator analyses adjusted for relevant comorbidities to measure the association of race-specific and race-neutral FEV 1 % with pulmonary complications. Results: Thirty-one percent of patients who underwent surgery experienced pulmonary complications. Higher FEV 1 , whether measured with race-neutral (odds ratio [OR], 0.98 per 1% change in FEV 1 % [95% confidence interval (CI), 0.98-0.99]; P  < 0.001) or race-specific (OR, 0.98 per 1% change in FEV 1 % [95% CI, 0.98-0.98]; P  < 0.001) normative equations, was associated with fewer postoperative pulmonary complications. The area under the receiver operator curve for pulmonary complications was similar for race-adjusted race-neutral (0.60) and race-specific (0.60) models. Using least absolute shrinkage and selection operator regression, higher FEV 1 % was similarly associated with a lower rate of pulmonary complications in race-neutral (OR, 0.99 per 1% [95% CI, 0.98-0.99]) and race-specific (OR, 0.99 per 1%; 95% CI, 0.98-0.99) models. The marginal effect of race on pulmonary complications was attenuated in all race-specific models compared with all race-neutral models. Conclusions: The choice of race-specific or race-neutral normative PFT equations does not meaningfully affect the association of lung function with pulmonary complications after lobectomy for NSCLC, but the use of race-neutral equations unmasks additional effects of self-identified race on pulmonary complications.

Background: Risk factors for carbapenem resistance in Enterobacterales bloodstream infections among children with cancer or post-HSCT have not been thoroughly explored., Methods: All children with cancer or post-HSCT who developed Enterobacterales bloodstream infections in two cancer referral centres in major Colombian cities between 2012 and 2021 were retrospectively examined. When the infection episode occurred, carbapenem resistance mechanisms were evaluated according to the available methods. Data were divided in a training set (80%) and a test set (20%). Three internally validated carbapenem-resistant Enterobacterales (CRE) prediction models were created: a multivariate logistic regression model, and two data mining techniques. Model performances were evaluated by calculating the average of the AUC, sensitivity, specificity and predictive values., Results: A total of 285 Enterobacterales bloodstream infection episodes (229 carbapenem susceptible and 56 carbapenem resistant) occurred [median (IQR) age, 9 (3.5-14) years; 57% male]. The risk of CRE was 2.1 times higher when the infection was caused by Klebsiella spp. and 5.8 times higher when a carbapenem had been used for ≥3 days in the previous month. A model including these two predictive variables had a discriminatory performance of 77% in predicting carbapenem resistance. The model had a specificity of 97% and a negative predictive value of 81%, with low sensitivity and positive predictive value., Conclusions: Even in settings with high CRE prevalence, these two variables can help early identification of patients in whom CRE-active agents are unnecessary and highlight the importance of strengthening antibiotic stewardship strategies directed at preventing carbapenem overuse., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Although immunotherapy (IO) has changed the paradigm for the treatment of patients with advanced non-small cell lung cancers (aNSCLC), only around 30% to 50% of treated patients experience a long-term benefit from IO. Furthermore, the identification of the 30 to 50% of patients who respond remains a major challenge, as programmed Death-Ligand 1 (PD-L1) is currently the only biomarker used to predict the outcome of IO in NSCLC patients despite its limited efficacy. Considering the dynamic complexity of the immune system-tumor microenvironment (TME) and its interaction with the host's and patient's behavior, it is unlikely that a single biomarker will accurately predict a patient's outcomes. In this scenario, Artificial Intelligence (AI) and Machine Learning (ML) are becoming essential to the development of powerful decision-making tools that are able to deal with this high-complexity and provide individualized predictions to better match treatments to individual patients and thus improve patient outcomes and reduce the economic burden of aNSCLC on healthcare systems. I 3 LUNG is an international, multicenter, retrospective and prospective, observational study of patients with aNSCLC treated with IO, entirely funded by European Union (EU) under the Horizon 2020 (H2020) program. Using AI-based tools, the aim of this study is to promote individualized treatment in aNSCLC, with the goals of improving survival and quality of life, minimizing or preventing undue toxicity and promoting efficient resource allocation. The final objective of the project is the construction of a novel, integrated, AI-assisted data storage and elaboration platform to guide IO administration in aNSCLC, ensuring easy access and cost-effective use by healthcare providers and patients., (Copyright © 2023. Published by Elsevier Inc.)

Coral reefs are declining worldwide primarily because of bleaching and subsequent mortality resulting from thermal stress. Currently, extensive efforts to engage in more holistic research and restoration endeavors have considerably expanded the techniques applied to examine coral samples. Despite such advances, coral bleaching and restoration studies are often conducted within a specific disciplinary focus, where specimens are collected, preserved, and archived in ways that are not always conducive to further downstream analyses by specialists in other disciplines. This approach may prevent the full utilization of unexpended specimens, leading to siloed research, duplicative efforts, unnecessary loss of additional corals to research endeavors, and overall increased costs. A recent US National Science Foundation-sponsored workshop set out to consolidate our collective knowledge across the disciplines of Omics, Physiology, and Microscopy and Imaging regarding the methods used for coral sample collection, preservation, and archiving. Here, we highlight knowledge gaps and propose some simple steps for collecting, preserving, and archiving coral-bleaching specimens that can increase the impact of individual coral bleaching and restoration studies, as well as foster additional analyses and future discoveries through collaboration. Rapid freezing of samples in liquid nitrogen or placing at -80 °C to -20 °C is optimal for most Omics and Physiology studies with a few exceptions; however, freezing samples removes the potential for many Microscopy and Imaging-based analyses due to the alteration of tissue integrity during freezing. For Microscopy and Imaging, samples are best stored in aldehydes. The use of sterile gloves and receptacles during collection supports the downstream analysis of host-associated bacterial and viral communities which are particularly germane to disease and restoration efforts. Across all disciplines, the use of aseptic techniques during collection, preservation, and archiving maximizes the research potential of coral specimens and allows for the greatest number of possible downstream analyses., Competing Interests: Robert J. Toonen is a PeerJ Section Editor. The authors declare that they have no competing interests.

Introduction: Complete pathologic response (CPR) is an acceptable surrogate for survival in clinical trials but it occurs infrequently in patients with NSCLC receiving neoadjuvant chemotherapy (NCT). Therefore, we studied the impact of major pathologic response (MPR) for predicting survival of patients with NSCLC receiving NCT. We also tested a newly reported scoring system-the prognostic score (PRSC)-which combines T category, lymph node status, and MPR status., Methods: We analyzed CPR and MPR, defined as 0% and less than or equal to 10% viable tumor cells, respectively, in 339 patients with NSCLC with various histologic types who had been treated with NCT followed by complete surgical resection. We evaluated the relationships between CPR, MPR, or PRSC and overall survival using the Kaplan-Meier method and Cox regression multivariate models, accounting for known prognostic factors, such as age, gender, histologic subtype, and pathologic stage., Results: Among all 339 patients, the Kaplan-Meier method revealed that patients with CPR and MPR had better survival. MPR identified a favorable group of patients who experienced survival similar to patients with CPR. Nevertheless, patients with no MPR had a significantly reduced probability of survival. Furthermore, univariate and multivariate Cox proportional hazards regression analysis revealed that MPR and PRSC were significantly associated with overall survival., Conclusions: Our data suggest that MPR can be used as an end point for overall survival in different histologic types for evaluation of therapeutic agents in clinical trials exploring NCT. We also confirmed that PRSC had a prognostic impact, differentiating patients into three prognostic groups, but not superior compared with MPR alone or the TNM8 systems., (© 2022 The Authors.)

Background: Little is known regarding the impact of operating room (OR) personnel generation on their perceptions to various surgeon behaviors. We aimed to characterize these relationships by evaluating their responses to 5 realistic intraoperative scenarios., Methods: Operating room personnel were asked to assess surgeon OR behavior across a standardized set of 5 scenarios via an online survey. For each scenario, respondents were asked to identify the behavior as either acceptable, unacceptable but would ignore, unacceptable and would confront the surgeon, or unacceptable and would report to management. Chi-squared analyses were used to compare responses to surgeon behavior with respondent generation., Results: There were 3101 respondents, of which 41% of respondents were baby boomers (n = 1280), 31% were generation (Gen) X (n = 955), and 28% were Gen Y (n = 866). Overall, when compared to Gen X or Gen Y, baby boomers were significantly more likely to find surgeon behaviors of impatience ( P < .001), being late for a case ( P < .001), swearing in the OR ( P < .001), and shouting with a bleeding patient ( P = .001) to be inappropriate and would talk to the surgeon. Alternatively, Gen Y respondents were more likely to find fault with surgeon behaviors that deviate from rules and regulations, such as forgetting a time-out ( P = .001), when compared to baby boomers and Gen X respondents., Discussion: Results of our study demonstrate that OR personnel generation affects their perceptions and response to surgeon behavior. Understanding these tendencies can guide efforts to improve OR interactions among team members.

Background: Multiple investigations have shown inferior outcomes for esophageal cancer patients with signet ring cell (SRC) histology. Traditionally, SRC adenocarcinoma has been defined by ≥50% of the tumor composed of SRC. We hypothesized that patients with SRC even <50% would show resistance to standard multimodality therapy with poorer long-term outcomes., Methods: Patients treated with trimodality therapy for adenocarcinoma from 2006 to 2018 were evaluated for SRC on pretreatment biopsy specimens. Available hematoxylin and eosin slides containing SRC tumors were re-reviewed by an esophageal pathologist to quantify the percent composition of SRC., Results: SRC histology was identified on at least 1 pathologic specimen in 106 of 819 (13%) patients. Rates of pathologic complete response (pCR) among usual-type and SRC tumors were 25% (177/713) and 10% (11/106), respectively (P = .006). The pretreatment SRC components did not independently affect the rate of pCR (1%-10% SRC: 4% [2/46] pCR; 11%-49% SRC: 25% [7/28] pCR; 50%-100% SRC: 7% [2/30] pCR). Kaplan-Meier analysis demonstrated worse survival among patients with any degree of SRC present on pretreatment biopsy, as compared with usual-type esophageal adenocarcinoma (P < .0001). Cox multivariable analysis failed to identify a relationship between increasing SRC component and poorer survival., Conclusions: We present the only known evaluation of the percentage of SRC component in esophageal carcinoma. Our data support the hypothesis that esophageal adenocarcinoma with any component of SRC are more resistant to chemoradiation with poorer survival. Pathologic reporting of esophageal adenocarcinoma should include any component of SRC. Alternative therapies in patients with any SRC component may be indicated., (Copyright © 2020 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Introduction: Major pathologic response (MPR), defined as residual viable tumor of less than or equal to 10%, currently serves as a surrogate end point for survival for patients with resectable NSCLC after neoadjuvant chemotherapy. However, the significance of pathologic response in lymph nodes harboring metastatic tumors in such patients remains uncertain. Therefore, we studied the effect of neoadjuvant chemotherapy on resected positive lymph nodes and determined if the degree of pathologic response in the lymph nodes alone (LN-MPR) or in combination with that of the primary tumor (PT-MPR) was able to predict the outcome., Methods: A total of 75 patients with NSCLC who underwent neoadjuvant chemotherapy and completed surgical resection were included in this study. Tissue specimens were retrospectively evaluated by two pathologists blinded to the patients' treatments and outcomes. Specimens were reviewed for the degree of pathologic response in the primary tumor and in any involved lymph nodes. The prognostic performance of LN-MPR alone or in combination with PT-MPR with respect to overall survival (OS) was evaluated using the Kaplan-Meier method and Cox regression model., Results: LN-MPR was significantly predictive of long-term OS after neoadjuvant chemotherapy. A combination of PT-MPR with LN-MPR was significantly associated with outcome and allowed stratification of patients into three prognostic groups (p = 0.001)., Conclusions: LN-MPR in isolation is a reliable predictor of OS in patients with NSCLC receiving neoadjuvant chemotherapy. A combination of LN-MPR with PT-MPR seems to correlate well with the outcome and can be used to predict prognosis in this patient population., (Published by Elsevier Inc.)

Thiamine deficiency is associated with cerebellar dysfunction; however, the consequences of thiamine deficiency on the electrophysiological properties of cerebellar Purkinje cells are poorly understood. Here, we evaluated these parameters in brain slices containing cerebellar vermis. Adult mice were maintained for 12-13 days on a thiamine-free diet coupled with daily injections of pyrithiamine, an inhibitor of thiamine phosphorylation. Morphological analysis revealed a 20% reduction in Purkinje cell and nuclear volume in thiamine-deficient animals compared to feeding-matched controls, with no reduction in cell count. Under whole-cell current clamp, thiamine-deficient Purkinje cells required significantly less current injection to fire an action potential. This reduction in rheobase was not due to a change in voltage threshold. Rather, thiamine-deficient neurons presented significantly higher input resistance specifically in the voltage range just below threshold, which increases their sensitivity to current at these critical membrane potentials. In addition, thiamine deficiency caused a significant decrease in the amplitude of the action potential afterhyperpolarization, broadened the action potential, and decreased the current threshold for depolarization block. When thiamine-deficient animals were allowed to recover for 1 week on a normal diet, rheobase, threshold, action potential half-width, and depolarization block threshold were no longer different from controls. We conclude that thiamine deficiency causes significant but reversible changes to the electrophysiology properties of Purkinje cells prior to pathological morphological alterations or cell loss. Thus, the data obtained in the present study indicate that increased excitability of Purkinje cells may represent a leading indicator of cerebellar dysfunction caused by lack of thiamine.

Introduction: The combination of programmed cell death protein-1 or programmed death-ligand 1 immune checkpoint blockade and chemotherapy has revolutionized the treatment of advanced NSCLC, but the mechanisms underlying this synergy remain incompletely understood. In this study, we explored the relationships between neoadjuvant chemotherapy and the immune microenvironment (IME) of resectable NSCLC to identify novel mechanisms by which chemotherapy may enhance the effect of immune checkpoint blockade., Methods: Genomic, transcriptomic, and immune profiling data of 511 patients treated with neoadjuvant chemotherapy followed by surgery (NCT) versus upfront surgery (US) were compared with determined differential characteristics of the IMEs derived from whole-exome sequencing (NCT = 18; US = 73), RNA microarray (NCT = 45; US = 202), flow cytometry (NCT = 17; US = 39), multiplex immunofluorescence (NCT = 10; US = 72), T-cell receptor sequencing (NCT = 16 and US = 63), and circulating cytokines (NCT = 18; US = 73)., Results: NCT was associated with increased infiltration of cytotoxic CD8 + T cells and CD20 + B cells. Moreover, NCT was associated with increases in CD8 + CD103 + and CD4 + CD103 + PD-1 + TIM3 - tissue resident memory T cells. Gene expression profiling supported memory function of CD8 + and CD4 + T cells. However, NCT did not affect T-cell receptor clonality, richness, or tumor mutational burden. Finally, NCT was associated with decreased plasma BDNF (TrkB) at baseline and week 4 after surgery., Conclusions: Our study supports that, in the context of resectable NSCLC, neoadjuvant chemotherapy promotes antitumor immunity through T and B cell recruitment in the IME and through a phenotypic change toward cytotoxic and memory CD8 + and CD4 + memory helper T cells., (Copyright © 2020 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Background: The improvement in the management of lung cancer have the potential to improve survival in patients undergoing resection for early-stage (stage I and II) non-small cell lung cancer (NSCLC), but few studies have evaluated time trends and identified predictors of overall survival (OS)., Methods: We identified surgically resected early-stage NSCLC between 1998 and 2016. The 3-year OS (1998-2014) and 5-year OS (1998-2012) rates were calculated for each year. Joinpoint regression was used to calculate annual percentage changes (APC) and to test time trends in OS. Multivariable Cox regression was used to identify predictors of OS., Results: There was a significant upward trend in the 3-year (1998, 56%; 2014, 83%; APC = 1.8) and 5-year (1998, 47%; 2012, 76%; APC = 3.1) OS. Older age; male sex; history of diabetes, coronary artery disease, and chronic obstructive pulmonary disease; high ASA score; smoking pack-years; high-grade tumor; pneumonectomy; thoracotomy; neoadjuvant therapy; nodal disease; and positive tumor margin were predictors of poor OS., Conclusion: The upward time trend in OS suggests that improved staging, patient selection, and management have conferred a survival benefit in early-stage NSCLC patients. The prediction model of OS could be used to refine selection criteria for resection and improve survival outcomes., (© 2020 Wiley Periodicals, Inc.)

Background: Asymptomatic carriers of SARS-CoV-2 can be a vehicle for transmission of the infection. This fact is of particular importance in the case of healthcare workers (HCWs)., Design: Cross-sectional study in HCWs in a medium size hospital in the South of Spain., Methods: between April 15 and 25, 2020, naso and oropharyngeal PCR determination was performed together with IgG and IgM antibody determination by immunochromatography to the HCWs of the Costa del Sol Hospital in Marbella of the units involved in patient care with CoVID-19: Emergencies, Intensive Care and Anesthesia, Internal Medicine and Pneumology. Other units not directly involved in the care of these patients were offered to participate. On the day of sampling, a health questionnaire was answered, reporting symptoms on the same day and in the previous fourteen days., Results: 498 HCWs were studied. Two individuals were detected with PCR for SARS-CoV-2 positive. Both were asymptomatic on the day of sampling, but one of them had had a CoVID-19 compatible picture in the previous two weeks and had positive IgG and IgM; therefore, only one subject was truly asymptomatic carrier (0.2%). 9 workers with positive IgG (1.8%) were detected., Conclusions: the prevalence of asymptomatic carriers among health workers of the services directly involved in the care of patients with CoVID-19 was very low in our center. This type of strategy can be one more tool in controlling the pandemic., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Introduction: The standard of care for stage IIIA (N2) non-small-cell lung cancer (NSCLC) includes concurrent definitive chemoradiation (dCRT) followed by durvalumab, thus challenging the role of surgery in resectable patients. We assessed locoregional disease control and survival in patients with surgically resected and unresected stage IIIA (N2) NSCLC disease., Patients and Methods: We conducted a retrospective analysis from prospectively collected databases at MD Anderson Cancer Center. Patients undergoing neoadjuvant chemotherapy and surgery or dCRT for clinical stage IIIA (N2) disease (2004-2014) were evaluated. Primary outcomes included locoregional disease control, disease-free survival (DFS), and overall survival (OS). Kaplan-Meier outcome analyses were performed., Results: Of the 159 resected patients, the majority had lobectomy (82.4%), followed by pneumonectomy (11.9%) and sublobar resection (5.7%). The 30- and 90-day mortality rates were 0.6% and 1.3%, respectively. At median follow-up of 52.8 months, recurrence was 55.3%, with 44.0% having distant and 15.1% locoregional recurrence. At 5 years, OS was 50.8% and DFS was 33.1% Median OS was 61.2 months. A total of 366 patients underwent dCRT, with intensity-modulated radiation in 64.5%, proton therapy in 26.0%, and 3-dimensional conformal radiotherapy in 9.6%. The mean dose was 68.1 Gy. At median follow-up of 20.8 months, recurrence was 53.6%, with distant and locoregional recurrence of 40.7% and 30.3%, respectively. At 5 years, OS was 29.2% and DFS was 20.5%. Median OS was 27.5 months., Conclusion: Stage IIIA (N2) NSCLC continues to be a heterogeneous disease, and patients with surgically resected and unresected disease represent different risk populations. Ongoing immunotherapy trials may further redefine treatment algorithms in this complex patient population., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: We have suggested that major pathologic response (MPR) could serve as a surrogate endpoint for survival and provide rapid means of comparing different neoadjuvant treatment regimens. Here, we confirm that MPR is predictive of long-term overall survival (OS) in patients with non-small-cell lung cancer (NSCLC) who underwent neoadjuvant chemotherapy and surgical resection, to assess agreement on MPR between 2 observers, and to determine the minimum number of slides needed to obtain an accurate determination of MPR., Patients and Methods: We identified 151 patients with NSCLC who had been treated with neoadjuvant chemotherapy followed by complete surgical resection from 2008 to 2012. Tissue specimens were retrospectively evaluated by 2 pathologists who had been blinded to patients' treatment and outcome. We assessed the relationships between MPR and OS, the levels of agreement between the pathologists, and determined the number of slides needed to obtain an accurate determination of MPR., Results: Our results reveal that MPR examined by either observer 1 (experienced) or by observer 2 (trained) was significantly predictive of long-term OS after neoadjuvant chemotherapy. MPR was associated with long-term OS in patients with NSCLC undergoing neoadjuvant chemotherapy on multivariable analysis (hazard ratio 2.68; P = .01). The levels of agreement between 2 pathologists were high after direct in-person training by one pathologist or the other (R 2  = 0.994). Our data suggest that at least 3 slides should be read to accurately determine MPR., Conclusions: MPR is significantly predictive of long-term OS in neoadjuvant chemotherapy-treated patients with NSCLC. MPR may serve as a surrogate endpoint for evaluating novel chemotherapies and immunotherapy response in biomarker-driven translational clinical trials., (Published by Elsevier Inc.)

Lung cancer patients are at risk for venous thromboembolism (VTE). Preoperative heparin administration may increase the risk of bleeding requiring reoperation. The purpose of this study was to evaluate preoperative heparin's effect on reoperation for bleeding. A retrospective review compared outcomes for patients undergoing pulmonary resection for primary lung cancer from January 2006 to April 2018. Preoperative heparin was administered at the discretion of the attending surgeon. Comparisons were performed between preoperative subcutaneous heparin (5000 U) and no heparin groups. A total of 3325 lung resections were reviewed, 1.4% (n = 48) required reoperation for bleeding. VTE occurred in 1.1% (n = 38). Four hundred sixty-four patients (14.0%) did not receive preoperative heparin. The preoperative heparin group had increased rates of prior thoracic surgery (5.1% [n = 146] vs 1.7% [n = 8], P < 0.001), minimally invasive approach (40.2% [n = 1150] vs 10.6% [n = 49], P < 0.001), and sublobar resections (17.7% [n = 506] vs 10.6% [n = 49], P < 0.001). There were no differences in blood loss/transfusions. Reoperation for bleeding was significantly increased in the preoperative heparin group (1.6% [n = 47] vs 0.2% [n = 1], P = 0.017). There were no differences in VTE (1.5% [n = 7] vs 1.1% [n = 31], P = 0.424). On logistic regression, preoperative heparin was independently associated with increased reoperation for bleeding (odds ratio 8.13, P = 0.039); however, preoperative heparin was not independently associated with VTE. Preoperative heparin was associated with increased reoperation for bleeding. VTE rates are low after pulmonary resection for lung cancer and are not decreased by preoperative heparin. Preoperative heparin use should be determined by risk factor stratification for VTE and reoperation for bleeding in patients undergoing lung cancer resection., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Multiple synchronous lung tumors (MSLT), particularly within a single lobe, represent a diagnostic and treatment challenge. While histologic assessment was once the only method to possibly distinguish multiple primary lung cancers, there is a growing interest in identifying unique genomic features or mutations to best characterize these processes., Methods: In order to differentiate multiple primary lung malignancies from intrapulmonary metastases in patients with MSLT, we performed whole exome sequencing (WES) on 10 tumor samples from 4 patients with MSLT., Results: Shared mutations between tumors from the same patient varied from 0-91%. Patient 3 shared no common mutations; however, in Patients 2 and 4, identical mutations were identified among all tumors from each patient, suggesting that the three tumors identified in Patient 3 represent separate primary lung cancers, while those of Patients 1, 2 and 4 signify hematogenous and lymphatic spread., Conclusions: A high proportion of shared mutations between different lung tumors is likely indicative of intrapulmonary metastatic disease, while tumors with distinct genomic profiles likely represent multiple primary malignancies driven by distinct molecular events. Application of genomic profiling in the clinical setting may prove to be important to precise management of patients with MSLT., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jtd-20-1). CG has a patent named “Markers associated with ribavirin-induced anemia” that was issued in 2012. CB and IIW report grants and personal fees from Genentech/Roche, grants and personal fees from Bayer, grants and personal fees from Bristol-Myers Squibb, grants and personal fees from AstraZeneca/Medimmune, grants and personal fees from Pfizer, grants and personal fees from HTG Molecular, grants and personal fees from Merck, personal fees from GlaxoSmithKline, grants and personal fees from Guardant Health, personal fees from MSD, grants from Oncoplex, grants from DepArray, grants from Adaptive, grants from Adaptimmune, grants from EMD Serono, grants from Takeda, grants from Amgen, grants from Karus, grants from Johnson & Johnson, grants from Iovance, grants from 4D, grants from Novartis, grants from Oncocyte, grants from Akoya, outside the submitted work. JVH reports grants and other from AstraZeneca, other from Bristol-Myers Squibb, other from GlaxoSmithKline, other from Kairos Venture Investments, other from BrightPath Therapeutics, other from Hengrui Therapeutics, other from Eli Lilly, other from EMD Serono, grants and personal fees from Spectrum, other from Foundation One Medicine, grants from NIH/NCI, grants from American Cancer Society, grants from Checkmate Pharmaceuticals, outside the submitted work. Jianjun Z reports grants from Merck, grants from Johnson and Johnson, personal fees from BMS, personal fees from AZ, personal fees from GenePlus, personal fees from Innovent, outside the submitted work. MBA serves as an unpaid editorial board member of Journal of Thoracic Disease from Aug 2019 to Jul 2021. The other authors have no conflicts of interest to declare., (2020 Journal of Thoracic Disease. All rights reserved.)

We present 783 surgical resections of typical and atypical carcinoid tumors of the lung identified in the pathology files of 20 different pathology departments. All cases were critically reviewed for clinical and pathological features and further correlated with clinical outcomes. Long-term follow-up was obtained in all the patients and statistically analyzed to determine significance of the different parameters evaluated. Of the histopathological features analyzed, the presence of mitotic activity of 4 mitoses or more per 2 mm 2 , necrosis, lymphatic invasion, and lymph node metastasis were identified as statistically significant. Tumors measuring 3 cm or more were also identified as statistically significant and correlated with clinical outcomes. Based on our analysis, we consider that the separation of low- and intermediate-grade neuroendocrine neoplasms of the lung needs to be readjusted in terms of mitotic count as the risk of overgrading these neoplasms exceeds 10% under the current criteria. We also consider that tumor size is an important feature to be considered in the assessment of these neoplasms and together with the histological grade of the tumor offers important features that can be correlated with clinical outcomes., (Crown Copyright © 2020. Published by Elsevier Inc. All rights reserved.)

Background: We previously reported that post-discharge nursing telephone assessments identified a frequent number of patient complaints. Our aim was to determine if telephone assessments can identify patients at risk for emergency room (ER) visits or hospital readmissions., Methods: A single-institution, retrospective review was performed on all patients undergoing pulmonary resection over a 12-month period. Standardized nursing telephone calls were conducted and records were reviewed to determine postoperative issues. ER visits and readmissions within 30 and 90 days were recorded., Results: In total, 521 patients underwent pulmonary resection and 245 (47%) were reached for telephone assessment. ER visits within 30/90 days were 8.1% (n=42) and 12.1% (n=63). Readmissions within 30/90 days were 3.1% (n=16) and 6% (n=31). For those reached by telephone assessment, patients with major issue demonstrated increased 30-day ER visits: 22.6% (n=7) vs . 8.0% (n=17), P=0.019. For all patients, those with 90-day ER visit and/or readmission were more likely to have pulmonary complications during initial admission (43.8% vs . 21.2%, P<0.001). Among patients who were reached by telephone, independent predictors of ER visit or readmission within 30 days were: major issue identified on telephone assessment (P=0.007), discharge with chest tube (<0.001), and reintubation postoperatively (P=0.047)., Conclusions: Standardized nursing telephone assessments were able to identify a high-risk population more likely to need ER visit or readmission. However, telephone assessments did not decrease ER visits or readmissions. Improved post-discharge protocols are needed for these high-risk patients in order to ensure patient safety, optimize patient experience, and limit unnecessary resource utilization., Competing Interests: Conflicts of Interest: MBA serves as the unpaid editorial board member of Journal of Thoracic Disease from Aug 2019 to Jul 2021. The other authors have no other conflicts of interest to declare., (2020 Journal of Thoracic Disease. All rights reserved.)

Background: Advances in perioperative and operative management hold great promise for improving perioperative outcomes in patients undergoing resection for early stage non-small cell lung cancer (NSCLC). The objective of this study was to evaluate time trends in the incidence of perioperative outcomes and to identify predictors of pulmonary complication in early stage NSCLC resection patients., Methods: An institutional database was reviewed to identify patients with primary, clinical stage I and II NSCLC who underwent resection from 1998 to 2016. Rates of perioperative pulmonary complication, pneumonia, and cardiovascular complication; and 30-day and 90-day mortality were calculated for each year. Joinpoint regression was used to calculate annual percentage change (APC) and to evaluate time trends in rates of these outcomes. Multivariable logistic regression was conducted to identify predictors of pulmonary complication., Results: Of the 3045 patients identified, 80% had stage I and 20% had stage II NSCLC. From 1998 to 2016, there was no trend in the rate of pulmonary complication, but there was a significant downward trend in the rates of pneumonia (APC -3.7), cardiovascular complication (APC -3.5), 30-day mortality (APC -9.8), and 90-mortality (APC -7.4). Older age, male sex, smoking status, percentage of predicted forced expiratory volume in 1 second and percentage of diffusion capacity of lung for carbon monoxide, and intraoperative blood transfusion were identified as predictors of pulmonary complication., Conclusions: Decrease in the rates of perioperative outcomes parallels improvements in patient selection and perioperative management of early stage NSCLC resection patients. Predictors of pulmonary complication could be used to improve selection criteria for surgery and to reduce the incidence of pulmonary complication in these patients., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Introduction: People with schizophrenia and bipolar disorder (BD) have a high risk of unwanted pregnancies and abortions, due to their condition of vulnerability or hypersexuality (common in BD). This is associated with difficulty in planning their actions and lack of sex education and counselling by medical personnel, and can lead to adverse obstetric outcomes and inability to care adequately for their children., Objective: To describe the characteristics in terms of sexual and reproductive health, and the use of contraception and counselling in psychiatric consultations, in a sample of patients with BD and schizophrenia in Medellin, Colombia., Methods: Observational cross-sectional study. We included the 160 participants from the clinical trial, "The effects of a multimodal intervention programme in patients with bipolar disorder and schizophrenia", who were recruited from the mood and psychosis disorders group clinic at Hospital Universitario de San Vicente Fundación in Medellin. They were contacted by phone by a third-year psychiatry resident, who applied a survey about the characteristics of their sex life, contraception and reproduction., Results: Almost all of the patients with schizophrenia were single, had no undergraduate studies and were unemployed. No significant differences were found regarding the age of starting sexual relations when comparing by diagnosis and gender. Almost all patients with schizophrenia and almost half of the patients with BD reported not having an active sexual life. Almost all of those who admitted to having an active sexual life claimed to always use contraception; in the BD group, only 48.8% of single women admitted to using contraception and a little over half of men stated that they used a condom when having sex. A quarter of the pregnancies were unplanned. Although the majority of the patients stated that they had never received information about family planning in the consultations with their psychiatrist, 57.4% of the patients with BD and 78.8% of those who had schizophrenia, considered themselves to be well informed on the subject., Conclusions: Patients with mental illness have cognitive and behavioural alterations that affect their sexual and reproductive lives. Psychiatrists should therefore address this issue, to ensure education in areas such as contraception, family planning and sexually transmitted diseases and help safeguard the safety and quality of life of their patients., (Copyright © 2018. Publicado por Elsevier España, S.L.U.)

Objective: Though interest in expansion of the use of less-invasive therapies among operable non-small-cell lung cancer (NSCLC) patients is growing, it is not clear that post-treatment surveillance has been comparable between treatment modalities. We sought to characterize institutional surveillance patterns after NSCLC therapy with stereotactic body radiation therapy (SBRT) and lobectomy., Methods: NSCLC patients treated with lobectomy or SBRT (2005 to 2016) at a single institution were identified. Natural language processing searched data fields within axial surveillance imaging reports for findings suggestive of recurrence. Duration and patterns of institutional surveillance were compared between the 2 groups., Results: Three thousand forty-two patients (73.5% lobectomy, 26.5% SBRT) met inclusion criteria. Patients had a longer median duration of surveillance after lobectomy (28.0 months vs SBRT 12.3 months, P < 0.001) and were more likely to undergo histopathological evaluation of clinically suspected relapse (206/274 [75.2%] vs SBRT 54/113 [47.8%], P < 0.001). Patients with clinical suspicion of recurrence had longer durations of institutional surveillance than those who did not among both cohorts (lobectomy 44.4 months vs 25.9, P < 0.001; SBRT 27.9 vs 10.3, P < 0.001). Landmark analyses at 1 and 3 years after therapy identified associations between receipt of lobectomy and ongoing surveillance at each time point (1 year odds ratio [OR] 2.10, P < 0.001; 3 years OR 1.71, P < 0.001) among all patients and those with documented stage I disease., Conclusions: We identified potential heterogeneity in institutional surveillance patterns after treatment of NSCLC with 2 therapeutic modalities. As less-invasive treatment options for operable patients expand, it will be critical to implement rigorous surveillance paradigms across all modalities.

Background: Patient-derived xenograft (PDX) models increasingly are used in translational research. However, the engraftment rates of patient tumor samples in immunodeficient mice to PDX models vary greatly., Methods: Tumor tissue samples from 308 patients with non-small cell lung cancer were implanted in immunodeficient mice. The patients were followed for 1.5 to approximately 6 years. The authors performed histological analysis of PDXs and some residual tumor tissues in mice with failed PDX growth at 1 year after implantation. Quantitative polymerase chain reaction and enzyme-linked immunoadsorbent assay were performed to measure the levels of Epstein-Barr virus genes and human immunoglobulin G in PDX samples. Patient characteristics were compared for PDX growth and overall survival as outcomes using Cox regression analyses. Disease staging was based on the 7th TNM staging system., Results: The overall engraftment rate for PDXs from patients with non-small cell lung cancer was 34%. Squamous cell carcinomas had a higher engraftment rate (53%) compared with adenocarcinomas. Tumor samples from patients with stage II and stage III disease and from larger tumors were found to have relatively high engraftment rates. Patients whose tumors successfully engrafted had worse overall survival, particularly those individuals with adenocarcinoma, stage III or stage IV disease, and moderately differentiated tumors. Lymphoma formation was one of the factors associated with engraftment failure. Human CD8-positive and CD20-positive cells were detected in residual samples of tumor tissue that failed to generate a PDX at 1 year after implantation. Human immunoglobulin G was detected in the plasma of mice that did not have PDX growth at 14 months after implantation., Conclusions: The results of the current study indicate that the characteristics of cancer cells and the tumor immune microenvironment in primary tumors both can affect engraftment of a primary tumor sample., (© 2019 American Cancer Society.)

Background: Adenocarcinoma of the gastroesophageal junction (AEG) poses a management challenge, as preoperative prediction of occult mediastinal nodal metastasis is difficult. We sought to identify factors predictive of mediastinal involvement among patients undergoing trimodality therapy., Methods: Patients undergoing trimodality therapy for Siewert II and III AEG at a single institution between 2000 and 2015 were identified. Mediastinal involvement was defined as pathologic nodal involvement after neoadjuvant chemoradiation (ypN+) in mediastinal stations or mediastinal recurrence 2 years or less after resection. Maximal χ 2 analysis and Youden's J index were used to identify the pretreatment proximal tumor extent that best discriminated mediastinal involvement., Results: In all, 204 patients (151 [74%] AEG II, 53 [26%] AEG III) were included, of whom 47 (23%) had clinical evidence of thoracic nodal disease. Thirty-one of the 204 patients (15%) met criteria for mediastinal involvement (24 of 31 ypN+, 10 of 31 mediastinal recurrence). Patients with mediastinal involvement had greater proximal tumor extent (median 2 cm [interquartile range, 1.0 to 3.0 cm] vs 1.4 cm [interquartile range, 0.7 to 3.0 cm], P = .030), were more frequently Siewert II lesions (27 of 31 [87.1%] vs 124 of 173 [71.7%], P = .071), and were more often observed to have clinical thoracic nodal metastasis (cN) evidence (13 of 31 [42%] vs 34 of 173 [20%], P = .007) than patients who did not. On multivariable analysis of patients with intrathoracic cN0, esophageal extent of 1.5 cm or greater was independently predictive of mediastinal involvement (odds ratio 5.46, P = .011), whereas Siewert classification was not (Siewert II odds ratio 3.48, P = .116)., Conclusions: Pretreatment proximal tumor extent, rather than Siewert classification, is an independent predictor of mediastinal involvement among AEG II/III patients without clinical evidence of mediastinal metastasis and should be considered during treatment planning., (Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: The benefit of adjuvant treatment for esophageal cancer patients with positive lymph nodes after induction therapy and esophagectomy is uncertain. This in-depth multicenter study assessed the benefit of adjuvant therapy in this population., Methods: A retrospective cohort study from 9 institutions included patients who received neoadjuvant treatment, underwent esophagectomy from 2000 to 2014, and had positive lymph nodes on pathology. Factors associated with administration of adjuvant therapy were assessed using multilevel random-intercept modeling to account for institutional variation in practice. Kaplan-Meier analyses were performed based on adjuvant treatment status. Variables associated with survival were identified using Cox proportional hazards modeling., Results: The study analyzed 1082 patients with node-positive cancer after induction therapy and esophagectomy: 209 (19.3%) received adjuvant therapy and 873 (80.7%) did not. Administration of adjuvant treatment varied significantly from 3.2% to 50.0% between sites (P < .001). Accounting for institution effect, factors associated with administration of adjuvant therapy included clinically positive and negative prognostic characteristics: younger age, higher pathologic stage, pathologic grade, no neoadjuvant radiotherapy nonsmoking status, and absence of postoperative infection. Kaplan-Meier analysis showed patients receiving adjuvant therapy had a longer median survival of 2.6 years vs 2.3 years (P = .02). Cox modeling identified adjuvant treatment as independently associated with improved survival, with a 24% reduction in mortality (hazard ratio, 0.76; P = .005)., Conclusions: Adjuvant therapy was associated with improved overall survival. Therefore, consideration should be given to administration of adjuvant therapy to esophageal cancer patients who have persistent node-positive disease after induction therapy and esophagectomy and are able to tolerate additional treatment., (Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: It is unclear whether the enhanced dexterity and visualization of the surgical robot lessens morbidity and influences staging or survival. We compared outcomes of robotic-assisted lobectomy (RAL) with thoracoscopic video-assisted lobectomy (VAL) or open lobectomy (OL) of non-small cell lung cancer., Methods: Using a prospective surgical database, perioperative and cancer-related outcomes of patients who received a lobectomy for non-small cell lung cancer from 2011 to 2017 were analyzed. Outcomes between each surgical approach were compared using inverse probability of treatment weighting generated from the inverse of the propensity score., Results: There were 831 patients: 106 RAL, 301 VAL, and 424 OL. More RAL patients than VAL received neoadjuvant therapy (16% vs 6%, P = .001), but less than OL (28% vs 16%, P = .014). After adjustment, RAL was associated with longer operative times, less blood loss, and improved nodal harvest (all P < .02). There were no differences in morbidity, nodal upstaging, or mortality between surgical approaches. Length of stay was shorter with RAL vs OL (P < .01). Unadjusted cost was higher after RAL vs VAL (P = .003), but after adjustment, cost differences disappeared., Conclusions: Robotic-assisted lobectomy was associated with improved nodal harvest and less blood loss as compared with VAL or OL. Length of stay was shorter with RAL as opposed to OL. Unexpectedly, cost was not higher with RAL. The profile of patients who received RAL more closely approximated OL, suggesting RAL may allow typical thoracotomy patients to receive minimally invasive surgery after adequate training and experience., (Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: CDK9 inhibitors are antitumorigenic against solid tumors, including esophageal adenocarcinoma (EAC). However, efficacy of a CDK9 inhibitor combined with 5-fluorouracil (5-FU) and target proteins that are targeted by these agents in EAC are unknown., Methods: The anti-EAC efficacy of a new CDK9 inhibitor, BAY1143572, with and without 5-FU was assessed in vitro and in xenograft models in athymic nu/nu mice. Synergy between BAY1143572 and 5-FU in inhibiting cell proliferation was analyzed by calculating the combination index using CompuSyn software. Potential targets of BAY1143572 and 5-FU were identified by reverse-phase protein array. The effects of BAY1143572 and 5-FU on MCL-1 in vitro were analyzed by Western blotting, quantitative real-time polymerase chain reaction, and chromatin immunoprecipitation assay. MCL-1 protein expression in tumors from patients with locoregional EAC treated with chemoradiation and surgery was assessed by immunohistochemistry., Results: BAY1143572 had dose-dependent antiproliferative and proapoptotic effects and demonstrated synergy with 5-FU against EAC in vitro . The median volumes of FLO-1 and ESO-26 xenografts treated with 5-FU plus BAY114352 were significantly smaller than those of xenografts treated with either agent alone ( p  < 0.05). BAY1143572 downregulated MCL-1 by inhibiting HIF-1α binding to the MCL-1 promoter. 5-FU enhanced BAY1143572-induced MCL-1 downregulation and stable MCL-1 overexpression reduced the apoptosis induced by BAY1143572 and 5-FU in vitro . High patients' tumor MCL-1 expression was correlated with shorter overall and recurrence-free survival., Conclusions: BAY1143572 and 5-FU have synergistic antitumorigenic effects against EAC. MCL-1 is a downstream target of CDK9 inhibitors and a predictor of response to neoadjuvant chemoradiation in EAC., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest.

Objective: Enhanced recovery after surgery integrates multiple evidence-based interventions to accelerate postoperative recovery. We hypothesized that enhanced recovery after surgery would also facilitate adjuvant chemotherapy for non-small cell lung cancer., Methods: An enhanced recovery after surgery pathway was implemented at a single institution, starting with a transitional rollout in 2012 and full rollout in 2015. Patients with clinical stage I or II non-small cell lung cancer without induction therapy and who were pathologic nodal positive or had 5-cm or larger tumor size were selected for analysis. Dates analyzed were pre-enhanced recovery after surgery (2006-2011), transitional (2012-8/2015), and enhanced recovery after surgery (9/2015-2017). Interrupted time series was used to analyze trends in time to receive adjuvant chemotherapy after resection by era. Logistic regression was used to determine factors associated with receiving 4 or more cycles of adjuvant chemotherapy., Results: A total of 471 patients were identified. The interval between lung resection and commencing adjuvant chemotherapy was progressively shorter after the transition era (P = .041). The rate of receiving adjuvant chemotherapy progressively increased (from 40% pre-enhanced recovery after surgery, to 50% transition era, to 62% enhanced recovery after surgery era, P < .001). Multivariable regression revealed the enhanced recovery after surgery era (odds ratio, 3.6, P < .001), the transitional era (odds ratio, 2.01, P = .007), pN status, tumor grade and histology, age, and preoperative performance status were associated with completing adjuvant therapy. The surgical approach, whether open or thoracoscopic, was not associated with completing adjuvant chemotherapy., Conclusions: Enhanced recovery after surgery was associated with facilitated delivery of adjuvant chemotherapy, with a shortened interval to receive adjuvant chemotherapy and a higher rate of receiving 4 or more cycles., (Copyright © 2019. Published by Elsevier Inc.)

Our recent study demonstrated that cancer cells with compromised glutathione homeostasis, including reduced expression of the glutathione reductase ( GSR ) gene, were selectively killed by inhibition of thioredoxin reductase. The human GSR gene is located on chromosome 8p, a region often lost in lung and other cancers. However, whether GSR is altered in primary lung cancer remains unknown. To analyze alterations of GSR in lung cancer, we performed fluorescence in situ hybridization with probes for GSR and the chromosome 8 centromere (CEP8) in 45 surgical specimens of primary lung cancer, including 24 lung adenocarcinomas, 10 squamous cell carcinomas, 8 neuroendocrine cancers, and 3 small cell lung cancers. Twenty-five surgically resected normal lung tissue specimens from these lung cancer patients were used as a controls. The signal ratio of GSR to CEP8 per cell was used to identify gain or loss of GSR . GSR loss was detected in 6 of 24 (25%) adenocarcinoma specimens and 5 of 10 (50%) squamous cell carcinoma specimens, but not in neuroendocrine cancer or small cell lung cancer specimens. We also found that 19 of 45 (42%) specimens had chromosome 8 aneuploidy (more or less than 2 signals for CEP8), including 8 with both aneuploidy and GSR deletion. Chromosome 8 aneuploidy was detected in all types of lung cancer analyzed. Univariate and multivariable logistic regression analyses indicated that male patients had an increased risk of GSR deletion (hazard ratio [HR] = 4.77, 95% confidence interval [CI] = 1.00-22.86, P = 0.051), and patients who had undergone preoperative radiation therapy or had a self-reported history of cigarette smoking had an increased risk of chromosome 8 aneuploidy (preoperative radiation: HR = 18.63, 95% CI = 0.90-384.17, P = 0.058; smoking: HR = 7.59, 95% CI = 0.86-66.75, P = 0.068), although the p values did not reach significance. Because GSR deficiency and chromosome 8 aneuploidy have implications in targeted therapy and/or immunotherapy for cancer, they might serve as predictive biomarkers for precision therapy of lung cancers., Competing Interests: None.

Objective: During resection of pulmonary metastases, the need to spare lung parenchyma is often weighed against the increased risk of local recurrence if an inadequate surgical margin is obtained. We sought to identify risk factors for local recurrence after wedge resection of pulmonary metastases of a colorectal origin., Methods: A retrospective study of patients who underwent a wedge resection for colorectal pulmonary metastases from 2006 to 2016 was performed. Cox regression with robust variance was used to estimate the risk of local recurrence per nodule treated., Results: We identified 335 patients who underwent 679 wedge resections. The 2-year local recurrence risk for each nodule was 11.8% (95% confidence interval, 8.9%-14.6%), and the 5-year risk was 20.6% (95% confidence interval, 16.2%-24.8%). Longer margin length decreased the risk of local recurrence (hazard ratio, 0.434 per additional cm of length; P = .015), whereas larger tumor size increased this risk (hazard ratio, 1.520 per additional cm of size; P = .012). However, other factors tested, including tumor grade, KRAS mutation status, and response to induction chemotherapy, did not affect recurrence risk. A pathologic margin length of at least half the tumor size was estimated to result in a local recurrence rate <11%., Conclusions: Among surgically resected colorectal pulmonary metastases, technical factors related to margin length and tumor size were associated with the risk of local recurrence, whereas tumor grade and KRAS status were not. However, the increased risk of local recurrence with larger tumors was diminished with a sufficient margin length., (Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Ground glass opacities (GGOs) on computed tomography (CT) have gained significant recent attention, with unclear incidence and epidemiologic patterns. Natural language processing (NLP) is a powerful computing tool that collects variables from unstructured data fields. Our objective was to characterize trends of GGO detection using NLP., Methods: Patients were identified at a large quaternary referral center who underwent chest CT from 2000 to 2016 via query of institutional databases. NLP was used to identify imaging reports with GGOs and to obtain additional demographic data. Incidence of reported GGOs was tracked over time. Multivariate regression was used to identify predictors of GGOs identified on chest CT., Results: A total of 244,391 chest CTs were included, with 35,386 (14.5%) revealing GGOs. There was a significant relationship between advancing year of chest CT and likelihood of reported GGOs (p < 0.001). GGOs were more likely to occur in older subjects (60.5 vs 58.5 years, p < 0.001), males (54.6% vs 51.5%, p < 0.001), and nonwhite races (21.2% Asian, 15.6% Hispanic, 14.4% black, 14.0% white; p < 0.001). Certain occupational histories predicted more frequent GGOs (p < 0.001), including transportation labor (47.4%), metal workers (42.3%), iron workers (33.3%), cabinetry (32.6%), and foremen (29.6%). Multivariate regression revealed age, sex, nonsmokers, increasing year of chest CT, and race as significant independent predictors of identifying GGOs., Conclusions: NLP explored a large cohort of patients who underwent chest CT over the study period. Demographic features predicting reported GGOs include age, sex, race, and occupation. GGO recognition continues to increase with time, and further studies investigating etiology and prognostic implications are necessary., (Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Patients may be found to have stage IIIA-N2 at the final pathology after the initial surgery. We want to determine the survival rate in this unique group of patients., Methods: We reviewed all patients who underwent surgical resection for lung cancer from 2000 to 2011 who had pathologic stage N2 without induction therapy. We determined the clinicopathologic characteristics and survival rate in this unique group of patients., Results: A total of 101 patients met the inclusion criteria. The average age of the group was 65 years old with 53 (53%) females. The chest computed tomography (CT) scans showed 30 patients (30%) with mediastinal lymphadenopathy (>1 cm) and 13 (13%) with multistation disease. The positron emission tomography-computed tomography (PET-CT) showed 24 patients (24%) with N2 positive uptake. Invasive mediastinal staging prior to surgery occurred in 43 patients (43%). Eighty-four patients underwent a lobectomy (83%), 7 with bilobectomy (7%), and 10 with pneumonectomy (10%). The most common pathology was adenocarcinoma with 73 patients (72%) and the second most common was squamous cell carcinoma with 22 patients (22%). Most of the patients completed the adjuvant chemoradiation therapy (86%). The 5-year survival rate was 48% and the 10-year survival rate was 24%., Conclusions: Pathologic stage IIIA-N2 non-small cell lung cancer (NSCLC) is a heterogeneous disease process with a very small group of patients undergoing initial surgery. Patients with occult stage IIIA-N2 who undergo initial surgery have an excellent overall survival rate., Competing Interests: Conflicts of Interest: MP Kim has consulted for Intuitive Surgical, Olympus, Boston Scientific and Medtronics. The other authors have no conflicts of interest to declare.

Background: Previous studies have highlighted important biologic and survival-related differences among men and women with non-small cell lung cancer (NSCLC). However, differences in perioperative or short-term outcomes have not been as well characterized. In this study, we investigated differences in the perioperative period and postoperative emergency department (ED) visits among men and women after lobectomy for stage I NSCLC., Methods: A retrospective review was performed of patients who underwent a lobectomy for clinical stage I NSCLC at a single institution from 2010 to 2015., Results: We identified 559 patients for inclusion, including 293 women (52%) and 266 men (48%). Women were more likely to present with clinical T1 status (p = 0.005) and to undergo a minimally invasive operation (p = 0.058). To reduce confounding, 206 case-matched pairs were identified. After matching, no differences were found in length of stay (p = 0.551) or pulmonary complications (p = 0.509); however, men experienced more cardiac complications (18% versus 7%, p = 0.001). Of importance, although rates of 30- and 90-day ED visits between sexes were similar (p = 0.531, p = 0.890, respectively) and no sex-related differences were found in presenting symptom on return to the ED (p = 0.478), women were more likely to be readmitted after presenting to the ED within 30 days (p = 0.038)., Conclusions: Women demonstrated an increased likelihood of being admitted after presenting to the ED within 30 days after discharge, indicating important differences between men and women in the short-term period after lobectomy. Further research will be required to further understand the cause for these differences., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Noise pollution is one of the leading environmental health risks for humans, linked to a myriad of stress-related health problems. Yet little is known about the long-term effects of noise on the health and fitness of wildlife. We experimentally investigated the direct and cross-generational effects of traffic noise on telomeres; a measure of cellular ageing that is predictive of disease and longevity in humans and other organisms. We exposed zebra finches ( Taenopygia guttata ) to three different treatment groups: 1) parents were exposed to traffic noise before and during breeding, together with their nestling young, 2) fledged juveniles but not their parents were exposed to traffic noise, and 3) control group birds were never exposed to traffic noise., Results: Although there was no significant effect of traffic noise exposure at early (pre-fledging) stages of offspring telomere length or loss rate, traffic noise exposure accelerated telomere loss in older (post-fledging) juveniles., Conclusions: The age-dependent differences found in this study in telomere loss could occur if parents buffer younger offspring against the detrimental effects of noise exposure and/or if younger offspring are less sensitive to noise exposure. Telomere length during early life has been shown to be positively related to lifespan and the observed noise-induced increase of telomere attrition rate could reduce the fitness of the affected birds and potentially alter the population dynamics of birds in noise polluted areas. Our data highlight the need to consider the developmental stage of an organism to better understand the ecological consequences of anthropogenic change., Competing Interests: Animal housing and care was all in accordance with European and local laws governing the care and use of laboratory animals (Council of Europe Treaty ETS-123). All experimental procedures were approved by and done under license from the Government of Upper Bavaria (Regierung von Oberbayern), licence number 55.2–1–54-2532-51-2013.Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.