Single-Cell Characterization of Pulmonary Nodules Implicates Suppression of Immunosurveillance across Early Stages of Lung Adenocarcinoma.

A greater understanding of molecular, cellular, and immunological changes during the early stages of lung adenocarcinoma development could improve diagnostic and therapeutic approaches in patients with pulmonary nodules at risk for lung cancer. To elucidate the immunopathogenesis of early lung tumorigenesis, we evaluated surgically resected pulmonary nodules representing the spectrum of early lung adenocarcinoma as well as associated normal lung tissues using single-cell RNA sequencing and validated the results by flow cytometry and multiplex immunofluorescence (MIF). Single-cell transcriptomics revealed a significant decrease in gene expression associated with cytolytic activities of tumor-infiltrating natural killer and natural killer T cells. This was accompanied by a reduction in effector T cells and an increase of CD4+ regulatory T cells (Treg) in subsolid nodules. An independent set of resected pulmonary nodules consisting of both adenocarcinomas and associated premalignant lesions corroborated the early increment of Tregs in premalignant lesions compared with the associated normal lung tissues by MIF. Gene expression analysis indicated that cancer-associated alveolar type 2 cells and fibroblasts may contribute to the deregulation of the extracellular matrix, potentially affecting immune infiltration in subsolid nodules through ligand-receptor interactions. These findings suggest that there is a suppression of immune surveillance across the spectrum of early-stage lung adenocarcinoma. SIGNIFICANCE: Analysis of a spectrum of subsolid pulmonary nodules by single-cell RNA sequencing provides insights into the immune regulation and cell-cell interactions in the tumor microenvironment during early lung tumor development.

The majority of patients with resectable incidental lung cancers are ineligible for lung cancer screening.

Objective: The study objective was to determine what proportion of asymptomatic patients had resectable lung cancer detected through lung cancer screening versus incidentally. Methods: We performed a retrospective study of patients who underwent resection for lung cancer between January 2015 and December 2020. We then assessed whether asymptomatic patients with incidentally found lung cancers were eligible for lung cancer screening using the National Comprehensive Cancer Network, United States Preventive Services Task Force, Centers for Medicare & Medicaid Services, American College of Chest Physicians, American Cancer Society, and American Society of Clinical Oncology guidelines. Results: Of 539 patients who underwent resection for primary lung cancer, 437 (81%) were asymptomatic and 355 (66%) of these patients had lung cancer found discovered incidentally. Of the 355 patients with incidentally detected lung cancer, 10 were excluded for insufficient data. Of the remaining 345 patients, 110 (32%) would have been eligible for screening using National Comprehensive Cancer Network guidelines, 65 (19%) using 2021 United States Preventive Services Task Force guidelines, 53 (15%) using 2013 United States Preventive Services Task Force guidelines, 64 (19%) using 2022 Centers for Medicare & Medicaid Services guidelines, 52 (15%) using 2015 Centers for Medicare & Medicaid Services/American College of Chest Physicians guidelines, and 45 (13%) using American Cancer Society/American Society of Clinical Oncology guidelines. Of the 280 patients who were screen ineligible by 2021 United States Preventive Services Task Force criteria, 143 patients (51%) never smoked, 112 patients (40%) quit smoking more than 15 years ago, 89 patients (32%) did not smoke at least 20 pack-years, and 44 patients (16%) were ineligible due to age. Conclusions: The majority of asymptomatic patients with resectable lung cancers had lung cancer identified incidentally and not through lung cancer screening. Most of these patients were not eligible for screening under current guidelines. This study suggests a need for improved lung cancer screening implementation and further investigation in the identification and assessment of risk factors for lung cancer.

Wedge Resection Versus Segmentectomy for Older Patients With Stage IA Non-Small-Cell Lung Cancer.

INTRODUCTION: Anatomic lung resection remains the standard of care for early-stage non-small-cell lung cancer (NSCLC), but wedge resection may offer similar survival in older adult patients. The objective of this study was to evaluate the survival of patients aged 80 y and older undergoing wedge resection versus segmentectomy for stage IA NSCLC using a large clinical registry. METHODS: Patients aged 80 y and older in the National Cancer Database who underwent wedge resection or segmentectomy for cT1a-b N0 M0 NSCLC between 2004 and 2018 were identified for an analysis. Survival was assessed using multivariable Cox proportional hazards analysis, propensity-score matching, and inverse probability weighting. A subgroup analysis of patients who underwent lymph node evaluation with their wedge resection or segmentectomy was also performed. RESULTS: Of the 2690 patients identified, 2272 (84%) underwent wedge resection and 418 (16%) underwent segmentectomy. Wedge resection was associated with worse 5-year overall survival relative to segmentectomy in multivariable-adjusted (adjusted Hazard Ratio: 1.26, [1.06-1.51], P = 0.01) and propensity score-matched analysis (49% [95% confidence interval {CI}: 42%-55%] versus 59% [95% CI: 52%-65%], P = 0.02). Among a subgroup of 1221 wedge resection and 347 segmentectomy patients who also received intraoperative lymph node evaluation, however, there were no significant differences in 5-year survival in multivariable-adjusted (adjusted Hazard Ratio: 1.12, [0.90-1.39], P = 0.31) or propensity score-matched analysis (55% [95% CI: 48%-62%] versus 61% [95% CI: 54%-68%], P = 0.10). CONCLUSIONS: In this national analysis, there were no significant differences in survival between older adult patients with stage IA NSCLC who underwent wedge resection versus segmentectomy when a lymph node evaluation was performed.

Genomic description of human clinical Aspergillus fumigatus isolates, California, 2020.

Aspergillus fumigatus, an environmental mold, causes life-threatening infections. Studies on the phylogenetic structure of human clinical A. fumigatus isolates are limited. Here, we performed whole genome sequencing of 24 A. fumigatus isolates collected from 18 patients in U.S. healthcare facilities in California. Single-nucleotide polymorphism (SNP) differences between patient isolates ranged from 187 to 70 829 SNPs. For five patients with multiple isolates, we calculated the within-host diversities. Three patients had a within-host diversity that ranged from 4 to 10 SNPs and two patients ranged from 2 to 16 977 SNPs. Findings revealed highly diverse A. fumigatus strains among patients and two patterns of diversity for isolates that come from the same patient, low and extremely high diversity.

Aspergillus fumigatus is an environmental mold. It can cause a severe infection called aspergillosis in patients with weakened immune systems. We analyzed A. fumigatus DNA from patients at California hospitals. We described genetic diversity between samples from the same patients and among different patients. Our findings provide insight on using genomic sequencing to investigate aspergillosis in hospitals.

A national analysis of open versus minimally invasive thymectomy for stage I-III thymic carcinoma.

OBJECTIVES: The oncological efficacy of minimally invasive thymectomy for thymic carcinoma is not well characterized. We compared overall survival and short-term outcomes between open and minimally invasive surgical (video-assisted thoracoscopic and robotic) approaches using the National Cancer Database. METHODS: Perioperative outcomes and overall survival of patients who underwent open versus minimally invasive thymectomy for Masaoka stage I-III thymic carcinoma from 2010 to 2015 in the National Cancer Database were evaluated using propensity score-matched analysis and multivariable Cox proportional hazards modelling. Outcomes by surgical approach were assessed using an intent-to-treat analysis. RESULTS: Of the 216 thymectomies that were evaluated, 43 (20%) were performed with minimally invasive techniques (22 video-assisted thoracoscopic and 21 robotic). The minimally invasive approach was associated with a shorter median length of stay when compared to the open approach (3 vs 5 days, P < 0.001). In the propensity score-matched analysis of 30 open and 30 minimally invasive thymectomies, the minimally invasive group did not differ significantly in median length of stay (3 vs 4.5 days, P = 0.27), 30-day readmission (P = 0.13), 30-day mortality (P = 0.60), 90-day mortality (P = 0.60), margin positivity (P = 0.39) and 5-year survival (78.6% vs 54.6%, P = 0.15) when compared to the open group. CONCLUSIONS: In this national analysis, minimally invasive thymectomy for stage I-III thymic carcinoma was found to have no significant differences in short-term outcomes and overall survival when compared to open thymectomy.

The Risk of Postoperative Complications After Major Elective Surgery in Active or Resolved COVID-19 in the United States.

OBJECTIVE: To assess the association between the timing of surgery relative to the development of Covid-19 and the risks of postoperative complications. SUMMARY BACKGROUND DATA: It is unknown whether patients who recovered from Covid-19 and then underwent a major elective operation have an increased risk of developing postoperative complications. METHODS: The risk of postoperative complications for patients with Covid-19 undergoing 18 major types of elective operations in the Covid-19 Research Database was evaluated using multivariable logistic regression. Patients were grouped by time of surgery relative to SARS-CoV-2 infection; that is, surgery performed: (1) before January 1, 2020 ("pre-Covid-19"), (2) 0 to 4 weeks after SARS-CoV-2 infection ("peri-Covid-19"), (3) 4 to 8 weeks after infection ("early post-Covid-19"), and (4) ≥8 weeks after infection ("late post-Covid-19"). RESULTS: Of the 5479 patients who met study criteria, patients with peri-Covid-19 had an elevated risk of developing postoperative pneumonia [adjusted odds ratio (aOR), 6.46; 95% confidence interval (CI): 4.06-10.27], respiratory failure (aOR, 3.36; 95% CI: 2.22-5.10), pulmonary embolism (aOR, 2.73; 95% CI: 1.35-5.53), and sepsis (aOR, 3.67; 95% CI: 2.18-6.16) when compared to pre-Covid-19 patients. Early post-Covid-19 patients had an increased risk of developing postoperative pneumonia when compared to pre-Covid-19 patients (aOR, 2.44; 95% CI: 1.20-4.96). Late post-Covid-19 patients did not have an increased risk of postoperative complications when compared to pre-Covid-19 patients. CONCLUSIONS: Major, elective surgery 0 to 4 weeks after SARS-CoV-2 infection is associated with an increased risk of postoperative complications. Surgery performed 4 to 8 weeks after SARS-CoV-2 infection is still associated with an increased risk of postoperative pneumonia, whereas surgery 8 weeks after Covid-19 diagnosis is not associated with increased complications.

A National Analysis of Short-term Outcomes and Long-term Survival Following Thoracoscopic Versus Open Lobectomy for Clinical Stage II Non-Small-Cell Lung Cancer.

OBJECTIVE: To compare outcomes after open versus thoracoscopic (VATS) lobectomy for clinical stage II (cN1) non-small-cell lung cancer (NSCLC). BACKGROUND: There have been no published studies evaluating the impact of a VATS approach to lobectomy for N1 NSCLC on short-term outcomes and survival. METHODS: Outcomes of patients with clinical T1-2, N1, M0 NSCLC who underwent lobectomy without induction therapy in the National Cancer Data Base (2010-2012) were evaluated using multivariable Cox proportional hazards modeling and propensity score-matched analysis. RESULTS: Median follow-up of 1559 lobectomies (1204 open and 355 VATS) was 43.2 months. The VATS approach was associated with a shorter median hospitalization (5 vs 6 d, P < 0.001) than the open approach. There were no significant differences between the VATS and open approach with regard to nodal upstaging (12.0% vs 10.5%, P = 0.41), 30-day mortality (2.3% vs 3.1%, P = 0.31), and overall survival (5-yr survival: 48.6% vs 48.7%, P = 0.76; multivariable-adjusted HR for VATS approach: 1.08, 95% CI: 0.90-1.30, P = 0.39). A propensity score-matched analysis of 334 open and 334 VATS patients who were well matched by 14 common prognostic covariates, including tumor size, and comorbidities, continued to show no significant differences in nodal upstaging, 30-day mortality, and 5-year survival between the VATS and open groups. CONCLUSION: In this national analysis, VATS lobectomy was used in the minority of N1 NSCLC cases but was associated with shorter hospitalization and similar nodal upstaging rates, 30-day mortality, and long-term survival when compared to open lobectomy. These findings suggest thoracoscopic techniques are feasible for the treatment of stage II (cN1) NSCLC.

A National Analysis of Minimally Invasive Vs Open Segmentectomy for Stage IA Non-Small-Cell Lung Cancer.

The objective of this study was to compare long-term outcomes of open vs minimally invasive (MIS) segmentectomy for early stage non-small-cell lung cancer (NSCLC), which has not been previouslyevaluated using national studies. Outcomes of open vs MIS segmentectomy for clinical T1, N0, M0 NSCLC in the National Cancer Data Base (2010-2015) were evaluated using propensity score matching. Of the 39,351 patients who underwent surgery for stage IA NSCLC from 2010 to 2015, 770 underwent segmentectomy by thoracotomy and 1056 by MIS approach (876 thoracoscopic [VATS], 180 robotic). The MIS to open conversion rate was 6.7% (n = 71). After propensity score matching, all baseline characteristics were well-balanced between the open (n = 683) and MIS (n = 683) groups. When compared to the open group, the MIS group had shorter median length of stay (4 vs 5 days, P< 0.001) and lower 30-day mortality (0.6% vs 1.9%, P = 0.037). There were no significant differences between MIS and open groups with regard to 30-day readmission (5.0% vs 3.7%, P = 0.43), or upstaging from cN0 to pN1/N2/N3 (3.1% vs 3.6%, P = 0.89). The MIS approach was associated with similar long-term overall survival as the open approach (5-year survival: 62.3% vs 63.5%, P = 0.89; multivariable-adjusted hazard ratio: 0.99, 95% Confidence Intervial (CI): 0.82-1.21, P = 0.96). In this national analysis of open vs MIS segmentectomy for clinical stage IA NSCLC, MIS was associated with shorter length of stay and lower perioperative mortality, and similar nodal upstaging and 5-year survival when compared to segmentectomy via thoracotomy. MIS segmentectomy does not appear to compromise oncologic outcomes for clinical stage IA NSCLC.

Leveraging social media to explore the barriers to treatment among individuals with depressive symptoms.

BACKGROUND: Individuals with depression may not seek treatment for their symptoms due to several types of barriers to treatment. In support of the growing research on mental health care access and the role of social media, this study aimed to increase knowledge of these barriers among social media users. METHODS: Participants were recruited from several social media platforms, including Instagram, Facebook, Twitter, Reddit, Tumblr, and online depression forums. Eligible participants had endorsed having posted about feeling sad or depressed on social media, or followed social media groups that post about depression-related topics. Participants completed an online survey about their depression symptoms, interest in treatment, and potential barriers to accessing treatment. RESULTS: Of the participants reaching criteria for depression, those with major depression were more likely to seek out treatment, to report an unmet need for treatment, and have a higher risk of suicide. For participants with major depression, barriers to treatment were more likely to be attitudinal, while participants with mild depression experienced more structural barriers. CONCLUSIONS: This study demonstrates several barriers to treatment that occur for individuals struggling with depression, and that online platforms are effective mediums to recruit individuals with depression symptoms who seek mental health support.

The Oldest Old: A National Analysis of Outcomes for Patients 90 Years or Older With Lung Cancer.

BACKGROUND: Most clinicians will encounter patients 90 years or older with non-small cell lung cancer (NSCLC), but evidence that informs treatment decisions for this extremely elderly population is lacking. This study evaluated outcomes associated with treatment strategies for this nonagenarian population. METHODS: Treatment and overall survival for patients 90 years and older with NSCLC in the National Cancer Data Base (2004-2014) were evaluated using logistic regression, the Kaplan-Meier method, and multivariable Cox proportional hazard models. RESULTS: The majority (n = 4152, 57.6%) of the 7205 patients 90 years or older with stage I-IV NSCLC did not receive any therapy. For the entire cohort, receiving treatment was associated with significantly better survival when compared with no therapy (5-year survival, 9.3% [95% confidence interval [CI], 8.0%-10.7%] vs 1.7% [95% CI, 1.2%-2.2%]; multivariable adjusted hazard ratio, 0.53; P < .001). Stage I patients had the most pronounced survival benefit with treatment (median survival, 27.4 months vs 10.0 months with no treatment; P < .001). Among this subset of patients with stage I disease (n = 1430), only 12.7% (n = 182) had surgery and 33% (n = 471) had no therapy. In these stage I patients surgery was associated with significantly better 5-year survival (33.7% [95% CI, 25.4%-42.1%]) than nonoperative therapy (17.1% [95% CI, 13.7%-20.8%]) and no therapy (6.2% [95% CI, 3.8%-9.4%]). CONCLUSIONS: Therapy for nonagenarians with NSCLC is associated with a significant survival benefit but is not used in most patients. Treatment should not be withheld for these "oldest old" patients based on their age alone but should be considered based on stage and patient preferences in a multidisciplinary setting.

Sublobar resection is associated with decreased survival for patients with early stage large-cell neuroendocrine carcinoma of the lung.

OBJECTIVES: Sublobar resection (SLR) for early non-small-cell lung carcinoma (NSCLC) has been shown to have a survival rate similar to that of lobectomy. Large-cell neuroendocrine carcinoma (LCNEC) of the lung, although treated like an NSCLC, has a poor prognosis compared to NSCLC. We sought to determine if outcomes are poor in patients with early stage LCNEC treated with SLR versus lobectomy. METHODS: We searched for patients with pathological stage I LCNEC ≤3 cm within the National Cancer Database between 2004 and 2014. Propensity score matching was used to compare the 5-year overall survival rate of patients having SLR (wedge or segmentectomy) to that of patients having a lobectomy. Patients were matched for age, node sampling, comorbidity score, tumour size, insurance status and other factors. Patients who received neoadjuvant therapy were excluded. Kaplan-Meier methods were used for analysis. RESULTS: A total of 1011 patients met the inclusion criteria: 263 were treated with SLR (223 wedges and 40 segmentectomies) and 748 patients, with lobectomy. Patients who received SLR were older, had more comorbidities and smaller tumours. On unadjusted Kaplan-Meier analysis, patients who had SLR had decreased 5-year overall survival compared to those who had a lobectomy (37.9% vs 56.6%, P < 0.001). Propensity score matching (1:1) across 12 demographic and tumour variables yielded 185 patients per group with 34 segmentectomies and 151 wedge resections in the SLR cohort. On Kaplan-Meier analysis of the matched cohort, patients who had SLR had a worse 5-year overall survival rate compared to those who had a lobectomy (41.5% vs 60.3%; P = 0.001). CONCLUSIONS: SLR for early stage LCNEC is associated with a lower 5-year overall survival rate compared to lobectomy on unadjusted and propensity matched analyses.

Mechanochromic Stretchable Electronics.

Soft and stretchable electronics are promising for a variety of applications such as wearable electronics, human-machine interfaces, and soft robotics. These devices, which are often encased in elastomeric materials, maintain or adjust their functionality during deformation, but can fail catastrophically if extended too far. Here, we report new functional composites in which stretchable electronic properties are coupled to molecular mechanochromic function, enabling at-a-glance visual cues that inform user control. These properties are realized by covalently incorporating a spiropyran mechanophore within poly(dimethylsiloxane) to indicate with a visible color change that a strain threshold has been reached. The resulting colorimetric elastomers can be molded and patterned so that, for example, the word "STOP" appears when a critical strain is reached, indicating to the user that further strain risks device failure. We also show that the strain at color onset can be controlled by layering silicones with different moduli into a composite. As a demonstration, we show how color onset can be tailored to indicate a when a specified frequency of a stretchable liquid metal antenna has been reached. The multiscale combination of mechanochromism and soft electronics offers a new avenue to empower user control of strain-dependent properties for future stretchable devices.

Surgical treatment for early stage non-small cell lung cancer.

Surgery is the standard of care for early stage non-small cell lung cancer. There is significant debate about the type of operation most effective for lung cancer. Minimally invasive techniques like video-assisted (VATS) and robot-assisted thoracoscopic surgery (RATS) have been shown to reduce postoperative complications and shorten hospitalization. However, there remains skepticism about their oncologic effectiveness when compared to an open approach, though recent literature suggests no differences in upstaging or survival between VATS and thoracotomy. The extent of resection for early lung cancer also remains a matter of debate. Lobectomy remains the preferred operation and is associated with better survival and lower locoregional recurrence, but there is increased interest in the role of sublobar resections. Sublobar resections have similar mortality to lobar resections in small ground glass-predominant tumors. We examine the literature surrounding these controversies in this review.

Design of interventional studies in thoracic surgery.

Interventional studies differ from observational studies in that one or more specific interventions are evaluated. Randomized controlled trials remain the gold standard for interventional studies and can take different forms. In surgical studies, the three types of randomized controlled trials most commonly encountered are: (I) trials that compare two different medical treatments for patients undergoing surgery; (II) trials that evaluate two different surgical techniques and (III) studies that compare surgery vs. non-operative management. When an intervention is to be evaluated but a randomized controlled trial is not feasible, alternative interventional study designs may be considered.

Anatomic thoracoscopic segmentectomy for early-stage lung cancer.

Over the past 20 years, there have been significant advancements in thoracoscopic surgical techniques as well as in lung cancer screening protocols, which have identified greater numbers of smaller lung tumors (<2 cm) that are more frequently operable and curable. These advancements have led to new interest in the thoracoscopic (VATS) approach to segmentectomy. This article will discuss the outcomes and technical considerations associated with VATS segmentectomy.

Closed-Tube Barcoding.

Here, we present a new approach for increasing the rate and lowering the cost of identifying, cataloging, and monitoring global biodiversity. These advances, which we call Closed-Tube Barcoding, are one application of a suite of proven PCR-based technologies invented in our laboratory. Closed-Tube Barcoding builds on and aims to enhance the profoundly important efforts of the International Barcode of Life initiative. Closed-Tube Barcoding promises to be particularly useful when large numbers of small or rare specimens need to be screened and characterized at an affordable price. This approach is also well suited for automation and for use in portable devices.

Polyanhydride implant for antibiotic delivery--from the bench to the clinic.

A polyanhydride implant (Septacin) containing gentamicin sulfate was developed for sustained local delivery of the drug to the site of infection in the treatment of osteomyelitis. Laboratory-scale injection molding equipment was utilized to fabricate the implant for in vitro characterization. Molding conditions were optimized to produce implants with a skin-core structure which was found to be critical in preventing the initial cracking of the implant during in vitro drug release test in water. A manufacturing process consisting of twin-screw extrusion, pelletizing, and injection molding was developed. Polymer-drug pellets were characterized with respect to copolymer molecular weight and drug content uniformity. The implants were terminally sterilized by gamma-radiation which was found to cause increase in copolymer molecular weight as a result of polymer chain extension. The stability of Septacin was evaluated as a function of storage temperature and time. A marked decline in copolymer molecular weight occurred in samples stored above freezing temperatures and significantly slower drug-release profiles were also exhibited by these samples. In vivo drug release from Septacin in rats showed that the gentamicin plasma levels were extremely low, indicating the low systemic exposure to gentamicin. Furthermore, Septacin samples have demonstrated efficacy in the rat skin-abscess and horse-joint infection models. Results from a human in vivo study also showed high local drug concentrations at implantation sites while systemic exposure to the drug was minimal.