Comparison of Quality of Life after Robotic, Video-Assisted, and Open Surgery for Lung Cancer.

Post-operative quality of life (QOL) has become crucial in choosing operative approaches in thoracic surgery. However, compared to VATS and thoracotomy, QOL results post-RATS are limited. We compared QOL before and after RATS and between RATS, VATS, and thoracotomy. We conducted a retrospective review of lung cancer surgical patients from 2015 to 2020. Patients completed validated EORTC QOL questionnaires (QLQ-C30 and QLQ-LC13). Results were analysed using the EORTC Scoring Guide, with statistical analysis. A total of 47 (94%) pre- and post-RATS questionnaires were returned. Forty-two patients underwent anatomical lung resections. In addition, 80% of patients experienced uncomplicated recovery. All global and functional QOL domains improved post-operatively, as did most symptoms (13/19). Only four symptoms worsened, including dyspnoea (p = 0.017), with two symptoms unchanged. Of the 148 returned questionnaires for all approaches (open-22/VATS-79/RATS-47), over 70% showed a high pre-operative performance status. Most patients underwent anatomical lung resection, with only VATS patients requiring conversion (n = 6). Complications were slightly higher in RATS, with one patient requiring re-intubation. RATS patients demonstrated the highest global and functional QOL. Physical QOL was lowest after thoracotomy (p = 0.002). RATS patients reported the fewest symptoms, including dyspnoea (p = 0.046), fatigue (p < 0.001), and pain (p = 0.264). Overall, RATS results in a significantly better post-operative QOL and should be considered the preferred surgical approach for lung cancer patients.

Conserved chamber-specific polyploidy maintains heart function in Drosophila.

Developmentally programmed polyploidy (whole-genome duplication) of cardiomyocytes is common across evolution. Functions of such polyploidy are essentially unknown. Here, in both Drosophila larvae and human organ donors, we reveal distinct polyploidy levels in cardiac organ chambers. In Drosophila, differential growth and cell cycle signal sensitivity leads the heart chamber to reach a higher ploidy/cell size relative to the aorta chamber. Cardiac ploidy-reduced animals exhibit reduced heart chamber size, stroke volume and cardiac output, and acceleration of circulating hemocytes. These Drosophila phenotypes mimic human cardiomyopathies. Our results identify productive and likely conserved roles for polyploidy in cardiac chambers and suggest that precise ploidy levels sculpt many developing tissues. These findings of productive cardiomyocyte polyploidy impact efforts to block developmental polyploidy to improve heart injury recovery.

Conserved Chamber-Specific Polyploidy Maintains Heart Function in Drosophila.

Developmentally programmed polyploidy (whole-genome-duplication) of cardiomyocytes is common across evolution. Functions of such polyploidy are essentially unknown. Here, we reveal roles for precise polyploidy levels in cardiac tissue. We highlight a conserved asymmetry in polyploidy level between cardiac chambers in Drosophila larvae and humans. In Drosophila , differential Insulin Receptor (InR) sensitivity leads the heart chamber to reach a higher ploidy/cell size relative to the aorta chamber. Cardiac ploidy-reduced animals exhibit reduced heart chamber size, stroke volume, cardiac output, and acceleration of circulating hemocytes. These Drosophila phenotypes mimic systemic human heart failure. Using human donor hearts, we reveal asymmetry in nuclear volume (ploidy) and insulin signaling between the left ventricle and atrium. Our results identify productive and likely conserved roles for polyploidy in cardiac chambers and suggest precise ploidy levels sculpt many developing tissues. These findings of productive cardiomyocyte polyploidy impact efforts to block developmental polyploidy to improve heart injury recovery.

Quality of Life in Octogenarians After Lung Resection Compared to Younger Patients.

INTRODUCTION: To evaluate postoperative outcome and quality of life (QOL), comparing patients <80 years old to patients ≥ 80. PATIENTS AND METHODS: EORTC questionnaires, QLQ-C30 and QLQ-LC13 was used to assess QOL, in patients after surgery. Results were evaluated according to 3 age groups: <70, 70 to 79, and ≥80. RESULTS: 106 patients were enrolled with 33 (<70), 25 (70-79), and 48 (≥80) patients per group. The median age was 74 years. 79% of patients had minimally invasive procedures, including 91% of those ≥80. Fifteen patients underwent wedge resections. Complication rates (18%, 32%, and 29%, P = .4) and median length of stay (4, 6, and 5 days, P = .2) were similar in all age groups, with no hospital mortality. One hundred one patients completed the questionnaires. Global QOL was highest among octogenarians. Overall functional and role QOL was higher among octogenarians than 70- to 79-year-olds, with emotional QOL higher than those <70 (P < .05). Social QOL in octogenarians was marginally lower than younger patients. Lung-specific symptom scores were at least 1.5 times lower than those <80 (P = .052). Patients aged 70 to 79 had the worst symptomatic and emotional effect on QOL. Surgical access and preoperative performance status did not affect final QOL across all age groups (P = .9 and P = .065). Among anatomical lung resections, QOL was higher in octogenarians than those 70 to 79 in all domains, and similar or higher than those <70 in most domains. CONCLUSION: Quality of life among octogenarians after surgery remains similar to younger patients even after anatomical lung resection. Surgery in octogenarians is safe, with minimal impact on postoperative QOL.

Maintaining safe lung cancer surgery during the COVID-19 pandemic in a global city.

BACKGROUND: SARS-CoV-2 has challenged health service provision worldwide. This work evaluates safe surgical pathways and standard operating procedures implemented in the high volume, global city of London during the first wave of SARS-CoV-2 infection. We also assess the safety of minimally invasive surgery(MIS) for anatomical lung resection. METHODS: This multicentre cohort study was conducted across all London thoracic surgical units, covering a catchment area of approximately 14.8 Million. A Pan-London Collaborative was created for data sharing and dissemination of protocols. All patients undergoing anatomical lung resection 1st March-1st June 2020 were included. Primary outcomes were SARS-CoV-2 infection, access to minimally invasive surgery, post-operative complication, length of intensive care and hospital stay (LOS), and death during follow up. FINDINGS: 352 patients underwent anatomical lung resection with a median age of 69 (IQR: 35-86) years. Self-isolation and pre-operative screening were implemented following the UK national lockdown. Pre-operative SARS-CoV-2 swabs were performed in 63.1% and CT imaging in 54.8%. 61.7% of cases were performed minimally invasively (MIS), compared to 59.9% pre pandemic. Median LOS was 6 days with a 30-day survival of 98.3% (comparable to a median LOS of 6 days and 30-day survival of 98.4% pre-pandemic). Significant complications developed in 7.3% of patients (Clavien-Dindo Grade 3-4) and 12 there were re-admissions(3.4%). Seven patients(2.0%) were diagnosed with SARS-CoV-2 infection, two of whom died (28.5%). INTERPRETATION: SARS-CoV-2 infection significantly increases morbidity and mortality in patients undergoing elective anatomical pulmonary resection. However, surgery can be safely undertaken via open and MIS approaches at the peak of a viral pandemic if precautionary measures are implemented. High volume surgery should continue during further viral peaks to minimise health service burden and potential harm to cancer patients. FUNDING: This work did not receive funding.

Risks and rewards of the surgical treatment of lung cancer in octogenarians.

OBJECTIVES: Surgeons will face an increasing number of octogenarians with lung cancer potentially curable by surgery. The goal of this study was to evaluate short- and long-term outcomes after lung resection. METHODS: We performed a single-centre study of consecutive patients ≥80 years old, surgically treated for suspected lung cancer between 2009 and 2016. Age, sex, performance status, lung function, surgical approach, type of lung resection, complications, in-hospital and 30- and 90-day deaths and long-term survival were analysed. RESULTS: Two hundred and fifty-seven patients were enrolled. The median age was 82 years (range 80-97). One hundred and thirty-four patients were treated by thoracotomy and 123 by video-assisted thoracic surgery [10 (8.1%) converted]. Two hundred and thirty-two underwent lobar resection and 25 underwent sublobar resection. There were no intraoperative deaths and 9 admissions to the intensive therapy unit; 112 (43.6%) patients suffered complications: More complications occurred after lobar versus after sublobar resections [45.7% vs 24% (P = 0.037)] and in those with chronic obstructive pulmonary disease (COPD) [57.4% vs 40% (P = 0.02)]. The 30-day mortality was 3.9% (n = 10) and the 90-day mortality was 6.22% (n = 16). One hundred and sixty-seven patients died during the study period; patients with non-small-cell lung cancer (n = 233) had a median survival of 46.5 months with 67.2% alive at 2 years and 40.8% at 5 years. Pathological stage and R status were independent prognostic factors for survival. CONCLUSIONS: Surgery for malignancies in octogenarians is feasible and safe with good long-term outcomes. The risk of postoperative complications, especially in those with COPD, is high but can be minimized with sublobar resection. Postoperative mortality is acceptable, and long-term survival is primarily governed by lung cancer stage. Age is no reason to deny patients surgery for early-stage disease.

The Pulmonary Metastasectomy in Colorectal Cancer (PulMiCC) burden of care study: Analysis of local treatments for lung metastases and systemic chemotherapy in 220 patients in the PulMiCC cohort.

AIM: The aim of this work was to examine the burden of further treatments in patients with colorectal cancer following a decision about lung metastasectomy. METHOD: Five teams participating in the Pulmonary Metastasectomy in Colorectal Cancer (PulMiCC) study provided details on subsequent local treatments for lung metastases, including the use of chemotherapy. For patients in three groups (no metastasectomy, one metastasectomy or multiple local interventions), baseline factors and selection criteria for additional treatments were examined. RESULTS: The five teams recruited 220 patients between October 2010 and January 2017. No lung metastasectomy was performed in 51 patients, 114 patients had one metastasectomy and 55 patients had multiple local interventions. Selection for initial metastasectomy was associated with nonelevated carcinoembryonic antigen, fewer metastases and no prior liver metastasectomy. These patients also had better Eastern Cooperative Oncology Group scores and lung function at baseline. Four sites provided information on chemotherapy in 139 patients: 79 (57%) had one to five courses of chemotherapy, to a total of 179 courses. The patterns of survival after one or multiple metastasectomy interventions showed evidence of guarantee-time bias contributing to an impression of benefit over no metastasectomy. After repeated metastasectomy, a significantly higher risk of death was observed, with no apparent reduction in chemotherapy usage. CONCLUSION: Repeated metastasectomy is associated with a higher risk of death without reducing the use of chemotherapy. Continued monitoring without surgery might reassure patients with indolent disease or allow response assessment during systemic treatment. Overall, the carefully collected information from the PulMICC study provides no indication of an important survival benefit from metastasectomy.

Using mobile brain/body imaging to advance research in arts, health, and related therapeutics.

The uses of mobile brain/body imaging (MoBI) are expanding and allow for more direct study of the neurophysiological signals associated with behavior in psychotherapeutic encounters. Neuroaesthetics is concerned with the cognitive and neural basis of art appreciation, and scientific correlations are being made in the field that might help to clarify theories claimed in the creative arts therapies. Yet, most neuroaesthetics studies are confined to the laboratory and do not propose a translation for research methods and clinical applications. The creative arts therapies have a long history of clinical success with various patient populations and will benefit from increased scientific explanation to support intervention strategies. Examining the brain dynamics and motor behaviors that are associated with the higher complex processes involved in artistic expression offers MoBI as a promising instrumentation to move forward in linking ideas from neuroaesthetics to the creative arts therapies. Tracking brain dynamics in association with behavioral change allows for more objective and quantitative physiological monitors to evaluate, and together with subjective patient reports provides insight into the psychological mechanisms of change in treatment. We outline a framework that shows how MoBI can be used to study the effectiveness of creative arts therapy interventions motivated by the 4E approach to cognition with a focus on visual art therapy. The article illuminates how a new partnership among the fields of art therapy, neuroscience, and neuroaesthetics might work together within the 4E/MoBI framework in efforts to advance transdisciplinary research for clinical health populations.

The Pulmonary Metastasectomy in Colorectal Cancer cohort study: Analysis of case selection, risk factors and survival in a prospective observational study of 512 patients.

AIM: We wanted to examine survival in patients with resected colorectal cancer (CRC) whose lung metastases are or are not resected. METHODS: Teams participating in the study of Pulmonary Metastasectomy in Colorectal Cancer (PulMiCC) identified potential candidates for lung metastasectomy and invited their consent to join Stage 1. Baseline data related to CRC and fitness for surgery were collected. Eligible patients were invited to consent for randomization in the PulMiCC randomized controlled trial (Stage 2). Sites were provided with case report forms for non-randomized patients to record adverse events and death at any time. They were all reviewed at 1 year. Baseline and survival data were analysed for the full cohort. RESULTS: Twenty-five clinical sites recruited 512 patients from October 2010 to January 2017. Data collection closed in October 2020. Before analysis, 28 patients with non-CRC lung lesions were excluded and three had withdrawn consent leaving 481. The date of death was known for 292 patients, 136 were alive in 2020 and 53 at earlier time points. Baseline factors and 5-year survival were analysed in three strata: 128 non-randomized patients did not have metastasectomy; 263 had elective metastasectomy; 90 were from the randomized trial. The proportions of solitary metastases for electively operated and non-operated patients were 69% and 35%. Their respective 5-year survivals were 47% and 22%. CONCLUSION: Survival without metastasectomy was greater than widely presumed. Difference in survival appeared to be largely related to selection. No inference can be drawn about the effect of metastasectomy on survival in this observational study.

Impact of the TNM staging system for thymoma.

BACKGROUND: Masaoka-Koga staging system remains the most frequently applied clinical staging system for thymic malignancy. However, the International Association for the Study of Lung Cancer (IASLC)/International Thymic Malignancy Interest Group (ITMIG) proposed a tumor-node-metastasis (TNM) staging system in 2014. This study aims to evaluate its impact on stage distribution, clinical implementation, and prognosis for thymomas. METHODS: We performed a single institution, retrospective analysis of 245 consecutive patients who underwent surgical resection for thymoma. 9 patients with thymic carcinoma were excluded. No patients were lost to follow up. Kaplan-Meier survival analysis was used to calculate overall survival. RESULTS: Median age was 62 years; 129 patients (53%) were female. The median overall survival was 158 months (range, 108-208 months), and disease-free survival 194 months (range, 170-218 months). At the end of follow up 63 patients were dead. Early Masaoka-Koga stages I (n=74) and II (n=129) shifted to the IASLC/ITMIG stage I (n=203). 8 patients were down staged from Masaoka-Koga stage III to IASLC/ITMIG stage II because of pericardial involvement. Advanced stages III (Masaoka-Koga: n=30; IASLC/ITMIG: n=22) and IV (Masaoka-Koga: n=12; IASLC/ITMIG: n=12) remained similar and were associated with more aggressive WHO thymoma histotypes (B2/B3). Masaoka-Koga (P=0.004), IASLC/ITMIG staging (P<0.0001) and complete surgical resection (P<0.0001) were statistically associated with survival. At multivariate analysis only R status was an independent prognostic factor for survival. CONCLUSIONS: The proportion of patients with stage I disease increased significantly when IASLC/ITMIG system used, whilst the proportion with stages III and IV were similar in both systems. Completeness of resection, Masaoka-Koga and the IASLC/ITMIG staging system are strong predictors of survival. The TNM staging system is useful in disease management and a strong predictor of overall survival.

New N1/N2 classification and lobe specific lymphatic drainage: Impact on survival in patients with non-small cell lung cancer treated with surgery.

OBJECTIVE: to validate the proposed N descriptor revision on a large cohort of patients and assess the impact of tumour location on the distribution pattern of lymph node metastases for patients with NSCLC. METHODS: This is a retrospective review of a consecutive series of patients who had anatomical lung resections. Systematic lymph node dissection was done for all patients. RESULTS: Between January 2009 and December 2019 2566 patients had surgical resection for NSCLC. 448 patients (17.5%) had histologically confirmed lymph node metastases: 257 (57.4 %) had pN1 and 191 pN2. Median age of the study population was 69.1 years. Overall survival (OS) for study population was 37.3 months with 5-year survival rate of 35.7 %. The survival analysis of the N subgroups showed the pN2 patients had a median OS of 27.9 months vs. 41.7 months for pN1 patients (p = 0.013). Analysis as per the new proposal of the N subgroups N1a vs N1b vs N2a1 vs N2a2 vs N2b showed that median survival OS was 41.7 vs. 39.2 mo vs. 33.3 mo vs. 28.9 mo vs. 24.6 mo (p = 0.099). There was statistically significant difference in survival between N2 patients with skip metastasis and N2 patients without skip metastases: OS 32.2 (95 % CI: 16.8-47.6) months vs. 24.2 months (p = 0.024). On multivariate analysis only pathological N (p = 0.011) and the new proposed N classification (p = 0.006) were independent prognostic factors for survival. CONCLUSIONS: N1 and N2 disease are heterogeneous groups and require further stratification. The number of N2 lymph node stations involved and the presence or not of N1 disease translated to significant differences in survival and therefore have to be included in N staging.

Cytoplasmic sharing through apical membrane remodeling.

Multiple nuclei sharing a common cytoplasm are found in diverse tissues, organisms, and diseases. Yet, multinucleation remains a poorly understood biological property. Cytoplasm sharing invariably involves plasma membrane breaches. In contrast, we discovered cytoplasm sharing without membrane breaching in highly resorptive Drosophila rectal papillae. During a six-hour developmental window, 100 individual papillar cells assemble a multinucleate cytoplasm, allowing passage of proteins of at least 62 kDa throughout papillar tissue. Papillar cytoplasm sharing does not employ canonical mechanisms such as incomplete cytokinesis or muscle fusion pore regulators. Instead, sharing requires gap junction proteins (normally associated with transport of molecules < 1 kDa), which are positioned by membrane remodeling GTPases. Our work reveals a new role for apical membrane remodeling in converting a multicellular epithelium into a giant multinucleate cytoplasm.

Most cells are self-contained ­ they have a cell membrane that delimits and therefore defines the cell, separating it from other cells and from its environment. But sometimes several cells interconnect and form collectives so they can pool their internal resources. Some of the best-known examples of this happen in animal muscle cells and in the placenta of mammals. These cell collectives share their cytoplasm ­ the fluid within the cell membrane that contains the cell organelles ­ in one of two ways. Cells can either remain linked instead of breaking away when they divide, or they can fuse their membranes with those of their neighbors. Working out how cells link to their neighbors is difficult when so few examples of cytoplasm sharing are available for study. One way to tackle this is to try and find undiscovered cell collectives in an animal that is already heavily studied in the lab, such as the fruit fly Drosophila melanogaster. Peterson et al. used a genetic system that randomly labels each cell of the developing fly with one of three fluorescent proteins. These proteins are big and should not move between cells unless they are sharing their cytoplasm. This means that any cell containing two or more different colors of fluorescent protein must be connected to at least one of its neighbors. The experiment revealed that the cells of the fruit fly rectum share their cytoplasm in a way never seen before. This sharing occurs at a consistent point in the development of the fruit fly and uses a different set of genes to those used by interconnecting cells in mammal muscles and placenta. These genes produce proteins that reshape the membranes of the cells and fit them with gap junctions ­ tiny pores that cross from one membrane to the next, allowing the passage of very small molecules. In this case, the gap junctions allowed the cells to share molecules much larger than seen before. The result is a giant cell membrane containing the cytoplasm and organelles of more than a hundred individual cells. These findings expand scientists' understanding of how cells in a tissue can share cytoplasm and resources. They also introduce a new tissue in the fruit fly that can be used in future studies of cytoplasm sharing. Relatives of fruit flies, including fruit pests and mosquitos, have similar cell structure to the fruit fly, which means that further investigations using this system could result in advances in agriculture or human health.

Retrospective Observational Study into the Early Causes of Death Following Surgery for NSCLC.

INTRODUCTION: Respiratory failure has historically been the major cause of mortality after elective lung resections. With improved intubation using fiber-optic scopes, better preoperative respiratory risk assessment, more advanced anesthetic single lung ventilation, and minimally invasive surgical technique, this may have changed. Our objective was to assess the main causes of mortality over the past 10 years in patients undergoing elective lung surgery in a major UK center. MATERIALS AND METHODS: A retrospective unit data search was made for all deaths during the 10-year period between January 2007 and December 2016 inclusive. All inpatient deaths within 30 days of an elective anatomical lung resection for lung malignancies were included. RESULTS: Three-thousand three-hundred sixteen lung resections for malignancy were performed in the 10-year period. There were 44 (1.3%) deaths during this period, 27 (61.4%) after open lobectomies, 8 (18.2%) after video-assisted thoracoscopic surgery lobectomies, 5 (11.4%) after sleeve lobectomies, and 4 (9%) after pneumonectomies. Causes of death included 24 (54.5%) respiratory failure, 10 (22.7%) ischemic bowel, 4 (9%) coronary events, 2 (4.5%) strokes, 2 (4.5%) on table hemorrhage, 1 (2.3%) massive pulmonary embolus, and 1 (2.3%) postoperative hemorrhage. CONCLUSION: Although respiratory failure is still a major cause of mortality in the postoperative patient, bowel ischemia has been found to be the second greatest cause of death. This study highlights the need to identify those at risk of this fatal complication during preoperative assessment and their postoperative management.

Differential Survival Characteristics of Sarcomatoid Subtype in Biphasic Pleural Mesothelioma.

BACKGROUND: Biphasic pleural mesothelioma (BPM) accounts for approximately 10% of all pleural mesothelioma. Our aim was to assess the clinical, radiologic, and pathologic factors impacting survival in BPM and to better identify patients most likely to benefit from active treatment. METHODS: A 10-year retrospective review was made of 214 biopsy-proven BPM cases with minimum 2-year follow-up. Patients with insufficient tissue for analysis were excluded (n = 96). Clinical and pathologic factors were evaluated along with radiologic assessment of pleural thickness. Survival was measured from time of diagnosis. Univariable and multivariable predictors of survival were evaluated. RESULTS: In all, 118 patients were included; 28 underwent pleurectomy/decortication, with 27 receiving additional modalities. Ninety patients underwent chemotherapy (n = 18) or radiotherapy alone (n = 9), 63 received combination therapy, and 27 received best supportive care. Median overall survival was 11.2 months (range, 0.3 to 36.2). At univariable analysis, pleurectomy/decortication (p = 0.0061), radiotherapy (p < 0.0001), and chemotherapy (p < 0.0001) were associated with superior survival when compared with best supportive care alone. Pleurectomy/decortication demonstrated 40% survival improvement compared with no surgery (p = 0.122). In a multivariable model, necrosis was negatively prognostic (hazard ratio 2.1, SE 0.76). Furthermore, increased sarcomatoid component was associated with worse survival without radiotherapy. CONCLUSIONS: BPM prognosis remains poor despite multimodality treatment. Anticancer treatment is associated with superior outcome in this nonrandomized retrospective series. Our findings suggest superior survival for patients with a lower proportion of sarcomatoid disease, with selective benefit of radiotherapy in higher proportions of sarcomatoid disease. When planning active treatment, the potential survival benefits require balancing against associated morbidity and recovery period.

Summary of Twenty-First Century Great Conversations in Art, Neuroscience and Related Therapeutics.

Transdisciplinary collaboration is the future of knowledge making in advanced post-industrial societies and there is a growing awareness that the most vexing problems we face cannot be solved by any single discipline. Best practices for complex and challenging physical and mental disorders require a multi-disciplinary approach, yet there is a void in bridging the gap between the most contemporary models. It is in this capacity that the Twenty-First Century Great Conversations in Art, Neuroscience, and Related Therapeutics serves as a missing link. It was with active minds and a collective spirit that artists, scientists, therapists, physicians, engineers, technology experts, healthcare practitioners, and researchers from across the globe transcended historical silos to explore the capacities for collaborative partnerships to influence the health of patients and the amelioration of disease. Hosted at Indiana University-Purdue University Indianapolis (IUPUI), presenters shared insights through didactic sessions and panel discussions aligned with three tracks led by prominent experts in their respective fields: (1) Neuroaesthetics, Anjan Chatterjee, MD; (2) Creativity and Consciousness, Arne Dietrich, PhD; and (3) Mobile Brain/Body Imaging (MoBI), Klaus Gramann, PhD. The goals for this symposium were developed from a vision which embraces cross-disciplinary intersectionality, a merging of viewpoints, and active dialogue surrounding the development of a common language with which to advance the Creative Arts Therapies and neurosciences. The goal was also to contribute to the development of a simplified roadmap to enhance and enrich the CATs with a greater understanding of neuroscience and the available technologies that can assist in research.

Prognostic factors including lymphovascular invasion on survival for resected non-small cell lung cancer.

OBJECTIVES: The aim of this study was to report on the influence of tumor lymphovascular invasion on overall survival and in patients with resected non-small cell lung cancer and identify prognostic factors for survival. METHODS: This is a retrospective observational study of a consecutive series of patients who had surgical resection of non-small cell lung cancer in a single institution. The study covers a 3-year period. Overall survival was estimated by Kaplan-Meier method and multivariate Cox regression analysis was used to evaluate the relationship of lymphovascular invasion and other clinicopathologic variables. A multivariate regression was used to assess the relationship between tumor lymphovascular invasion and other clinical and pathologic characteristics. RESULTS: A total of 524 patients were identified and included in the study. Two hundred twenty-five patients (43%) had tumors with lymphovascular invasion. Patients with tumor lymphovascular invasion had a lower overall survival (P < .0001). Tumor lymphovascular invasion was independently associated with visceral pleural involvement (P < .0001). In a multivariable model, lymphovascular invasion (hazard ratio [HR], 2.58; 95% confidence interval [CI], 1.63-4.09; P < .0001), parietal pleural invasion (HR, 45.4; 95% CI, 2.08-990; P = .015), advanced age (HR, 1.028; 95% CI, 1.009-1.048; P = .004), and N2 lymph node involvement (HR, 1.837; 95% CI, 1.257-2.690; P = .002) were independent prognostic factors for lower overall survival. CONCLUSIONS: Lymphovascular invasion is associated with a worse overall survival in patients with resected non-small cell lung cancer regardless of tumor stage. Parietal pleural involvement, N2 nodal disease, and advanced age independently predict poor overall survival.

Demographic drivers of a refugee species: large-scale experiments guide strategies for reintroductions of hirola.

Effective reintroduction strategies require accurate estimates of vital rates and the factors that influence them. The hirola (Beatragus hunteri) is the rarest antelope on Earth, with a global population size of <500 individuals restricted to the Kenya-Somali border. We estimated vital rates of hirola populations exposed to varying levels of predation and rangeland quality from 2012 to 2015, and then built population matrices to estimate the finite rate of population change (λ) and demographic sensitivities. Mean survival for all age classes and population growth was highest in the low-predation-high-rangeland-quality setting (λ = 1.08 ± 0.03 [mean ± SE]), and lowest in the high-predation-low-rangeland-quality setting (λ = 0.70 ± 0.22). Retrospective demographic analyses revealed that increased fecundity (the number of female calves born to adult females annually) and female calf survival were responsible for higher population growth where large carnivores were absent. In contrast, variation in adult female survival was the primary contributor to differences in population growth attributable to rangeland quality. Our analyses suggest that hirola demography is driven by a combination of top-down (predation) and bottom-up (rangeland quality) forces, with populations in the contemporary geographic range impacted both by declining rangeland quality and predation. To enhance the chances of successful reintroductions, conservationists can consider rangeland restoration to boost both the survival and fecundity of adult females within the hirola's historical range.

Intracavitary 'T4 immunotherapy' of malignant mesothelioma using pan-ErbB re-targeted CAR T-cells.

Malignant mesothelioma remains an incurable cancer. We demonstrated that mesotheliomas expressed EGFR (79.2%), ErbB4 (49.0%) and HER2 (6.3%), but lacked ErbB3. At least one ErbB family member was expressed in 88% of tumors. To exploit ErbB dysregulation in this disease, patient T-cells were engineered by retroviral transduction to express a panErbB-targeted chimeric antigen receptor (CAR), co-expressed with a chimeric cytokine receptor that allows interleukin (IL)-4 mediated CAR T-cell proliferation. This combination is referred to as T4 immunotherapy. T-cells from mesothelioma patients were uniformly amenable to T4 genetic modification and expansion/enrichment thereafter using IL-4. Patient-derived T4+ T-cells were activated upon contact with a panel of four mesothelioma cell lines, leading to cytotoxicity and cytokine release in all cases. Adoptive transfer of T4 immunotherapy to SCID Beige mice with an established bioluminescent LO68 mesothelioma xenograft was followed by regression or eradication of disease in all animals. Despite the established ability of T4 immunotherapy to elicit cytokine release syndrome in SCID Beige mice, therapy was very well tolerated. These findings provide a strong rationale for the clinical evaluation of intracavitary T4 immunotherapy to treat mesothelioma.

New-onset atrial fibrillation after anatomic lung resection: predictive factors, treatment and follow-up in a UK thoracic centre.

Objectives: Postoperative atrial fibrillation (POAF) increases morbidity, hospital stay and healthcare expenditure. This study aims to determine the perioperative factors correlating with POAF as well as to evaluate both treatment strategies and AF persistence beyond discharge. Methods: The records of all patients undergoing anatomical lung resection over a 1-year period were retrospectively reviewed. Patients with a history of arrhythmia were excluded. POAF was defined by clinical diagnosis and electrocardiography. Pre- and postoperative demographic and clinical data were collected, and uni- and multivariable regression were performed to determine the factors associated with POAF. Results: POAF occurred in 11.4% (43/377) of patients with a mean of 3.55 days postoperatively and significantly increased hospital stay (6.78 ± 4.42 vs 10.8 ± 5.8 days (P = 0.0014)). No correlation was found with gender, hypertension, ischaemic heart disease, beta-blocker use, alcohol consumption or thyroid dysfunction. However, older age (P = 0.001) and postoperative infection (P < 0.0001; χ2 = 26.03) were found to be significant uni- and multivariable predictors of POAF. Open surgery rather than video assisted thoracoscopic surgery (VATS) (open 26/189 (13.8%); VATS 17/188 (9.0%); P = 0.150) demonstrated a tendency towards increased postoperative AF; however, this was not statistically significant. Four (9.3%) patients remained in AF on discharge, and three required long-term anticoagulation. Three (7%) patients were found to have ongoing AF at 1-month follow-up. Conclusions: Increasing age and postoperative infection are most strongly associated with POAF. Adoption of enhanced recovery protocols, along with more rigorous monitoring and early treatment of postoperative infection may help reduce POAF and its associated morbidity. Rhythm assessment is crucial to identify persistent AF after discharge, and clinicians should be vigilant for recurrence of AF at follow-up.