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Background This study evaluates the safety and feasibility of combined resection for patients with synchronous pulmonary and esophageal cancer. Methods Patients undergoing esophagectomy between 1997 and 2019 were identified from prospectively collected databases at three tertiary referral centers, and those with combined anatomic lung resection at the same setting were identified. This cohort was then matched in a 1:3 ratio to esophagectomy alone cases, based on age, sex, pathologic stage, neoadjuvant therapy, and surgical procedure. Demographic data, peri-operative data, post-operative complications were compared. Statistical analysis included unpaired t-test, Fisher’s exact or chi-squared test and Gehan-Breslow analysis. Results Of 4729 esophagectomies, combined anatomic lung resection was performed in 18 patients with discrete pulmonary lesions. Matching yielded 49 patients who underwent esophagectomy only and was statistically similar compared to patients undergoing combined resections. Ivor Lewis esophagectomy and lobectomy were the most frequent procedures. Combined resections did not have a higher overall complication rate than esophagectomy alone, rather these patients had fewer overall complications (56% vs 84%; p=0.02). Specifically, there was not difference in anastomotic leak (17% vs. 18%) or pulmonary complications (39% vs. 33%) between combined resection and esophagectomy alone. No post-operative mortality was identified, and median overall survival was 4.1 years versus 6.5 years (p=0.10). Conclusions Patients with synchronous localized lung and esophageal cancer, although rare, should not be biased towards non-surgical therapy, as the morbidity associated with combined esophagectomy and anatomic lung resection does not differ significantly from esophagectomy alone in this highly selected group of patients.

Coptis chinensis Franch. (CC), as a commonly used heat-clearing and toxin-resolving traditional Chinese herbal medicine, has gained increased attention for its anti-tumor activity. However, little is known about the anti-tumor angiogenesis effect of CC and its possible bioactive components. Also, it has been shown that temperature affects the quality of CC, albeit whether and how it affects the anti-angiogenic activity of CC is currently unknown.To determine the processing temperatures (40, 60, 80, 120, 140, 150, 160 and 200 °C) at which CC has the strongest anti-angiogenic effect and speculate the possible bioactive components.The q-CAM model was constructed to explore the anti-angiogenesis agents of CC. The angiogenesis inhibition effects of CC samples at different processing temperatures and its seven alkaloids were determined based on morphological observation and vascular area proportion analysis. UPLC-MS/MS was employed to screen the potent active components of CC on anti-angiogenesis.All the intervention by CC at different processing temperatures and its seven alkaloids could inhibit angiogenesis on q-CAM vessels, as evidenced by a poor vasular development in morphological observation and a low vascular area proportion in vascular quantitative analysis, most evident in CC processed at 40 °C and palmatine. LC-MS revealed that palmatine displayed strongest inhibitory effect on q-CAM vessels with a high absorption due to its stable structure. And the maternal nucleus transformation phenomenon of CC alkaloids was found in the quail embryo metabolism.The q-CAM models in conjunction with the UPLC-MS/MS technique could be a useful tool for assessing tumor angiogenesis and screening tumor-targeted medicines. Processing temperature can affect the anti-angiogenesis effect of CC because of its function on the content of alkaloids, and palmatine can be considered as a prospective anti-angiogenic drug.

BackgroundRespiratory viruses pose an important public health threat to most communities. Nonpharmaceutical interventions (NPIs) such as masks, hand hygiene or physical distancing, among others, are believed to play an important role in reducing transmission of respiratory viruses. In this umbrella review, we summarise the evidence of the effectiveness of NPIs for the prevention of respiratory virus transmission in the community setting.ObservationsA systematic search of PubMed, Embase, Medline and Cochrane reviews resulted in a total of 24 studies consisting of 11 systematic reviews and meta-analyses, 12 systematic reviews without meta-analyses and one standalone meta-analysis. The current evidence from these data suggests that hand hygiene is protective against respiratory viral infection. The use of hand hygiene and facemasks, facemasks alone and physical distancing were interventions with inconsistent evidence. Interventions such as school closures, oral hygiene or nasal saline rinses were shown to be effective in reducing the risk of influenza; however, the evidence is sparse and mostly of low and critically low quality.ConclusionsStudies on the effectiveness of NPIs for the prevention of respiratory viral transmission in the community vary in study design, quality and reported effectiveness. Evidence for the use of hand hygiene or facemasks is the strongest; therefore, the most reasonable suggestion is to use hand hygiene and facemasks in the community setting.

Recent interest has focused on innate-type cytokines as promoters of type 2 immunity and targets for drug development in asthma. IL-33 induces production of IL-4 and/or IL-13, which is associated with STAT6-dependent responses in innate cells, including group 2 innate lymphoid cells (ILC2s), macrophages, and eosinophils. Our published data show that STAT6-immunomodulatory peptide (STAT6-IP), an immunomodulatory peptide designed to inhibit the STAT6 transcription factor, reduces induction of Th2 adaptive immunity in respiratory syncytial virus infection and asthma models. Nevertheless, the mechanism of STAT6-IP–dependent inhibition has remained obscure. In this study, we demonstrate that STAT6-IP reduced IL-33–induced type 2 innate lung inflammation. Specifically, our data show that STAT6-IP reduced recruitment and activation of eosinophils as well as polarization of alternatively activated macrophages. Decreases in these cells correlated with reduced levels of IL-5 and IL-13 as well as several type 2 chemokines in the bronchoalveolar lavage fluid. STAT6-IP effectively inhibited expansion of ILC2s as well as the number of IL-5– and IL-13–producing ILC2s. Our data suggest that STAT6-IP effectively disrupts IL-13–dependent positive feedback loops, initiated by ILC2 activation, to suppress IL-33–induced type 2 innate immunity in the murine lung.

Canadian lung transplant centers currently use a subjective and dichotomous "Status" ranking to prioritize waitlisted patients for lung transplantation. The lung allocation score (LAS) is an objective composite score derived from clinical parameters associated with both waitlist and post-transplant survival. We performed a retrospective cohort study to determine whether clinical judgment (Status) or LAS better predicted waitlist mortality. All adult patients listed for lung transplantation between 2007 and 2012 at three Canadian lung transplant programs were included. Status and LAS were compared in their ability to predict waitlist mortality using Cox proportional hazards models and C-statistics. Status and LAS were available for 1122 patients. Status 2 patients had a higher LAS compared to Status 1 patients (mean 40.8 (4.4) vs 34.6 (12.5), P = .0001). Higher LAS was associated with higher risk of waitlist mortality (HR 1.06 per unit LAS, 95% CI 1.05, 1.07, P < .001). LAS predicted waitlist mortality better than Status (C-statistic 0.689 vs 0.674). Patients classified as Status 2 and LAS ≥ 37 had the worst survival awaiting transplant, HR of 8.94 (95% CI 5.97, 13.37). LAS predicted waitlist mortality better than Status; however, the best predictor of waitlist mortality may be a combination of both LAS and clinical judgment.

Sex differences in asthma prevalence are well-documented but poorly understood. Murine models have contributed to our understanding of mechanisms that could regulate this sex disparity, though the majority of these studies have examined responses present after Th2 adaptive immunity is established. We have now investigated how sex influences acute activation of innate cell populations in the lung upon initial exposure to the model antigen, ovalbumin (OVA), in the presence of IL-33 (OVA+IL-33), to prime the lungs for type 2 immunity. We also examined how inflammatory responses induced by OVA+IL-33 were altered in mice lacking the STAT6 transcription factor, which is activated by IL-13, an effector cytokine of IL-33. Our data demonstrate that type 2 inflammation induced by OVA+IL-33 was more severe in female mice compared to males. Females exhibited greater cytokine and chemokine production, eosinophil influx and activation, macrophage polarization to the alternatively activated phenotype, and expansion of group 2 innate lymphoid cells (ILC2s). While increases in ILC2s and eosinophils were largely independent of STAT6 in both males and females, many other responses were STAT6-dependent only in female mice. Our findings indicate that a subset of type 2 inflammatory responses induced by OVA+IL-33 require STAT6 in both males and females and that enhanced type 2 inflammation in females, compared to males, is associated with greater IL-13 protein production. Our findings suggest blunted IL-13 production in males may protect against type 2 inflammation initiated by OVA+IL-33 delivery to the lung.

341 Background: Resection is the best treatment for both esophagus and lung cancer, however, concerns that a combined resection of synchronous lung/esophagus tumors might be associated with higher morbidity may preclude surgical therapy. We sought to review a multi-institutional experience on combined esophagus/lung cancer resections. Methods: Patients undergoing esophagectomy and those with concurrent anatomic resection for bronchogenic carcinoma between 1997-2018 at three high-volume North American centers were identified from prospectively collected databases. Combined resection cases (E+L) were matched in a 1:3 ratio to patients who underwent esophagectomy alone (E), based on age, sex, stage, neoadjuvant therapy, procedure (2/3hole), and approach (MIE/open). Patient demographics, tumour characteristics, and post-operative outcomes were compared. Statistical analysis was performed using unpaired t-test or Wilcoxon sum-rank test for continuous variables and Fisher’s exact test for categorical data. Statistical significance was defined as p < 0.05. Results: Of over 2500 patients undergoing esophagectomy, synchronous anatomic lung resection was performed in 20; 4 were excluded due to incomplete data (n = 16). Matching yielded 48 patients and 4 duplicates were removed (n = 44); there were no significant differences in patient demographics, neoadjuvant therapy, clinical stage, or procedure. Anatomic resection consisted of lobectomy (16/20), segmentectomy (3/20) and pneumonectomy (1/20), combined with 2-hole (14/20), 3-hole (4/20), or left thoraco-abdominal (2/20) esophagectomy. The proportion of patients with any complication in E+L was 50%, and 66% in E (p = 0.42). Pulmonary complications were 19% and 27% in the respective groups (p = 0.74). Mortality did not differ (E+L = 0/16:E = 1/44)NS. The median length of stay for both groups was similar (E+L = 10.5 days(IQR 5.7): E = 10.0 days (IQR 8.7))NS. Conclusions: Patients with synchronous localized lung and esophageal cancer, although rare, should not be biased towards non-surgery therapy, as the morbidity associated with combined esophagectomy and anatomic lung resection does not differ significantly from esophagectomy alone.