Responses of Birds and Reptiles in Warrumbungle National Park after the Extensive 2013 Wildfire

In 2013 extensive wildfire burnt 90% (22104 ha) of Warrumbungle National Park in New South Wales, Australia. In 2014-2016 we assessed how species composition and abundance of birds and reptiles varied with fire severity and habitat characteristics. Of 91 bird species observed during surveys of 35 sites, 47 were more often on low severity sites. Bird species composition did not differ among vegetation communities although activity levels (species per 10 minutes) were reduced in woodland on sedimentary geology as compared with volcanic areas. With increasing fire severity bird activity and total number of species detected decreased, and species composition changed. Differences in species composition were due mainly to lower numbers of detections of small to medium-sized insectivores and nectarivores on high severity sites. Results were more complicated for the 36 species of reptiles observed during surveys than for birds. Reptile species composition varied with fire severity, geology, presence of rock outcrops and between vegetation communities. Species richness and abundance of many reptile groups, as well as the total number of individuals, decreased with increasing fire severity, but for reptiles overall and diurnal reptiles, presence of rock outcrops had a stronger effect on number of species and abundance. Differences between reptiles and birds and among reptile groups suggest that fire management for conservation needs to be at a range of scales and consider habitat attributes

Postoperative Immune Suppression in Visceral Surgery: Characterisation of an Intestinal Mouse Model

Background: Postoperatively acquired immune dysfunction is associated with a higher mortality rate in case of septic complications. As details of this severe clinical problem are still unknown, animal models are essential to characterise the mechanisms involved. Methods: Mice were laparotomised and the small intestine was pressed smoothly in antegrade direction. For extension of trauma, the intestine was manipulated three times consecutively. Following this, the ex vivo cytokine release of splenocytes was determined. The degree of surgical trauma was analysed by detection of HMGB1 and IL-6 in serum and by neutrophil staining in the muscularis mucosae. Results: We adapted the previously described animal model of intestinal manipulation to provide a model of surgically induced immune dysfunction. Following intestinal manipulation, the mice showed elevated serum levels of HMGB1 and IL-6 and increased infiltration of granulocytes into the muscularis mucosae. Ex vivo cytokine release by splenocytes was suppressed in the postoperative period. The degree of suppression correlated with the extent of surgical trauma. Conclusions: In this study, we describe a surgically induced immune dysfunction animal model, in which a significant surgical trauma is followed by an immune dysfunction. This model may be ideal for the characterisation of the postoperative immune dysfunction syndrome

Treatment and Outcomes of Non-Small-Cell Lung Cancer Patients with High Comorbidity

Background: The life expectancy of untreated non-small-cell lung cancer (NSCLC) is dismal, while treatment for NSCLC improves survival. The presence of comorbidities is thought to play a significant role in the decision to treat or not treat a given patient. We aim to evaluate the association of comorbidities with the survival of patients treated for NSCLC. Methods: We performed a retrospective study of patients aged ≥66 years with invasive NSCLC between the years 2007 and 2011 in the Surveillance, Epidemiology, and End Results Kentucky Cancer Registry. Comorbidity was measured using the Klabunde Comorbidity Index (KCI), and univariate and multivariate logistic regression models were used to measure association between receiving treatment and comorbidity. Kaplan-Meier plots were constructed to estimate time-to-event outcomes. Results: A total of 4014 patients were identified; of this, 94.9% were white and 55.7% were male. The proportion of patients who did not receive any treatment was 8.7%, 3.9%, 19.1%, and 23.5% for stages I, II, III, and IV, respectively (p \u3c 0.0001). In multivariate analysis, older age, higher stage, and higher comorbidity (KCI ≥ 3) were associated with a lower likelihood of receiving any treatment. The median overall survival (OS) for untreated and KCI=0 was 17.7 months for stages I and II, 2.3 months for stage III, and 1.3 months for stage IV. The median OS for treated and KCI=0 was 58.9 months for stages I and II, 16.8 months for stage III, and 5.8 months for stage IV (p \u3c 0.01). Treatment was an independent predictor of OS in multivariate analysis that included KCI scores. Conclusion: Our data suggest that lung cancer patients may derive a survival benefit from therapies, regardless of the presence of comorbidities, although the degree of benefit seems to decrease with higher KCI scores

Pemetrexed with or without Matuzumab as second-line treatment for patients with stage IIIB/IV non-small cell lung cancer

Introduction: This randomized phase II study investigated pemetrexed in combination with the epidermal growth factor receptor (EGFR)-targeting monoclonal antibody matuzumab compared with pemetrexed alone as second-line therapy for patients with advanced non-small cell lung cancer. Methods: Patients received pemetrexed 500 mg/m2 every 3 weeks either alone (n = 50) or in combination with matuzumab at either 800 mg weekly (n = 51) or 1600 mg every 3 weeks (n = 47). The primary end point was objective response, as assessed by an independent review committee. Results: Tumor EGFR expression was detected in 87% of randomized patients. The objective response rate for the pooled matuzumab-treated arms was 11% compared with 5% for pemetrexed alone (p = 0.332). Apart from one patient in the pemetrexed alone group, all responses occurred in patients whose tumors expressed EGFR. The objective response rate for patients receiving weekly matuzumab was 16% compared with 2% for those receiving matuzumab every 3 weeks. There was also a trend for improved overall survival in patients receiving matuzumab weekly versus every 3 weeks (12.4 months versus 5.9 months, respectively, versus 7.9 months for pemetrexed alone). The combination of pemetrexed and matuzumab demonstrated an acceptable safety profile, with the most common grade 3/4 adverse event being neutropenia. Conclusion: Although the analysis on the pooled matuzumab-treated arms did not demonstrate a statistically significant improvement in objective response for the addition of matuzumab to pemetrexed compared with pemetrexed alone, the trends for improvement in objective response and overall survival for pemetrexed plus weekly matuzumab compared with pemetrexed alone warrant confirmation in additional clinical trials

Use of metformin and cardiovascular effects of new classes of glucose-lowering agents: A meta-analysis of cardiovascular outcome trials in type 2 diabetes

Over the last two decades, the large majority of clinical guidelines on the treatment of hyperglycemia in subjects with type 2 diabetes have suggested metformin as the first-line glucose-lowering treatment alongside lifestyle changes to reach personalized glycemic targets. Recently, the European Society of Cardiology recommended using glucagon-like peptide 1 receptor agonists (GLP-1RA) or sodium–glucose cotransporter 2 inhibitors (SGLT-2i) as first-line glucose-lowering therapy in subjects with type 2 diabetes at high or very high risk of cardiovascular disease, ahead of metformin treatment, to reduce cardiovascular event

Lung cancer screening: from imaging to biomarker.

Despite several decades of intensive effort to improve the imaging techniques for lung cancer diagnosis and treatment, primary lung cancer is still the number one cause of cancer death in the United States and worldwide. The major causes of this high mortality rate are distant metastasis evident at diagnosis and ineffective treatment for locally advanced disease. Indeed, approximately forty percent of newly diagnosed lung cancer patients have distant metastasis. Currently, the only potential curative therapy is surgical resection of early stage lung cancer. Therefore, early detection of lung cancer could potentially increase the chance of cure by surgery and underlines the importance of screening and detection of lung cancer. In the past fifty years, screening of lung cancer by chest X-Ray (CXR), sputum cytology, computed tomography (CT), fluorescence endoscopy and low-dose spiral CT (LDCT) has not improved survival except for the recent report in 2010 by the National Lung Screening Trial (NLST), which showed a 20 percent mortality reduction in high risk participants screened with LDCT compared to those screened with CXRs. Furthermore, serum biomarkers for detection of lung cancer using free circulating DNA and RNA, exosomal microRNA, circulating tumor cells and various lung cancer specific antigens have been studied extensively and novel screening methods are being developed with encouraging results. The history of lung cancer screening trials using CXR, sputum cytology and LDCT, as well as results of trials involving various serum biomarkers, are reviewed herein

Surgical Trauma and Postoperative Immune Dysfunction

Background: In postoperative sepsis, mortality is increased due to the surgically induced immune dysfunction. Further causes of this traumatic effect on the immune system include burn injuries and polytrauma, as well as endogenous traumata like stroke. Several animal models have been defined to analyse the characteristics of trauma-induced immune suppression. This article will correlate our results from animal studies and clinical observations with the recent literature on postoperative immune suppression. Methods: The previously described model of surgically induced immune dysfunction (SID) was performed in mice by laparotomy and manipulation of the small intestine in the antegrade direction. Blood samples were collected 6 and 72 h following SID to analyse the white blood cell count and corticosterone levels. To assess the postoperative immune status in humans, we analysed expression of HLA-DR on monocytes of 118 patients by flow cytometry prior to and 24, 48 and 72 h after surgery. Results: The postoperative immune suppression in our SID model is characterised by lymphocytopenia and significantly increased corticosterone levels in mice dependent on the degree of surgical trauma. This is comparable to the postoperative situation in humans: major and especially long-lasting surgery results in a significantly reduced expression of HLA-DR on circulating monocytes. Previous studies describe a similar situation following burn injury and endogenous trauma, i.e. stroke. Conclusions: We suggest the completion of our previously published sepsis classification due to the immune status at the onset of sepsis: type A as the spontaneously acquired sepsis and type B as sepsis in trauma-induced pre-existing immune suppression

Association Between Accelerometer-Assessed Physical Activity and Severity of COVID-19 in UK Biobank.

Funder: UKRI Science and Technology Facilities CouncilOBJECTIVE: To quantify the association between accelerometer-assessed physical activity and coronavirus disease 2019 (COVID-19) outcomes. METHODS: Data from 82,253 UK Biobank participants with accelerometer data (measured 2013-2015), complete covariate data, and linked COVID-19 data from March 16, 2020, to March 16, 2021, were included. Two outcomes were investigated: severe COVID-19 (positive test result from in-hospital setting or COVID-19 as primary cause of death) and nonsevere COVID-19 (positive test result from community setting). Logistic regressions were used to assess associations with moderate to vigorous physical activity (MVPA), total activity, and intensity gradient. A higher intensity gradient indicates a higher proportion of vigorous activity. RESULTS: Average MVPA was 48.1 (32.7) min/d. Physical activity was associated with lower odds of severe COVID-19 (adjusted odds ratio per standard deviation increase: MVPA, 0.75 [95% CI, 0.67 to 0.85]; total, 0.83 [0.74 to 0.92]; intensity, 0.77 [0.70 to 0.86]), with stronger associations in women (MVPA, 0.63 [0.52 to 0.77]; total, 0.76 [0.64 to 0.90]; intensity, 0.63 [0.53 to 0.74]) than in men (MVPA, 0.84 [0.73 to 0.97]; total, 0.88 [0.77 to 1.01]; intensity, 0.88 [0.77 to 1.00]). In contrast, when mutually adjusted, total activity was associated with higher odds of a nonsevere infection (1.10 [1.04 to 1.16]), whereas the intensity gradient was associated with lower odds (0.91 [0.86 to 0.97]). CONCLUSION: Odds of severe COVID-19 were approximately 25% lower per standard deviation (∼30 min/d) MVPA. A greater proportion of vigorous activity was associated with lower odds of severe and nonsevere infections. The association between total activity and higher odds of a nonsevere infection may be through greater community engagement and thus more exposure to the virus. Results support calls for public health messaging highlighting the potential of MVPA for reducing the odds of severe COVID-19

Detection of Immunoglobulin G against E7 of Human Papillomavirus in Non-Small-Cell Lung Cancer

Background. A significant number of non-small-cell lung cancers (NSCLC) have human papillomavirus (HPV) DNA integrated in their genome. This study sought to further establish HPV’s possible etiologic link to NSCLC by evaluating an immune response to HPV’s oncogene, E7, in patients with NSCLC. Patients and Methods. Antibodies (IgG) in serum against E7 for HPV 16 and 18 in 100 patients with NSCLC were examined by enzyme-linked immunosorbent assay (ELISA). Results. Sixteen NSCLC patients were found to have a high titration of IgG for HPV oncogenic E7 protein. 23.5% of adenocarcinomas (AC,) and 15.4% of squamous cell carcinomas (SCC) were positive for IgG against HPV E7. HPV-18 (11%) had a slightly higher frequency than HPV-16 (6%). Of the six positive cases for HPV-16, 3 were AC, 2 SCC, and 1 NOS (not otherwise specified). For the 11 HPV-18 positives, 7 were AC, and 4 SCC. The one case with IgG against HPV 16 and 18 was AC. One case had high cross-reactive levels against E7 of HPV 16 and 18. Two (28%) of 7 patients who reported never smoking were positive for HPV, and 12 (13.6%) of 88 smokers were HPV positive. Conclusions. The study detected high levels of IgG against E7 in 16% of NSCLC patients. This adds evidence to a potential role of HPV in the pathogenesis of NSCLC