Sports Utility Vehicles: A Public Health Model of Their Climate and Air Pollution Impacts in the United Kingdom.

The emission benefits of shifting towards battery electric vehicles have so far been hampered by a trend towards sports utility vehicles (SUVs). This study assesses the current and future emissions from SUVs and their potential impact on public health and climate targets. We modelled five scenarios of varying SUV sales and electrification rates, and projected associated carbon dioxide (CO2) and nitrogen oxide (NOx) emissions. Multiple linear regression was used to determine the relationship between vehicle characteristics and emissions. Cumulative CO2 emissions were valued using the social cost of carbon approach. Life table analyses were used to project and value life years saved from NOx emission reductions. Larger SUVs were disproportionately high emitters of CO2 and NOx. Replacing these with small SUVs achieved significant benefits, saving 702 MtCO2e by 2050 and 1.8 million life years from NO2 reductions. The largest benefits were achieved when combined with electrification, saving 1181 MtCO2e and gaining 3.7 million life years, with a societal value in the range of GBP 10-100s billion(s). Downsizing SUVs could be associated with major public health benefits from reduced CO2 and NOx emissions, in addition to the benefits of electrification. This could be achieved by demand-side mass-based vehicle taxation and supply-side changes to regulations, by tying emission limits to a vehicle's footprint rather than its mass.

Diagnostic Accuracy and Safety of Coaxial System in Oncology Patients Treated in a Specialist Cancer Center With Prospective Validation Within Clinical Trial Data.

BACKGROUND: Image-guided tissue biopsies are critically important in the diagnosis and management of cancer patients. High-yield samples are also vital for biomarker and resistance mechanism discovery through molecular/genomic analyses. PATIENTS AND METHODS: All consecutive patients who underwent plugged image-guided biopsy at Royal Marsden from June 2013 until September 2016 were included in the analysis. In the next step, a second cohort of patients prospectively treated within two clinical trials (PROSPECT-C and PROSPECT-R) were assessed for the DNA yield from biopsies assessed for complex genomic analysis. RESULTS: A total of 522 plugged core biopsies were performed in 457 patients [men, 52%; median age, 63 years (range, 17-93)]. Histological diagnosis was achieved in 501 of 522 (96%) performed biopsies. Age, gender, modality, metastatic site, and seniority of the interventionist were not found to be significant factors associated with odds of failure on a logistic regression. Seventeen (3.3%) were admitted due to biopsy-related complications; nine, three, two, one, one, and one were admitted for grade I/II pain control, sepsis, vasovagal syncope, thrombosis, hematuria, and deranged liver functions, respectively; two patients with right upper quadrant pain after liver biopsy were found to have radiologically confirmed subcapsular hematoma requiring conservative treatment. One patient (0.2%) developed grade III hemorrhage following biopsy of a gastric gastrointestinal stromal tumor (GIST). Overall molecular analysis was successful in 89% (197/222 biopsies). Prospective validation in 62 biopsies gave success rates of 92.06 and 79.03% for DNA extraction of >1 µm and tmour content of >20%, respectively. CONCLUSION: The probability of diagnostic success for complex molecular analysis is increased with plugged large coaxial needle biopsy technique, which also minimizes complications and reduces hospital stay. High-yield DNA acquisition allows genomic molecular characterization for personalized medicine.

Immunotherapy in gastrointestinal cancer: The current scenario and future perspectives.

Gastrointestinal cancers include colorectal, gastric, oesophageal, pancreatic and liver cancers. They continue to be a significant cause of mortality and morbidity worldwide. Current treatment strategies include chemotherapy, surgery, radiotherapy and targeted therapies. Immunotherapy has recently been incorporated in treatment regimens for some gastrointestinal malignancies and research into different immune modifying treatments is being carried out in this context. Approaches to immune modulation such as vaccination, adoptive cell therapy and checkpoint inhibition have shown varying clinical benefit, with most of the benefit seen in checkpoint inhibition. This review summarises recent advances and future direction of immunotherapy in patients with gastrointestinal malignancies.

Targeting EGFR pathway in metastatic colorectal cancer- tumour heterogeniety and convergent evolution.

Despite significant progress in management of metastatic colorectal cancer (mCRC) pertaining to better screening procedures and amelioration of the therapeutic armamentarium with targeted therapies, prognosis remains poor. Targeting epidermal growth factor receptor (EGFR) has been of particular interest owing to favourable efficacy benefits demonstrated by monoclonal antibodies (cetuximab and panitumumab) in various clinical settings and development of predictive biomarkers informing treatment decisions respectively. In spite of optimal patient selection based on RAS mutation status, primary and secondary resistance to monoclonal antibodies is higher than desired. Further research into predictive biomarkers is therefore essential, but has, to date, been conducted with considerable limitations. Whilst molecular heterogeneity has been demonstrated by several studies in mCRC, for incomprehensible reasons, multiple resistant genetic alterations that emerge under the selective pressure of EGFR-targeted therapies are somehow able to influence the biological and clinical behaviour of cancer cells, despite being detectable at extremely low frequencies. Intriguingly, these subclonal events largely seem to converge on RAS/RAF/MAPK pathway in patients treated with EGFR-targeted monoclonal antibodies. This review describes the clinical and biological evolution and development of EGFR targeted therapies in mCRC, the challenges in the presence of molecular complexities, the role of cell free (cf)-DNA and future strategies that could lead to further optimal discovery of clinically meaningful biomarkers and application of precision medicine.

Management of a thyroid "incidentaloma" in a patient with cancer: a case report.

The routine use of (18)F-fluorodeoxyglucose-positron emission tomography (PET)/computed tomography scans for staging and assessment of treatment response for cancer has resulted in a large number of thyroid abnormalities being detected as incidental findings ("incidentalomas"). Since most PET/CT scans are performed in the setting of a known nonthyroid malignancy, the need for "incidentalomas" to be further investigated and managed depends on the stage, prognosis, and current treatment plan for the known malignancy. We present a case describing the management of an incidental F-fluorodeoxyglucose-avid thyroid nodule detected in a patient with known metastatic colorectal cancer. On the basis of this case, we discuss the management of incidental PET-detected thyroid nodules in patients with metastatic cancer. Thyroid "incidentalomas" must be seen in the context of the prognosis and treatment plan for the known malignancy.

What dose of tranexamic acid is most effective and safe for adult patients undergoing cardiac surgery?

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was: what dose of tranexamic acid is most effective and safe for adult patients undergoing cardiac surgery? Altogether 586 papers were found using the reported search, of which 12 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. Current evidence shows clinical benefit of using high-dose tranexamic acid (>80 mg/kg total dose) as opposed to low-dose tranexamic acid (<50 mg/kg total dose) in cardiac surgery with cardiopulmonary bypass. Evidence from a large randomized controlled trial shows that patients receiving high-dose tranexamic acid lose less blood postoperatively than patients receiving low-dose tranexamic acid (590 vs 820 ml, P = 0.01). Patients receiving high-dose tranexamic acid also require fewer units of blood product transfusion (2.5 units vs 4.1 units; P = 0.02) and are less likely to undergo repeat surgery to achieve haemostasis. This effect is larger in those who are at high risk of bleeding. Several prospective studies comparing doses found no difference in clinical outcomes between high- and low-dose regimens, but excluded patients at high risk of bleeding. However, data from numerous observational studies demonstrate that tranexamic acid use is associated with an increased risk of postoperative seizure; one analysis showed tranexamic acid use to be a very strong independent predictor (odds ratio = 14.3, P < 0.001). There is also evidence that this risk of seizure is dose-dependent, with the greatest risk at higher doses of tranexamic acid. We conclude that, in general, patients with a high risk of bleeding should receive high-dose tranexamic acid, while those at low risk of bleeding should receive low-dose tranexamic acid with consideration given to potential dose-related seizure risk. We recommend the regimens of high-dose (30 mg kg(-1) bolus + 16 mg kg(-1) h(-1) + 2 mg kg(-1) priming) and low-dose (10 mg kg(-1) bolus + 1 mg kg(-1) h(-1) + 1 mg kg(-1) priming) tranexamic acid, as these are well established in terms of safety profile and have the strongest evidence for efficacy.