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Background Immunotherapy with PD-1 or PD-L1 blockade fails to induce a response in about 80% of patients with unselected non-small cell lung cancer (NSCLC), and many of those who do initially respond then develop resistance to treatment. Agonists that target the shared interleukin-2 (IL-2) and IL-15Rβγ pathway have induced complete and durable responses in some cancers, but no studies have been done to assess the safety or efficacy of these agonists in combination with anti-PD-1 immunotherapy. We aimed to define the safety, tolerability, and activity of this drug combination in patients with NSCLC. Methods In this non-randomised, open-label, phase 1b trial, we enrolled patients (aged ≥18 years) with previously treated histologically or cytologically confirmed stage IIIB or IV NSCLC from three academic hospitals in the USA. Key eligibility criteria included measurable disease, eligibility to receive anti-PD-1 immunotherapy, and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients received the anti-PD-1 monoclonal antibody nivolumab intravenously at 3 mg/kg (then 240 mg when US Food and Drug Administration [FDA]-approved dosing changed) every 14 days (either as new treatment or continued treatment at the time of disease progression) and the IL-15 superagonist ALT-803 subcutaneously once per week on weeks 1–5 of four 6-week cycles for 6 months. ALT-803 was administered at one of four escalating dose concentrations: 6, 10, 15, or 20 μg/kg. The primary endpoint was to define safety and tolerability and to establish a recommended phase 2 dose of ALT-803 in combination with nivolumab. Analyses were per-protocol and included any patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, number NCT02523469; phase 2 enrolment of patients is ongoing. Findings Between Jan 18, 2016, and June 28, 2017, 23 patients were enrolled and 21 were treated at four dose levels of ALT-803 in combination with nivolumab. Two patients did not receive treatment because of the development of inter-current illness during enrolment, one patient due to leucopenia and one patient due to pulmonary dysfunction. No dose-limiting toxicities were recorded and the maximum tolerated dose was not reached. The most common adverse events were injection-site reactions (in 19 [90%] of 21 patients) and flu-like symptoms (15 [71%]). The most common grade 3 adverse events, occurring in two patients each, were lymphocytopenia and fatigue. A grade 3 myocardial infarction occurred in one patient. No grade 4 or 5 adverse events were recorded. The recommended phase 2 dose of ALT-803 is 20 μg/kg given once per week subcutaneously in combination with 240 mg intravenous nivolumab every 2 weeks. Interpretation ALT-803 in combination with nivolumab can be safely administered in an outpatient setting. The promising clinical activity observed with the addition of ALT-803 to the regimen of patients with PD-1 monoclonal antibody relapsed and refractory disease shows evidence of anti-tumour act...

Purpose To evaluate three coronary artery calcification (CAC) scoring methods to assess risk of coronary heart disease (CHD) death and all-cause mortality in National Lung Screening Trial (NLST) participants across levels of CAC scores. Materials and Methods The NLST was approved by the institutional review board at each participating institution, and informed consent was obtained from all participants. Image review was HIPAA compliant. Five cardiothoracic radiologists evaluated 1575 low-dose computed tomographic (CT) scans from three groups: 210 CHD deaths, 315 deaths not from CHD, and 1050 participants who were alive at conclusion of the trial. Radiologists used three scoring methods: overall visual assessment, segmented vessel-specific scoring, and Agatston scoring. Weighted Cox proportional hazards models were fit to evaluate the association between scoring methods and outcomes. Results In multivariate analysis of time to CHD death, Agatston scores of 1–100, 101–1000, and greater than 1000 (reference category 0) were associated with hazard ratios of 1.27 (95% confidence interval: 0.69, 2.53), 3.57 (95% confidence interval: 2.14, 7.48), and 6.63 (95% confidence interval: 3.57, 14.97), respectively; hazard ratios for summed segmented vessel-specific scores of 1–5, 6–11, and 12–30 (reference category 0) were 1.72 (95% confidence interval: 1.05, 3.34), 5.11 (95% confidence interval: 2.92, 10.94), and 6.10 (95% confidence interval: 3.19, 14.05), respectively; and hazard ratios for overall visual assessment of mild, moderate, or heavy (reference category none) were 2.09 (95% confidence interval: 1.30, 4.16), 3.86 (95% confidence interval: 2.02, 8.20), and 6.95 (95% confidence interval: 3.73, 15.67), respectively. Conclusion By using low-dose CT performed for lung cancer screening in older, heavy smokers, a simple visual assessment of CAC can be generated for risk assessment of CHD death and all-cause mortality, which is comparable to Agatston scoring and strongly associated with outcome.

Despite recent advances in prehospital care, multidetector computed tomographic (CT) technology, and rapid definitive therapy, trauma to the aorta continues to be a substantial source of morbidity and mortality in patients with blunt trauma. The imaging evaluation of acute aortic injuries has undergone radical change over the past decade, mostly due to the advent of multidetector CT. Regardless of recent technologic advances, imaging of the aorta in the trauma setting remains a multimodality imaging practice, and thus broad knowledge by the radiologist is essential. Likewise, the therapy for acute aortic injuries has changed substantially. Though open surgical repair continues to be the mainstay of therapy, percutaneous endovascular repair is becoming commonplace in many trauma centers. Here, the historical and current status of imaging and therapy of acute traumatic aortic injuries will be reviewed.

Four cases of Lemierre syndrome are reported in which metastatic abscesses resulted from septic thrombosis of the internal jugular vein secondary to bacterial pharyngitis. While chest radiographic findings were nonspecific, results of computed tomography (CT) of the thorax in each case were highly suggestive of septic pulmonary emboli. Internal jugular venous thrombosis was demonstrated at ultrasonography and contrast material-enhanced CT.