Objectives To assess whether late surfactant treatment of extremely low gestational age newborn (ELGAN) infants requiring ventilation at 7–14 days, who often have surfactant deficiency and dysfunction, safely improves survival without bronchopulmonary dysplasia (BPD). Study design ELGAN infants (≤ 28 0/7 weeks) who required mechanical ventilation at 7–14 days were enrolled in a randomized, masked controlled trial at 25 US centers. All infants received inhaled nitric oxide (INO) and either surfactant (calfactant/Infasurf®) or sham instillation every 1–3 days to a maximum of 5 doses while intubated. The primary outcome was survival at 36 weeks postmenstrual age (PMA) without BPD, evaluated by physiologic oxygen/flow reduction. Results Between January 2010 and September 2013, 511 infants were enrolled. There were no differences between treatment groups in mean birth weight (701±164 g), gestational age (25.2±1.2 weeks), percentage <26 weeks (70.6%), race, sex, severity of lung disease at enrollment, or co-morbidities of prematurity. Survival without BPD was not different between treated vs. controls at 36 weeks PMA (31.3% vs. 31.7%; relative benefit 0.98 (95% CI: 0.75, 1.28 p=0.89) or 40 weeks (58.7% vs. 54.1%; relative benefit 1.08:0.92, 1.27 p=0.33). There were no differences between groups in serious adverse events, co-morbidities of prematurity, nor in the severity of lung disease to 36 weeks. Conclusions Late treatment with up to 5 doses of surfactant in ventilated premature infants receiving iNO was well tolerated but did not improve survival without BPD at 36 or 40 weeks. Pulmonary and neurodevelopmental assessments are ongoing.

The MULTI-LINK (ML) stent is a novel second generation coronary stent. The ACS MultiLink Stent Clinical Equivalence in De Novo Lesions Trial (ASCENT) randomized 1,040 patients with single, de novo native vessel lesions to treatment with the ML stent or the benchmark Palmaz-Schatz (PS) stent, to demonstrate that the ML stent was not inferior to (i.e., equivalent or better than) the PS stent in terms of target vessel failure by 9 months. Successful stent delivery was achieved in 98.8% versus 96.9% of patients, with a slightly lower postprocedural diameter stenosis (8% vs 10%, p = 0.04), and no difference in 30-day major adverse cardiac events (5.0% vs 6.5%) for the ML stent versus the PS stent. The primary end point of target vessel failure at 9 months was seen in 15.1% of ML-treated patients versus 16.7% of PS-treated patients, with the ML proving to be equal or superior to the PS stent (p <0.001 by test for equivalency). In a prespecified subset, angiographic restudy showed a nonsignificant trend for reduced ML restenosis (16.0% vs 22.1%). Thus, the ML stent showed excellent deliverability and acute results, with 9-month clinical and 6-month angiographic outcomes that were equivalent or better than the PS stent.

ObjectiveTo describe the clinical, pathological and genomic characteristics of pancreatic cancer with DNA mismatch repair deficiency (MMRD) and proficiency (MMRP).DesignWe identified patients with MMRD and MMRP pancreatic cancer in a clinical cohort (N=1213, 519 with genetic testing, 53 with immunohistochemistry (IHC)) and a genomic cohort (N=288 with whole-genome sequencing (WGS)).Results12 out of 1213 (1.0%) in the clinical cohort were MMRD by IHC or WGS. Of the 14 patients with Lynch syndrome, 3 (21.4%) had an MMRP pancreatic cancer by IHC, and 4 (28.6%) were excluded because tissue was unavailable for testing. MMRD cancers had longer overall survival after surgery (weighted HR after coarsened exact matching 0.11, 95% CI 0.02 to 0.78, p=0.001). One patient with an unresectable MMRD cancer has an ongoing partial response 3 years after starting treatment with PD-L1/CTLA-4 inhibition. This tumour showed none of the classical histopathological features of MMRD. 9 out of 288 (3.1%) tumours with WGS were MMRD. Despite markedly higher tumour mutational burden and neoantigen loads, MMRD cancers were significantly less likely to have mutations in usual pancreatic cancer driver genes like KRAS and SMAD4, but more likely to have mutations in genes that drive cancers with microsatellite instability like ACV2RA and JAK1. MMRD tumours were significantly more likely to have a basal-like transcriptional programme and elevated transcriptional markers of immunogenicity.ConclusionsMMRD pancreatic cancers have distinct clinical, pathological and genomic profiles. Patients with MMRD pancreatic cancer should be considered for basket trials targeting enhanced immunogenicity or the unique genomic drivers in these malignancies.

Clinical trials in mNSCLC consistently report significantly lower rates of hospitalization than reports of real world cohorts of patients undergoing similar therapies. However, very few clinical trials report hospitalization information.