Citations

ObjectivesTo develop a novel delivery technique to overcome vascular size limitations for device closure of a secundum ASD in the young patient.BackgroundThe efficacy, clinical utility, and safety of transcatheter closure in comparison to surgical closure are well established; however, access vessel size remains a potential limitation to device selection in the young patient.MethodsA retrospective medical record review of all cases of secundum ASD closure between April 2015 and April 2016 utilizing a novel delivery method described herein at two separate academic institutions. The device is disassembled allowing the delivery sheath to serve as the introducer. It is advanced to the RA with re‐introduction of the device allowing for deployment in the standard fashion.ResultsOverall, 10 patients underwent secundum ASD closure via this novel delivery technique. There were six females (60%) and the average age at time of the procedure was 4.2 years ± 1.6 years (range 2–6 years). The majority of patients had an isolated secundum ASD (70%) with the primary indication for closure being right ventricular volume overload (90%). All patients had successful placement of a GORE® CARDIOFORM® Septal Occluder (GCSO) with no or trivial residual shunt. No patients had vascular complications related to the procedure.ConclusionsWe describe a novel technique for ASD closure using the GCSO delivery sheath as the access sheath, which reduces the vascular access size requirement by 25%, thus addressing one common limitation for percutaneous device closure of a secundum ASD in young patients. © 2016 Wiley Periodicals, Inc.

Key Points Mass spectrometry is a high-throughput, low-resource technique that can identify immunoglobulin variable region gene from tissue specimens. IGVL gene usage is restricted and different between systemic and localized AL and only partially explains organ tropism in this disease.

SummaryA 51‐year‐old male was admitted to the intensive care unit following a cardiac arrest during which he received chest compressions and suffered rib fractures. The patient's condition subsequently improved and tracheal extubation was eventually planned. However, he was unable to tolerate spontaneous breathing trials due to pain from his rib fractures. Systemic analgesia provided either insufficient pain control or over‐sedation. Neuraxial techniques were contraindicated as he was receiving systemic anticoagulation and antiplatelet medications. Intercostal nerve blocks with liposomal bupivacaine were performed under ultrasound guidance without complications. Approximately six hours after the injections, the patients trachea was successfully extubated with no further need for respiratory support through to discharge. In appropriately selected patients, intercostal nerve blocks with liposomal bupivacaine can adequately treat pain from rib fractures and improve respiratory mechanics.

Objective Limited efficacy of immune checkpoint inhibitors in pancreatic ductal adenocarcinoma (PDAC) has prompted investigation into combination therapy. We hypothesised that interleukin 6 (IL-6) blockade would modulate immunological features of PDAC and enhance the efficacy of anti-programmed death-1-ligand 1 (PD-L1) checkpoint inhibitor therapy. Design Transcription profiles and IL-6 secretion from primary patient-derived pancreatic stellate cells (PSCs) were analyzed via Nanostring and immunohistochemistry, respectively. In vivo efficacy and mechanistic studies were conducted with antibodies (Abs) targeting IL-6, PD-L1, CD4 or CD8 in subcutaneous or orthotopic models using Panc02, MT5 or KPC-luc cell lines; and the aggressive, genetically engineered PDAC model (Kras LSL−G12D , Trp53 LSL−R270H , Pdx1-cre, Brca2 F/F (KPC-Brca2 mice)). Systemic and local changes in immunophenotype were measured by flow cytometry or immunohistochemical analysis. Results PSCs (n=12) demonstrated prominent IL-6 expression, which was localised to stroma of tumours. Combined IL-6 and PD-L1 blockade elicited efficacy in mice bearing subcutaneous MT5 (p<0.02) and Panc02 tumours (p=0.046), which was accompanied by increased intratumoural effector T lymphocytes (CD62L − CD44 − ). CD8-depleting but not CD4-depleting Abs abrogated the efficacy of combined IL-6 and PD-L1 blockade in mice bearing Panc02 tumours (p=0.0016). This treatment combination also elicited significant antitumour activity in mice bearing orthotopic KPC-luc tumours and limited tumour progression in KPC-Brca2 mice (p<0.001). Histological analysis revealed increased T-cell infiltration and reduced α-smooth muscle actin cells in tumours from multiple models. Finally, IL-6 and PD-L1 blockade increased overall survival in KPC-Brca2 mice compared with isotype controls (p=0.0012). Conclusions These preclinical results indicate that targeted inhibition of IL-6 may enhance the efficacy of anti-PD-L1 in PDAC.