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BackgroundPercutaneous paravalvular leak (PVL) closure is an alternative treatment option for severely symptomatic, high‐surgical risk patients with PVL. Some patients require multiple percutaneous PVL closure procedures. However, the procedural characteristics and success rate of re‐do PVL closure have not been well studied.AimsThe aim of this study is to investigate the indications, procedural characteristics, technical success rate, and 30‐day major adverse cardiovascular events (MACE) in patients who underwent re‐do PVL closure.MethodsConsecutive patients who underwent percutaneous paramitral or paraaortic leak closure at Mayo Clinic, Rochester, Minnesota from 2004 through 2015 were studied. Clinical and procedural characteristics of patients who underwent re‐do PVL closure were compared to age‐ and sex‐matched patients who underwent their first percutaneous PVL closure. Procedure success and 30‐day MACE were compared in both the groups.ResultsAmong 223 identified percutaneous PVL closures, 16 (7%) were re‐do procedures. Patients who underwent re‐do PVL closure were predominantly men (87.5%) with a mean age of 68 ± 15 years and an estimated mean Society of Thoracic Surgery (STS) 30‐day mortality of 4.6 ± 2.8. Half of the re‐do PVL closures were performed on mechanical valves and 62.5% were performed on paramitral defects. Indications for re‐do PVL closure were: (1) emergence of new significant paravalvular defects in 50%, (2) incomplete index defect closure in 43.75%, and (3) index procedural complication in 6.25% of the cases. Procedural success was 75% in re‐do procedures vs. 85.4% in age‐ and sex‐matched control group (P = 0.45). Thirty‐day MACE was 12.5% in the re‐do group compared to 4.2% in the age‐ and‐sex matched patients who underwent PVL closure for the first time (P = 0.35).ConclusionRe‐do percutaneous PVL closure is feasible with favorable procedural success rate and low 30‐day MACE. Development of new paravalvular defects is the most common indication for re‐do PVL closure, highlighting the importance of careful longitudinal monitoring and follow‐up. © 2017 Wiley Periodicals, Inc.

Abstract Objectives: To develop evidence-based guideline recommendations through a systematic review of the literature to establish standard molecular biomarker testing of colorectal cancer (CRC) tissues to guide epidermal growth factor receptor (EGFR) therapies and conventional chemotherapy regimens. Methods: The American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology, and American Society of Clinical Oncology convened an expert panel to develop an evidence-based guideline to establish standard molecular biomarker testing and guide therapies for patients with CRC. A comprehensive literature search that included more than 4,000 articles was conducted. Results: Twenty-one guideline statements were established. Conclusions: Evidence supports mutational testing for EGFR signaling pathway genes, since they provide clinically actionable information as negative predictors of benefit to anti-EGFR monoclonal antibody therapies for targeted therapy of CRC. Mutations in several of the biomarkers have clear prognostic value. Laboratory approaches to operationalize CRC molecular testing are presented.

Objectives.— To develop evidence-based guideline recommendations through a systematic review of the literature to establish standard molecular biomarker testing of colorectal cancer (CRC) tissues to guide epidermal growth factor receptor (EGFR) therapies and conventional chemotherapy regimens. Methods.— The American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology, and American Society of Clinical Oncology convened an expert panel to develop an evidence-based guideline to establish standard molecular biomarker testing and guide therapies for patients with CRC. A comprehensive literature search that included more than 4,000 articles was conducted. Results.— Twenty-one guideline statements were established. Conclusions.— Evidence supports mutational testing for EGFR signaling pathway genes, since they provide clinically actionable information as negative predictors of benefit to anti-EGFR monoclonal antibody therapies for targeted therapy of CRC. Mutations in several of the biomarkers have clear prognostic value. Laboratory approaches to operationalize CRC molecular testing are presented.

Abnormalities in zinc homeostasis are indicated in many human diseases, including Alzheimer disease (AD). 63 Zn-zinc citrate was developed as a positron emission tomography (PET) imaging probe of zinc transport and used in a first-in-human study in 6 healthy elderly individuals and 6 patients with clinically confirmed AD. Dynamic PET imaging of the brain was performed for 30 minutes following intravenous administration of 63 Zn-zinc citrate (∼330 MBq). Subsequently, body PET images were acquired. Urine and venous blood were analyzed to give information on urinary excretion and pharmacokinetics. Regional cerebral 63 Zn clearances were compared with 11 C-Pittsburgh Compound B ( 11 C-PiB) and 18 F-fluorodeoxyglucose ( 18 F-FDG) imaging data. 63 Zn-zinc citrate was well tolerated in human participants with no adverse events monitored. Tissues of highest uptake were liver, pancreas, and kidney, with moderate uptake being seen in intestines, prostate (in males), thyroid, spleen, stomach, pituitary, and salivary glands. Moderate brain uptake was observed, and regional dependencies were observed in 63 Zn clearance kinetics in relationship with regions of high amyloid-β plaque burden ( 11 C-PiB) and 18 F-FDG hypometabolism. In conclusion, zinc transport was successfully imaged in human participants using the PET probe 63 Zn-zinc citrate. Primary sites of uptake in the digestive system accent the role of zinc in gastrointestinal function. Preliminary information on zinc kinetics in patients with AD evidenced regional differences in clearance rates in correspondence with regional amyloid-β pathology, warranting further imaging studies of zinc homeostasis in patients with AD.

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.