Citations

Background— Prior cardiac surgery, especially the presence of coronary artery bypass grafts, is thought to preclude percutaneous epicardial access (EpiAcc) and, therefore, mapping and ablation. We evaluated the feasibility and safety of EpiAcc in patients with a prior cardiac operation. Methods and Results— We retrospectively analyzed all patients who underwent EpiAcc for ablation for ventricular tachycardia or symptomatic premature ventricular complexes between 2004 and 2013 at Mayo Clinic, Rochester, MN. Of 162 patients who underwent EpiAcc, 18 had prior cardiac surgery (median age, 64 years, all men). This included 10 coronary artery bypass grafts, 2 epicardial implantable cardioverter defibrillator placement, 5 valve surgery, 2 septal myectomy, 1 aortic arch replacement, 1 myocardial bridge unroofing, and 1 myocardial perforation repair (3 patients had multiple procedures). Access was successful in 12 of 18; the inferior approach was used in 78%. Successful access was achieved in 6 of 10 patients with prior coronary artery bypass grafts. Adhesiolysis was required in 10 patients with the sheath, access wire, and pigtail or ablation catheter. Intraprocedural coronary angiography was performed in 8 patients. A total of 45 ventricular tachycardias/premature ventricular complexes were ablated. Thirteen patients underwent endocardial-only ablation, 2 had epicardial-only ablation, whereas 3 had endocardial–epicardial ablation. Ablation was deemed successful in 13 of 18 patients. Four patients had bleeding complications (pericardial effusion, pericardial hematoma, hemoperitoneum, and pericardial tamponade). In patients with coronary grafts, there was no evidence of acute graft disruption. Conclusions— Percutaneous EpiAcc is feasible in patients with previous cardiac surgery, including coronary artery bypass grafts. However, adhesiolysis is frequently required. Although the risk of coronary graft injury is low, life-threatening complications may occur.

Background Identification of genetic markers of antihypertensive drug responses could assist in individualization of hypertension treatment. Methods and Results We conducted a genome‐wide association study to identify gene loci influencing the responsiveness of 228 male patients to 4 classes of antihypertensive drugs. The Genetics of Drug Responsiveness in Essential Hypertension ( GENRES ) study is a double‐blind, placebo‐controlled cross‐over study where each subject received amlodipine, bisoprolol, hydrochlorothiazide, and losartan, each as a monotherapy, in a randomized order. Replication analyses were performed in 4 studies with patients of European ancestry ( PEAR Study, N=386; GERA I and II Studies, N=196 and N=198; SOPHIA Study, N=372). We identified 3 single‐nucleotide polymorphisms within the ACY 3 gene that showed associations with bisoprolol response reaching genome‐wide significance ( P <5×10 −8 ); however, this could not be replicated in the PEAR Study using atenolol. In addition, 39 single‐nucleotide polymorphisms showed P values of 10 −5 to 10 −7 . The 20 top‐associated single‐nucleotide polymorphisms were different for each antihypertensive drug. None of these top single‐nucleotide polymorphisms co‐localized with the panel of >40 genes identified in genome‐wide association studies of hypertension. Replication analyses of GENRES results provided suggestive evidence for a missense variant (rs3814995) in the NPHS 1 (nephrin) gene influencing losartan response, and for 2 variants influencing hydrochlorothiazide response, located within or close to the ALDH 1A3 (rs3825926) and CLIC 5 (rs321329) genes. Conclusions These data provide some evidence for a link between biology of the glomerular protein nephrin and antihypertensive action of angiotensin receptor antagonists and encourage additional studies on aldehyde dehydrogenase–mediated reactions in antihypertensive drug action.

CD38 is a cell-surface protein involved in calcium signaling and contractility of airway smooth muscle. It has a role in normal airway responsiveness and in airway hyperresponsiveness (AHR) developed following airway exposure to IL-13 and TNF-α but appears not to be critical to airway inflammation in response to the cytokines. CD38 is also involved in T cell-mediated immune response to protein antigens. In this study, we assessed the contribution of CD38 to AHR and inflammation to two distinct allergens, ovalbumin and the epidemiologically relevant environmental fungus Alternaria. We also generated bone marrow chimeras to assess whether Cd38+/+inflammatory cells would restore AHR in the CD38-deficient ( Cd38−/−) hosts following ovalbumin challenge. Results show that wild-type (WT) mice develop greater AHR to inhaled methacholine than Cd38−/−mice following challenge with either allergen, with comparable airway inflammation. Reciprocal bone marrow transfers did not change the native airway phenotypic differences between WT and Cd38−/−mice, indicating that the lower airway reactivity of Cd38−/−mice stems from Cd38−/−lung parenchymal cells. Following bone marrow transfer from either source and ovalbumin challenge, the phenotype of Cd38−/−hosts was partially reversed, whereas the airway phenotype of the WT hosts was preserved. Airway inflammation was similar in Cd38−/−and WT chimeras. These results indicate that loss of CD38 on hematopoietic cells is not sufficient to prevent AHR and that the magnitude of airway inflammation is not the predominant underlying determinant of AHR in mice.

Although transformation to Hodgkin lymphoma (HL) is a recognized complication in patients with chronic lymphocytic leukemia (CLL), its incidence, clinical characteristics and outcomes are not well defined. We used the Mayo Clinic CLL and Lymphoma Databases to identify CLL patients who developed biopsy‐proven HL (CLL/HL) on follow‐up, as well as cases of de novo HL (i.e., without prior CLL). Among 3887 CLL patients seen at Mayo Clinic from January 1995 through August 2011, 26 (0.7%) developed HL. In a nested cohort of 2,465 newly diagnosed CLL patients followed prospectively, the incidence of HL was 0.05%/year (10 year risk = 0.5%). The median overall survival (OS) from date of HL diagnosis in patients with CLL/HL was 3.9 years compared to not reached for de novo HL patients ( n = 709) seen during the same time interval ( P < 0.001). The shorter OS of CLL/HL patients persisted after adjusting for differences in age and Ann Arbor stage of disease. The International Prognostic score (IPS) developed for de novo HL stratified prognosis among CLL/HL patients with median survival of not reached, 6.2, 2.4, and 0.3 years ( P = 0.006) for those with IPS scores of ≤2, 3, 4, and ≥5, respectively. In summary, approximately 1 of every 200 CLL patients will develop HL within 10 years. Survival after HL diagnosis in patients with CLL is shorter than de novo HL patients. The IPS for de novo HL may be useful for stratifying survival in CLL/HL patients. Am. J. Hematol. 90:334–338, 2015. © 2015 Wiley Periodicals, Inc.

Objective Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) allows preoperative tissue confirmation of malignancy, but fear of tumour cell dissemination along the needle track has limited its use. We hypothesised that if tumour cell dissemination occurs with EUS-FNA, survival after complete resection would be impaired. We aimed to evaluate the association of preoperative EUS-FNA with long-term outcomes of patients with resected pancreatic cancer. Design Using the linked Surveillance, Epidemiology, and End Results (SEER)–Medicare data, we identified patients with locoregional pancreatic cancer who underwent curative intent surgery from 1998 to 2009. The patients who received EUS-FNA within the peridiagnostic period were included in the EUS-FNA group. Patients who did not receive EUS evaluation or who underwent EUS without FNA were included in the non-EUS-FNA group. Overall survival and pancreatic cancer-specific survival were compared after controlling for relevant covariates. Results A total of 2034 patients with pancreatic cancer were included (90% pancreatic adenocarcinoma). Of these, 498 (24%) patients were in EUS-FNA group. Patients with multiple comorbidities and more recent diagnosis were more likely to receive EUS-FNA. In multivariate analysis, after controlling for age, race, gender, tumour histology, tumour stage, tumour grade, tumour location, SEER site, year of diagnosis, undergoing percutaneous aspiration/biopsy, Charlson Comorbidity Index, radiation and chemotherapy, EUS-FNA was marginally associated with improved overall survival (HR 0.84, 95% CI 0.72 to 0.99), but did not affect cancer-specific survival (HR 0.87, 95% CI 0.74 to 1.03). Conclusions Preoperative EUS-FNA was not associated with increased risk of mortality. These data suggest that EUS-FNA can be safely performed for the work-up of suspicious pancreatic lesions.

AbstractWe report a 65‐year‐old heart transplant recipient who presented with conjunctivitis, likely acquired from a family member who worked at a daycare center during an outbreak of conjunctivitis. He developed a severe adenoviral pneumonitis, which was successfully treated with intravenous cidofovir combined with a reduction of immunosuppression.

Abstract Motivation: RNA-seq has been widely used to study the transcriptome. Comparing to microarray, sequencing-based RNA-seq is able to identify splicing variants and single nucleotide variants in one experiment simultaneously. This provides unique opportunity to detect variants that associated with aberrant splicing. Despite the popularity of RNA-seq, no bioinformatics tool has been developed to leverage this advantage to identify variants associated with aberrant splicing. Results: We have developed PVAAS, a tool to identify single nucleotide variants that associated with aberrant alternative splicing from RNA-seq data. PVAAS works in three steps: (i) identify aberrant splicings; (ii) use user-provided variants or perform variant calling; (iii) assess the significance of association between variants and aberrant splicing events. Availability and implementation: PVAAS is written in Python and C. Source code and a comprehensive user’s manual are freely available at: http://pvaas.sourceforge.net/. Contact: wang.liguo@mayo.edu or kocher.jeanpierre@mayo.edu Supplementary information: Supplementary data are available at Bioinformatics online.

The management of women with mechanical heart valves during pregnancy remains difficult and controversial. There is no ideal anticoagulation regimen for this unique population, as there are inherent risks and benefits of each approach for both mother and fetus. There has been limited data available to guide the clinician in the optimal treatment strategy for an individual patient. The AHA/ACC Guidelines for the Management of Patients with Valvular Heart Disease created class recommendations for this population based upon current evidence, which is summarized in this review.