Initial experience with a novel remote-guided magnetic catheter navigation system for left ventricular scar mapping and ablation in a porcine model of healed myocardial infarction

Objective: This study examined the feasibility of using a remote magnetic catheter navigation system (MNS) in concert with an EAM system to perform detailed left ventricular scar mapping and ablation in a porcine model of healed myocardial infarction.
Background : Substrate-based catheter ablation of ventricular tachycardia (VT) involves detailed electroanatomical mapping (EAM) of the ventricles. While a safe and effective procedure, VT ablation is nonetheless uncommonly performed, due in part to the technical challenges related to ventricular mapping.
Methods: Using a prototype EAM system (CARTO-RMT), seven chronically infarcted swine were mapped using either: (i) a standard manually manipulated catheter or (ii) a magnetic remotely manipulated (Niobe) catheter. A total of 191 ± 54 and 221 ± 64 points were acquired to map the chamber either manually or remotely, respectively.
Results: Procedure times were longer remotely (94 ± 22 vs. 59 ± 19 minute, P = 0.004; and 27 ± 8 vs. 18 ± 3 sec/point, P = 0.04), but this became less apparent with increased operator experience. However, the fluoroscopy time was significantly shorter with remote mapping (56 ± 56 vs. 244 ± 67 sec/map, P = 0.03). The calculated scar size was comparable between the two methods (16.3 ± 4.9 vs. 16.4 ± 4.8 cm², P = 0.37). Pathologic examination confirmed that the MNS was able to precisely deliver radiofrequency lesions to the scar borders. Using the MNS, the error to reach an evenly distributed set of endocardial targets was 6.6 ± 3.6 mm and 4.6 ± 2.0 mm, using transseptal and retrograde approaches, respectively.
Conclusions: Ventricular mapping using this remote navigation paradigm is technically possible and requires minimal fluoroscopy exposure, potentially facilitating ventricular substrate mapping and ablation.     

Pancreatic acinar cell carcinoma: A comprehensive review

Acinar cell carcinoma (ACC) is a rare pancreatic malignancy with distinctive clinical, molecular, and morphological features. The long-term survival of ACC patients is substantially superior to that of pancreatic adenocarcinoma patients. As there are no significant patient series about ACCs, our understanding of this illness is mainly based on case reports and limited patient series. Surgical resection is the treatment of choice for patients with the disease restricted to one organ; however, with recent breakthroughs in precision medicine, medicines targeting the one-of-a-kind molecular profile of ACC are on the horizon. There are no standard treatment protocols available for people in which a total surgical resection to cure the condition is not possible. As a result of shared genetic alterations, ACCs are chemosensitive to agents with activity against pancreatic adenocarcinomas and colorectal carcinomas. The role of neoadjuvant or adjuvant chemoradiotherapy has not been established. This article aims to do a comprehensive literature study and present the most recent information on acinar cell cancer.     

Prevention of chronic diseases: a call to action

Chronic (non-communicable) diseases—principally cardiovascular diseases, cancer, chronic respiratory diseases, and diabetes—are leading causes of death and disability but are surprisingly neglected elements of the global-health agenda. They are underappreciated as development issues and underestimated as diseases with profound economic effects. Achievement of the global goal for prevention and control of chronic diseases would avert 36 million deaths by 2015 and would have major economic benefits. The main challenge for achievement of the global goal is to show that it can be reached in a cost-effective manner with existing interventions. This series of papers in The Lancet provides evidence that this goal is not only possible but also realistic with a small set of interventions directed towards whole populations and individuals who are at high risk. The total yearly cost of the interventions in 23 low-income and middle-income countries is about US$5·8 billion (as of 2005). In this final paper in the Series we call for a serious and sustained worldwide effort to prevent and control chronic diseases in the context of a general strengthening of health systems. Urgent action is needed by WHO, the World Bank, regional banks and development agencies, foundations, national governments, civil society, non-governmental organisations, the private sector including the pharmaceutical industry, and academics. We have established the Chronic Disease Action Group to encourage, support, and monitor action on the implementation of evidence-based efforts to promote global, regional, and national action to prevent and control chronic diseases.     

Arrhythmogenic right ventricular dysplasia: initial presentation in a middle-aged woman

Arrhythmogenic right ventricular dysplasia is a rare disorder that is familial in 30% to 50% of cases. It is characterized by structural and functional abnormalities of the right ventricle and a propensity for ventricular arrhythmias and sudden death. We report the case of a 59-year-old woman who had idiopathic, severe, right-sided heart failure and nonsustained ventricular tachycardia. She was diagnosed with arrhythmogenic right ventricular dysplasia by means of cardiac magnetic resonance imaging. We discuss the clinical features, diagnostic criteria, and role of cardiac magnetic resonance imaging in the diagnosis of arrhythmogenic right ventricular dysplasia.     

Lipid profile and apolipoprotein E polymorphism in essential hypertension

BACKGROUND: Studies in several populations have indicated that genetic variation at the apolipoprotein E structural locus influences atherosclerosis leading to cardiovascular diseases. The possible role of apolipoprotein E polymorphism in the development of essential hypertension has not been sufficiently investigated. In this case-control study, we aimed to determine the significance of association between essential hypertension and apolipoprotein E genotypes. In addition, apolipoprotein E genotypes were correlated with serum lipid levels in order to understand the possible interaction between the specific genotype and the lipid profiles that can contribute to hypertension. METHODS AND RESULTS: The apolipoprotein E genotypes were assayed in 185 patients and 200 controls by polymerase chain reaction followed by enzymatic digestion with Hha I. Using logistic regression analysis, the multivariate-adjusted odds of hypertension were calculated. The incidence of epsilon4 allele was found to be significantly higher in patients (12.16%) than in controls (5.75%, chi2=10.87; p<0.05) and also in patients with positive family history (16.7%) as compared to negative family history (8.87%, chi2 = 8.45; p<0.1). Further, it was observed that carriers of epsilon4 allele have twice as much risk (p<0.05) for developing hypertension as compared to carriers of other alleles. Patients with epsilon4 allele had significantly higher levels of total cholesterol and low-density lipoprotein- cholesterol as compared to epsilon4 allele non-carriers (p<0.05). The adjusted odds ratios for epsilon4 and epsilon2 alleles versus epsilon3 allele were 2.2 (95% confidence interval 1.2 to 3.8, p<0.05) and 1.2 (95% CI, 0.75 to 1.77, p<0.514), respectively. CONCLUSIONS: Our study revealed a strong association of apolipoprotein E locus with hypertension and lipid profile. However, large population-based studies are needed to understand the exact role played by the locus in causing the condition.     

Hydroxyurea therapy for sickle cell disease in community-based practices: a survey of Florida and North Carolina hematologists/oncologists

Little is known about patterns of hydroxyurea (HU) use by community-based hematologist/oncologists (H/Os) for the treatment of sickle cell disease (SCD). Determination of these practice patterns pertaining to adult SCD patients was the focus of this study. A self-administered survey was mailed to H/Os in two southeastern states. Replies were received from 70% of eligible physicians. This study focuses on responses from 184 community H/Os and a comparison group of 30 university-based/affiliated H/Os providing ongoing care for at least 3 SCD patients/month. The majority of community H/O respondents saw less than 3 SCD patients/month. HU was prescribed by more than half (55%) of community H/Os in at least 10% of their patients. The most common reasons cited for prescribing HU include frequent painful crises (76%), chronic pain with frequent narcotic use (58%), and acute chest syndrome (43%). Although the majority of community H/Os care for few patients with SCD, the reported indications for HU were consistent with currently accepted recommendations. However, community H/Os reported acute chest syndrome, stroke, and pulmonary hypertension as indications for HU less often than the academic H/O group. Barriers to wider use of HU include physician concerns about carcinogenic potential, doubts about HU effectiveness, perceived patient apprehension about adverse effects, concern about lack of contraceptive use, and patient compliance. Further resources should focus on updating physicians on recently published material supporting the effectiveness of HU in symptomatic SCD as well as providing management guidelines to optimize the use of HU.     

Cytoplasmic LEK1 is a regulator of microtubule function through its interaction with the LIS1 pathway

LIS1 and nuclear distribution gene E (NudE) are partner proteins in a conserved pathway regulating the function of dynein and microtubules. Here, we present data that cytoplasmic LEK1 (cytLEK1), a large protein containing a spectrin repeat and multiple leucine zippers, is a component of this pathway through its direct interaction with NudE, as determined by a yeast two-hybrid screen. We identified the binding domains in each molecule, and coimmunoprecipitation and colocalization studies confirmed the specificity of the interaction between cytLEK1 and NudE. Confocal deconvolution analysis revealed that cytLEK1 exhibits colocalization with endogenous NudE and with the known NudE binding partners, LIS1 and dynein. By localizing the NudE-binding domain of cytLEK1 to a small domain within the molecule, we were able to disrupt cytLEK1 function by using a dominant negative approach in addition to LEK1 knockdown and, thus, examine the role of the cytLEK1-NudE interaction in cells. Consistent with a defect in the LIS1 pathway, disruption of cytLEK1 function resulted in alteration of microtubule organization and cellular shape. The microtubule network of cells became tightly focused around the nucleus and resulted in a rounded cell shape. Additionally, cells exhibited a severe inability to repolymerize their microtubule networks after nocodazole challenge. Taken together, our studies revealed that cytLEK1 is essential for cellular functions regulated by the LIS1 pathway.     

Endoscopic ultrasound-guided trucut biopsy of the cyst wall for diagnosing cystic pancreatic tumors.

BACKGROUND & AIMS: Nonoperative methods for diagnosis of pancreas cysts often lack sufficient accuracy. Accurate diagnosis is needed to determine prognosis and guide clinical management. The aim of this study was to determine whether the tissue obtained by endoscopic ultrasound-guided trucut biopsy (EUS TCB) is sufficient for histologic diagnosis of cystic pancreatic tumors (CPTs). METHODS: EUS TCB was performed in patients with a suspected CPT. A dedicated gastrointestinal pathologist reviewed the core biopsies. The final diagnosis was based on clinical, laboratory, imaging, and biopsy findings, and resected specimens when available. RESULTS: EUS TCB was performed in 10 patients with a suspected CPT. Final diagnoses included serous cystadenoma (SCA, n=5), islet cell tumor (n=2), mixed seromucinous lesion (n=1), polycystic disease of the pancreas (n=1), and pseudocyst (n=1). EUS TCB was nondiagnostic in 3 of 10 patients. Among the other 7 patients, TCB diagnosed 4 SCAs, obviating the need for planned surgery in 3 patients. In the fourth patient with an SCA, the TCB result ruled out metastatic disease from locally recurrent lung cancer, allowing a narrowed radiation field. EUS TCB confirmed the need for surgery in 2 patients with an islet cell tumor. In 1 patient, EUS TCB findings were "partially" diagnostic, leading to previously unplanned surgery. CONCLUSIONS: This report establishes the capability and safety of EUS TCB to collect sufficient tissue for diagnosing CPTs. The results might help guide clinical management.