Radiofrequency catheter ablation of septal accessory pathways in the pediatric age group

Radiofrequency catheter ablation (RCA) of septal accessory pathways may be technically challenging in children due to the risk of inadvertent atrioventricular (AV) block in the setting of small cardiac dimensions. Outcomes were reviewed for all patients aged < or =19 years with manifest and concealed septal accessory pathways undergoing RCA since 1990 at a single institution. One hundred forty-five procedures were performed in 127 patients (mean age 11.6 years). The number of studies according to accessory pathway location were: anteroseptal (n = 36), midseptal (n = 20), mouth of coronary sinus (n = 40), middle cardiac vein (n = 6), right posteroseptal (n = 21), and left posteroseptal (n = 22). Ablation was deferred for 9 patients (6 anteroseptal and 3 midseptal) in favor of additional pharmacologic trials. Acute success rates for targeted accessory pathways were: anteroseptal (96%), midseptal (94%), mouth of coronary sinus (88%), middle cardiac vein (100%), right posteroseptal (100%), and left posteroseptal (96%). Recurrence rates during follow-up were: anteroseptal (14%), midseptal (12%), mouth of coronary sinus (3%), right posteroseptal (4%), and left posteroseptal (4%). Permanent second or third degree AV block occurred in 4 of 136 RCA attempts (3%), involving 2 anteroseptal and 2 midseptal pathways. In 3 of these 4 cases, a high probability of block was anticipated from prior ablation efforts, prompting pacemaker insertion before or in conjunction with RCA. Thus, in the pediatric age group, acute RCA success rates for septal accessory pathways can exceed 90%. The risks of AV block and accessory pathway recurrence are most relevant to anteroseptal and midseptal pathways. These data may be factored into patient selection and the decision whether to ablate.     

Early Prosthetic Valve Dysfunction Due to Bioprosthetic Valve Thrombosis: The Role of Echocardiography

Objectives

The purpose of this study was to review the institutional practice of surveillance transthoracic echocardiography (TTE) for diagnosing early prosthetic valve dysfunction (PVD).

Decreased VMAT2 in the pancreas of humans with type 2 diabetes mellitus measured in vivo by PET imaging

Aims/hypothesis

The progressive loss of beta cell function is part of the natural history of type 2 diabetes. Autopsy studies suggest that this is, in part, due to loss of beta cell mass (BCM), but this has not been confirmed in vivo. Non-invasive methods to quantify BCM may contribute to a better understanding of type 2 diabetes pathophysiology and the development of therapeutic strategies. In humans, the localisation of vesicular monoamine transporter type 2 (VMAT2) in beta cells and pancreatic polypeptide cells, with minimal expression in other exocrine or endocrine pancreatic cells, has led to its development as a measure of BCM. We used the VMAT2 tracer [¹⁸F]fluoropropyl-(+)-dihydrotetrabenazine to quantify BCM in humans with impaired glucose tolerance (prediabetes) or type 2 diabetes, and in healthy obese volunteers (HOV).

Methods

Dynamic positron emission tomography (PET) data were obtained for 4 h with metabolite-corrected arterial blood measurement in 16 HOV, five prediabetic and 17 type 2 diabetic participants. Eleven participants (six HOV and five with type 2 diabetes) underwent two abdominal PET/computed tomography (CT) scans for the assessment of test–retest variability. Standardised uptake value ratio (SUVR) was calculated in pancreatic subregions (head, body and tail), with the spleen as a reference region to determine non-specific tracer uptake at 3–4 h. The outcome measure SUVR minus 1 (SUVR-1) accounts for non-specific tracer uptake. Functional beta cell capacity was assessed by C-peptide release following standard (arginine stimulus test [AST]) and acute insulin response to the glucose-enhanced AST (AIRargMAX). Pearson correlation analysis was performed between the binding variables and the C-peptide AUC post-AST and post-AIRargMAX.

Results

Absolute test–retest variability (aTRV) was ≤15% for all regions. Variability and overlap of SUVR-1 was measured in all groups; HOV and participants with prediabetes and with type 2 diabetes. SUVR-1 showed significant positive correlations with AIRargMAX (all groups) in all pancreas subregions (whole pancreas p?=?0.009 and pancreas head p?=?0.009; body p?=?0.019 and tail p?=?0.023). SUVR-1 inversely correlated with HbA_1c (all groups) in the whole pancreas (p?=?0.033) and pancreas head (p?=?0.008). SUVR-1 also inversely correlated with years since diagnosis of type 2 diabetes in the pancreas head (p?=?0.049) and pancreas tail (p?=?0.035).

Conclusions/interpretation

The observed correlations of VMAT2 density in the pancreas and pancreas regions with years since diagnosis of type 2 diabetes, glycaemic control and beta cell function suggest that loss of BCM contributes to deficient insulin secretion in humans with type 2 diabetes.

     

Antacids reduce Campylobacter pylori colonization without healing the gastritis in patients with nonulcer dyspepsia and erosive prepyloric changes

Antral biopsy specimens from 89 consecutive patients with nonulcer dyspepsia and erosive prepyloric changes included in a prospective, randomized, double-blind 4-wk study of the effect of an aluminum-magnesium antacid (120 mmol/day) or pirenzepine (50 mg b.i.d.) vs. placebo were examined histologically. Campylobacter pylori (CP) was found by light microscopy of silver-stained sections in 25 patients (28%). Campylobacter pylori-positive patients were on average older than CP-negative patients (p = 0.02). There was a strong association between CP colonization and acute inflammation (p less than 0.001), both being rare in the absence of chronic inflammation. During treatment with antacids, the density of CP decreased (p less than 0.001) without any improvement of the inflammatory reaction. On the contrary, the number of patients with gastritis tended to increase after antacids as compared with placebo (p less than 0.10). A separate analysis showed no symptomatic effect of the drugs. Thus, neither nonulcer dyspepsia nor erosive prepyloric changes are strongly associated with antral CP colonization or acute inflammation. Aluminum-magnesium antacids may suppress antral CP infection without healing the gastritis or relieving symptoms.     

A PKR-like eukaryotic initiation factor 2alpha kinase from zebrafish contains Z-DNA binding domains instead of dsRNA binding domains

The double-stranded RNA (dsRNA)-dependent protein kinase (PKR) is induced as part of the IFN response in mammals and acts to shut down protein synthesis by the phosphorylation of eukaryotic initiation factor 2alpha (eIF2alpha). In fish, a PKR-like kinase activity has been detected, but the enzyme responsible has eluded characterization. Here, we describe a PKR-like kinase from zebrafish. Phylogenetic analysis shows that the C-terminal kinase domain is more closely related to the kinase domain of PKR than to any of the other three known eIF2alpha kinases. Surprisingly, instead of the two dsRNA binding domains found at the N terminus of PKR, there are two Zalpha domains. Zalpha domains specifically bind dsDNA and RNA in the left-handed Z conformation, often with high affinity. They have been found previously in two other IFN-inducible proteins, the dsRNA editing enzyme, ADAR1, and Z-DNA binding protein 1 (ZBP1), as well as in the poxvirus virulence factor, E3L. This previously undescribed kinase, designated PKZ (protein kinase containing Z-DNA binding domains), is transcribed constitutively at low levels and is highly induced after injection of poly(inosinic)-poly(cytidylic) acid, which simulates viral infection. Binding of Z-DNA by the Zalpha domain of PKZ was demonstrated by circular dichroism. PKZ inhibits translation in transfected cells; site-directed mutagenesis indicates that this inhibition depends on its catalytic activity. Identification of a gene combining Zalpha domains with a PKR-like kinase domain strengthens the hypothesis that the ability to bind left-handed nucleic acid plays a role in the host response to viruses.     

Perioperative management of patients receiving oral anticoagulants: a systematic review

BACKGROUND: The safety and efficacy of various management strategies for patients receiving oral anticoagulants (OACs) who need to undergo surgery or invasive procedures are unknown. METHODS: We performed a systematic review and synthesis of the English-language literature examining the perioperative management and outcomes of patients receiving long-term OAC therapy. RESULTS: Thirty-one reports were identified. The quality of the identified reports was generally poor; no randomized controlled trials have been performed and duration of follow-up was typically not stated. Overall, 29 thromboembolic events occurred amont 1868 patients (1.6%; 95% confidence interval, 1.0%-2.1%), including 7 strokes (0.4%; 95% confidence interval, 0%-0.7%). Thromboembolic event rates by management strategy were 0.4% (1 of 237) for continuation of OAC, 0.6% (6 of 996) for discontinuation of OAC therapy without administration of intravenous heparin, 0% (0 of 166) for discontinuation of OAC therapy with administration of intravenous heparin, 0.6% (1 of 180) for discontinuation of OAC therapy with administration of low-molecular-weight heparin, and 8.0% (21 of 263) for unspecified or unclear strategies. Major bleeding while receiving therapeutic OAC was rare for dental procedures (0.2% [4 of 2014]), arthrocentesis (0% [0 of 32]), cataract surgery (0% [0 of 203]), and upper endoscopy or colonoscopy with or without biopsy (0% [0 of 111]). CONCLUSIONS: Most patients can undergo dental procedures, arthrocentesis, cataract surgery, and diagnostic endoscopy without alteration of their regimen. For other invasive and surgical procedures, oral anticoagulation needs to be withheld, and the decision whether to pursue an aggressive strategy of perioperative administration of intravenous heparin or subcutaneous low-molecular-weight heparin should be individualized. The current literature is substantially limited in its ability to help choose an optimal strategy. Further and more rigorous studies are needed to better inform this decision.     

Outcomes of coronary artery bypass grafting versus percutaneous coronary intervention and medical therapy for multivessel disease with and without left ventricular dysfunction

Multiple randomized trials support the treatment of patients with multivessel coronary artery disease (CAD) and relatively normal left ventricular (LV) ejection fraction (EF) by either percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). However, there has been a paucity of trials in the recent literature that have compared the outcomes of patients with multivessel CAD and low EF who undergo PCI or CABG. This review examines some of the clinical trials and series in this subgroup of patients and also compares the outcome of patients undergoing either procedure in the absence and presence of LV dysfunction. These trials and series support the notion that PCI can be successfully performed in patients with low EF with relatively low mortality, but that CABG is associated with greater freedom from repeat revascularization and from angina or congestive heart failure symptoms. In addition, most of the data published thus far indicate a long-term survival advantage among patients with ventricular dysfunction who have undergone CABG. Further studies, including randomized trials incorporating the evolving techniques of CABG and the recent advances in PCI, will be needed to assess the proper role and outcome of these two interventions.     

New aspects of adjuvant therapy in endometrial cancer: current standards and future directions

Endometrial cancer is one of the most common gynaecological cancers in western countries. Most women are diagnosed at an early stage of the disease and can be cured by surgery alone. In patients with poor prognostic factors or an advanced disease, the chance of progression-free survival and overall survival is greatly diminished. Adjuvant chemotherapy is effective for patients with advanced disease. The combination of doxorubicin and cisplatin achieves overall response rates ranging from 34 to 60%, and the addition of paclitaxel seems to improve the outcome of patients with advanced disease, but it induces a significantly higher toxicity. A Gynecologic Oncology Study Group phase-III study is currently exploring the triplet paclitaxel+doxorubicin+cisplatin plus G-CSF vs. the less toxic combination of paclitaxel+carboplatin. Ongoing and planned phase-III trials are evaluating newer combination chemotherapy regimens, a combination of irradiation and chemotherapy and the implementation of targeted therapies with the goal of improving the tumour control rate and quality of life.     

Comparison of effectiveness of sirolimus-eluting stents versus bare metal stents for percutaneous coronary intervention in patients at high risk for coronary restenosis or clinical adverse events

We evaluated the clinical effect of selective use of sirolimus-eluting stents (SESs) in real-world, high-risk patients. A total of 4,237 consecutive patients who underwent percutaneous coronary intervention (SES, n = 872, bare metal stents [BMSs], n = 3,365) was enrolled in a prospective regional survey. A prespecified high-risk subset of patients was selected on the basis of clinical and angiographic characteristics. A propensity score analysis was performed to compare patients who received SESs with those who received BMSs. Patients in the SES group more often had diabetes and more frequently had previous myocardial infarction or coronary revascularization, type C lesions, and multivessel procedures. Patients who presented with acute myocardial infarction were treated more often with BMSs. At 9 months, the use of SESs was associated with fewer major adverse cardiac events (death, myocardial infarction, or target lesion revascularization; hazard ratio 0.56, 95% confidence interval 0.37 to 0.85) and target lesion revascularizations (hazard ratio 0.43, 95% confidence interval 0.20 to 0.91). This decrease was more evident in a prespecified high-risk subgroup of patients (major adverse cardiac events, 8.0% SES vs 15.6% BMS, hazard ratio 0.45, 95% confidence interval 0.29 to 0.72). We conclude that selective SES use in real-world patients who have high-risk clinical and angiographic characteristics is associated with significant decreases in major adverse cardiac events and repeat revascularizations compared with BMS use.