Incidence of nonsustained and sustained ventricular tachyarrhythmias in patients with an implantable cardioverter defibrillator

INTRODUCTION: Nonsustained ventricular tachycardia (NSVT) is a frequent phenomenon in some patients with heart disease, but its association with sustained ventricular tachycardias (ventricular tachycardia [VT]/ventricular fibrillation [VF]) is still not clear. The aim of this study was to determine whether NSVT incidence was associated with sustained VT/VF in patients with an implantable cardioverter defibrillator (ICD). METHODS AND RESULTS: Retrospective data analysis was conducted in 923 ICD patients with a mean follow-up of 4 months. NSVT and sustained VT/VF were defined as device-detected tachycardias. The incidence rates of NSVT and sustained VT/VF as well as ICD therapies were determined as episodes per patient. The NSVT index was defined as the product of NSVT episodes/day times the mean number of beats per episode, i.e., total beats/day. The NSVT index peak was defined as the highest value on or prior to the day with sustained VT/VF episodes. Patients (n = 393) with NSVT experienced a higher incidence of sustained VT/VF (17.2 +/- 63.0 episodes/patient) and ICD therapies (15.2 +/- 61.4 episodes/patient) than patients (n = 530) without NSVT (sustained VT/VF: 0.5 +/- 6.6 and therapies: 0.5 +/- 5.6; P < 0.0001). Approximately 74% of NSVT index peaks occurred on the same day or <3 days prior to sustained VT/VF episodes. The index was higher for peaks < or =3 days prior to the day with sustained VT/VF (94.3 +/- 140.1 total beats/day) than for peaks >3 days prior to the day with sustained VT/VF (32.7 +/- 55.9 total beats/day; P < 0.0001). CONCLUSION: ICD patients with NSVT represent a population more likely to experience sustained VT/VF episodes with a temporal association between an NSVT surge and sustained VT/VF occurrence.     

Exploring the utility of whole‐exome sequencing as a diagnostic tool in a child with atypical episodic muscle weakness

The advent of whole‐exome next‐generation sequencing (WES) has been pivotal for the molecular characterization of Mendelian disease; however, the clinical applicability of WES has remained relatively unexplored. We describe our exploration of WES as a diagnostic tool in a 3½‐year old female patient with a 2‐year history of episodic muscle weakness and paroxysmal dystonia who presented following a previous extensive but unrevealing diagnostic work‐up. WES was performed on the proband and her two parents. Parental exome data was used to filter potential de novo genomic events in the proband and suspected variants were confirmed using di‐deoxy sequencing. WES revealed a de novo non‐synonymous mutation in exon 21 of the calcium channel gene CACNA1S that has been previously reported in a single patient as a rare cause of atypical hypokalemic periodic paralysis. This was unexpected, as the proband's original differential diagnosis had included hypokalemic periodic paralysis, but clinical and laboratory features were equivocal, and standard clinical molecular testing for hypokalemic periodic paralysis and related disorders was negative. This report highlights the potential diagnostic utility of WES in clinical practice, with implications for the approach to similar diagnostic dilemmas in the future.     

Double Solitaire Mechanical Thrombectomy in Acute Stroke: Effective Rescue Strategy for Refractory Artery Occlusions?

BACKGROUND AND PURPOSE:Mechanical thrombectomy by using a single stent retriever system has demonstrated high efficacy for recanalization of large-artery occlusions in acute stroke. We aimed to evaluate the feasibility, safety, and efficacy of a novel double Solitaire stent retriever technique as an escalating treatment for occlusions that are refractory to first-line single stent retriever mechanical thrombectomy.MATERIALS AND METHODS:All patients treated with the double stent retriever technique by using the Solitaire system were retrospectively selected from 2 large neurointerventional centers. Time to recanalization, angiographic (TICI) and clinical outcomes (mRS), and complications were assessed.RESULTS:Ten patients (median NIHSS score, 16; mean age, 70 years) with MCA M1 segment (n = 5) and terminal ICA (n = 5 including 2 ICA tandem) occlusions were included. Prior single stent retriever mechanical thrombectomy had been performed in 9 patients (median number of passes, 3). Median time to recanalization was 60 minutes (interquartile range, 45–87 minutes). Procedure-related complications occurred in 1 patient; overall mortality was 20%. Recanalization of the target vessel (TICI 2b/3) was achieved in 80%. Good clinical outcome (mRS 0–2) was 50%.CONCLUSIONS:In this preliminary feasibility study, the double Solitaire stent retriever technique proved to be an effective method for recanalization of anterior circulation large-artery occlusions refractory to standard stent retriever mechanical thrombectomy.

In acute ischemic stroke, recanalization of an occluded cerebral artery is strongly linked with improved clinical outcome and reduced mortality.¹ The potential of IV thrombolysis for achieving successful vessel recanalization is significantly limited by the extent of clot burden in proximal cerebral artery occlusions.² With the recent introduction of stent retrievers (SR) for mechanical thrombectomy (MT), fast, safe, and efficient large-artery recanalization treatment can be achieved, and their superiority over older MT devices has been demonstrated in randomized controlled trials.^3,4Despite considerable recanalization rates of 61%–86% (Thrombolysis in Myocardial Infarction/TICI scores of ≥2/2b),^3–5 up to 33.3% of patients are still left without sufficient recanalization after standard SR MT.⁶ In these refractory cases, different rescue treatments have been proposed with variable rates of success.^4,5,7–10 These include local intra-arterial fibrinolysis, MT with the Penumbra device (Penumbra, Alameda, California), mechanical thrombus disruption, thromboaspiration through a distal-access catheter (DAC), balloon angioplasty, and/or stent placement.Here, we describe a novel escalating strategy for MT by using 2 Solitaire SR devices (Covidien, Irvine, California), hence termed the “double Solitaire SR technique,” for proximal anterior circulation occlusions that are refractory to first-line single SR MT. In a retrospective series of patients from 2 large neurointerventional centers, we assessed the feasibility, safety, and angiographic and clinical outcomes of this technique.     

Characterization of the expression of MHC proteins in human embryonic stem cells

Human embryonic stem (ES) cells are pluripotent cells that may be used in transplantation medicine. These cells can be induced to differentiate into cells from the three embryonic germ layers both in vivo and in vitro. To determine whether human ES cells might be rejected after transplantation, we examined cell surface expression of the MHC proteins in these cells. Our results show very low expression levels of MHC class I (MHC-I) proteins on the surface of human ES cells that moderately increase on in vitro or in vivo differentiation. A dramatic induction of MHC-I proteins was observed when the cells were treated with IFN-gamma but not with IFN-alpha or -beta. However, all three IFNs induced expression of MHC-I proteins in differentiated human ES cells. MHC-II proteins and HLA-G were not expressed on the surface of undifferentiated or differentiated cells. Ligands for natural killer cell receptors were either absent or expressed in very low levels in human ES cells and in their differentiated derivatives. In accordance, natural killer cytotoxic assays demonstrated only limited lysis of both undifferentiated and differentiated cells. To initiate a histocompatibility databank of human ES cells, we have isotyped several of the published ES cell lines for their human leukocyte antigens. In conclusion, our results demonstrate that human ES cells can express high levels of MHC-I proteins and thus may be rejected on transplantation.     

A high-throughput, near-saturating screen for type III effector genes from Pseudomonas syringae

Pseudomonas syringae strains deliver variable numbers of type III effector proteins into plant cells during infection. These proteins are required for virulence, because strains incapable of delivering them are nonpathogenic. We implemented a whole-genome, high-throughput screen for identifying P. syringae type III effector genes. The screen relied on FACS and an arabinose-inducible hrpL sigma factor to automate the identification and cloning of HrpL-regulated genes. We determined whether candidate genes encode type III effector proteins by creating and testing full-length protein fusions to a reporter called Delta79AvrRpt2 that, when fused to known type III effector proteins, is translocated and elicits a hypersensitive response in leaves of Arabidopsis thaliana expressing the RPS2 plant disease resistance protein. Delta79AvrRpt2 is thus a marker for type III secretion system-dependent translocation, the most critical criterion for defining type III effector proteins. We describe our screen and the collection of type III effector proteins from two pathovars of P. syringae. This stringent functional criteria defined 29 type III proteins from P. syringae pv. tomato, and 19 from P. syringae pv. phaseolicola race 6. Our data provide full functional annotation of the hrpL-dependent type III effector suites from two sequenced P. syringae pathovars and show that type III effector protein suites are highly variable in this pathogen, presumably reflecting the evolutionary selection imposed by the various host plants.     

Application of full field optical studies for pulsatile flow in a carotid artery phantom

A preliminary comparative measurement between particle imaging velocimetry (PIV) and laser speckle contrast analysis (LASCA) to study pulsatile flow using ventricular assist device in a patient-specific carotid artery phantom is reported. These full-field optical techniques have both been used to study flow and extract complementary parameters. We use the high spatial resolution of PIV to generate a full velocity map of the flow field and the high temporal resolution of LASCA to extract the detailed frequency spectrum of the fluid pulses. Using this combination of techniques a complete study of complex pulsatile flow in an intricate flow network can be studied.OCIS codes: (100.0100) Image processing, (170.0170) Medical optics and biotechnology, (230.0230) Optical devices, (290.0290) Scattering     

Rasmussen encephalitis: Incidence and course under randomized therapy with tacrolimus or intravenous immunoglobulins

Purpose: Rasmussen encephalitis (RE) leads to progressive tissue and function loss of one brain hemisphere and often intractable epilepsy. This is the first randomized prospective treatment trial in RE. Methods: Germany‐wide, patients with suspected recent‐onset RE were recruited and if eligible randomized to tacrolimus or intravenous immunoglobulins (IVIGs). A loss of motor function or hemispheric volume by ≥15% (in patients >12 years at disease onset: ≥8%) led to study exit. Untreated patients served as a historical control group. Key Findings: Over 6.3 years, 21 patients with recent‐onset RE were identified. Sixteen were randomized to tacrolimus (n = 9) or IVIG (n = 7). Immunotreated patients had a longer “survival” than the historical controls. Neither treatment was more efficacious than the other. Two tacrolimus patients experienced serious adverse events. No immunotreated but several untreated patients developed intractable epilepsy. No patient with refractory epilepsy became treatment‐responsive under immunotherapy. Significance: The countrywide incidence rate of diagnosed RE is estimated as 2.4 cases/10⁷ people ≤ age 18/year. Treatment with tacrolimus or IVIG may slow down tissue and function loss and prevent development of intractable epilepsy. However, immunotherapy may “arrest” patients in a dilemma state of pharmacoresistant epilepsy but too good function to be offered functional hemispherectomy. These compounds may therefore contribute to the therapeutic armamentarium for RE patients without difficult‐to‐treat epilepsies.