Prognostic Value of J (Osborn) Waves on Surface Electrocardiogram Tracing during Therapeutic Hypothermia in Out-of-Hospital Cardiac Arrest Survivors (JOW trial).

BACKGROUND: Patients admitted to the hospital after successful resuscitation from sudden cardiac death (SCD) are treated with therapeutic hypothermia (TH) to facilitate brain preservation. The prognostic significance of J (Osborn) waves (JOW) in the 12 leads electrocardiogram in this setting has not been elucidated as yet. OBJECTIVES: To ascertain retrospectively the prognostic significance of JOW recorded during TH in SCD survivors. METHODS: The study comprised 55 consecutive patients who underwent TH. All patients achieved a core temperature of 33°C at the time of electrocardiogram analysis. We compared 33 patients with JOW to 22 patients without JOW. The endpoints were in-hospital, long-term all-cause mortality, and irreversible anoxic brain injury (IABI). RESULTS: Patients with JOW compared to patients without JOW were younger (55.1 ± 11.6 vs. 64.5 ± 11.7 years, respectively, P < 0.006), with a lower incidence of hypertension (52% vs. 86%, P < 0.007), diabetes mellitus (15% vs. 50%, P < 0.005), and congestive heart failure (15% vs. 45%, P < 0.013). In-hospital and long-term mortality were significantly higher in patients without JOW (86% vs. 21%, 91% vs. 24%, respectively, P < 0.000001). Among patients without JOW who survived hospitalization, 66.7% presented with IABI versus 7.7% of the patients with JOW (P < 0.0001). In multivariate analysis, the absence of JOW was a significant predictor for poor prognosis. CONCLUSIONS: The absence of J (Osborn) waves on electrocardiograms obtained during TH is associated with poor prognosis among SCD survivors.

The Essentials of Molecular Testing in CNS Tumors: What to Order and How to Integrate Results.

PURPOSE OF REVIEW: Molecular testing has become essential for the optimal workup of central nervous system (CNS) tumors. There is a vast array of testing from which to choose, and it can sometimes be challenging to appropriately incorporate findings into an integrated report. This article reviews various molecular tests and provides a concise overview of the most important molecular findings in the most commonly encountered CNS tumors. RECENT FINDINGS: Many molecular alterations in CNS tumors have been identified over recent years, some of which are incorporated into the 2016 World Health Organization (WHO) classification and the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy-Not Official WHO (cIMPACT-NOW) updates. Array-based methylation profiling has emerged over the past couple of years and will likely replace much of currently used ancillary testing for diagnostic purposes. A combination of next-generation sequencing (NGS) panel and copy number array is ideal for diffuse gliomas and embryonal tumors, with a low threshold to employ in other tumor types. With the recent advances in molecular diagnostics, it will be ever more important for the pathologist to recognize the molecular testing available, which tests to perform, and to appropriately integrate results in light of clinical, radiologic, and histologic findings.

[STRATEGIES FOR IMPLEMENTATIONS OF REMOTE MONITORING FOR PATIENTS WITH CARDIOVASCULAR IMPLANTABLE ELECTRONIC DEVICES (CIED) IN ISRAEL].

INTRODUCTION: Remote monitoring (RM) of patients with cardiovascular implantable electronic devices (CIED) offers clinical benefits by providing early alert for system failure and actionable changes in patient health. Professional societies recommend utilization of RM for CIED patients (Level of recommendation I Level of evidence A). It must be emphasized that RM technology does not provide continuous monitoring but rather "remote snapshot clinics". On the other hand, pacemakers (PCM) and implantable cardiac defibrillators (ICD) are designed to work automatically and continuously without any need for immediate external intervention. Therefore, the guidelines recommend that the clinical response to RM notification will take place during the normal office hours. With appropriate organization, the utilization of RM will save a significant number of unnecessary pacemaker clinic visits and will allow better utilization of healthcare resources on patients in whom early intervention may prevent hospitalization, complication and mortality. The guidelines recommend offering RM to all patients with CIED. In Israel however, RM is offered sporadically only to a few patients. If a patient will suffer from delayed or inadequate treatment due to lack of RM, grave ethical and legal consequences may occur. Follow-up of CIED patients utilizing RM should be performed by a team including a primary physician, primary cardiologist, electrophysiologist, nurses and CIED technologist working in concert utilizing modern information technologies. Data should be shared electronically (with strict data security protocols) utilizing the electronic patient file with secure connection to RM systems. In summary, we believe that RM should be offered to all CIED patients in Israel.

CD5 positive B-ALL, a uniquely aggressive subcategory of B-ALL? A case report and brief review of the literature.

CD5 antigen expression in B-cell acute lymphoblastic leukemia (B-ALL) is exceptionally rare. There are six detailed case reports in the literature, with only 16 cases described. Case series analyzing the frequency of aberrant B-ALL immunophenotypes suggest that this variant may occur in as little as 2-4.5% of all B-ALL cases, with one series having no CD5+ positive cases. Herein we report a case of CD5+ B-ALL in a 15-year-old female, and review the previously reported cases. As limited information is available, more data from prospective clinical trials are required to determine whether CD5 positivity portends a poorer prognosis.

Management of chronic myeloid leukemia in the setting of pregnancy: when is leukocytapheresis appropriate? A case report and review of the literature.

BACKGROUND: Chronic myeloid leukemia (CML) is a common hematologic malignancy; however, its occurrence during pregnancy is unusual due to its low prevalence in females of childbearing age. There are conflicting reports of how to best manage CML in pregnancy, particularly in the setting of leukocytosis. HEMAPHERESIS: A 30-year-old female was diagnosed with CML at 18 weeks' estimated gestational age. On initial presentation she reported fatigue, night sweats, and early satiety, and was found to have a white blood cell (WBC) count of 69.3 × 109 /L and platelet count of 366 × 109 /L. Her disease was managed during pregnancy using interferon-α alone despite persistent leukocytosis. CONCLUSION: CML may be effectively managed during pregnancy, even in the setting of leukocytosis, without the application of leukocytapheresis. Management relies not only upon the coordination of drug therapy and fetal monitoring, but requires close communication between multiple medical disciplines. Leukocytapheresis has been safely performed during pregnancy and may be a suitable adjunct management strategy in pregnant patients diagnosed with CML with specific clinical presentations, such as hyperleukocytosis (WBC count > 150 × 109 /L) and/or symptomatic leukostasis.

Clinical Outcomes of Single- versus Dual-Chamber Implantable Cardioverter Defibrillators: Lessons from the Israeli ICD Registry.

OBJECTIVE: To compare the clinical outcomes of a single- versus dual-chamber ICD for primary prevention of sudden cardiac death in a large, national ICD registry. METHODS: Data were collected from the prospective Israeli ICD Registry. Baseline characteristics and clinical outcomes including mortality, admissions for heart failure (HF), and ICD therapy were compared between the two groups. RESULTS: A total of 1,125 subjects, 37% with a single-chamber and 63% with a dual-chamber ICD, constructed the baseline cohort. Approximately 80% had ischemic heart disease (IHD). Mean follow-up was 22 months, mean ejection fraction was 30%, and mean QRS width was 103 milliseconds in both groups. During follow-up, there were no significant differences in the rate of mortality, admissions for HF, appropriate or inappropriate therapy, or in time to any of the clinical outcomes. Using multivariate analysis, single-chamber ICD was not associated with increased risk of death or admission for HF. In a subgroup of patients with IHD, single-chamber ICD was associated with a higher rate of inappropriate therapy. CONCLUSIONS: In this large retrospective population-based cohort, dual-chamber ICD showed no benefit in reducing the incidence of death or HF admissions, whereas in a subgroup of patients with IHD, single-chamber ICD was associated with increased inappropriate therapy. Further prospective studies are necessary to assess the benefit of dual-chamber ICD in reducing the rate of inappropriate therapy.

Permanent pacing in nonagenarians over 20-year period.

INTRODUCTION: Life expectancy increases progressively and nonagenarians are a growing population. We report trends in pacing and long-term outcome in nonagenarians over a 20-year period in a single center compared with those of younger patients. METHODS: We retrospectively reviewed all the patients who underwent their first pacemaker implantation from January 1, 1991 to December 31, 2010 and were followed through December 31, 2013. RESULTS: During the study period, 1,009 patients underwent first pacemaker implantation: 45 patients were older than 90 years (mean age 92.5 ± 2.6) (4.5%); 21 were men. Battery replacement was performed in four patients in whom first implant was made at age ≥ 90 years (8.9%) and in 231 patients aged <90 (24%; P < 0.01). Syncope was the most common symptom leading to pacing, followed by dizziness and fatigue in all age groups; no significant difference of symptoms was found between patient age groups. In patients aged ≥ 90 atrioventricular block and atrial fibrillation with slow ventricular response were more frequent, while sick sinus syndrome and carotid sinus hypersensitivity were less frequent than in younger patients. Ventricular chamber pacemakers were implanted with significant growing frequency, according to the older patients' age. Neither the indication for pacemaker implantation nor pacing mode influenced survival. CONCLUSIONS: Nonagenarians are a growing population. Symptoms leading to pacing in patients aged ≥ 90 were similar to those of younger patients, but different frequency was found in the electrocardiographic indications. Ventricular chamber pacemakers were significantly more implanted than dual-chamber pacemakers but without negative survival influence.

[TRENDS OF PERMANENT PACEMAKER IMPLANTATION IN A SINGLE CENTER OVER A 20-YEAR PERIOD].

AIMS: To review the changes in permanent pacemaker implantation indications, pacing modes and patients' demographics over a 20-year period. METHODS AND RESULTS: We retrospectively retrieved data on patients who underwent first implantation of the pacemaker between 1-1-1991 and 31-12-2010. One thousand and nine (1,009) patients underwent a first pacemaker implantation during that period; 535 were men (53%), their mean age was 74.6±19.5 years; the highest rate of implanted pacemaker was in patients ranging in age from 70-79 years, however there was an increasing number of patients aged over 80 years. The median survival time after initial pacemaker implantation was 8 years. Syncope was the most common symptom (62.5%) and atrioventricular block was the most common electrocardiographic indication (56.4%) leading to pacemaker implantation. There was increased utilization of dual chamber and rate responsive pacemakers over the years. There was no difference regarding mode selection between genders. CONCLUSIONS: Pacemaker implantation rates have increased over a 20-year period. Dual chamber replaced most of the single ventricular chamber pacemaker and rate responsive pacemakers became the norm. The data of a small volume center are similar to those reported in pacemaker surveys of high volume pacemaker implantation centers. They confirm adherence to the published guidelines for pacing.

Permanent lone atrial fibrillation and atrioventricular valve regurgitation: may the former lead to the latter?

BACKGROUND AND AIM OF THE STUDY: Atrioventricular valve regurgitation (AVVR) has been described in patients with long-standing atrial fibrillation (AF) despite normal valve anatomy and leaflet mobility. The study aim was to examine the association between permanent lone AF and AVVR. METHODS: A total of 47 patients with lone AF was studied. Patients provided information regarding the time since onset of arrhythmia, and mitral regurgitation (MR) and tricuspid regurgitation (TR) were graded using color-mapping Doppler echocardiography. AVVR was defined as any degree of valve regurgitation. Annular diameters (in mm) and atrial areas (in cm2) were measured at enddiastole, using digital analysis. RESULTS: Of the 47 patients, 19 (40%) had paroxysmal AF and 28 (60%) had permanent AF. Mild MR was present in nine of 19 patients (47%) with paroxysmal AF and in 15 of 28 (53%) with permanent AF (p = 0.68). Mild TR was identified in nine (47%) patients with paroxysmal AF, and in 16 (58%) of those with permanent AF (p = 0.08). None of the patients with paroxysmal AF had either moderate or severe AVVR. In 28 patients with permanent lone AF, significant MR and TR were detected in six (21%) and five (19%) patients, respectively. Patients with permanent lone AF had a 6.5-fold higher likelihood of having TR (p = 0.0031) and were marginally more likely to have MR (p = 0.053) compared to those with paroxysmal AF. Relative to patients with paroxysmal AF, those with permanent AF had larger atrial areas and annular diameters, while patients with TR had higher atrial areas and mitral annular diameters than those without. The mean follow up of patients with permanent AF and significant AVVR was 54 + 13 months, compared to 13 +/- 7 months for those without significant AVVR (p = 0.002). CONCLUSION: Permanent lone AF is associated with TR and, less strongly, with MR. Atrial size and mitral annular diameter are increased in patients with lone AF who have TR.

Photonic nanojets generated using square-profile microsteps.

We have shown experimentally that square-profile microsteps on a silica substrate, with square sides of 0.4, 0.5, 0.6, and 0.8 µm and height of 500 nm, illuminated through the substrate by a linearly polarized laser beam of wavelength λ=633 nm, produce, near the surface, enhanced-intensity regions (termed photonic nanojects), with their intensity being six times higher than that of the incident light and their respective full width at half-maximum diameters being 0.44λ, 0.43λ, 0.39λ, and 0.47λ, which is below the diffraction limit of 0.51λ. It is worth noting that when the step side is smaller than the wavelength, the focus is found within the step; otherwise the focus is outside the step, which is similar to an optical candle.

Axillary vein puncture without contrast venography for pacemaker and defibrillator leads implantation.

BACKGROUND: Axillary vein puncture has been demonstrated to be an effective method for pacemaker and defibrillator leads implantation, without the complications encountered with the standard intrathoracic approach. OBJECTIVE: Different techniques have been adopted for the cannulation of the axillary vein. We report our experience using the outer edge of the first rib below the inferior border of the clavicle as fluoroscopic landmark. METHOD: A subcutaneous pocket is created 1-cm medially and parallel to the delto-pectoral groove and 2 cm below the clavicle. An 18-gauge needle from the upper border of the pocket is directed perpendicularly to the outer edge of the first rib just below the inferior border of the clavicle. If the vein is not entered, the needle is withdrawn and the puncture is repeated with slight variations of needle direction for a maximum of four to five times, then contrast-guided vein puncture is performed. Upon successful vein puncture, a guidewire is inserted and positioned in the superior vena cava. The remainder of the implantation is carried out in a routine manner. RESULTS: The axillary vein was successfully cannulated without venography in 172 of 182 consecutive patients (94.5%); the vein could not be found in 10 patients (5.5%): in these patients the vein was successfully cannulated after venography performance. No pneumothorax, hemothorax, or brachial plexus injury occurred. CONCLUSIONS: Our approach of axillary venipunture using fluoroscopic landmark, without contrast venography, is simple, safe, and effective.

Accumulation of pTau231 at the Postsynaptic Density in Early Alzheimer's Disease.

BACKGROUND: Phosphorylated cytoplasmic tau inclusions correlate with and precede cognitive deficits in Alzheimer's disease (AD). However, pathological tau accumulation and relationships to synaptic changes remain unclear. OBJECTIVE: To address this, we examined postmortem brain from 50 individuals with the full spectrum of AD (clinically and neuropathologically). Total tau, pTau231, and AMPA GluR1 were compared across two brain regions (entorhinal and middle frontal cortices), as well as clinically stratified groups (control, amnestic mild cognitive impairment, AD dementia), NIA-AA Alzheimer's Disease Neuropathologic Change designations (Not, Low, Intermediate, High), and Braak tangle stages (1-6). Significant co-existing pathology was excluded to isolate changes attributed to pathologic AD. METHODS: Synaptosomal fractionation and staining were performed to measure changes in total Tau, pTau231, and AMPA GluR1. Total Tau and pTau231 were quantified in synaptosomal fractions using Quanterix Simoa HD-X. RESULTS: Increasing pTau231 in frontal postsynaptic fractions correlated positively with increasing clinical and neuropathological AD severity. Frontal cortex is representative of early AD, as it does not become involved by tau tangles until late in AD. Entorhinal total tau was significantly higher in the amnestic mild cognitive impairment group when compared to AD, but only after accounting for AD associated synaptic changes. Alterations in AMPA GluR1 observed in the entorhinal cortex, but not middle frontal cortex, suggest that pTau231 mislocalization and aggregation in postsynaptic structures may impair glutamatergic signaling by promoting AMPA receptor dephosphorylation and internalization. CONCLUSION: Results highlight the potential effectiveness of early pharmacological interventions targeting pTau231 accumulation at the postsynaptic density.

Acute pericardial tamponade due to screw-in atrial lead heart perforation.

A case of peri-procedural perforation of right atrium following the implantation of atrial screw-in lead in a 74-year-old man is reported. The perforation caused acute pericardial tamponade and worsening of the patient's clinical and haemodynamic conditions. Urgent surgical intervention with lead extraction was performed.

Mild rheumatic mitral regurgitation in the presence of dominant stenotic pliable valve: an echocardiographic structural valve analysis in patients undergoing balloon valvuloplasty.

BACKGROUND: Understanding the mechanism and the main components involved in rheumatic mitral regurgitation (MR) associated with dominant pliable mitral stenosis (MS) may improve our ability to repair some mixed rheumatic mitral valve pathologies. OBJECTIVES: To assess mitral valve structural components in pure mitral stenosis versus mitral stenosis associated with mild regurgitation METHODS: Using two-dimensional echocardiography, we performed mitral valve structural analysis in two groups of patients prior to balloon mitral valvuloplasty (BMV). The first group, consisting of 13 females and 2 males (mean age 39 +/- 5 years), suffered from pure pliable mitral stenosis (PPMS), while the second group, with 22 females and 2 males (mean age 44 +/- 5 years), had mixed mitral valve disease (MMVD) characterized by mild MR in the presence of dominant pliable MS. All echocardiographic measurements relating to the mechanism of MR were undertaken during the systolic phase. RESULTS: The mean Wilkins scores of the PPMS and MMVD groups were 7 +/- 1 and 8 +/- 1 respectively (P = 0.004). No significant differences were found between the MMVD group and the PPMS group regarding annular circumference (15.5 +/- 1.4 cm vs. 15.4 +/- 1.6cm, P = 0.84), annular diameter (36 +/- 4 mm vs. 38 +/- 5 mm, P = 0.18), and chordae tendinae length directed to the anterior mitral leaflet (AML) (10 +/- 2 mm vs. 11 +/- 2 mm, P = 0.137). However, anterior vs. posterior mitral leaflet length during systole was significantly lower in the MMVD than in the PPMS group (2.2 +/- 0.5 vs. 2.8 +/- 0.4, P = 0.02), whereas the AML thickness at the co-aptation point was greater in the MMVD than in the PPMS group (7 +/- 1 vs. 5 +/- 1 mm, P = 0.0004). CONCLUSIONS: In rheumatic valves, thickening and shortening of the AML are the main factors determining the appearance of mild MR in the presence of dominant pliable MS.

Alternate site right ventricular pacing: defining template scoring.

BACKGROUND: Prolonged right ventricular (RV) apical pacing produces dysynchronous ventricular contraction, which may result in left ventricular (LV) dysfunction, whereas septal pacing sites might reflect a more synchronous LV activation. This study examined a method of evaluating alternate RV pacing sites using a template scoring system based on measuring the angle of lead attachment in the 40° left anterior oblique (LAO) fluoroscopic view and its effect on altering the loop of lead in the RV. METHODS: Twenty-three consecutive patients for RV pacing were enrolled. Conventional active fixation leads were positioned in either the RV outflow tract (RVOT) or mid RV using a stylet designed for septal placement (Model 4140, St. Jude Medical, St. Paul, MN, USA). Using LAO cine fluoroscopy, a generous loop of lead was inserted into the RV chamber and the change in angle of attachment determined. RESULTS: Successful positioning of pacing leads at the RVOT septum (18 patients) and mid-RV septum (five patients) was achieved. With introduction of more lead into the RV chamber, the angle of attachment in the LAO projection altered over a range of 6°-32° for all patients with a mean of 14.6 ± 6.6°. In 87% of patients, the range was predominantly within the same template score with only minor overlap into another zone. CONCLUSIONS: This study shows that the angle of lead attachment in the RV is altered by introducing more lead, but in most cases, the template score remains the same. Further studies are required to determine the accuracy and efficacy of the templates.

Predictors of acute and long-term success of slow pathway ablation for atrioventricular nodal reentrant tachycardia: a single center series of 1,419 consecutive patients.

BACKGROUND: Atrioventricular nodal reentrant tachycardia (AVNRT) is the most common mechanism of supraventricular tachycardia. Slow pathway (SP) ablation is the first-line treatment approach with a high acute success rate and a low risk of inadvertent complete atrioventricular (AV) block. However, there is still some uncertainty as to the most appropriate procedural endpoints and the impact of these on risk of recurrence. We report the acute and long-term results of SP ablation in a large single-center consecutive series and analyze predictors of acute success and late recurrence. METHODS: The study included 1,448 consecutive procedures in 1,419 patients with AVNRT (mean age 49 ± 17 years, 66% women) who underwent SP ablation using a combined electrophysiologic and anatomic approach. Univariate and multivariate analysis was performed for potential predictors of acute success and late recurrence. RESULTS: Acute success was achieved in 98.1%. Transient (first, second, or third degree) AV block occurred during the procedure in 20 (1.41%) patients. One patient (0.07%) had persistent first-degree and transient second-degree AV block after ablation and underwent pacemaker implant at day 21. Of the 1,391 patients with successful ablation, 22 patients (1.5%) developed AVNRT recurrence during a follow-up period of 63 ± 38 months. The only independent predictor of reduced procedural success was the presence of atypical AVNRT (hazard ratio 3.1, P = 0.04). Independent predictors of AVNRT recurrence were age <20 years and female gender (hazard ratios 14.1 and 3.7, respectively). No significant difference in the incidence of late recurrence was observed in patients with or without residual slow-pathway conduction, or according to use of isoproterenol testing or general anesthesia. However, patients with a single echo with recurrence had a significantly larger echo window (median 85 ms) than those without (median 30 ms, P = 0.01). CONCLUSIONS: This study demonstrates in a large consecutive single-center series that SP ablation using radiofrequency energy is a highly effective procedure with an extremely low risk of inadvertent AV block and a low recurrence rate. We found that single-AV nodal echo beats represented a procedural endpoint that did not predict AVNRT recurrence but that a large echo window is associated with recurrence. Recurrence rates in this series were higher in young women, possibly reflecting a more conservative approach to ablation in this age group.