Non-oral manifestations in adults with a clinical and molecularly confirmed diagnosis of periodontal Ehlers-Danlos syndrome.

Introduction: Periodontal Ehlers-Danlos Syndrome (pEDS) is a rare autosomal dominant type of EDS characterised by severe early-onset periodontitis, lack of attached gingiva, pretibial plaques, joint hypermobility and skin hyperextensibility as per the 2017 International EDS Classification. In 2016, deleterious pathogenic heterozygous variants were identified in C1R and C1S, which encode components of the complement system. Materials and Methods: Individuals with a clinical suspicion of pEDS were clinically and molecularly assessed through the National EDS Service in London and Sheffield and in genetic services in Austria, Sweden and Australia. Transmission electron microscopy and fibroblast studies were performed in a small subset of patients. Results: A total of 21 adults from 12 families were clinically and molecularly diagnosed with pEDS, with C1R variants in all families. The age at molecular diagnosis ranged from 21-73 years (mean 45 years), male: female ratio 5:16. Features of easy bruising (90%), pretibial plaques (81%), skin fragility (71%), joint hypermobility (24%) and vocal changes (38%) were identified as well as leukodystrophy in 89% of those imaged. Discussion: This cohort highlights the clinical features of pEDS in adults and contributes several important additional clinical features as well as novel deleterious variants to current knowledge. Hypothetical pathogenic mechanisms which may help to progress understanding and management of pEDS are also discussed.

Total annulus excision tympanoplasty - a solution to recurrent myringitis: double blind randomised trial.

OBJECTIVE: In spite of continuous refinements in tympanoplasty techniques, results are variable, and it is not uncommon to see a discharging eardrum even after a good graft uptake. This study aimed to evaluate the efficacy of total annulus excision tympanoplasty in comparison with conventional underlay tympanoplasty. METHOD: This was a double blinded, randomised, controlled trial performed at a tertiary care centre. After inclusion and exclusion criteria were met, 56 patients were enrolled and randomised, and 28 patients were allocated to each group (group A (conventional tympanoplasty) and group B (total annulus excision)). Patients and evaluators were blind to the procedure performed. RESULTS: Patients in group B (total annulus excision) showed better graft uptake and no discharge with better gains in air conduction thresholds (p < 0.05) when compared with group A (conventional tympanoplasty). CONCLUSION: In view of the advantages it offers, total annulus excision tympanoplasty may be preferred over the conventional techniques in patients with central perforations.

NeuroThera® Efficacy and Safety Trial-3 (NEST-3): a double-blind, randomized, sham-controlled, parallel group, multicenter, pivotal study to assess the safety and efficacy of transcranial laser therapy with the NeuroThera® Laser System for the treatment of acute ischemic stroke within 24 h of stroke onset.

RATIONALE: Transcranial laser therapy is undergoing clinical trials in patients with acute ischemic stroke. The NeuroThera® Efficacy and Safety Trial-1 was strongly positive for 90-day functional benefit with transcranial laser therapy, and post hoc analyses of the subsequent NeuroThera® Efficacy and Safety Trial-2 trial suggested a meaningful beneficial effect in patients with moderate to moderately severe ischemic stroke within 24 h of onset. These served as the basis for the NeuroThera® Efficacy and Safety Trial-3 randomized controlled trial. AIM: The purpose of this pivotal study was to demonstrate safety and efficacy of transcranial laser therapy with the NeuroThera® Laser System in the treatment of subjects diagnosed with acute ischemic stroke. DESIGN: NeuroThera® Efficacy and Safety Trial-3 is a double-blind, randomized, sham-controlled, parallel group, multicenter, pivotal study that will enroll 1000 subjects at up to 50 sites. All subjects will receive standard medical management based on the American Stroke Association and European Stroke Organization Guidelines. In addition to standard medical management, both groups will undergo the transcranial laser therapy procedure between 4·5 and 24 h of stroke onset. The study population will be randomized into two arms: the sham control group will receive a sham transcranial laser therapy procedure and the transcranial laser therapy group will receive an active transcranial laser therapy procedure. The randomization ratio will be 1:1 and will be stratified to ensure a balanced subject distribution between study arms. STUDY OUTCOMES: The primary efficacy end point is disability at 90 days (or the last rating), as assessed on the modified Rankin Scale, dichotomized as a success (a score of 0-2) or a failure (a score of 3 to 6).

Magnetic versus manual guidewire manipulation in neuroradiology: in vitro results.

INTRODUCTION: Standard microguidewires used in interventional neuroradiology have a predefined shape of the tip that cannot be changed while the guidewire is in the vessel. We evaluated a novel magnetic navigation system (MNS) that generates a magnetic field to control the deflection of a microguidewire that can be used to reshape the guidewire tip in vivo without removing the wire from the body, thereby potentially facilitating navigation along tortuous paths or multiple acute curves. METHOD: The MNS consists of two permanent magnets positioned on either side of the fluoroscopy table that create a constant precisely controlled magnetic field in the defined region of interest. This field enables omnidirectional rotation of a 0.014-inch magnetic microguidewire (MG). Speed of navigation, accuracy in a tortuous vessel anatomy and the potential for navigating into in vitro aneurysms were tested by four investigators with differing experience in neurointervention and compared to navigation with a standard, manually controlled microguidewire (SG). RESULTS: Navigation using MG was faster (P=0.0056) and more accurate (0.2 mistakes per trial vs. 2.6 mistakes per trial) only in less-experienced investigators. There were no statistically significant differences between the MG and the SG in the hands of experienced investigators. One aneurysm with an acute angulation from the carrier vessel could be navigated only with the MG while the SG failed, even after multiple reshaping manoeuvres. CONCLUSION: Our findings suggest that magnetic navigation seems to be easier, more accurate and faster in the hands of less-experienced investigators. We consider that the features of the MNS may improve the efficacy and safety of challenging neurointerventional procedures.

Nesiritide use for critically ill children awaiting cardiac transplantation.

BACKGROUND: This study aimed to explore the effects of nesiritide in children awaiting cardiac transplantation. METHODS: At the discretion of the attending physician, nesiritide was added to standard therapy for seven children (median age, 11 months) and continued until clinical improvement or transplantation. Blood pressure and urine output data were compared with data from the day before nesiritide institution. Safety parameters were assessed throughout the study. RESULTS: Urine output increased from 2.6 to 3.6 ml/kg/h (p = 0.04). No significant blood pressure changes or adverse effects related to nesiritide were noted. CONCLUSION: Nesiritide may be safe and effective for children with severe heart failure.

Atrial tachycardia masquerading as atrial flutter following ablation of the subeustachian isthmus.

We report a case of atrial tachycardia masquerading as atrial flutter in a man who had previously undergone catheter ablation for atrial flutter. The recurrent arrhythmia was electrocardiographically almost identical to the prior atrial flutter; at repeat electrophysiologic study, although bidirectional conduction block was observed in the tricuspid annulus-inferior vena caval isthmus, the atrial arrhythmia was readily initiated. Activation mapping suggested typical atrial flutter, but entrainment techniques demonstrated intra-atrial reentry not involving the ablated isthmus. This case illustrates the need to apply entrainment techniques even in cases of apparent "typical" atrial flutter to confirm that putative ablation targets are necessary for tachycardia perpetuation.

Effect of radiofrequency catheter ablation of accessory pathways on autonomic tone in children.

BACKGROUND: Radiofrequency catheter ablation is standard treatment for children with re-entrant supraventricular tachycardias. Autonomic changes have been noted after such ablation for atrioventricular nodal re-entry tachycardia, but not as well documented with atrioventricular re-entry over an accessory pathway. METHODS AND RESULTS: In 10 normal paediatric volunteers and 12 children referred for electrophysiologic testing and radiofrequency ablation of supraventricular tachycardia, non-invasive autonomic function tests and tilt-table testing were performed, and the variability in 24-h heart rate was analysed. Patients with supraventricular tachycardia underwent these tests both 24-72 h before and 24 h after ablation. Patients with tachycardia underwent additional autonomic testing to assess the sensitivity of baroreceptors and the intrinsic heart rate with autonomic blockade immediately before and after ablation. One non-invasive autonomic function test, namely handgrip, demonstrated significant differences (p < 0.05) in diastolic blood pressure before and after ablation, though these values did not differ from controls. Significant decreases were noted in two indexes of the variability of heart rate before and after ablation (p < 0.05). Certain tilt test variables also demonstrated significant differences between controls and those with tachycardia subsequent to ablation. Intracardiac testing demonstrated changes (p < 0.05) in sinus cycle lengths, effective refractory periods and/or blood pressures at baseline and during testing of the sensitivity of baroreceptors before and after ablation. These changes were consistent with increased sympathetic or decreased parasympathetic tone. With autonomic blockade, these differences were abolished. CONCLUSIONS: Catheter ablation of accessory pathways in children was associated with changes consistent with increased sympathetic or decreased parasympathetic tone. These autonomic changes persisted 24 h after the ablation procedure.

Autonomic changes and heart rate variability in children with neurocardiac syncope.

This study evaluated resting autonomic function and autonomic responses to head-up tilt-table testing in children who experienced neurocardiac syncope to determine whether predictable differences existed between these patients and normal volunteers. Neurocardiac syncope is a common cause of syncope in children. The mechanism, though related to abnormalities in autonomic function, has not been fully elucidated, particularly in pediatric patients. This study evaluated resting autonomic tone using noninvasive autonomic function tests (i.e., Valsalva, handgrip, and deep breathing) and 24-hour heart rate variability (HRV). In addition, heart rate and blood pressure were evaluated during head-up tilt examination. Values from patients who experienced neurocardiac syncope were compared to those from age-matched normal volunteers. No significant differences were noted during noninvasive testing. Some time domain HRV variables demonstrated a trend toward significant difference (p < 0.10). Tilt testing data were significantly different in sinus beat to sinus beat (RR) intervals between controls and syncope patients at 2, 5, and 10 minutes after tilting. In addition, significant differences were noted in RR interval and the standard deviation of RR interval 1 or 2 minutes prior to syncope when compared to controls at 5 and 10 minutes after tilting. Children with syncope exhibited abnormalities during tilt testing indicating an increased sympathetic or decreased parasympathetic tone, particularly prior to syncope. Some measures of HRV might constitute noninvasive parameters that correlate with the positive tilt table test.

Persistent eustachian valves in infants: course and management in symptomatic patients.

Although commonly found on echocardiograms, persistent Eustachian valves rarely result in clinical symptoms in newborns and infants without other significant structural heart disease. Previous reports have suggested that such patients require surgical treatment. The goal of this study is to delineate better the clinical course in infants presenting with symptoms that are a result of persistent Eustachian valves. A review of all patients with symptoms attributed to persistent Eustachian valves over a 10-year period at Riley Hospital for Children showed 3 of 4 patients improved, with eventual resolution of symptoms, with conservative management alone. This suggests that, contrary to previous reports, clinical observation may be warranted in many of these infants.