...the hypothesis of an autoimmune etiology was supported by association with a polymorphism in the T cell receptor alpha locus, involved in the HLA-peptide presentation, and with a polymorphism of ...the T cell and natural killer P2RY11 receptor, involved in the regulation of immune-cell survival 61,62. ...patients with recent onset narcolepsy showed elevated anti-streptolysin-O titers, suggesting recent streptococcal infections 63, and increased titers of antibodies against Tribbles homolog 2, an intracellular and membrane protein enriched in hypocretin neurons, were detected in a small but significant proportion of recent onset narcolepsy patients 64. Note: cataplexy in children may or may not be triggered by 'emotional' circumstances (e.g., watching funny cartoons, eating certain foods, playing games or video-games) NOT - partial or generalized seizure OR - neuromuscular disorders - any other known explanation d 4 or 5 nap MSLT performed according to the American Academy of Sleep Medicine (AASM) protocol 101 eExclusion of other conditions The following conditions must be clinically/instrumentally assessed, since they could either mimic one or more narcolepsy symptoms (mainly excessive daytime sleepiness) or constitute co-morbidities with narcolepsy: - other sleep disorders, according to ICSD-2 criteria: - sleep related disorder breathing - behaviorally induced insufficient sleep - circadian rhythm disorders - recurrent hypersomnias secondary to medical or psychiatric conditions - use of sedating medication and antidepressants - focal cerebral lesions, indicated by neurological examination and/or brain imaging
BackgroundNeurocardiogenic syncope is a common condition with significant associated psychological and physical morbidity. The effectiveness of therapeutic options for neurocardiogenic syncope beyond ...placebo remains uncertain.MethodsThe primary endpoint was the risk ratio (RR) of spontaneously recurring syncope following any therapeutic intervention. We also examined the effect of blinding on treatment efficacy. We identified all randomised trials which evaluated the effect of any pharmacological, device-based or supportive intervention on patients with a history of syncope. A systematic search was conducted on Medline, Embase, PubMed databases and Cochrane Central Register for Controlled Trials from 1950 to 25 April 2023. Event rates, their RRs and 95% CIs were calculated, and a random-effects meta-analysis was conducted for each intervention. Data analysis was performed in R using RStudio.ResultsWe identified 47 eligible trials randomising 3518 patients. Blinded trials assessing syncope recurrence were neutral for beta blockers, fludrocortisone and conventional dual-chamber pacing but were favourable for selective serotonin reuptake inhibitors (SSRIs) (RR 0.40, 95% CI 0.26 to 0.63, p<0.001), midodrine (RR 0.70, 95% CI 0.53 to 0.94, p=0.016) and closed-loop stimulation (CLS) pacing (RR 0.15, 95% CI 0.07 to 0.35, p<0.001). Unblinded trials reported significant benefits for all therapy categories other than beta blockers and consistently showed larger benefits than blinded trials.ConclusionsUnder blinded conditions, SSRIs, midodrine and CLS pacing significantly reduced syncope recurrence. Future trials for syncope should be blinded to avoid overestimating treatment effects.PROSPERO registration numberCRD42022330148.
His-bundle pacing (HBP) has emerged as an alternative to conventional ventricular pacing because of its ability to deliver physiological ventricular activation. Pacing at the His bundle produces ...different electrocardiographic (ECG) responses: selective His-bundle pacing (S-HBP), non-selective His bundle pacing (NS-HBP), and myocardium-only capture (MOC). These 3 capture types must be distinguished from each other, which can be challenging and time-consuming even for experts.
The purpose of this study was to use artificial intelligence (AI) in the form of supervised machine learning using a convolutional neural network (CNN) to automate HBP ECG interpretation.
We identified patients who had undergone HBP and extracted raw 12-lead ECG data during S-HBP, NS-HBP, and MOC. A CNN was trained, using 3-fold cross-validation, on 75% of the segmented QRS complexes labeled with their capture type. The remaining 25% was kept aside as a testing dataset.
The CNN was trained with 1297 QRS complexes from 59 patients. Cohen kappa for the neural network’s performance on the 17-patient testing set was 0.59 (95% confidence interval 0.30 to 0.88; P <.0001), with an overall accuracy of 75%. The CNN’s accuracy in the 17-patient testing set was 67% for S-HBP, 71% for NS-HBP, and 84% for MOC.
We demonstrated proof of concept that a neural network can be trained to automate discrimination between HBP ECG responses. When a larger dataset is trained to higher accuracy, automated AI ECG analysis could facilitate HBP implantation and follow-up and prevent complications resulting from incorrect HBP ECG analysis.
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The prognostic impact of ventricular tachycardia (VT) catheter ablation is an important outstanding research question. We undertook a reconstructed individual patient data meta-analysis of randomised ...controlled trials comparing ablation to medical therapy in patients developing VT after MI.
We systematically identified all trials comparing catheter ablation to medical therapy in patients with VT and prior MI. The prespecified primary endpoint was reconstructed individual patient assessment of all-cause mortality. Prespecified secondary endpoints included trial-level assessment of all-cause mortality, VT recurrence or defibrillator shocks and all-cause hospitalisations. Prespecified subgroup analysis was performed for ablation approaches involving only substrate modification without VT activation mapping. Sensitivity analyses were performed depending on the proportion of patients with prior MI included.
Eight trials, recruiting a total of 874 patients, were included. Of these 874 patients, 430 were randomised to catheter ablation and 444 were randomised to medical therapy. Catheter ablation reduced all-cause mortality compared with medical therapy when synthesising individual patient data (HR 0.63; 95% CI 0.41-0.96; p=0.03), but not in trial-level analysis (RR 0.91; 95% CI 0.67-1.23; p=0.53; I
=0%). Catheter ablation significantly reduced VT recurrence, defibrillator shocks and hospitalisations compared with medical therapy. Sensitivity analyses were consistent with the primary analyses.
In patients with postinfarct VT, catheter ablation reduces mortality.
Background Choroid plexus tumors (CPT) are rare pediatric tumors. A population-based study on choroid plexus carcinoma (CPC) and choroid plexus papilloma (CPP) was carried out to describe the ...incidence, demographic, and outcome data and to identify potential prognostic factors. Methods The CPT population from the Canadian databank of CNS tumor in children ≤36 months diagnosed between 1990 and 2005 was reviewed Results Out of the 579 reported cases of CNS tumors, 37 were CPT. The annual age-adjusted incidence rate was 0.22 + 0.12 (95% CI 0.16-0.28)/100,000 children <3 years. There were 21 (56.7%) CPP and 16 (43.3.5%) CPC. Twenty patients (54%) were males. Median age at diagnosis was 7 months(range 0-30). Ten patients(62.5%) with CPC and one with CPP were metastatic at diagnosis. Twenty patients with CPP (95%) had a complete resection, whereas 6/16 CPC (37.5%) achieved a resection >90%. Fourteen CPC patients received adjuvant chemotherapy. None of the 37 patients received adjuvant radiation. At completion of survey, all CPP and five CPC were alive. Median survival time for CPC patients was 15 months (0-120). One death was related to intraoperative hemorrhage, another to chemotherapy-induced toxicity, and one to secondary AML. Age at diagnosis, degree of resection and metastatic status were not significant prognostic factors for CPC. Conclusion By contrast to CPC, CPP have an excellent prognosis following surgery alone. Survival of CPC remains poor. However, these data may suggest adjuvant chemotherapy can alter the aggressive natural history of CPC. As with other rare CNS tumors, international collaboration is required to identify optimal therapy.
Introduction
Supratentorial primitive neuroectodermal tumors (SPNET) are rare tumors accounting for only 2.5% of childhood brain tumors. The purpose of this study was to describe the range of ...treatment regimens used to treat pediatric SPNET in Canada and to identify prognostic factors for overall survival in this population.
Methods
This study was a retrospective clinical analysis of SPNET patients treated over the last 10 years in Canada. A questionnaire was developed and distributed to all institutions in Canada who treat pediatric patients. Data were collected for patients <19 years of age who were diagnosed and treated for SPNET between 1995 and 2005.
Results
Data were obtained for 48 eligible patients. The stages of patients for whom complete data were provided were 80, 3, and 16% for metastatic stage M0, M1, and M2/3, respectively. The best responses to therapy included complete response in 44%, partial response in 8%, still on therapy in 2%, progressive disease in 31%, toxic death in 2%, and no therapy given in 12%. The 4-year survival was 37.7 ± 7.6%. The factors associated with an increase in survival were the use of radiation therapy and chemotherapy, and age >2 years. Overall survival was not affected by metastatic disease at diagnosis, tumor site, or degree of initial resection.
Conclusions
Survival is poor in SPNET patients but highest in those who received chemotherapy and radiation therapy. Further studies are needed to improve the survival of these patients.
Cerebral vascular disease has been reported as a long-term complication of cranial radiotherapy. The purpose of this study was to examine the frequency and risk factors associated with development of ...cerebral vascular disease in children after cranial radiation.
A retrospective chart review of all cancer patients treated between 1985 and 2003 who were under the age of 18 years at the time of initial radiotherapy was performed. Variables examined include diagnosis and site of malignancy, age at the time of radiotherapy, sex, total radiation dosage, number of fractions, duration, and whether the patient had proven cerebral vascular event.
Two hundred and forty-four patients met the study criteria. One hundred and 13 cases involved tumors of the central nervous system. The remaining patients had systemic neoplastic disease. Post radiation cerebral vascular disease occurred in 11 (5%) patients, and all but one patient had a tumor involving the central nervous system (mainly in the posterior fossa and supratentorial midline).
There is an increased risk of cerebral vascular disease after radiation therapy in childhood, especially in children who received high dose radiation at the posterior fossa and supratentorial axial region.
The purpose of this study was to examine cognitive functioning and neuroimaging in children with leukemia treated with the Pediatric Oncology Group 9605 protocol at the Children's Hospital of Eastern ...Ontario. Mean age at diagnosis was 4.88 ± 2.54 years. The mean (n = 24) Wechsler Verbal and Performance IQ fell in the low-average range (87.33 ± 15.69 and 84.83 ± 19.11, respectively). Mean (n = 20) Verbal and Visual Memory Indexes of 82.95 ± 15.46 and 88.30± 10.80, respectively, were obtained. The proportion of scores on measures of intelligence and memory falling > 1 SD below the normative mean was substantially higher than expected. Paired t-test suggested that Wechsler Verbal IQ and memory remained stable, whereas Wechsler Performance IQ declined significantly. The results of growth curve analyses replicated these findings and suggested a significant adverse effect of cumulative dosage of intrathecal methotrexate on estimated Wechsler Performance IQ. Although only two children experienced seizures, 78% of the group showed leukoencephalopathy on at least one magnetic resonance image. Reliance on seizures as a predictor of leukoencephalopathy might underestimate the incidence of neurotoxicity. (J Child Neurol 2005;20:129—133).
Catheter-based renal denervation has significantly reduced blood pressure in previous studies. Following a positive pilot trial, the SPYRAL HTN-OFF MED (SPYRAL Pivotal) trial was designed to assess ...the efficacy of renal denervation in the absence of antihypertensive medications.
In this international, prospective, single-blinded, sham-controlled trial, done at 44 study sites in Australia, Austria, Canada, Germany, Greece, Ireland, Japan, the UK, and the USA, hypertensive patients with office systolic blood pressure of 150 mm Hg to less than 180 mm Hg were randomly assigned 1:1 to either a renal denervation or sham procedure. The primary efficacy endpoint was baseline-adjusted change in 24-h systolic blood pressure and the secondary efficacy endpoint was baseline-adjusted change in office systolic blood pressure from baseline to 3 months after the procedure. We used a Bayesian design with an informative prior, so the primary analysis combines evidence from the pilot and Pivotal trials. The primary efficacy and safety analyses were done in the intention-to-treat population. This trial is registered at ClinicalTrials.gov, NCT02439749.
From June 25, 2015, to Oct 15, 2019, 331 patients were randomly assigned to either renal denervation (n=166) or a sham procedure (n=165). The primary and secondary efficacy endpoints were met, with posterior probability of superiority more than 0·999 for both. The treatment difference between the two groups for 24-h systolic blood pressure was −3·9 mm Hg (Bayesian 95% credible interval −6·2 to −1·6) and for office systolic blood pressure the difference was −6·5 mm Hg (−9·6 to −3·5). No major device-related or procedural-related safety events occurred up to 3 months.
SPYRAL Pivotal showed the superiority of catheter-based renal denervation compared with a sham procedure to safely lower blood pressure in the absence of antihypertensive medications.
Medtronic.
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