A homozygous mutation in the NDUFS1 gene presents with a mild cavitating leukoencephalopathy

We report a case of mild cavitating leukoencephalopathy associated with a homozygous c.755A > G (p.Asp252Gly) NDUFS1 mutation in a 7-year old boy. Biochemical analysis confirmed an isolated reduction in complex I activity. Magnetic resonance imaging of the brain showed a diffuse cystic leukoencephalopathy with the involvement of the corpus callosum and sparing of the gray matter. The clinical course was marked by an acute presentation of neurological deficits at 24 months followed by recurrent episodes of mild neurological deterioration, subsequent remissions, and prolonged periods of stability. This is one of the mildest known clinical presentations of complex I deficiency secondary to mutations in NDUFS1, expanding the clinical spectrum and natural history of this disorder. Consideration of clinical variability needs to be taken into account in patient management and family counseling.     

Patient subgroup analyses of the treatment effect of subcutaneous interferon β-1a on development of multiple sclerosis in the randomized controlled REFLEX study

The REFLEX study (NCT00404352) established that subcutaneous (sc) interferon (IFN) β-1a reduced the risks of McDonald MS (2005 criteria) and clinically definite multiple sclerosis (CDMS) in patients with a first clinical demyelinating event suggestive of MS. The aim of this subgroup analysis was to assess the treatment effect of sc IFN β-1a in patient subgroups defined by baseline disease and demographic characteristics (age, sex, use of steroids at the first event, classification of first event as mono- or multifocal, presence/absence of gadolinium-enhancing lesions, count of <9 or ≥9 T2 lesions), and by diagnosis of MS using the revised McDonald 2010 MS criteria. Patients were randomized to the serum-free formulation of IFN β-1a, 44 μg sc three times weekly or once weekly, or placebo, for 24 months or until diagnosis of CDMS. Treatment effects of sc IFN β-1a on McDonald 2005 MS and CDMS in the predefined subgroups were similar to effects found in the intent-to-treat population. McDonald 2010 MS was retrospectively diagnosed in 37.7 % of patients at baseline. Both regimens of sc IFN β-1a significantly reduced the risk versus placebo of McDonald 2005 MS and CDMS, irrespective of McDonald 2010 status at baseline (risk reductions between 29 and 51 %). The effect of sc IFN β-1a was not substantially influenced by baseline patient demographic and disease characteristics, or baseline presence/absence of McDonald 2010 MS.     

Optimizing study design for interobserver reliability: IUGA–ICS classification of complications of prostheses and graft insertion

Introduction and hypothesis

Results of interobserver reliability studies for the International Urogynecological Association–International Continence Society (IUGA-ICS) Complication Classification coding can be greatly influenced by study design factors such as participant instruction, motivation, and test-question clarity. We attempted to optimize these factors.

Methods

After a 15-min instructional lecture with eight clinical case examples (including images) and with classification/coding charts available, those clinicians attending an IUGA Surgical Complications workshop were presented with eight similar-style test cases over 10 min and asked to code them using the Category, Time and Site classification. Answers were compared to predetermined correct codes obtained by five instigators of the IUGA-ICS prostheses and grafts complications classification. Prelecture and postquiz participant confidence levels using a five-step Likert scale were assessed.

Results

Complete sets of answers to the questions (24 codings) were provided by 34 respondents, only three of whom reported prior use of the charts. Average score [n (%)] out of eight, as well as median score (range) for each coding category were: (i) Category: 7.3 (91 %); 7 (4–8); (ii) Time: 7.8 (98 %); 7 (6–8); (iii) Site: 7.2 (90 %); 7 (5–8). Overall, the equivalent calculations (out of 24) were 22.3 (93 %) and 22 (18–24). Mean prelecture confidence was 1.37 (out of 5), rising to 3.85 postquiz. Urogynecologists had the highest correlation with correct coding, followed closely by fellows and general gynecologists.

Conclusions

Optimizing training and study design can lead to excellent results for interobserver reliability of the IUGA-ICS Complication Classification coding, with increased participant confidence in complication-coding ability.     

Synthesis and Characterization of a “Turn-On” photoCORM for Trackable CO Delivery to Biological Targets

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Migration of murine intestinal dendritic cell subsets upon intrinsic and extrinsic TLR3 stimulation

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Fast pathway ablation in a patient with PR prolongation

The classical form of typical atrioventricular node reentrant tachycardia (AVNRT) is a “slow-fast” pathways tachycardia, and the usual therapy is an ablation of the slow pathway since it carries a low risk of atrioventricular (AV) block. In patients with long PR interval and/or living on the anterograde slow pathway, an alternative technique is required. We report a case of a 42-year-old lady with idiopathic restrictive cardiomyopathy, persistent atrial fibrillation status post pulmonary vein isolation, and premature ventricular complex ablation with a systolic dysfunction, who presented with incessant slow narrow complex tachycardia of 110 bpm that appeared to be an AVNRT. Her baseline EKG revealed a first-degree AV block with a PR of 320 ms. EP study showed no evidence of anterograde fast pathway conduction. Given this fact, the decision was to attempt an ablation of the retrograde fast pathway. The fast pathway was mapped during tachycardia to its usual location into the anteroseptal region, then radiofrequency ablation in this location terminated tachycardia. After ablation, she continued to have her usual anterograde conduction through slow pathway and the tachycardia became uninducible. In special populations with prolonged PR interval or poor anterograde fast pathway conduction, fast pathway ablation is the required ablation for typical AVNRT.