Abstract Background Recently, several studies revealed a much higher prevalence of later onset Fabry disease (FD) than previously expected. It suggested that later onset FD might present as an ...important hidden health issue in certain ethnic or demographic populations in the world. However, the natural history of its phenotype has not been systemically investigated, especially the cardiac involvement. Objectives The study analyzed a large-scale newborn screening program for FD to understand the natural course of later onset FD. Methods To date, 916,383 newborns have been screened for FD in Taiwan, including more than 1,200 individuals with the common, later onset IVS4+919G>A (IVS4) mutation. Echocardiography was performed in 620 adults with the IVS4 mutation to analyze the prevalence of left ventricular hypertrophy (LVH), and gadolinium-enhanced cardiac magnetic resonance imaging was performed in 129 patients with FD, including 100 IVS4 adults. Results LVH was observed in 67% of men and 32% of women older than 40 years. Imaging evidenced significant late gadolinium enhancement in 38.1% of IVS4 men and 16.7% of IVS4 women with the IVS4 mutation but without LVH. Seventeen patients underwent endomyocardial biopsies, which revealed significant globotriaosylceramide substrate accumulation in their cardiomyocytes. Conclusions Significant cardiomyocyte substrate accumulation in IVS4 patients led to severe and irreversible cardiac fibrosis before development of LVH or other significant cardiac manifestations. Thus, it might be too late to start enzyme replacement therapy after the occurrence of LVH or other significant cardiac manifestations in patients with later onset FD. This study also indicated the importance of newborn screening for early detection of the insidious, ongoing, irreversible cardiac damage in patients with later onset FD.
The iScore is a validated tool to predict mortality and functional outcome after acute ischemic stroke. It incorporates stroke subtype according to the Trial of Org 10172 in Acute Stroke Treatment ...(TOAST) classification as one of its factors. However, the TOAST stroke subtype may not be easily determined without extensive investigations. We aimed to test if the stroke subtype can be substituted by the Oxfordshire Community Stroke Project (OCSP) classification. We applied the iScore and the revised iScore, in which the TOAST subtype was replaced by the OCSP classification, to patients admitted to a single hospital for acute ischemic stroke. Outcome measures included poor functional status (modified Rankin scale score, 3-6) at discharge and 3 months. The performance between the iScore and the revised iScore was assessed by determining the discrimination and calibration of the scores. We studied 3196 patients at the acute stage, and among them 2349 patients were available for the 3-month assessment. The discrimination of the revised iScore was comparable with the iScore for poor outcome at discharge (area under the receiver operating characteristic curve, .767 versus .775; P = .06) and at 3-month (.801 versus .810; P = .06). The correlation between the observed and the expected outcomes was high for both the iScore (Pearson correlation coefficient, .993 at discharge and .995 at 3 months; both P < .0001) and the revised iScore (.985 and .993, respectively; both P < .0001). The revised iScore reliably predicts clinical outcomes at discharge and 3 months for patients with acute ischemic stroke.
Background About one third of stroke patients have renal dysfunction. Effect of renal dysfunction on outcome of intravenous thrombolysis (IVT) for acute ischemic stroke (AIS) has not been determined ...in Asia using patients without IVT as comparators. The aim of this study was to examine the interaction between renal dysfunction and IVT on the outcomes in AIS patients admitted within 4.5 hours of onset in a multicenter stroke registry of Taiwan. Methods We identified all consecutive AIS patients admitted within 4.5 hours of onset between 2007 and 2013. Renal dysfunction was defined by an estimated glomerular filtration rate less than 60 mL/minute/1.73 m2 on initial admission. Patients older than 80 years of age and a National Institute of Health Stroke Scale score less than 4 or greater than 25 were excluded. The primary outcome was a modified Rankin Scale score 3-6 at 3 months. We determined the effect of IVT and renal dysfunction on outcome in a multivariate analysis. Results Of the 929 patients analyzed, 39% had renal dysfunction, and 51% received IVT. Primary outcomes occurred in 45% versus 41% of patients with and without renal dysfunction, respectively, ( P = .197). In a multivariate analysis, the odds ratios (95% confidence interval; P value) of IVT and renal dysfunction for primary outcome were .70 (.51-.96; P = .029) and .97 (.71-1.33; P = .865), respectively. No significant interaction was noted between IVT and renal dysfunction ( P = .218). Conclusions Renal dysfunction did not modify the effect of IVT for AIS and should not be a reason for withholding treatment from otherwise-eligible patients.
Avian influenza A H6N1 virus is one of the most common viruses isolated from wild and domestic avian species, but human infection with this virus has not been previously reported. We report the ...clinical presentation, contact, and environmental investigations of a patient infected with this virus, and assess the origin and genetic characteristics of the isolated virus.
A 20-year-old woman with an influenza-like illness presented to a hospital with shortness of breath in May, 2013. An unsubtyped influenza A virus was isolated from her throat-swab specimen and was transferred to the Taiwan Centres for Disease Control (CDC) for identification. The medical records were reviewed to assess the clinical presentation. We did a contact and environmental investigation and collected clinical specimens from the case and symptomatic contacts to test for influenza virus. The genomic sequences of the isolated virus were determined and characterised.
The unsubtyped influenza A virus was identified as the H6N1 subtype, based on sequences of the genes encoding haemagglutinin and neuraminidase. The source of infection was not established. Sequence analyses showed that this human isolate was highly homologous to chicken H6N1 viruses in Taiwan and had been generated through interclade reassortment. Notably, the virus had a G228S substitution in the haemagglutinin protein that might increase its affinity for the human α2-6 linked sialic acid receptor.
This is the first report of human infection with a wild avian influenza A H6N1 virus. A unique clade of H6N1 viruses with a G228S substitution of haemagglutinin have circulated persistently in poultry in Taiwan. These viruses continue to evolve and accumulate changes, increasing the potential risk of human-to-human transmission. Our report highlights the continuous need for preparedness for a pandemic of unpredictable and complex avian influenza.
Taiwan Centres for Disease Control.
Summary Extranodal natural killer (NK)/T-cell lymphoma, nasal type, is a predominantly extranodal lymphoma associated with Epstein-Barr virus occurring most frequently in the upper aerodigestive ...tract. There are limited reports on cellular origin and prognostic factors. We retrospectively investigated 73 cases with a median age of 54 years and a male-female ratio of 2.0:1. The upper aerodigestive tract (nasal group) was the most common site of involvement (51 cases; 70%). The other organs (n = 22; extranasal group) included the skin (12 cases; 16%) and gastrointestinal tract (5; 7%). Of the 70 cases with complete staging, 71% had stage I/II disease. All cases were positive for Epstein-Barr virus by in situ hybridization. Using immunohistochemistry and clonality assay for T-cell receptor gene rearrangement, these tumors were classified into NK (n = 39; 53%), T (n = 13; 18%), and indeterminate lineage (n = 21; 29%). The only clinicopathological difference among these 3 groups was rare CD5 expression in the NK-cell group. Nasal tumors were more frequently of NK-cell origin, and extranasal tumors were equally of either T- or NK-cell origin. The 5-year overall survival rate was 35.6%. The overall survival time was shorter in the extranasal group, although there was no statistical difference in age, sex, and histologic or immunophenotypic features between the 2 groups. Excluding the cases with indeterminate lineage, 75% of cases were of NK lineage; and 25%, T lineage. Extranasal tumors were more aggressive than their nasal counterparts. A prospective national study is warranted for a better understanding of the clinicopathological and genetic features of this uncommon tumor and the prognostic factors.
Abstract Background Enhancing detection of undiagnosed atrial fibrillation (AF) in hospitalized patients with a recent ischemic stroke is important because of the treatment implications; especially ...since presence of paroxysmal AF may not be picked up in a single 12-lead electrocardiogram (ECG) test. While several trials have shown improved detection of AF with prolonged ECG monitoring, this strategy is associated with relatively high cost, labor intensity, and patient inconvenience, thereby making it challenging to routinely implement in all hospitals. Fortunately, conventional 24-h Holter monitoring and repeated 12-lead ECGs are readily available to detect paroxysmal AF in all hospitals, but is unclear which is the better strategy for evaluating undiagnosed AF. The objective of his study is to conduct a randomized trial of serial 12-lead ECGs vs. 24-hour Holter monitoring in the detection of AF in ischemic stroke patients without known AF. Methods and analysis We plan to enroll 1200 participants from six hospitals in Taiwan. Patients will be eligible for enrollment if they are admitted for an acute ischemic stroke within 2 days, are ≥65 years of age, and have no known AF by history or on baseline ECG at admission. We will randomly assign participants in a 1:1 ratio to undergo daily 12-lead ECG once daily for 5 days (intervention group) or 24-h Holter monitoring (control group). Primary outcome is newly detected AF on a 12-lead ECG or AF lasting ≥30 s on Holter monitoring. Trial registration number ClinicalTrials.gov Identifier: NCT02578979.
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