Prior use of direct oral anticoagulants has been associated with reduced stroke severity in patients with non-valvular atrial fibrillation (NVAF). The aim of this study was to investigate the impact ...of prothrombin time (PT) and activated partial thromboplastin time (aPTT) on stroke severity in patients who were receiving dabigatran or rivaroxaban at the time of stroke onset.
We enrolled 107 patients with NVAF who developed acute ischemic stroke while on dabigatran or rivaroxaban and presented within 24 hours to nine hospitals between January 2014 and December 2018. The results of PT and aPTT assays were obtained within 24 hours of stroke onset in all patients. We analyzed PT and aPTT in relation to stroke severity and ischemic lesion volume using correlation and multivariable regression analyses.
Of the 107 patients included, 46 (43.0%) were on dabigatran and 61 (57.0%) were on rivaroxaban. In patients with prior dabigatran use, while aPTT was inversely correlated with admission National Institutes of Health Stroke Scale (NIHSS) score (r = -0.369, p = 0.012) and ischemic lesion volume (r = -0.480, p = 0.005), there was no correlation between PT and either of these variables. Multivariable analysis confirmed the existence of a significant independent inverse relationship between aPTT and NIHSS score at admission (B, -0.201; 95% confidence interval CI, -0.370 to -0.032; p = 0.005) and between aPTT and ischemic lesion volume (B, -0.076; 95% CI, -0.130 to -0.023; p = 0.007). In patients with prior rivaroxaban use, neither PT nor aPTT was associated with admission NIHSS score or ischemic lesion volume in the correlation and multivariable analyses.
In patients with NVAF who were receiving dabigatran, prolonged aPTT was associated with reduced stroke severity.
Despite the great socioeconomic burden of stroke, there have been few reports of stroke statistics in Korea. In this scenario, the Epidemiologic Research Council of the Korean Stroke Society launched ...the "Stroke Statistics in Korea" project, aimed at writing a contemporary, comprehensive, and representative report on stroke epidemiology in Korea. This report contains general statistics of stroke, prevalence of behavioral and vascular risk factors, stroke characteristics, pre-hospital system of care, hospital management, quality of stroke care, and outcomes. In this report, we analyzed the most up-to-date and nationally representative databases, rather than performing a systematic review of existing evidence. In summary, one in 40 adults are patients with stroke and 232 subjects per 100,000 experience a stroke event every year. Among the 100 patients with stroke in 2014, 76 had ischemic stroke, 15 had intracerebral hemorrhage, and nine had subarachnoid hemorrhage. Stroke mortality is gradually declining, but it remains as high as 30 deaths per 100,000 individuals, with regional disparities. As for stroke risk factors, the prevalence of smoking is decreasing in men but not in women, and the prevalence of alcohol drinking is increasing in women but not in men. Population-attributable risk factors vary with age. Smoking plays a role in young-aged individuals, hypertension and diabetes in middle-aged individuals, and atrial fibrillation in the elderly. About four out of 10 hospitalized patients with stroke are visiting an emergency room within 3 hours of symptom onset, and only half use an ambulance. Regarding acute management, the proportion of patients with ischemic stroke receiving intravenous thrombolysis and endovascular treatment was 10.7% and 3.6%, respectively. Decompressive surgery was performed in 1.4% of patients with ischemic stroke and in 28.1% of those with intracerebral hemorrhage. The cumulative incidence of bleeding and fracture at 1 year after stroke was 8.9% and 4.7%, respectively. The direct costs of stroke were about ₩1.68 trillion (KRW), of which ₩1.11 trillion were for ischemic stroke and ₩540 billion for hemorrhagic stroke. The great burden of stroke in Korea can be reduced through more concentrated efforts to control major attributable risk factors for age and sex, reorganize emergency medical service systems to give patients with stroke more opportunities for reperfusion therapy, disseminate stroke unit care, and reduce regional disparities. We hope that this report can contribute to achieving these tasks.
The majority of clinical genetic testing focuses almost exclusively on regions of the genome that directly encode proteins. The important role of variants in non-coding regions in penetrant disease ...is, however, increasingly being demonstrated, and the use of whole genome sequencing in clinical diagnostic settings is rising across a large range of genetic disorders. Despite this, there is no existing guidance on how current guidelines designed primarily for variants in protein-coding regions should be adapted for variants identified in other genomic contexts.
We convened a panel of nine clinical and research scientists with wide-ranging expertise in clinical variant interpretation, with specific experience in variants within non-coding regions. This panel discussed and refined an initial draft of the guidelines which were then extensively tested and reviewed by external groups.
We discuss considerations specifically for variants in non-coding regions of the genome. We outline how to define candidate regulatory elements, highlight examples of mechanisms through which non-coding region variants can lead to penetrant monogenic disease, and outline how existing guidelines can be adapted for the interpretation of these variants.
These recommendations aim to increase the number and range of non-coding region variants that can be clinically interpreted, which, together with a compatible phenotype, can lead to new diagnoses and catalyse the discovery of novel disease mechanisms.
Lower education level could be a risk factor for higher peritoneal dialysis (PD)-associated peritonitis, potentially resulting in technique failure. This study evaluated the influence of lower ...education level on the development of peritonitis, technique failure, and overall mortality.
Patients over 18 years of age who started PD at Seoul National University Hospital between 2000 and 2012 with information on the academic background were enrolled. Patients were divided into three groups: middle school or lower (academic year≤9, n = 102), high school (9<academic year≤12, n = 229), and higher than high school (academic year>12, n = 324). Outcomes were analyzed using Cox proportional hazards models and competing risk regression.
A total of 655 incident PD patients (60.9% male, age 48.4±14.1 years) were analyzed. During follow-up for 41 (interquartile range, 20-65) months, 255 patients (38.9%) experienced more than one episode of peritonitis, 138 patients (21.1%) underwent technique failure, and 78 patients (11.9%) died. After adjustment, middle school or lower education group was an independent risk factor for peritonitis (adjusted hazard ratio HR, 1.61; 95% confidence interval CI, 1.10-2.36; P = 0.015) and technique failure (adjusted HR, 1.87; 95% CI, 1.10-3.18; P = 0.038), compared with higher than high school education group. However, lower education was not associated with increased mortality either by as-treated (adjusted HR, 1.11; 95% CI, 0.53-2.33; P = 0.788) or intent-to-treat analysis (P = 0.726).
Although lower education was a significant risk factor for peritonitis and technique failure, it was not associated with increased mortality in PD patients. Comprehensive training and multidisciplinary education may overcome the lower education level in PD.
Copy number variants (CNVs) at chromosome 16p13.11 have been associated with a range of neurodevelopmental disorders including autism, ADHD, intellectual disability and schizophrenia. Significant sex ...differences in prevalence, course and severity have been described for a number of these conditions but the biological and environmental factors underlying such sex-specific features remain unclear. We tested the burden and the possible sex-biased effect of CNVs at 16p13.11 in a sample of 10,397 individuals with a range of neurodevelopmental conditions, clinically referred for array comparative genomic hybridisation (aCGH); cases were compared with 11,277 controls. In order to identify candidate phenotype-associated genes, we performed an interval-based analysis and investigated the presence of ohnologs at 16p13.11; finally, we searched the DECIPHER database for previously identified 16p13.11 copy number variants. In the clinical referral series, we identified 46 cases with CNVs of variable size at 16p13.11, including 28 duplications and 18 deletions. Patients were referred for various phenotypes, including developmental delay, autism, speech delay, learning difficulties, behavioural problems, epilepsy, microcephaly and physical dysmorphisms. CNVs at 16p13.11 were also present in 17 controls. Association analysis revealed an excess of CNVs in cases compared with controls (OR = 2.59; p = 0.0005), and a sex-biased effect, with a significant enrichment of CNVs only in the male subgroup of cases (OR = 5.62; p = 0.0002), but not in females (OR = 1.19, p = 0.673). The same pattern of results was also observed in the DECIPHER sample. Interval-based analysis showed a significant enrichment of case CNVs containing interval II (OR = 2.59; p = 0.0005), located in the 0.83 Mb genomic region between 15.49-16.32 Mb, and encompassing the four ohnologs NDE1, MYH11, ABCC1 and ABCC6. Our data confirm that duplications and deletions at 16p13.11 represent incompletely penetrant pathogenic mutations that predispose to a range of neurodevelopmental disorders, and suggest a sex-limited effect on the penetrance of the pathological phenotypes at the 16p13.11 locus.
The number of elderly patients with end-stage renal disease is increasing rapidly. The higher prevalence of comorbidities and shorter life expectancy in these patients make it difficult to decide on ...the type of vascular access (VA). We explored the optimal choice for VA in elderly hemodialysis patients.
We included elderly patients (> 65 years) visiting our VA clinic and divided them into three groups as follows: radiocephalic arteriovenous fistula (AVF), brachiocephalic AVF, and prosthetic arteriovenous graft (AVG). The primary outcomes were VA abandonment and all-cause mortality. The secondary outcome was maturation failure (MF).
Of 529 patients, 61.2% were men. The mean age was 73.6 ± 6.0 years. The VA types were as follows: 49.9% radiocephalic AVF, 31.8% brachiocephalic AVF, and 18.3% AVG. Patients with an AVG tended to be older, female, and have a lower body mass index. More than half of patients (n = 302, 57.1%) started dialysis with central catheters, but the proportion of predialysis central catheter placement was not different among the VA types. Radiocephalic AVF was significantly superior to AVG in terms of VA abandonment (P = 0.005) and all-cause mortality (P < 0.001) in spite of a higher probability of MF. Brachiocephalic AVF was associated with a shorter time to the first needling and fewer interventions before maturation than radiocephalic AVF.
Autologous AVF was suggested as the preferred VA choice in terms of long-term outcomes in elderly patients.
Background
Dyslipidemia is common in kidney transplant (KT) recipients. We analyzed the ratio of triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) in KT recipients to identify risk ...factors for major cardiovascular events (MACE).
Methods
We retrospectively included KT recipients with a lipid profile performed 1 year after transplantation. We classified patients according to the TG/HDL-C divided into quintiles. Subsequently, we analyzed the association between TG/HDL-C and MACE, defined as heart failure, coronary artery disease, and cerebrovascular disease confirmed by imaging studies.
Results
A total of 1301 KT recipients were enrolled. The median follow-up duration was 7.4 years (interquartile range 4.4–11.1 years). During the follow-up period, 80 (6.2%) patients developed MACE, which included 38 of unstable anginas, 9 of MIs, 19 of heart failures, 18 of cerebral infarcts, and 4 of cerebral hemorrhages. The fourth and fifth quintiles of TG/HDL-C showed a significantly increased risk of MACE fourth quintile: adjusted hazard ratio (aHR), 3.38; 95% confidence interval (CI) 1.44–7.95;
p
= 0.005, fifth quintile: aHR, 2.67; 95% CI 1.13–6.30;
p
= 0.02) compared to the second quintile of TG/HDL-C. This association is particularly evident in subgroups of non-DM, HTN, no history of CVD, and statin users.
Conclusions
Higher TG/HDL-C levels may be associated with MACE risk in KT recipients.
Maintaining residual renal function (RRF) is a crucial issue in peritoneal dialysis (PD). Incremental dialysis is the practice of initiating PD exchanges less than four times a day in consideration ...of RRF, and increasing dialysis dose in a step-wise manner as the RRF decreases. We aimed to compare the outcomes of incremental PD and full-dose PD in terms of RRF preservation and other outcomes. This was a single-center, observational study. Data were extracted retrospectively from a cohort of incident PD patients over 16 years old who started PD between 2007 and 2015 in the PD Unit of Seoul National University Hospital. We used inverse probability weighting (IPW) adjustment based on propensity scores to balance covariates between the incremental and full-dose PD groups. Multivariate, time-dependent Cox analyses were performed. Among 347 incident PD patients, 176 underwent incremental PD and 171 underwent conventional full-dose PD. After IPW adjustment, the incremental PD group exhibited a lower risk of developing anuria (hazard ratio HR 0.61, 95% confidence interval CI 0.43-0.88). Patient survival, technique survival, and peritonitis-free survival were all similar between these groups (P > 0.05 by log-rank test). Incremental PD was beneficial for preserving RRF and showed similar patient survival when compared to conventional full-dose PD.
This study was conducted to evaluate the usefulness of human leukocyte antigen (HLA) typing in preventing allopurinol-induced severe cutaneous adverse reactions (SCARs) through the application of an ...allopurinol tolerance induction protocol or prescription of other alternative medications in high-risk patients.
HLA typing was performed in patients with chronic renal insufficiency who needed allopurinol. HLA-B*58:01-negative patients were prescribed the usual dose of allopurinol. For HLA-B*58:01-positive patients, administration of either allopurinol based on a 28-day tolerance induction protocol or alternative medications was initiated. Hypersensitivity reactions were surveyed for 90 days and compared with the result of a previous retrospective cohort study.
Among a total of 401 study subjects, no SCARs were noted in HLA-B*58:01-positive patients with application of the tolerance induction protocol (n = 30) or alternative medications (n = 16), nor were any SCARs observed in HLA-B*58:01-negative patients who started allopurinol at the usual dose (n = 355). Compared with the previous retrospective cohort study, a significant reduction in SCARs was observed in HLA-B*58:01-positive patients (0 vs. 18%; P = 0.002).
This study shows the usefulness of HLA-B*58:01 screening in identifying patients at high risk for the development of allopurinol-induced SCARs and suggests that application of a tolerance induction protocol or alternative medications could be an effective strategy to prevent allopurinol-induced SCARs in HLA-B*58:01-positive patients.
Vitamin D deficiency is an important health concern because it is related to several comorbidities and mortality. However, its relationship with the risk of hematuria remains undetermined in the ...general population. In this study, we analyzed the association between vitamin D deficiency and hematuria.
We conducted cross-sectional analysis using data of participants from the Korean National Health and Nutrition Examination Survey (KNHANES) 2010-2014. A total of 20,240 participants, aged ≥18 years old, were analyzed. Serum 25-hydroxyvitamin D (25(OH)D) levels were measured in a central laboratory and hematuria was defined as ≥1+ on a dipstick test. Multivariate logistic regression was conducted to calculate the odds ratio (OR) of hematuria risk according to serum 25(OH)D quartiles, after adjusting several covariates.
A total 3144 (15.5%) participants had hematuria. The mean 25(OH)D level was 17.4 ± 6.2 ng/mL (median, 16.6 ng/mL (interquartile range, 13.1-20.8 ng/mL)). The 3rd and 4th quartiles had a higher risk of hematuria than the 1st quartile, with adjusted ORs 1.26 (1.114-1.415) and 1.40 (1.240-1.572) in the 3rd and 4th quartiles, respectively. However, this relationship was only significant in women, not in men. When stratified analyses were conducted according to menopausal status, there was a significant increase of hematuria risk according to quartiles in postmenopausal but not in premenopausal women.
We found that vitamin D deficiency is correlated with hematuria in women, particularly after menopause. Further interventional studies are warranted to address whether correcting vitamin D deficiency can lower the risk of hematuria.
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