non-East Asian Research Articles

A meta-analysis on immune checkpoint inhibitor efficacy for advanced non-small cell lung cancer between East Asians versus non-East Asians.

BackgroundWe conducted a meta-analysis to assess the efficacy of immune checkpoint inhibitors (ICIs) (PD-1/L1 and CTLA-4 inhibitors) in first and subsequent lines in East Asians and non-East Asians.MethodsWe searched PubMed-MEDLINE, Embase and Scopus, from inception to 20 Sep 2019, and reviewed major conferences’ abstracts, for randomised controlled trials of ICI in advanced-stage NSCLC (Stage IIIB or IV) without EGFR mutation that reported hazard ratios (HRs) stratified by geographical region including the region “Asia” or “East Asia”. The primary outcome measures were overall survival (OS) and progression-free survival (PFS). The pooled HR and its 95% confidence interval (CI) for OS and PFS in East Asians and non-East Asians were calculated using a random effect model and the difference compared using an interaction test.ResultsA total of 5,465 patients from 7 randomised controlled trials involving CTLA-4 and/or PD-1/L1 inhibitors were included, with 1,740 (32%) East Asians and 3,725 (68%) non-East Asians. ICI was associated with an improvement in OS and PFS for both East Asian (OS HR, 0.74; 95% CI, 0.65–0.85; PFS HR, 0.56; 95% CI, 0.40–0.79) and non-East Asian patients (OS HR, 0.78; 95% CI, 0.72–0.85; PFS HR, 0.69; 95% CI, 0.56–0.85), with no significant difference between the two groups (Pinteraction=0.55 for OS; Pinteraction=0.33 for PFS). Subgroup analyses showed a statistically significant superior PFS (but not OS) for East Asians than non-East Asians in trials that used immune checkpoint inhibitor in the first-line treatment (Pinteraction=0.02). No significant regional difference was found in further subgroups of pure ICI and combination of ICI with chemotherapy.ConclusionsThere is no significant difference in response to ICI between East Asians and non-East Asians with advanced stage NSCLC, and the statistically significant subgroup difference in PFS in the first line use of ICI may not be clinically significant.

Ethnic Differences in Childhood Moyamoya Presentation and Evolution

Background Emerging evidence suggests that moyamoya natural history differs based on ethnic background and underlying cause. We sought to compare clinical and radiographic presentation and evolution of moyamoya vasculopathy based on ethnic background. Methods We conducted a single-institution retrospective review a cohort of children with moyamoya followed from 2003 to 2019. Clinical and radiographic characteristics at diagnosis were obtained. Clinical evolution and radiographic progression were assessed on subsequent clinical visits and neuroimaging. We compared moyamoya subtypes (moyamoya disease (MMD) vs moyamoya syndrome (MMS) and MMD vs neurofibromatosis type 1 (MMS-NF1) vs sickle cell disease (MMS-SCD)), clinical and radiographic features at presentation, time to clinical event recurrence and radiographic progression and PSOM at last follow-up based on ethnic background. Comparisons were conducted using t-test, chi-square test, logistic and Cox regressions (p Results One hundred and seven patients were identified, of whom 46 had MMD and 61 MMS (22 MMS-NF1, 21 MMSSCD, 18 others). Thirty percent were Caucasian, 19.63% were Black, 17.76% were East Asian and 15% were non-East Asian. The ethnic background of the remainder was unknown. Ethnic distribution based on moyamoya subtype was significant (p Conclusion There are ethnic differences at presentation and follow-up in childhood moyamoya. East Asian patients are more likely to present with TIA and have TIA recurrence and Black patients are less likely to have an ivy sign at presentation. These differences are most likely due to different underlying diagnosis.

Characterization of a Human ALDH2 Mutant that Causes Alcohol Flushing in Non‐east Asians

Mitochondrial aldehyde dehydrogenase 2 (ALDH2) is a ~55 kDa protein responsible for the metabolism of the alcohol derived intermediate, acetaldehyde, in addition to a variety of toxic aldehydes including 4‐hydroxynonenal (4HNE) and acrolein. A single nucleotide polymorphism (SNP) of the ALDH2 gene (rs671) is highly prevalent among East Asians with ~540 million people in the world with the ALDH2 genetic variant (ALDH2*2 or E504K) that causes facial flushing and tachycardia after alcohol consumption due inefficient acetaldehyde metabolism. However, anecdotal reports exist of non‐East Asians who flush after alcohol consumption. Therefore, we hypothesize that other dysfunctional human genetic variants exist, besides ALDH2*2, that cause inefficient acetaldehyde metabolism.To address our hypothesis, after receiving IRB approval, we recruited human volunteers with self‐reported alcohol‐induced facial flushing. Volunteers were genotyped in addition to being subjected to an alcohol challenge (0.25g/kg) where levels of acetaldehyde in the breath were quantified by gas mass spectrometry for the 2 hours after an alcohol challenge. In addition, to support these findings, we carried out site‐directed mutagenesis, expressed, and purified an ALDH2 mutant we identified in humans using a nickel affinity column for histidine tagged protein. We measured enzymatic activity of the ADLH2 mutant using wild type ALDH2 and ALDH2*2 as comparators. All data are presented as mean ± SEM. Statistical analysis was performed by ANOVA and Tukey’s post hoc with significance set at P<0.05.We discovered a novel non‐East Asian ALDH2 mutation (R114W) that also causes alcohol‐induced facial flushing and acetaldehyde accumulation. Acetaldehyde levels measured in human breath showed that a human heterozygous for ALDH2 R114W had ~30% more acetaldehyde accumulation compared to homozygote wild‐type ALDH2 human subjects. The heart rate of ALDH2 R114W was not affected by alcohol intake, whereas skin temperature increased after alcohol consumption. To confirm these findings in humans, enzymatic activity of the purified proteins showed that E504K and R114W had 49±3 and 603±11 nmol/min/mg protein, respectively compared to 1209±15 nmol/min/mg protein for wild‐type ALDH2 (n=3, p<0.05). When mixed in the 1:1 ratio with wild‐type enzyme to mimic the heterozygous condition, the activity of E504K and R114W increased to 683±6 and 838±16 nmol/min/mg of pure protein, respectively, but still significantly below the activity of the wild‐type ALDH2. The results presented here demonstrate that a newly found ALDH2 variant, R114W, is also responsible for alcohol‐induced acetaldehyde accumulation and facial flushing. In conclusion, individuals carrying this mutation are more potentially also more susceptible to esophageal cancer similar to those heterozygous for the ALDH2*2 genetic variant.Support or Funding InformationNIGMS HL119522 (ERG) and a Stanford ChEM‐H seed grant (ERG, DMR).

Reexamining the Mechanisms of East Asian Summer Monsoon Changes in Response to Non–East Asian Anthropogenic Aerosol Forcing

AbstractThis study examines the mechanisms by which the East Asian summer monsoon (EASM) changes in response to non–East Asian (NEA) anthropogenic aerosol forcing by distinguishing the fast direct atmospheric response and slow ocean-mediated response to forcing using a global aerosol–climate coupled model. The results show that NEA aerosol forcing significantly exacerbates the weakening of the EASM due to local aerosol forcing. The fast response is dominant in the weakening of the EASM and an anomalous precipitation pattern over eastern China resembling the “southern flood and northern drought” pattern in the total response to NEA aerosol forcing. Changes in upper-tropospheric temperature caused by the fast response play a major role in the impact of NEA aerosol forcing on the EASM. Anomalous cooling occurs during summer in the upper troposphere (at ~40°N) over East Asia caused by the fast response. This is due to the combined effects of strong eastward cold advection in the Northern Hemisphere midlatitudes caused by increased aerosol loading in Europe and the resulting change in local meridional heat transport in East Asia. Subsequently, the zonal wind speed changes on either side of the anomalous cooling, and the East Asian subtropical jet shifts equatorward, thereby weakening the EASM. The changes in atmospheric temperature and the local Hadley cell caused by the slow response to NEA aerosol forcing are conducive to strengthening the southwesterly winds over eastern China. Our study suggests the importance of NEA aerosol forcing in driving changes in the EASM on a fast time scale.

The Relevance of Docetaxel-related Febrile Neutropenia to Patient-reported Symptoms and the Quality of Life in Japanese, East Asian (Korean, Taiwanese), and Non-East Asian Patients Based on Post-hoc Analyses of Two Randomized Clinical Trials of Docetaxel with and Without Anti-angiogenic Agent in Advanced Non-small Cell Lung Cancer After Progression on Platinum-based Chemotherapy

The Relevance of Docetaxel-related Febrile Neutropenia to Patient-reported Symptoms and the Quality of Life in Japanese, East Asian (Korean, Taiwanese), and Non-East Asian Patients Based on Post-hoc Analyses of Two Randomized Clinical Trials of Docetaxel with and Without Anti-angiogenic Agent in Advanced Non-small Cell Lung Cancer After Progression on Platinum-based Chemotherapy

Genetic characteristics of retinitis pigmentosa in 1204 Japanese patients

BackgroundThe genetic profile of retinitis pigmentosa (RP) in East Asian populations has not been well characterised. Therefore, we conducted a large-scale sequencing study to investigate the genes and variants causing...

An Association of Cryptococcus Neoformans/C. gattii Genotype and HIV Status in Asia: A Systematic Review

Objective : It has been known that VNI molecular type of Cryptococcus neoformans / C . gattii is strongly associated with HIV patients. However, this paradigm has recently been challenged because of the high prevalence of VNI molecular type among non-HIV patients with cryptococcosis in East Asia. The purpose of this study was to answer the question: “Among cryptococcosis in Asia, is there an association between the genotype and the patient’s HIV status?”. Methods : Using a systematic review and meta-analysis study design, we included all relevant published data, which were any type of study designs, mainly studied clinical Cryptococcus neoformans / C . gattii strains isolated in Asia and had available molecular typing data. The primary study variables were Cryptococcus neoformans molecular type (VNI/non-VNI or ST5/non-ST5) and the HIV status of the patients at the time of diagnosis. We used a random-effects meta-analysis model to estimate the prevalence of HIV infection. Results : Sixteen retrospective descriptive studies during 2005 – 2018 (1,584 isolates) were included. Most of the cryptococcosis cases in East Asian countries were in non-HIV patients (72.4-81.8%), which differed from non-East Asian countries (2.6-28.3% associated with non-HIV patients). In East Asia, the HIV prevalence among VNI and ST5 infected patients ranged from 7.5% - 46.7% with the pooled prevalence of 19.8% (95% CI, 12.2% - 30.4%) and 5.3% - 52.4% with the pooled prevalence of 19.9% (95% CI, 6.9% - 45.3%), respectively. In non-East Asia, the HIV prevalence among VNI and ST5 infected patients ranged from 48.3% - 98.8% with the pooled prevalence of 81.9% (95% CI, 73.3% - 88.2%) and 52.3% - 88.0% with the pooled prevalence of 74.9% (95% CI, 40.7% - 92.8%), respectively. Statistical heterogeneity was high in both analyses with the I 2 of 79-89% in all analyses. Conclusion : Our results confirmed the low prevalence of HIV prevalence among VNI and ST5 strains in East Asian countries. The emergence of high virulence genotype causing disease in non-HIV patient is highly unlikely, because the VNI and ST5 were associated with HIV patients in other Asian countries. It can be hypothesized that the low HIV prevalence among VNI and ST5 strains in East Asian is due to the high susceptibility to cryptococcosis of people living in this region. This requires further investigation.

Comparative Efficacy of Sirolimus-Eluting Stents and Paclitaxel-Eluting Stents in East Asian Versus non-East Asian Patients: A Systematic Review & Meta-Analysis.

First-generation drug-eluting stents - such as the sirolimus-eluting stent (SES) and paclitaxel-eluting stent (PES) - have become attractive options for percutaneous coronary intervention (PCI) and are still widely used in Asia. However, the effect of East Asian ethnicity on their efficacy remains unclear. Pubmed, EMBASE, and the Cochrane Central Register of Controlled Trials were searched for randomized controlled trials comparing the efficacy of the Cypher SES and Taxus PES. The outcomes of interest were stent thrombosis, target lesion revascularization (TLR), target vessel revascularization (TVR), myocardial infarction (MI), cardiac mortality, and all-cause mortality. Pooled 'East Asian' studies were compared against pooled 'non-East Asian' studies. SES significantly reduced stent thrombosis incidence in East Asian patients relative to PES. Irrespective of East Asian status, SES significantly reduced the incidence of TLR and TVR as compared to PES. The Cypher SES appears to be a superior choice over the Taxus PES for East Asian patients on account of its reduced risk of stent thrombosis in these patients. Irrespective of East Asian ethnic status, the Cypher SES also yields a significantly reduced incidence of TLR and TVR as compared to the Taxus PES. This article is protected by copyright. All rights reserved.

Actionable secondary findings from whole-genome sequencing of 954 East Asians.

Recently, the American College of Medical Genetics (ACMG) recommended the return of actionable secondary findings detected from clinical sequencing. The reported frequency of secondary findings in Asian populations were highly variable and it is unclear whether the uniformity in coverage offered by whole-genome sequencing (WGS) may impact the estimate. In this analysis, we aimed to refine the rate of secondary findings on East Asians through a large-scale WGS study. We classified 1256 protein-altering or splicing variants of the 59 actionable genes detected from WGS of 954 East Asians in strict accordance with the ACMG and the Association for Molecular Pathology guidelines. A total of 21 pathogenic or likely pathogenic variants were detected in 24 of the 954 East Asian genomes with an estimate of 2.5% of East Asians carrying actionable variants. Although the overall estimate of secondary findings was consistent with those reported for non-East Asian ethnicities, genetic and allelic heterogeneity was observed. WGS offers a wider breadth of coverage over WES, which highlights the need to further investigate the variable sensitivity of WES and WGS in the detection of secondary findings. Identifying secondary findings in populations underrepresented in previous genetic literature might improve variant interpretation and has a profound impact on local decision-making with regard to the cost-effectiveness of returning the secondary findings from clinical sequencing.

Cross-cultural and hemispheric laterality effects on the ensemble coding of emotion in facial crowds.

In many social situations, we make a snap judgment about crowds of people relying on their overall mood (termed "crowd emotion"). Although reading crowd emotion is critical for interpersonal dynamics, the sociocultural aspects of this process have not been explored. The current study examined how culture modulates the processing of crowd emotion in Korean and American observers. Korean and American (non-East Asian) participants were briefly presented with two groups of faces that were individually varying in emotional expressions and asked to choose which group between the two they would rather avoid. We found that Korean participants were more accurate than American participants overall, in line with the framework on cultural viewpoints: Holistic versus analytic processing in East Asians versus Westerners. Moreover, we found a speed advantage for other-race crowds in both cultural groups. Finally, we found different hemispheric lateralization patterns: American participants were more accurate to perceive the facial crowd to be avoided when it was presented in the left visual field than the right visual field, indicating a right hemisphere advantage for processing crowd emotion of both European American and Korean facial crowds. However, Korean participants showed weak or nonexistent laterality effects, with a slight right hemisphere advantage for European American facial crowds and no advantage in perceiving Korean facial crowds. Instead, Korean participants showed positive emotion bias for own-race faces. This work suggests that culture plays a role in modulating our crowd emotion perception of groups of faces and responses to them.

Cholesterol Levels and Hemorrhagic Stroke Risk in East Asian Versus Non-East Asian Populations: A Systematic Review and Meta-Analysis.

The aim of this work was to evaluate the relationships between cholesterol levels and risk of hemorrhagic stroke [including intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH)] in East Asian versus non-East Asian populations. Relevant prospective studies were identified from systematic searches of PubMed and EMBASE. A random-effects model was used to calculate summary relative risks (RRs) and 95% confidence intervals (CIs) that were used to compare the relationships between cholesterol levels and risk of hemorrhagic stroke in East Asian versus non-East Asian populations. In terms of overall hemorrhagic stroke risk, both East Asians and non-East Asians displayed no significant difference between high versus low total cholesterol (TC) (RR=1.26, 95% CI, 0.92-1.72; I=74.4%, P<0.001; RR=1.69, 95% CI, 1.15-2.49; I=92.4%, P<0.001, respectively). In terms of ICH risk, East Asians displayed no significant difference between high versus low TC (RR=1.30, 95% CI, 0.89-1.90; I=78.6%, P<0.001), whereas non-East Asians displayed a significant difference between high versus low TC with low TC showing a higher ICH risk (RR=1.70, 95% CI, 1.08-2.67; I=91.2%, P<0.001). With respect to SAH risk, East Asians displayed a significant difference between high versus low TC with low TC showing a higher SAH risk (RR=1.48, 95% CI, 1.057-2.08; I=0%, P=0.682), whereas non-East Asians displayed no significant difference between high versus low TC (RR=1.14, 95% CI, 0.56-2.31; I=89.9%, P<0.001). Under low cholesterol conditions, East Asian ethnic status favors SAH development, whereas non-East Asian ethnic status favors ICH development.

Defamilisation and leave policies – a comparative study of 14 East Asian and non-East Asian countries

ABSTRACTThis article joins the international debate on whether there is a unique East Asian welfare model. It examines the concept of defamilisation and compares various leave policies (maternity leave, paternity leave and extended parental leave) in five East Asian and nine non-East Asian countries. The welfare index method is used to classify these countries into different groupings. The findings show that the East Asian countries are not always internally homogeneous (being similar in key features), nor are they externally heterogeneous (showing significant differences from the others). Therefore, the existence of a unique East Asian welfare model is still in doubt.

WHITDRAWAL: Comparative efficacy of sirolimus-eluting stents and paclitaxel-eluting stents in East Asian versus non-East Asian patients: a systematic review and meta-analysis.

The article by Zhao R, Lu Q, Yang R, DU J, Deng S, She Q. entitled "Comparative efficacy of sirolimus-eluting stents and paclitaxel-eluting stents in East Asian versus non-East Asian patients: a systematic review and meta-analysis" was published ahead of print in the journal Minerva Cardioangiologica on January 31, 2017. The corresponding author of the article, Prof. She, and his group submitted the same manuscript to two different journals (to Minerva Cardioangiologica - Edizioni Minerva Medica on June 25, 2016 and to Cardiovascular therapeutics - Wiley on May 31, 2015), despite a properly handsigned copyright form stating the paper had not been submitted to any other journals was provided, with subsequent redundant publications. The publisher Minerva Medica S.p.A. asks for the Epub ahead of print publication of the paper in Minerva Cardioangiologica to be withdrawn.

Efficacy of Eltrombopag in Adult East Asian and Non-East Asian Patients with Chronic Immune Thrombocytopenia (cITP): Results from the Extend Study

Introduction: Eltrombopag is an oral thrombopoietin receptor agonist, approved for the treatment of patients with cITP (persisting >12 months) aged ≥1 year, who are refractory to other treatments (eg corticosteroids, immunoglobulins). Pharmacokinetic studies of eltrombopag have demonstrated that patients of East Asian origin (eg Japanese, Chinese, Taiwanese and Korean) experience increased plasma exposure to eltrombopag compared to non-East Asian patients (predominantly Caucasian). As such, the recommended starting dose is 25 mg/day for East Asian patients, compared with 50 mg/day in non-East Asians. In the EXTEND (Eltrombopag eXTENded Dosing) study, all patients, irrespective of ancestry, received 50 mg/day starting dose that was subsequently adjusted to the platelet response. Unpublished anecdotal reports of platelet responses in East Asian patients from EXTEND describe lower doses of eltrombopag. Here, we examine the responses to eltrombopag in East Asian and non-East Asian patients who completed the EXTEND study.Methods: Adult patients (≥18 years old) diagnosed with cITP who had completed a previous ITP study of eltrombopag were enrolled in EXTEND. All patients received eltrombopag starting at 50 mg/day, titrated to 25-75 mg/day or less often as required, based on individual platelet count responses (range ≥50-200x109/L). Maintenance dosing continued after minimization of concomitant ITP medication and optimization of eltrombopag dosing. Patients who received 2 years of treatment and transitioned off due to commercial availability of eltrombopag were considered to have completed the study. Patients could remain on study beyond 2 years until eltrombopag became commercially available. Here we describe the efficacy and durability of response in East Asian and non-East Asian patients. Analyses were conducted using the safety population, defined as all patients who had taken at least one dose of the study medication.Results: Of 302 patients enrolled and exposed to treatment (median duration 2.4 years [range, 2 days to 8.8 years]), 41 (14%) were of East Asian origin. Mean average eltrombopag dose in East Asian and non-East Asian patients was 48.9 (range 4.2-74.9) mg/day and 50.4 (range 1.0-74.6) mg/day, respectively. Maintenance of platelet counts ≥30×109/L for at least 25 weeks was seen in 25/35 (71%) East Asian and 158/222 (71%) non-East Asian patients. In total, 13/35 (37%) East Asian patients and 120/222 (54%) non-East Asian patients maintained continuous platelet counts ≥50×109/L for at least 25 weeks, without rescue therapy (Figure). At the start of response, mean daily dose in East Asian and non-East Asian patients was 45.2 and 45.4 mg/day, respectively. The number of patients receiving dose adjustments according to platelet response was similar in East Asian and non-East Asian patients (Table).Conclusions: Treatment with eltrombopag in East Asian and non-East Asian patients resulted in sustained platelet responses ≥30×109/L for at least 25 weeks in a similar proportion of patients. However, a higher proportion of non-East Asian patients achieved continuous platelet counts ≥50×109/L. Direct comparisons should be interpreted with caution because: a) of limited patient numbers in the East Asian group; b) the possible selection bias of patients entering the EXTEND study following completion of earlier eltrombopag studies, eg, primarily responders; and c) the absence of PK data from these patient groups. All patients received similar doses of eltrombopag irrespective of racial background, and dose modifications according to platelet responses were similar. Further investigations are ongoing to determine whether there were any differences in terms of safety and tolerability outcomes in East Asian and non-East Asian patients. [Display omitted] [Display omitted] DisclosuresWong:Bayer, Biogen-Idec, Bristol-Myers Squibb, GlaxoSmithKline, Johnson & Johnson, Merck Sharp & Dohme, Novartis, Pfizer, and Roche: Research Funding; Biogen-Idec and Novartis: Membership on an entity’s Board of Directors or advisory committees; Bayer, Biogen-Idec and Novartis: Consultancy. Bussel:Amgen, Novartis & GSK: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Boehringer Ingleheim, Prophylix Pharma, Protalex, Rigel Pharmaceuticals: Research Funding; Momenta Pharmaceuticals, Novartis, Prophylix Pharma, Protalex, Rigel Pharmaceutical: Membership on an entity’s Board of Directors or advisory committees; UptoDate: Patents & Royalties; Physicians Education Resource: Speakers Bureau. Saleh:GSK: Consultancy, Research Funding, Speakers Bureau. El-Ali:Novartis: Employment. Quebe-Fehling:Novartis: Employment.

Second-line ramucirumab therapy for advanced hepatocellular carcinoma (REACH): an East Asian and non-East Asian subgroup analysis

PurposeREACH investigated second-line ramucirumab therapy for advanced hepatocellular carcinoma.ResultsMedian overall survival was 8.2 months for ramucirumab and 6.9 months for placebo (HR, 0.835; 95% CI, 0.634–1.100; p = 0.2046) for East Asians, and 10.1 months for ramucirumab and 8.0 months for placebo (HR, 0.895; 95% CI, 0.690–1.161; p = 0.4023) for non-East Asians. Median overall survival in patients with baseline alpha-fetoprotein ≥ 400 ng/mL was 7.8 months for ramucirumab and 4.2 months for placebo (HR, 0.749; 95% CI, 0.519–1.082; p = 0.1213) for East Asians (n = 139), and 8.2 months for ramucirumab and 4.5 months for placebo (HR, 0.579; 95% CI, 0.371–0.904; p = 0.0149) for non-East Asians (n = 111). The most common grade ≥ 3 treatment-emergent adverse events in East Asians and non-East Asians included hypertension and malignant neoplasm progression.Materials and methodsA post-hoc analysis of East Asians (N = 252) and non-East Asians (N = 313) in the intent-to-treat population was performed.ConclusionsIn East Asians and non-East Asians, ramucirumab did not significantly prolong overall survival. In patients with baseline alpha-fetoprotein ≥ 400 ng/mL, a potentially larger survival benefit was observed in both subgroups. Safety for East Asians was similar to non-East Asians.

Clinical and molecular characteristics of East Asian patients with von Hippel-Lindau syndrome.

BackgroundVon Hippel–Lindau (VHL) syndrome is a dominantly inherited multisystem cancer syndrome caused by a heterozygous mutation in the VHL tumor suppressor gene. Previous studies suggested that similar populations of Caucasian and Japanese patients have similar genotype or phenotype characteristics. In this comprehensive study of East Asian patients, we investigated the genetic and clinical characteristics of patients with VHL syndrome.MethodsTo create a registry of clinical characteristics and mutations reported in East Asian patients with VHL syndrome, we conducted a comprehensive review of English language and non-English language articles identified through a literature search. Publications in Japanese or Chinese language were read by native speakers of the language, who then performed the data extraction.ResultsOf 237 East Asian patients with VHL syndrome, 154 unique kindreds were identified for analysis. Analyzed by kindred, missense mutations were the most common (40.9%, 63/154), followed by large/complete deletions (32.5%, 50/154) and nonsense mutations (11.7%, 18/154). Compared with a previously reported study of both East Asian and non-East Asian patients, we found several key differences. First, missense and frameshift mutations in the VHL gene occurred less commonly in our population of East Asian patients (40.9% vs. 52.0%; P = 0.012 and 8.4% vs. 13.0%; P < 0.001, respectively). Second, large/complete deletions were more common in our population of East Asian patients (32.5% vs. 10.5%; P < 0.001). Third, phenotypically, we observed that, in our population of East Asian patients with VHL syndrome, the incidence of retinal capillary hemangioblastoma was lower, whereas the incidence of renal cell carcinoma was higher.ConclusionsEvidence suggests that the genotypic and phenotypic characteristics of East Asian patients with VHL syndrome differ from other populations. This should be considered when making screening recommendations for VHL syndrome in Asia.Electronic supplementary materialThe online version of this article (doi:10.1186/s40880-016-0141-z) contains supplementary material, which is available to authorized users.

A study of the influence of ethnicity on serology and clinical features in lupus.

The objective of this study was to review the links between ethnicity, serology and clinical expression in systemic lupus erythematosus (SLE) in a single cohort that was followed over a 36-year period. Patients with SLE treated at the University College London Hospitals (UCLHs) between January 1978 and December 2013 formed the cohort. We assessed the demographic, clinical and serological data. Standard methods were used for laboratory testing. The Student t test and Mann-Whitney U test were used for the continuous variables; the Fisher's exact test was used for the categorical variables. We studied 624 SLE patients: There were 571 women (91.5%), with a mean age at diagnosis of 29.0 ± 6.5 years; and 53 men (8.5%), with a mean age at diagnosis of 29.4 ± 15.3 years. Ethnically, 369 of the patients were European, 100 were Afro-Caribbean, 77 were East Asian, 56 were South Asian and 21 were of mixed ethnicity. The East Asian patients developed the disease at a younger age than the other ethnic groups (p < 0.0001). The Afro-Caribbean patients were less frequently associated with the presence of rash and photosensitivity, and the non-European patients were more likely to have alopecia and renal involvement. The South Asian patients were significantly associated with musculoskeletal and neurological involvement, serositis, Sicca syndrome and hematological features. The Afro-Caribbean patients had the highest prevalence of anti-Smith, anti-RNP, anti-Ro and anti-La antibodies. Anti-IgG anticardiolipin (aCL) antibodies were significantly associated with the non-East Asian groups; and hypocomplementemia was common in the East Asians. Rash, alopecia, mouth ulcers, serositis, neurological, joint and renal involvement were significantly associated with the presence of anti-Smith and anti-RNP antibodies in the Afro-Caribbean group. We also observed an association of joint involvement and the presence of anti-Ro and anti-La antibodies in this group. The East Asian patients developed their SLE disease at a younger age than the other ethnic groups. Cutaneous involvement was more frequent in those who were not Afro-Caribbean. Serositis, joint and neurological involvement were more frequently diagnosed in the South Asian patients. Anti-ENA antibodies were frequently associated with the Afro-Caribbean patients.

Preventing preeclampsia and its fetal complications with low-dose aspirin in East Asians and non-East Asians:A systematic review and meta-analysis

ABSTRACTBackground: Low-dose aspirin can reduce the incidence of preeclampsia and intrauterine growth restriction (IUGR). However, the effects of ethnicity upon low-dose aspirin’s efficacy has not been analyzed. Here, we comparatively evaluated the efficacy of low-dose aspirin in preventing preeclampsia and related fetal complications in East Asian and non-East Asian pregnant women at risk for preeclampsia. Methods: Several databases were searched for randomized controlled trials (RCTs) comparing low-dose aspirin with either placebo or no treatment in pregnant women at risk for preeclampsia. Odds ratios (ORs) and associated 95% confidence intervals (CIs) for preeclampsia and related fetal outcomes were tabulated. Results: Low-dose aspirin significantly reduced preeclampsia risk in both East Asians (OR = 0.20, 95% CI: 0.11–0.35) and non-East Asians (OR = 0.84, 95% CI: 0.77–0.92). Low-dose aspirin significantly reduced IUGR risk in East Asians (OR = 0.36, 95% CI: 0.20–0.67) but not in non-East Asians (OR = 0.85, 95% CI: 0.41–1.77). Low-dose aspirin did not significantly reduce the risk of cesarean section in either East Asians (OR = 0.67, 95% CI: 0.14–3.22) or non-East Asians (OR = 1.01, 95% CI: 0.86–1.19). Conclusions: Low-dose aspirin is effective in reducing preeclampsia risk in both East Asians and non-East Asians and has differential effects in East Asians and non-East Asians with respect to IUGR.

Efficacy and Safety of Apixaban Compared with Warfarin for Stroke Prevention in Patients with Atrial Fibrillation from East Asia: A Subanalysis of the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) Trial

The perceived risk of serious bleeding is an obstacle to the use of oral anticoagulation in East Asia. The efficacy and safety of apixaban in East Asian patients with atrial fibrillation are unknown. ARISTOTLE included 18,201 patients with nonvalvular atrial fibrillation randomized to apixaban 5mg twice daily or warfarin. The efficacy and safety of apixaban and warfarin among patients recruited from East Asia (n = 1,993) were compared with those recruited from outside East Asia (n = 16,208). Compared with warfarin, apixaban resulted in a consistent reduction in stroke or systemic embolism in East Asian (hazard ratio [HR] 0.74, 95% CI 0.50-1.10) and non-East Asian (HR 0.81, 95% CI 0.66-0.99) patients (interaction P = .70). Consistent benefits of apixaban over warfarin were also seen for major bleeding in East Asian (HR 0.53, 95% CI 0.35-0.80) and non-East Asian (HR 0.72, 95% CI 0.62-0.83) patients (interaction P = .17). There was a greater reduction in major or clinically relevant nonmajor bleeding with apixaban compared with warfarin in East Asian (HR 0.49, 95% CI 0.35-0.67) than in non-East Asian (HR 0.71, 95% CI 0.63-0.79) patients (interaction P = .03). Numerically higher rates of intracranial bleeding were seen in East Asian patients with warfarin but not with apixaban. Apixaban resulted in similar reductions in stroke or systemic embolism and major bleeding and greater reductions in major or clinically relevant nonmajor bleeding in patients from East Asia. Warfarin is associated with more intracranial bleeding, particularly in patients from East Asia.

Association of glutathione peroxidase-1 (GPx-1) rs1050450 Pro198Leu and Pro197Leu polymorphisms with cardiovascular risk: a meta-analysis of observational studies.

ObjectiveTo clarify the association between rs1050450 polymorphism in Glutathione peroxidase-1 (GPx-1) and the risk of cardiovascular diseases (CVD) by performing a meta-analysis of published studies. There is growing evidence from different study types for an association of the GPx-1 polymorphism and cardiovascular outcomes, but observational studies have so far shown inconsistent results.MethodsRelevant publications were searched through PubMed, Embase database databases and the Cochrane Library. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of association under the best genetic model. Both Q statistic and the I2 were used to check heterogeneity. Meta-regression analysis was performed to explore heterogeneity source. Sensitivity analysis, cumulative meta-analysis analysis and publication bias were used to test the reliability of the results.ResultsData were available from two cohort studies and 8 case-control studies involving 1,430 cases and 3,767 controls. The pooled ORs for overall CVD risk was 1.36 with 95% CI: 1.08–1.70 under a co-dominant model, and that for East Asian subgroup was 1.84 (95% CI: 1.39–2.43). Substantial heterogeneity for ORs were detected among all the included studies, mainly caused by ethnic differences between East Asian and non-East Asian populations. Although Egger's regression test suggested no statistical significant publication bias, Begg's funnel plot exhibited obvious asymmetry. The statistical significance disappeared after adjusting for potential publication bias in the overall studies. However, no substantial publication bias was found in the East Asian subgroup.ConclusionsGPx-1 gene Pro198Leu and Pro197Leu polymorphisms considerably increased the risk of CVD in the East Asian population. Large-scale investigations are needed to confirm the results in different ethnicities.