Publications by authors named "Lawrence Wong"

160 Publications

Understanding the Clinical Implications of Intracranial Arterial Calcification Using Brain CT and Vessel Wall Imaging.

Front Neurol 2021 15;12:619233. Epub 2021 Jul 15.

Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Kowloon, Hong Kong.

Intracranial arterial calcification (IAC) has been the focus of much attention by clinicians and researchers as an indicator of intracranial atherosclerosis, but correlations of IAC patterns (intimal or medial) with the presence of atherosclerotic plaques and plaque stability are still a matter of debate. Our study aimed to assess the associations of IAC patterns identified on computed tomography (CT) with the presence of plaque detected on vessel wall magnetic resonance imaging and plaque stability. Patients with stroke or transient ischemic attack and intracranial artery stenosis were recruited. IAC was detected and localized (intima or media) on non-contrast CT images. Intracranial atherosclerotic plaques were identified using vessel wall magnetic resonance imaging and matched to corresponding CT images. Associations between IAC patterns and culprit atherosclerotic plaques were assessed by using multivariate regression. Seventy-five patients (mean age, 63.4 ± 11.6 years; males, 46) were included. Two hundred and twenty-one segments with IAC were identified on CT in 66 patients, including 86 (38.9%) predominantly intimal calcifications and 135 (61.1%) predominantly medial calcifications. A total of 72.0% of intimal calcifications coexisted with atherosclerotic plaques, whereas only 10.2% of medial calcifications coexisted with plaques. Intimal calcification was more commonly shown in non-culprit plaques than culprit plaques (25.9 vs. 9.4%, = 0.008). The multivariate mixed logistic regression adjusted for the degree of stenosis showed that intimal calcification was significantly associated with non-culprit plaques (OR, 2.971; 95% CI, 1.036-8.517; = 0.043). Our findings suggest that intimal calcification may indicate the existence of a stable form of atherosclerotic plaque, but plaques can exist in the absence of intimal calcification especially in the middle cerebral artery.
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http://dx.doi.org/10.3389/fneur.2021.619233DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8319500PMC
July 2021

Retinal Differential Light Sensitivity Variation Across the Macula in Healthy Subjects: Importance of Cone Separation and Loci Eccentricity.

Transl Vis Sci Technol 2021 05;10(6):16

Centre for Ophthalmology and Visual Science (Incorporating Lions Eye Institute), The University of Western Australia, Nedlands, Western Australia, Australia.

Purpose: Microperimetry measures differential light sensitivity (DLS) at specific retinal locations. The aim of this study is to examine the variation in DLS across the macula and the contribution to this variation of cone distribution metrics and retinal eccentricity.

Methods: Forty healthy eyes of 40 subjects were examined by microperimetry (MAIA) and adaptive optics imaging (rtx1). Retinal DLS was measured using the grid patterns: foveal (2°-3°), macular (3°-7°), and meridional (2°-8° on horizontal and vertical meridians). Cone density (CD), distribution regularity, and intercone distance (ICD) were calculated at the respective test loci coordinates. Linear mixed-effects regression was used to examine the association between cone distribution metrics and loci eccentricity, and retinal DLS.

Results: An eccentricity-dependent reduction in DLS was observed on all MAIA grids, which was greatest at the foveal-parafoveal junction (2°-3°) (-0.58 dB per degree, 95% confidence interval [CI]; -0.91 to -0.24 dB, P < 0.01). Retinal DLS across the meridional grid changed significantly with each 1000 cells/deg2 change in CD (0.85 dB, 95% CI; 0.10 to 1.61 dB, P = 0.03), but not with each arcmin change in ICD (1.36 dB, 95% CI; -2.93 to 0.20 dB, P = 0.09).

Conclusions: We demonstrate significant variation in DLS across the macula. Topographical change in cone separation is an important determinant of the variation in DLS at the foveal-parafoveal junction. We caution the extrapolation of changes in DLS measurements to cone distribution because the relationship between these variables is complex.

Translational Relevance: Cone density is an independent determinant of DLS in the foveal-parafoveal junction in healthy eyes.
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http://dx.doi.org/10.1167/tvst.10.6.16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8114004PMC
May 2021

Varying degrees of homostructurality in a series of cocrystals of antimalarial drug 11-azaartemisinin with salicylic acids.

Acta Crystallogr C Struct Chem 2021 06 6;77(Pt 6):262-270. Epub 2021 May 6.

Department of Chemistry, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, People's Republic of China.

The X-ray structures of three new 1:1 pharmaceutical cocrystals of 11-azaartemisinin (11-Aza; systematic name: 1,5,9-trimethyl-14,15,16-trioxa-11-azatetracyclo[10.3.1.0.0]hexadecan-10-one, CHNO) with bromo-substituted salicylic acids [namely, 5-bromo- (5-BrSalA, CHBrO), 4-bromo- (4-BrSalA, CHBrO) and 3,5-dibromosalicylic acid (3,5-BrSalA, CHBrO)] are reported. All the structures are related to the parent 11-Aza:SalA cocrystal (monoclinic P2) reported previously. The 5-BrSalA analogue is isostructural with the parent, with lattice expansion along the c axis. The 4-BrSalA and 3,5-BrSalA cocrystals retain the highly preserved 2 stacks of the molecular pairs, but these pack with a varying degree of slippage with respect to neighbouring stacks, altering the close contacts between them, and represent two potential alternative homostructural arrangements for the parent compound. Structure redeterminations of the bromosalicylic acids 5-BrSalA, 4-BrSalA and 3,5-BrSalA at 100 K show that the packing efficiency of the cocrystals need not be higher than the parent coformers, based on specific-volume calculations, attributable to the strong O-H...O=C hydrogen bonds of 2.54 Å in the cocrystals.
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http://dx.doi.org/10.1107/S2053229621004460DOI Listing
June 2021

Evolving ischemic stroke subtypes in 15 years: A hospital-based observational study.

Int J Stroke 2021 Apr 7:17474930211005953. Epub 2021 Apr 7.

Division of Neurology, Department of Medicine and Therapeutics, 26451The Chinese University of Hong Kong, Hong Kong.

Background: Depicting the time trends of ischemic stroke subtypes may inform healthcare resource allocation on etiology-based stroke prevention and treatment.

Aim: To reveal the evolving ischemic stroke subtypes from 2004 to 2018.

Methods: We determined the stroke etiologies of consecutive first-ever transient ischemic attack or ischemic stroke patients admitted to a regional hospital in Hong Kong from 2004 to 2018. We analyzed the age-standardized incidences and the two-year recurrence rate of major ischemic stroke subtypes.

Results: Among 6940 patients admitted from 2004 to 2018, age-standardized incidence of ischemic stroke declined from 187.0 to 127.4 per 100,000 population (p < 0.001), driven by the decrease in large artery disease (43.0-9.67 per 100,000 population (p < 0.001)), and small vessel disease (71.9-45.7 per 100,000 population (p < 0.001)). Age-standardized incidence of cardioembolic stroke did not change significantly (p = 0.2). Proportion of cardioembolic stroke increased from 20.4% in 2004-2006 to 29.3% in 2016-2018 (p < 0.001). Two-year recurrence rate of intracranial atherothrombotic stroke reduced from 19.3% to 5.1% (p < 0.001) with increased prescriptions of statin (p < 0.001) and dual antiplatelet therapy (p < 0.001). In parallel with increased anticoagulation use across the study period (p < 0.001), the two-year recurrence of AF-related stroke reduced from 18.9% to 6% (p < 0.001).

Conclusion: Etiology-based risk factor control might have led to the diminishing stroke incidences related to atherosclerosis. To tackle the surge of AF-related strokes, arrhythmia screening, anticoagulation usage, and mechanical thrombectomy service should be reinforced. Comparable preventive strategies might alleviate the enormous stroke burden in mainland China.
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http://dx.doi.org/10.1177/17474930211005953DOI Listing
April 2021

Properties of the Extracellular Polymeric Substance Layer from Minimally Grown Planktonic Cells of .

Biomolecules 2021 02 22;11(2). Epub 2021 Feb 22.

Division of Food, Nutrition and Dietetics, School of Biosciences, University of Nottingham, Nottingham LE12 5RD, UK.

The bacterium is a serious concern to food processing facilities because of its persistence. When liquid cultures of were prepared in defined media, it was noted that planktonic cells rapidly dropped out of suspension. Zeta potential and hydrophobicity assays found that the cells were more negatively charged (-22, -18, -10 mV in defined media D10, MCDB 202 and brain heart infusion [BHI] media, respectively) and were also more hydrophobic. A SEM analysis detected a capsular-like structure on the surface of cells grown in D10 media. A crude extract of the extracellular polymeric substance (EPS) was found to contain cell-associated proteins. The proteins were removed with pronase treatment. The remaining non-proteinaceous component was not stained by Coomassie blue dye and a further chemical analysis of the EPS did not detect significant amounts of sugars, DNA, polyglutamic acid or any other specific amino acid. When the purified EPS was subjected to attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy, the spectra obtained did not match the profile of any of the 12 reference compounds used. An x-ray diffraction (XRD) analysis showed that the EPS was amorphous and a nuclear magnetic resonance (NMR) analysis detected the presence of glycerol. An elemental energy dispersive x-ray (EDX) analysis showed traces of phosphorous as a major component. In conclusion, it is proposed that the non-proteinaceous component may be phospholipid in nature, possibly derived from the cell wall lipoteichoic acid.
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http://dx.doi.org/10.3390/biom11020331DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7926710PMC
February 2021

Dabigatran or Aspirin in East Asian Patients With Embolic Stroke of Undetermined Source: RE-SPECT ESUS Subgroup Analysis.

Stroke 2021 Mar 16;52(3):1069-1073. Epub 2021 Feb 16.

Department of Neurology, University of California, San Francisco (J.D.E.).

Background And Purpose: We assessed the outcomes of dabigatran versus aspirin in a prespecified subgroup analysis of East Asian patients with embolic stroke of undetermined source in the RE-SPECT ESUS trial (Randomized, Double-Blind, Evaluation in Secondary Stroke Prevention Comparing the Efficacy and Safety of the Oral Thrombin Inhibitor Dabigatran Etexilate Versus Acetylsalicylic Acid in Patients With Embolic Stroke of Undetermined Source).

Methods: Patients with a recent embolic stroke of undetermined source were randomized to dabigatran (150 or 110 mg BID) or aspirin (100 mg QD). The primary efficacy outcome was recurrent stroke; the primary safety outcome was major bleeding. The East Asia cohort was compared with patients from all other countries (non-East Asia cohort).

Results: Overall, 988 of 5390 patients (18%) were randomized in East Asia. During a median follow-up of 18.8 months, there was no statistically significant difference in recurrent stroke (hazard ratio, 0.65 [95% CI, 0.41-1.03]) or major bleeding (hazard ratio, 1.04 [95% CI, 0.57-1.91]) in East Asian patients receiving dabigatran versus aspirin. Death from any cause occurred more often in the dabigatran versus the aspirin group (hazard ratio, 3.98 [95% CI, 1.32-12.01]).

Conclusions: The treatment effect of dabigatran versus aspirin was consistent between cohorts, with no apparent superiority for dabigatran over aspirin in preventing recurrent stroke in patients with embolic stroke of undetermined source. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02239120.
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http://dx.doi.org/10.1161/STROKEAHA.120.031891DOI Listing
March 2021

Anticoagulant selection in relation to the SAMe-TTR score in patients with atrial fibrillation: The GLORIA-AF registry.

Hellenic J Cardiol 2021 Mar-Apr;62(2):152-157. Epub 2020 Dec 15.

University of Iowa, Mercy Hospital, Mason City, Iowa and Covenant Hospital, Waterloo, IA, USA.

Aim: The SAMe-TTR score helps identify patients with atrial fibrillation (AF) likely to have poor anticoagulation control during anticoagulation with vitamin K antagonists (VKA) and those with scores >2 might be better managed with a target-specific oral anticoagulant (NOAC). We hypothesized that in clinical practice, VKAs may be prescribed less frequently to patients with AF and SAMe-TTR scores >2 than to patients with lower scores.

Methods And Results: We analyzed the Phase III dataset of the Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF), a large, global, prospective global registry of patients with newly diagnosed AF and ≥1 stroke risk factor. We compared baseline clinical characteristics and antithrombotic prescriptions to determine the probability of the VKA prescription among anticoagulated patients with the baseline SAMe-TTR score >2 and ≤ 2. Among 17,465 anticoagulated patients with AF, 4,828 (27.6%) patients were prescribed VKA and 12,637 (72.4%) patients an NOAC: 11,884 (68.0%) patients had SAMe-TTR scores 0-2 and 5,581 (32.0%) patients had scores >2. The proportion of patients prescribed VKA was 28.0% among patients with SAMe-TTR scores >2 and 27.5% in those with scores ≤2.

Conclusions: The lack of a clear association between the SAMe-TTR score and anticoagulant selection may be attributed to the relative efficacy and safety profiles between NOACs and VKAs as well as to the absence of trial evidence that an SAMe-TTR-guided strategy for the selection of the type of anticoagulation in NVAF patients has an impact on clinical outcomes of efficacy and safety. The latter hypothesis is currently being tested in a randomized controlled trial.

Clinical Trial Registration: URL: https://www.clinicaltrials.gov//Unique identifier: NCT01937377, NCT01468701, and NCT01671007.
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http://dx.doi.org/10.1016/j.hjc.2020.11.009DOI Listing
August 2021

Intracranial Arterial Calcification Relates to Long-Term Risk of Recurrent Stroke and Post-stroke Mortality.

Front Neurol 2020 9;11:559158. Epub 2020 Oct 9.

Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hung Hom, Hong Kong.

Intracranial arterial calcification (IAC) is highly prevalent in ischemic stroke patients. However, data on the association of IAC with stroke recurrence and mortality remains limited. We examined the effect of IAC on the long-term recurrence of stroke and the risk of post-stroke mortality. Using a prospective stroke registry, we recruited 694 patients (mean age 71.6 ± 12.4; male sex 50.3%) since December 2004. IAC was visualized using the computed tomography exam that was made at hospital admission and was quantified with the Agatston method. All patients were regularly followed up till July 2016. The impacts of IAC on stroke recurrence and mortality were assessed using Cox-regression models with adjustments for age, sex, and relevant cardiovascular risk factors. During a median follow-up period of 8.8 years, 156 patients (22.5%) suffered a recurrent stroke and 84 died (12.1%). We found that a higher IAC Agatston score related to a higher risk of stroke recurrence (HR per 1-SD increase in IAC: 1.30; 95% CI, 1.08-1.56, = 0.005) and a higher risk of post-stroke mortality (HR per 1-SD increase, 1.44; 95% CI, 1.06-1.96, = 0.019). After investigating etiology-specific risks of stroke-recurrence, we found that a higher IAC Agatston score specifically associated with small-vessel occlusive stroke. IAC is a strong risk factor for recurrent stroke and post-stroke mortality. Among stroke subtypes, IAC relates to higher risk of stroke recurrence among patients with small-vessel disease, which indicates chronic calcification detected in large cerebral arteries may have potential effects on the cerebrovascular beds extending to small vessels.
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http://dx.doi.org/10.3389/fneur.2020.559158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7581678PMC
October 2020

Five-Year Prognosis After TIA or Minor Ischemic Stroke in Asian and Non-Asian Populations.

Neurology 2021 01 12;96(1):e54-e66. Epub 2020 Oct 12.

From the Department of Neurology and Stroke Center (T.H., H.C., J.L., P.C.L., P.-J.T., P.A.), Bichat Hospital, AP-HP and INSERM LVTS-U1148, DHU FIRE, Université Paris-Diderot, Sorbonne-Paris Cité, France; Center for Brain and Cerebral Vessels (S.U.), Sanno Hospital and Sanno Medical Center, International University of Health and Welfare, Tokyo, Japan; Department of Medicine and Therapeutics (L.K.S.W.), Chinese University of Hong Kong, Prince of Wales Hospital; Department of Neurology (T.H., K.K.), Tokyo Women's Medical University, Japan; Université Lille (J.L.), Centre Hospitalier Universitaire Lille, Équipe d'Accueil 2694-Santé Publique: Épidémiologie et Qualité des Soins, Lille, France; Stanford Stroke Center (G.W.A.), Department of Neurology and Neurological Sciences, Stanford University Medical Center, CA; Cerebrovascular Disease Service (L.R.C.), Beth Israel Deaconess Medical Center, Harvard University, Boston, MA; Melbourne Brain Centre (G.A.D.), Royal Melbourne Hospital, University of Melbourne, Parkville, Australia; Department of Neurosciences (J.M.F.), Service of Neurology, Hospital Santa Maria, University of Lisbon, Portugal; Department of Neurology (M.G.H.), Universitäts Medizin Mannheim, Heidelberg University, Germany; Stroke Unit, Department of Neurology (C.M.), Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Spain; Stroke Prevention Research Unit (P.M.R.), Nuffield Department of Clinical Neuroscience, University of Oxford, UK; Department of Cardiology (P.G.S.), Bichat Hospital, AP-HP, Paris, France; National Heart and Lung Institute Imperial College (P.G.S.), Institute of Cardiovascular Medicine and Science Royal Brompton Hospital, London, UK; Department of Biostatistics (É.V.), Université Paris-Diderot, Sorbonne-Paris Cité, Fernand Widal Hospital, AP-HP, Paris, France.

Objective: To determine long-term vascular outcomes of Asian patients who experienced TIA or minor ischemic stroke and to compare the outcomes of Asian patients with those of non-Asian patients, in the context of modern guideline-based prevention strategies.

Methods: This is a subanalysis of the TIAregistry.org project, in which 3,847 patients (882 from Asian and 2,965 from non-Asian countries) with a recent TIA or minor ischemic stroke were assessed and treated by specialists at 42 dedicated units from 14 countries and followed for 5 years. The primary outcome was a composite of cardiovascular death, nonfatal stroke, and nonfatal acute coronary syndrome.

Results: No differences were observed in the 5-year risk of the primary outcome (14.0% vs 11.7%; hazard ratio [HR], 1.10; 95% confidence interval [CI], 0.88-1.37; = 0.41) and stroke (10.7% vs 8.5%; HR, 1.17; 95% CI, 0.90-1.51; = 0.24) between Asian and non-Asian patients. Asian participants were at higher risk of intracranial hemorrhage (1.8% vs 0.8%; HR, 2.23; 95% CI, 1.09-4.57; = 0.029). Multivariable analysis showed that the presence of multiple acute infarctions on initial brain imaging was an independent predictor of primary outcome and modified Rankin Scale score of >1 in both Asian (HR, 1.91; 95% CI, 1.11-3.29; = 0.020) and non-Asian (HR, 1.39; 95% CI, 1.02-1.90; = 0.037) patients.

Conclusion: The long-term risk of vascular events in Asian patients was as low as that in non-Asian patients, while Asian participants had a 2.2-fold higher intracranial hemorrhage risk. Multiple acute infarctions were independently associated with future disability in both groups.

Classification Of Evidence: This study provides Class I evidence that among people who experienced TIA or minor stroke, Asian patients have a similar 5-year risk of cardiovascular death, stroke, and acute coronary syndrome as non-Asian patients.
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http://dx.doi.org/10.1212/WNL.0000000000010995DOI Listing
January 2021

Validity of diagnosis and procedure codes for identifying neural tube defects in infants.

Pharmacoepidemiol Drug Saf 2020 11 15;29(11):1489-1493. Epub 2020 Sep 15.

Kaiser Permanente Washington Health Research Institute, Seattle, Washington, USA.

Purpose: The use of validated criteria to identify birth defects in electronic healthcare databases can avoid the cost and time-intensive efforts required to conduct chart reviews to confirm outcomes. This study evaluated the validity of various case-finding methodologies to identify neural tube defects (NTDs) in infants using an electronic healthcare database.

Methods: This analysis used data generated from a study whose primary aim was to evaluate the association between first-trimester maternal prescription opioid use and NTDs. The study was conducted within the Medication Exposure in Pregnancy Risk Evaluation Program. A broad approach was used to identify potential NTDs including diagnosis and procedure codes from inpatient and outpatient settings, death certificates and birth defect flags in birth certificates. Potential NTD cases were chart abstracted and confirmed by clinical experts. Positive predictive values (PPVs) and 95% confidence intervals (95% CI) are reported.

Results: The cohort included 113 168 singleton live-born infants: 55 960 infants with opioid exposure in pregnancy and 57 208 infants unexposed in pregnancy. Seventy-three potential NTD cases were available for the validation analysis. The overall PPV was 41% using all diagnosis and procedure codes plus birth certificates. Restricting approaches to codes recorded in the infants' medical record or to birth certificate flags increased the PPVs (72% and 80%, respectively) but missed a substantial proportion of confirmed NTDs.

Conclusions: Codes in electronic healthcare data did not accurately identify confirmed NTDs. These results indicate that chart review with adjudication of outcomes is important when conducting observational studies of NTDs using electronic healthcare data.
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http://dx.doi.org/10.1002/pds.5128DOI Listing
November 2020

Regional High Wall Shear Stress Associated With Stenosis Regression in Symptomatic Intracranial Atherosclerotic Disease.

Stroke 2020 10 4;51(10):3064-3073. Epub 2020 Sep 4.

Shenzhen Research Institute, The Chinese University of Hong Kong, China (X.L.).

Background And Purpose: Understanding the mechanisms underlying progression/regression of symptomatic intracranial atherosclerotic stenosis (sICAS) will inform secondary prevention of the patients. Focal wall shear stress (WSS) may play an important role, which, however, had seldom been investigated.

Methods: Patients with acute ischemic stroke or transient ischemic attack (TIA) attributed to 50% to 99% intracranial atherosclerotic stenosis were recruited. All patients underwent cerebral computed tomography angiography at baseline, and a computational fluid dynamics model was built based on computed tomography angiography to simulate blood flow and quantify WSS in the vicinity of the sICAS lesion. All patients received optimal medical treatment and a second computed tomography angiography at 1 year. The change in the luminal stenosis from baseline to 1 year in sICAS was defined as progression (increased >10%), quiescence (±10%), or regression (decreased >10%). Associations between baseline WSS metrics and sICAS regression were analyzed.

Results: Among 39 patients (median age 62 years; 27 males), sICAS luminal stenosis progressed, remained quiescent and regressed in 6 (15.4%), 15 (38.5%), and 18 (46.2%) cases, respectively. A higher maximum WSS and larger high-WSS area, throughout the sICAS lesion or obtained separately in the proximal and distal parts of the lesion, were independently associated with regression of luminal stenosis in sICAS over 1 year.

Conclusions: A majority of sICAS lesions regress or stay quiescent in the luminal stenosis over 1 year after stroke under optimal medical treatment, when higher focal WSS may facilitate stenosis regression. Further studies of the effects of hemodynamics including WSS in altering plaque vulnerability and stroke risks are needed.
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http://dx.doi.org/10.1161/STROKEAHA.120.030615DOI Listing
October 2020

Real-world efficacy and safety of immune checkpoint inhibitors in advanced hepatocellular carcinoma: Experience of a tertiary Asian Center.

Asia Pac J Clin Oncol 2020 Sep 1. Epub 2020 Sep 1.

Division of Medical Oncology, National Cancer Centre Singapore, Singapore.

Introduction: Immune checkpoint inhibitor (ICI) use in advanced hepatocellular carcinoma (HCC) is increasing. Real-world data on efficacy and safety, however, are lacking.

Methods: We conducted a retrospective review of all patients with advanced HCC seen at our center who received at least one dose of an ICI between May 2015 and June 2018. Data cutoff was December 31, 2018. Responses were evaluated using Response Evaluation Criteria in Solid Tumors version 1.1 criteria.

Results: Of 114 patients, 88.6% were male. Median age was 66 years, 96.5% had an Eastern Cooperative Oncology Group of 0-1. 62.3% received monotherapy ICI. 18.4% of patients had Child-Pugh (CP) B disease on initiation of ICI, and 69.3% had an ALBI grade of 2. 54.4% were known to have chronic hepatitis B (HBV) or were previously infected, and 11.4% had hepatitis C. Baseline HBV viral load (VL) ranged from undetectable to 8 210 000 IU/mL. 35.1% received prior systemic treatment. 28.9% received prior sorafenib. Over a median follow-up duration of 13.8 months (10.4-15.8), ORR was 18.4%, and DCR was 50.9%. Median progression-free survival was 2.7 months (1.3-4.0), and median overall survival (OS) was 13.9 months (6.9-16.2). Thirty-one patients (27.2%) received further systemic therapy after ICI discontinuation. On multivariable analyses, lower albumin level, higher bilirubin level, diuretic-refractory ascites, and HBV-associated HCC were associated with poorer OS. 69.3% of patients experienced adverse events (AE) of any grade, 14.9% of these being grade 3-4. No grade 5 AE were observed. Use of antiviral therapy was associated with a lower risk of grade 3 or above hepatic AEs (P = 0.048), whereas high baseline HBV VL was not associated with an increased risk of reactivation or hepatic AE.

Discussion: We have demonstrated that the real-world performance of ICIs in advanced HCC appears comparable to that observed in clinical trials for HCC patients with CP A cirrhosis. While prognosis of patients with advanced HCC and CP B cirrhosis remains poor even with ICI, usage of ICI is likely to be safe. Patients with HBV with a baseline HBV VL ≥100 IU/mL may receive ICI safely, especially if they are on antiviral treatment.
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http://dx.doi.org/10.1111/ajco.13454DOI Listing
September 2020

Chiral anionic layers in tartramide spiroborate salts and variable solvation for [NR][B(TarNH)] (R = Et, Pr or Bu).

Acta Crystallogr C Struct Chem 2020 Jul 30;76(Pt 7):695-705. Epub 2020 Jun 30.

Department of Chemistry, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, People's Republic of China.

The spiroborate anion, namely, 2,3,7,8-tetracarboxamido-1,4,6,9-tetraoxa-5λ-boraspiro[4.4]nonane, [B(TarNH)], derived from the diol L-tartramide TarNH, [CH(O)(CONH)], shows a novel self-assembly into two-dimensional (2D) layer structures in its salts with alkylammonium cations, [NR] (R = Et, Pr and Bu), and sparteinium, [HSpa], in which the cations and anions are segregated. The structures of four such salts are reported, namely, the tetrapropylazanium salt, CHN·CHBNO, the tetraethylazanium salt hydrate, CHN·CHBNO·6.375HO, the tetrabutylazanium salt as the ethanol monosolvate hemihydrate, CHN·CHBNO·CHOH·0.5HO, and the sparteinium (7-aza-15-azoniatetracyclo[7.7.1.0.0]heptadecane) salt as the ethanol monosolvate, CHN·CHBNO·CHOH. The 2D anion layers have preserved intermolecular hydrogen bonding between the amide groups and a typical metric repeat of around 10 × 15 Å. The constraint of matching the interfacial area organizes the cations into quite different solvated arrangements, i.e. the [NEt] salt is highly hydrated with around 6.5HO per cation, the [NPr] salt apparently has a good metric match to the anion layer and is unsolvated, whilst the [NBu] salt is intermediate and has EtOH and HO in its cation layer, which is similar to the arrangement for the chiral [HSpa] cation. This family of salts shows highly organized chiral space and offers potential for the resolution of both chiral cations and neutral chiral solvent molecules.
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http://dx.doi.org/10.1107/S2053229620008384DOI Listing
July 2020

Automated Process Incorporating Machine Learning Segmentation and Correlation of Oral Diseases with Systemic Health.

Annu Int Conf IEEE Eng Med Biol Soc 2019 Jul;2019:3387-3393

Imaging fluorescent disease biomarkers in tissues and skin is a non-invasive method to screen for health conditions. We report an automated process that combines intraoral fluorescent porphyrin biomarker imaging, clinical examinations and machine learning for correlation of systemic health conditions with periodontal disease. 1215 intraoral fluorescent images, from 284 consenting adults aged 18-90, were analyzed using a machine learning classifier that can segment periodontal inflammation. The classifier achieved an AUC of 0.677 with precision and recall of 0.271 and 0.429, respectively, indicating a learned association between disease signatures in collected images. Periodontal diseases were more prevalent among males (p=0.0012) and older subjects (p=0.0224) in the screened population. Physicians independently examined the collected images, assigning localized modified gingival indices (MGIs). MGIs and periodontal disease were then cross-correlated with responses to a medical history questionnaire, blood pressure and body mass index measurements, and optic nerve, tympanic membrane, neurological, and cardiac rhythm imaging examinations. Gingivitis and early periodontal disease were associated with subjects diagnosed with optic nerve abnormalities (p<; 0.0001) in their retinal scans. We also report significant co-occurrences of periodontal disease in subjects reporting swollen joints (p=0.0422) and a family history of eye disease (p=0.0337). These results indicate cross-correlation of poor periodontal health with systemic health outcomes and stress the importance of oral health screenings at the primary care level. Our screening process and analysis method, using images and machine learning, can be generalized for automated diagnoses and systemic health screenings for other diseases.
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http://dx.doi.org/10.1109/EMBC.2019.8857965DOI Listing
July 2019

Cilostazol Versus Aspirin in Ischemic Stroke Patients With High-Risk Cerebral Hemorrhage: Subgroup Analysis of the PICASSO Trial.

Stroke 2020 03 20;51(3):931-937. Epub 2019 Dec 20.

Department of Neurology (S.U.K., D.-W.K.), Asan Medical Center, Ulsan University, Seoul, Korea.

Background and Purpose- Although cilostazol has shown less hemorrhagic events than aspirin, only marginal difference was observed in hemorrhagic stroke events among patients at high risk for cerebral hemorrhage. To identify patients who would most benefit from cilostazol, this study analyzed interactions between treatment and subgroups of the PICASSO trial (Prevention of Cardiovascular Events in Asian Ischemic Stroke Patients With High Risk of Cerebral Hemorrhage). Methods- Ischemic stroke patients with a previous intracerebral hemorrhage or multiple microbleeds were randomized to treatment with cilostazol or aspirin and followed up for a mean 1.8 years. Efficacy, defined as the composite of any stroke, myocardial infarction, and vascular death, and safety, defined as the incidence of hemorrhagic stroke, were analyzed in the 2 groups. Interactions between treatment and age, sex, presence of hypertension and diabetes mellitus, index of high-risk cerebral hemorrhage, and white matter lesion burden were analyzed for primary and key secondary outcomes. Changes in vital signs and laboratory results were compared in the 2 groups. Results- Among all 1534 patients enrolled, a significant interaction between treatment group and index of high risk for cerebral hemorrhage on hemorrhagic stroke ( for interaction, 0.03) was observed. Hemorrhagic stroke was less frequent in the cilostazol than in the aspirin group in patients with multiple microbleeds (1 versus 13 events; hazard ratio, 0.08 [95% CI, 0.01-0.61]; =0.01). A marginal interaction between treatment group and white matter change on any stroke ( for interaction, 0.08) was observed. Cilostazol reduced any stroke significantly in patients with mild (5 versus 16 events; hazard ratio, 0.36 [95% CI, 0.13-0.97]; =0.04)-to-moderate (16 versus 32 events; hazard ratio, 0.50 [95% CI, 0.29-0.92]; =0.03) white matter changes. Heart rate and HDL (high-density lipoprotein) cholesterol level were significantly higher in the cilostazol group than in the aspirin group at follow-up. Conclusions- Cilostazol may be more beneficial for ischemic stroke patients with multiple cerebral microbleeds and before white matter changes are extensive. Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT01013532.
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http://dx.doi.org/10.1161/STROKEAHA.119.023855DOI Listing
March 2020

Tandem crystallization strategies for resolution of 3,3,3-trifluorolactic acid [CF CH(OH)COOH] by chiral benzylamines.

Chirality 2019 11 30;31(11):979-991. Epub 2019 Sep 30.

Department of Chemistry, Hong Kong University of Science and Technology, Kowloon, Hong Kong, China.

Resolution of rac-3,3,3-trifluorolactic acid by diastereomeric salt formation was reinvestigated. The use of (S)-1-phenylethylamine gives coprecipitation of two diastereomeric phases, 1 (S)-[NH CH(CH )Ph](S)-[CF CH(OH)COO] and 2 (S)-[NH CH(CH )Ph](R)-[CF CH(OH)COO]·H O. Pure phase 1 may be obtained using molecular sieves as desiccants. Resolution by (S,S)-2-amino-1-phenylpropan-1,3-diol gives monoclinic (S,S)-[NH CH(CH OH)CHOHPh] (R)-[CF CH(OH)-COO] 3 with minor (S)-3,3,3-trifluorolactate contamination, which is precluded in the recrystallized orthorhombic form 4. A new resolution using inexpensive phenylglycinol gives pure phase 5 (S)-[NH CH(CH OH)Ph] (S)-[CF CH(OH)COO] in 76% yield, 94% ee in a single step, in preference to its (S)-(R) diastereomer 6. Overall efficient resolution for both enantiomers of the trifluorolactic acid (each ca. 70% yield, 99% ee) may be achieved by various two-step "tandem" crystallizations, involving direct addition of either water or a second base to the filtrate from the initial reaction.
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http://dx.doi.org/10.1002/chir.23127DOI Listing
November 2019

A multi-body model for comparative study of cervical traction simulation - comparison between inclined and sitting traction.

Comput Methods Biomech Biomed Engin 2019 Jun 13;22(8):861-868. Epub 2019 Apr 13.

c Fujino Orthopedics Hospital , Hamamatsu , Japan.

A computer simulation model was developed to compare the result of cervical traction therapy in inclined and sitting traction positions. The behavior of the model was shown to match with the intervertebral changes in the upper and lower spine from the data of a radiographic experiment. Both the results of the experiment and the simulation also showed that in the inclined position, the amount of posterior separations in the upper cervical spine remains constant regardless of traction angle, while the posterior separations at lower cervical spine increases along with traction angles. Using the simulation model, parametric studies were conducted to investigate the intervertebral space changes in response to different traction angles in the inclined and sitting positions. When using the sitting position, the subject's hip joint stiffness was shown to cause larger variations in the intervertebral space than in the inclined position. In addition, variations in the tension/compression stiffness was shown to cause the largest changes in the resulting separations in both positions but the variations in anterior space changes were larger in the sitting position. Our study suggests that the inclined position is less sensitive to variations in the subject's body parameters and is able to provide a more reliable and predictable traction result than the sitting position.
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http://dx.doi.org/10.1080/10255842.2019.1600684DOI Listing
June 2019

A multi-body model for comparative study of cervical traction simulation - development, improvement and validation.

Comput Methods Biomech Biomed Engin 2019 Jun 1;22(8):806-814. Epub 2019 Apr 1.

c Fujino Orthopedics Hospital , Hamamatsu , Japan.

A computer simulation model was developed to study the dynamic behavior of the cervical spine during cervical traction therapy in inclined and sitting traction positions. The model improved upon an old model with additional components to represent the behavior of the intervertebral discs and the posterior ligaments. The simulation result of the new model was compared against the cervical traction data from a radiographic experiment in both positions. The simulation results of the old model and new model were compared to illustrate the improvement. Using the new model, we compared the timing response of cervical traction in the inclined and sitting positions.
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http://dx.doi.org/10.1080/10255842.2019.1597063DOI Listing
June 2019

Beat-to-beat blood pressure variability and heart rate variability in relation to autonomic dysregulation in patients with acute mild-moderate ischemic stroke.

J Clin Neurosci 2019 Jun 12;64:187-193. Epub 2019 Mar 12.

Department of Medicine & Therapeutics, The Chinese University of Hong Kong, Hong Kong, China.

Autonomic dysregulation is common in post-stroke patients. We aimed to correlate beat-to-beat blood pressure variability (BPV) and heart rate variability (HRV) with Ewing's test classification. We enrolled patients with acute ischemic stroke. Autonomic function was assessed by Ewing battery and dichotomized into minor or significant group. Beat-to-beat blood pressure and heart rate were monitored for calculating the frequency components of BPV and HRV using power spectral analysis [very low frequency (VLF; <0.04 Hz); low frequency (LF; 0.04-0.15 Hz); high frequency (HF; 0.15-0.40 Hz); power spectral density (PSD; <0.40 Hz) and LF/HF ratio]. In minor autonomic dysregulation group, BPV and HRV were similar with those in controls (all p > 0.05). However, LF/HF ratio in BPV and HRV significantly reduced in significant autonomic dysregulation group compared with that in controls (all p < 0.05). LF BPV in significant group was lower than that in controls. In patients, LF and LF/HF BPVs were positively correlated with parasympathetic parameters, while VLF HRV was negatively correlated with sympathetic parameters and the others were positively correlated with parasympathetic parameters. With cut-off values of 1.80 for LF/HF diastolic BP, 0.96 for the LF/HF systolic BP and 1.80 for LF/HF HRV, the sensitivity (53.80%, 69.20% and 53.80%, respectively) and specificity (92.50%, 80.00% and 92.50%, respectively) of these parameters were observed to predict autonomic dysregulation. Autonomic dysregulation is associated with lower variation of blood pressure and heart rate in acute ischemic stroke. Non-invasive monitoring of beat-to-beat BPV and HRV may be an alternative to autonomic dysregulation measure.
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http://dx.doi.org/10.1016/j.jocn.2019.03.003DOI Listing
June 2019

Postmortem Study Exploring Distribution and Patterns of Intracranial Artery Calcification.

Stroke 2018 11;49(11):2767-2769

Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Kowloon (X.-Y.C.).

Background and Purpose- Intracranial artery calcification detected by computed tomography is associated with ischemic stroke as an indicator of intracranial atherosclerosis. However, little is known about its histopathology. This study aimed to explore the intracranial calcification patterns and their associations with atherosclerotic plaques. Methods- We recruited 32 adult autopsy cases to assess the calcification patterns and distributions in the middle cerebral artery, vertebral artery, and basilar artery. The relationships of calcification patterns with plaque phenotype and luminal stenosis were evaluated. The calcification patterns on computed tomography were correlated with that on histology. Results- Visible calcifications were detected within 37 (39%) segments, including 25 segments with intimal calcification, 6 segments with internal elastic lamina calcification, 3 segments with adventitial calcification, and 3 segments with concurrent calcification. Calcification occurred more often in the vertebral artery (51%), followed by the middle cerebral artery (35%) and basilar artery (14%; P<0.01 for vertebral artery versus basilar artery). Internal elastic lamina calcification was predominantly detected in the vertebral artery (7/8, 88%). All of the 27 (100%) intimal calcifications were present in the progressive atherosclerotic lesions ( P<0.001), whereas only 3/8 (38%) internal elastic lamina calcifications and 4/6 (67%) adventitial calcifications were associated with progressive plaques. Arteries with intimal calcification had more severe luminal stenosis than those without (46% versus 21%; P<0.001). Conclusions- Our histological findings indicate that the presence of intracranial artery calcification has 3 patterns, including intimal, internal elastic lamina, and adventitial calcifications. But only intimal calcification is related with progressive atherosclerotic lesions, indicative of a proxy for intracranial atherosclerosis.
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http://dx.doi.org/10.1161/STROKEAHA.118.022591DOI Listing
November 2018

The utility of the Milan System as a risk stratification tool for salivary gland fine needle aspiration cytology specimens.

Cytopathology 2019 01 12;30(1):91-98. Epub 2018 Nov 12.

Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania.

Objective: To perform a retrospective investigation of our institutional experience with salivary gland fine needle aspirations (FNA) through the framework of The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) and assess the risks of neoplasm and malignancy for each diagnostic category.

Methods: All salivary gland FNAs performed from January 2009 to December 2016 were retrospectively categorised according to the MSRSGC. When available, pre-operative cytological results were correlated with subsequent histological follow-up.

Results: In total, 893 FNAs were reviewed. The specimens were retrospectively classified as nondiagnostic (ND: 13.5%), non-neoplastic (NN: 16.1%), atypia of undetermined significance (AUS: 10.8%), benign neoplasm (BN: 34.9%), salivary gland neoplasm of uncertain malignant potential (SUMP: 8.2%), suspicious for malignancy (SM: 2.7%) and malignant (M: 13.8%). Histological follow-up was available for 429 cases (48%); the majority (68.1%) were benign. The risks of neoplasm and malignancy for each category were as follows: ND: 64.5%, 16.1%; NN: 42.9%, 17.9%; AUS: 79.6%, 30.6%; BN: 100%, 2.2%; SUMP: 100%, 46.6%; SM: 94.7%, 78.9%; and M: 100%, 98.5%.

Conclusions: The MSRSGC is a useful classification scheme for stratifying salivary gland lesions according to their associated risk of malignancy and guiding clinicians toward appropriate management. Diagnostic pitfalls are seen in a small proportion of cases and a multidisciplinary approach for assessing salivary gland pathology is essential in their evaluation.
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http://dx.doi.org/10.1111/cyt.12642DOI Listing
January 2019

Cocrystals of the antimalarial drug 11-azaartemisinin with three alkenoic acids of 1:1 or 2:1 stoichiometry.

Acta Crystallogr C Struct Chem 2018 06 24;74(Pt 6):742-751. Epub 2018 May 24.

Department of Chemistry, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, People's Republic of China.

The stoichiometry, X-ray structures and stability of four pharmaceutical cocrystals previously identified from liquid-assisted grinding (LAG) of 11-azaartemisinin (11-Aza; systematic name: 1,5,9-trimethyl-14,15,16-trioxa-11-azatetracyclo[10.3.1.0.0]hexadecan-10-one) with trans-cinnamic (Cin), maleic (Mal) and fumaric (Fum) acids are herein reported. trans-Cinnamic acid, a mono acid, forms 1:1 cocrystal 11-Aza:Cin (1, CHNO·CHO). Maleic acid forms both 1:1 cocrystal 11-Aza:Mal (2, CHNO·CHO), in which one COOH group is involved in self-catenation, and 2:1 cocrystal 11-Aza:Mal (3, 2CHNO·CHO). Its isomer, fumaric acid, only affords 2:1 cocrystal 11-Aza:Fum (4). All cocrystal formation appears driven by acid-lactam R(8) heterosynthons with short O-H...O=C hydrogen bonds [O...O = 2.56 (2) Å], augmented by weaker C=O...H-N contacts. Despite a better packing efficiency, cocrystal 3 is metastable with respect to 2, probably due to a higher conformational energy for the maleic acid molecule in its structure. In each case, the microcrystalline powders from LAG were useful in providing seeding for the single-crystal growth.
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http://dx.doi.org/10.1107/S2053229618006320DOI Listing
June 2018

Validity and reliability of two alternate versions of the Montreal Cognitive Assessment (Hong Kong version) for screening of Mild Neurocognitive Disorder.

PLoS One 2018 23;13(5):e0196344. Epub 2018 May 23.

Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China.

Objective: Repeated testing using the Montreal Cognitive Assessment (MoCA) increases risks for practice effects which may bias measurements of cognitive change. The objective of this study is to develop two alternate versions of the MoCA (Hong Kong version; HK-MoCA) and to investigate the validity and reliability of the alternate versions in patients with DSM-5 Mild Neurocognitive Disorder (Mild NCD) and cognitively healthy controls.

Methods: Concurrent validity and inter-scale agreement were examined by Pearson correlation of the total scores between the original and alternate versions and the Bland-Altman Method. Criterion validity of the two alternate versions in differentiating patients with Mild NCD was tested using receiver operating characteristic curve (ROC) analysis. One-month test-retest and inter-rater reliability were examined in 20 participants. Internal consistency of the alternate versions was measured by the Cronbach's α.

Results: 30 controls (age 73.4 [4.5] years, 60% female) and 30 patients (age 75.4 [5.5] years, 73% female) with Mild NCD were recruited. Both alternate versions significantly correlated with the original version (r = 0.79-0.87, p<0.001). Mean differences of 0.17 and -0.40 points were found between the total scores of the alternate with the original versions with a consistent level of agreement observed throughout the range of cognitive abilities. Both alternate versions significantly differentiated patients with Mild NCD from healthy controls (area under ROC 0.922 and 0.724, p<0.001) and showed good one-month test-retest reliability (intra-class correlation [ICC] = 0.92 and 0.82) and inter-rater reliability (ICC = 0.99 and 0.87) and high internal consistency (Cronbach α = 0.79 and 0.75).

Conclusion: The two alternate versions of the HK-MoCA are useful for Mild NCD screening.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0196344PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5965815PMC
August 2018

Prevention of cardiovascular events in Asian patients with ischaemic stroke at high risk of cerebral haemorrhage (PICASSO): a multicentre, randomised controlled trial.

Lancet Neurol 2018 06;17(6):509-518

Department of Neurology, University of Ulsan, Ulsan, South Korea.

Background: The optimal treatment for patients with ischaemic stroke with a high risk of cerebral haemorrhage is unclear. We assessed the efficacy and safety of cilostazol versus aspirin, with and without probucol, in these patients.

Methods: In this randomised, controlled, 2 × 2 factorial trial, we enrolled patients with ischaemic stroke with a history of or imaging findings of intracerebral haemorrhage or two or more microbleeds from 67 centres in three Asian countries. Patients were randomly assigned (1:1:1:1) to receive oral cilostazol (100 mg twice a day), aspirin (100 mg once a day), cilostazol plus probucol (250 mg twice a day), or aspirin plus probucol with centralised blocks stratified by centre. Cilostazol versus aspirin was investigated double-blinded; probucol treatment was open-label, but the outcome assessor was masked to assignment. The co-primary outcomes were incidence of the composite of stroke, myocardial infarction, or vascular death (efficacy) and incidence of haemorrhagic stroke (safety), which were assessed in intention-to-treat and modified intention-to-treat populations. Efficacy was analysed with a non-inferiority test and a superiority test if non-inferiority was satisfied. Safety was assessed with a superiority test only. This trial is registered with ClinicalTrials.gov, NCT01013532.

Findings: Between Aug 1, 2009, and Aug 31, 2015, we randomly assigned 1534 patients to one of the four study groups, of whom 1512 were assessed for the co-primary endpoints. During a median follow-up of 1·9 years (IQR 1·0-3·0), the incidence of composite vascular events was 4·27 per 100 person-years in patients who received cilostazol and 5·33 per 100 person-years in patients who received aspirin (HR 0·80, 95% CI 0·57-1·11; non-inferiority p=0·0077; superiority p=0·18). Incidence of cerebral haemorrhage was 0·61 per 100 person-years in patients who received cilostazol and 1·20 per 100 person-years in those who received aspirin (HR 0·51, 97·5% CI 0·20-1·27; superiority p=0·18). The incidence of vascular events was 3·91 per 100 person-years in the probucol group compared with 5·75 per 100 person-years in the non-probucol group (HR 0·69, 95% CI 0·50-0·97; superiority p=0·0316). The incidence of cerebral haemorrhage was 0·72 per 100 person-years in the probucol group and 1·11 per 100 person-years in the non-probucol group (HR 0·65, 97·5% CI 0·27-1·57; p=0·55). Adverse events were similar across the four study groups; the most common events were dizziness, headache, diarrhoea, and constipation.

Interpretation: In patients with ischaemic stroke at high risk of cerebral haemorrhage, cilostazol was non-inferior to aspirin for the prevention of cardiovascular events, but did not reduce the risk of haemorrhagic stroke. Addition of probucol to aspirin or cilostazol could be beneficial for reducing the incidence of cardiovascular events.

Funding: Korea Otsuka Pharmaceutical.
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http://dx.doi.org/10.1016/S1474-4422(18)30128-5DOI Listing
June 2018

Five-Year Risk of Stroke after TIA or Minor Ischemic Stroke.

N Engl J Med 2018 Jun 16;378(23):2182-2190. Epub 2018 May 16.

From Assistance Publique-Hôpitaux de Paris (AP-HP), Department of Neurology and Stroke Center (P.A., P.C.L., L.M.T., J.L., P.-J.T.), and the Department of Cardiology (P.G.S.), Bichat Hospital, INSERM Laboratory for Vascular Translational Science-Unité 1148, Département Hospitalo-Universitaire Fibrose Inflammation Remodelage, Université Paris-Diderot, Sorbonne-Paris Cité, and AP-HP, Department of Biostatistics, Université Paris-Diderot, Sorbonne-Paris Cité, Fernand Widal Hospital (É.V.), Paris, and Université Lille, Centre Hospitalier Universitaire Lille, Équipe d'Accueil 2694-Santé Publique: Épidémiologie et Qualité des Soins, Lille (J.L.) - all in France; the Stanford Stroke Center, Department of Neurology and Neurological Sciences, Stanford University Medical Center, Stanford, CA (G.W.A.); the Department of Neurology, Hôtel-Dieu de France, Saint Joseph University, Beirut, Lebanon (H. Abboud); the Stroke Unit, San Camillo Hospital, Rome (S.A.); Ärztliche Leitung der Klinik für Neurologie, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, Berlin (H. Audebert), Klinik für Neurologie, Allgemeines Krankenhaus Celle, Celle (W.H.), and the Department of Neurology, Universitäts Medizin Mannheim, Heidelberg University, Heidelberg (M.G.H.) - all in Germany; Shaare Zedek Medical Center, Jerusalem, Israel (N.M.B.); the Cerebrovascular Disease Service, Beth Israel Deaconess Medical Center, Harvard University, Boston (L.R.C.); Serviço de Neurologia, Hospital de Santo António-Centro Hospitalar do Porto, Porto (M.C.), and the Department of Neurosciences, Service of Neurology, Hospital Santa Maria, University of Lisbon, Lisbon (J.M.F.) - both in Portugal; the Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, Australia (G.A.D.); the Stroke Unit and Neurology Service, University Hospital José Eleuterio González, Universidad Autónoma de Nuevo León, Monterrey, Mexico (F.G.-R.); the Neurovascular Research Unit and Health Research Board, Stroke Clinical Trials Network Ireland, University College Dublin, Dublin (P.J.K.); the Comprehensive Stroke Center, Palacký University and University Hospital Olomouc (M.K.), and the Department of Nursing, Faculty of Health Science, Palacký University (D.Š), Olomouc, Czech Republic; the Department of Neurology, Kaohsiung Medical University Chung-Ho Memorial Hospital and Kaohsiung Medical University, Kaohsiung, Taiwan (H.-F.L.); the Stroke Unit, Department of Neurology, Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona (C.M.), the Stroke Unit, Hospital Universitari Arnau de Vilanova, Universitat de Lleida, Lleida (F.P.), and the Stroke Unit, Department of Neurology, Albacete University Hospital, Universidad de Castilla-La Mancha, Albacete (T.S.) - all in Spain; the Department of Neurology, Nowon Eulji Medical Center, Eulji University, Seoul, South Korea (J.M.P.); the Stroke Prevention Research Unit, Nuffield Department of Clinical Neuroscience, University of Oxford, Oxford (P.M.R.), and the National Heart and Lung Institute Imperial College, Institute of Cardiovascular Medicine and Science Royal Brompton Hospital, London (P.G.S.) - both in the United Kingdom; the International University of Health and Welfare, Center for Brain and Cerebral Vessels, Sanno Hospital and Sanno Medical Center, Tokyo (S.U.); the Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing (Y.W.); and the Department of Medicine and Therapeutics, Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong (L.K.S.W.).

Background: After a transient ischemic attack (TIA) or minor stroke, the long-term risk of stroke and other vascular events is not well known. In this follow-up to a report on 1-year outcomes from a registry of TIA clinics in 21 countries that enrolled 4789 patients with a TIA or minor ischemic stroke from 2009 through 2011, we examined the 5-year risk of stroke and vascular events.

Methods: We evaluated patients who had had a TIA or minor stroke within 7 days before enrollment in the registry. Among 61 sites that participated in the 1-year outcome study, we selected 42 sites that had follow-up data on more than 50% of their enrolled patients at 5 years. The primary outcome was a composite of stroke, acute coronary syndrome, or death from cardiovascular causes (whichever occurred first), with an emphasis on events that occurred in the second through fifth years. In calculating the cumulative incidence of the primary outcome and secondary outcomes (except death from any cause), we treated death as a competing risk.

Results: A total of 3847 patients were included in the 5-year follow-up study; the median percentage of patients with 5-year follow-up data per center was 92.3% (interquartile range, 83.4 to 97.8). The composite primary outcome occurred in 469 patients (estimated cumulative rate, 12.9%; 95% confidence interval [CI], 11.8 to 14.1), with 235 events (50.1%) occurring in the second through fifth years. At 5 years, strokes had occurred in 345 patients (estimated cumulative rate, 9.5%; 95% CI, 8.5 to 10.5), with 149 of these patients (43.2%) having had a stroke during the second through fifth years. Rates of death from any cause, death from cardiovascular causes, intracranial hemorrhage, and major bleeding were 10.6%, 2.7%, 1.1%, and 1.5%, respectively, at 5 years. In multivariable analyses, ipsilateral large-artery atherosclerosis, cardioembolism, and a baseline ABCD score for the risk of stroke (range, 0 to 7, with higher scores indicating greater risk) of 4 or more were each associated with an increased risk of subsequent stroke.

Conclusions: In a follow-up to a 1-year study involving patients who had a TIA or minor stroke, the rate of cardiovascular events including stroke in a selected cohort was 6.4% in the first year and 6.4% in the second through fifth years. (Funded by AstraZeneca and others.).
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http://dx.doi.org/10.1056/NEJMoa1802712DOI Listing
June 2018

Correlation of non-vitamin K antagonist oral anticoagulant exposure and cerebral microbleeds in Chinese patients with atrial fibrillation.

J Neurol Neurosurg Psychiatry 2018 07 29;89(7):680-686. Epub 2018 Mar 29.

Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong.

Background And Purpose: Cerebral microbleeds (CMBs) are radiological markers which predict future intracerebral haemorrhage. Researchers are exploring how CMBs can guide anticoagulation decisions in atrial fibrillation (AF). The purpose of this study is to evaluate the correlation of non-vitamin K antagonist oral anticoagulants (NOAC) exposure and prevalence of CMBs in Chinese patients with AF.

Methods: We prospectively recruited Chinese patients with AF on NOAC therapy of ≥30 days for 3T MRI brain for evaluation of CMBs and white matter hyperintensities. Patients with AF without prior exposure to oral anticoagulation were recruited as control group.

Results: A total of 282 patients were recruited, including 124 patients in NOAC group and 158 patients in control group. Mean duration of NOAC exposure was 723.8±500.3 days. CMBs were observed in 103 (36.5%) patients. No significant correlation was observed between duration of NOAC exposure and quantity of CMBs. After adjusting for confounding factors (ie, age, hypertension, labile hypertension, stroke history and white matter scores), previous intracerebral haemorrhage was predictive of CMBs (OR 15.28, 95% CI 1.81 to 129.16), particularly lobar CMBs (OR 5.37, 95% CI 1.27 to 22.6). While white matter score was predictive of mixed lobar CMBs (OR 1.65, 95% CI 1.1 to 2.5), both exposure and duration of NOAC use were not predictive of presence of CMBs.

Conclusions: In Chinese patients with AF, duration of NOAC exposure did not correlate with prevalence and burden of CMBs. Further studies with follow-up MRI are needed to determine if long-term NOAC therapy can lead to development of new CMBs.
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http://dx.doi.org/10.1136/jnnp-2017-317151DOI Listing
July 2018

Assess BA10 activity in slide-based and immersive virtual reality prospective memory task using functional near-infrared spectroscopy (fNIRS).

Appl Neuropsychol Adult 2019 Sep-Oct;26(5):465-471. Epub 2018 Mar 16.

a Graduate School of System Informatics, Kobe University , Kobe , Japan.

By using slide-based task in a laboratory setting, previous studies have found that activation of the rostral prefrontal cortex (BA10) is related to prospective memory performance. In this present study, we used immersive virtual reality (VR) technology to measure PM performance in a real-life task in a simulated virtual environment. Functional near-infrared spectroscopy was used simultaneously to record the rostral prefrontal cortex activities of the subjects. By comparing the data against the ones from the slide-based task, the result suggested that the activation of BA10 in the VR tasks were greater than the one in the slide-based tasks, and the VR tasks have the potential to identify the particular location of BA10 that is connected to the PM performance in our daily lives.
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http://dx.doi.org/10.1080/23279095.2018.1443104DOI Listing
January 2020

Guidance on home blood pressure monitoring: A statement of the HOPE Asia Network.

J Clin Hypertens (Greenwich) 2018 03 16;20(3):456-461. Epub 2018 Feb 16.

Department of Hypertension, Centre for Epidemiological Studies and Clinical Trials, The Shanghai Institute of Hypertension, Shanghai Key Laboratory of Hypertension, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Hypertension is an important modifiable cardiovascular risk factor and a leading cause of death throughout Asia. Effective prevention and control of hypertension in the region remain a significant challenge despite the availability of several regional and international guidelines. Out-of-office measurement of blood pressure (BP), including home BP monitoring (HBPM), is an important hypertension management tool. Home BP is better than office BP for predicting cardiovascular risk and HBPM should be considered for all patients with office BP ≥ 130/85 mm Hg. It is important that HBPM is undertaken using a validated device and patients are educated about how to perform HBPM correctly. During antihypertensive therapy, monitoring of home BP control and variability is essential, especially in the morning. This is because HBPM can facilitate the choice of individualized optimal therapy. The evidence and practice points in this document are based on the Hypertension Cardiovascular Outcome Prevention and Evidence (HOPE) Asia Network expert panel consensus recommendations for HBPM in Asia.
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http://dx.doi.org/10.1111/jch.13216DOI Listing
March 2018

White Matter Hyperintensity Predicts the Risk of Incident Cognitive Decline in Community Dwelling Elderly.

J Alzheimers Dis 2018 ;61(4):1333-1341

Department of Medicine and Therapeutics, Therese Pei Fong Chow Research Centre for Prevention of Dementia, Lui Che Woo Institute of Innovative Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China.

Background: Unlike western countries, data on white matter hyperintensity (WMH) in community dwelling elderly in Asian population is very limited.

Objective: To examine the relation between baseline WMH burden and the risk of incident cognitive decline in a community-based cohort with Chinese-dwelling elderly.

Methods: We prospectively evaluated the incident cognitive decline for 226 participants in the Shanghai Aging Study. Baseline WMH severity was visually rated by the age-related white matter changes (ARWMC) scale based on MRI. Cox proportional hazards regression model was used to estimate the relative risk (RR) of total ARWMC scale, global ARWMC score, presence of lacune and microbleed, for incident cognitive decline by adjusting potential confounders.

Results: Forty subjects were identified with incident cognitive decline (new onset 34 mild cognitive impairment and 6 dementia) during a median duration of 6 years follow-up. The incidence of cognitive decline was 3.0 (95% confidence interval [CI] 2.2-4.1) per 100 person-years. Increasing total ARWMC scale [RR1.21 (95% CI 1.06-1.39), p = 0.004)], confluent WMH [RR3.16 (95% CI 1.50-6.64), p = 0.002), and presence of lacunes [RR 2.73 (95% CI 1.21-6.15)] at baseline were independent predictors of incident cognitive decline.

Conclusion: Our study demonstrated that confluent WMH may increase the risk of incident cognitive decline by 3 folds in community dwelling subjects. Small vessel disease may cause heavy burden of cognitive impairment in the elderly in China.
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http://dx.doi.org/10.3233/JAD-170876DOI Listing
January 2019

Converting MMSE to MoCA and MoCA 5-minute protocol in an educationally heterogeneous sample with stroke or transient ischemic attack.

Int J Geriatr Psychiatry 2018 05 2;33(5):729-734. Epub 2018 Jan 2.

Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong.

Background: The Montreal Cognitive Assessment (MoCA) is psychometrically superior over the Mini-mental State Examination (MMSE) for cognitive screening in stroke or transient ischemic attack (TIA). It is free for clinical and research use. The objective of this study is to convert scores from the MMSE to MoCA and MoCA-5-minute protocol (MoCA-5 min) and to examine the ability of the converted scores in detecting cognitive impairment after stroke or TIA.

Methods: A total of 904 patients were randomly divided into training (n = 623) and validation (n = 281) samples matched for demography and cognition. MMSE scores were converted to MoCA and MoCA-5 min using (1) equipercentile method with log-linear smoothing and (2) Poisson regression adjusting for age and education. Receiver operating characteristics curve analysis was used to examine the ability of the converted scores in differentiating patients with cognitive impairment.

Results: The mean education was 5.8 (SD = 4.6; ranged 0-20) years. The entire spectrum of MMSE scores was converted to MoCA and MoCA-5 min using equipercentile method. Relationship between MMSE and MoCA scores was confounded by age and education, and a conversion equation with adjustment for age and education was derived. In the validation sample, the converted scores differentiated cognitively impaired patients with area under receiver operating characteristics curve 0.826 to 0.859.

Conclusion: We provided 2 methods to convert scores from the MMSE to MoCA and MoCA-5 min based on a large sample of patients with stroke or TIA having a wide range of education and cognitive levels. The converted scores differentiated patients with cognitive impairment after stroke or TIA with high accuracy.
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May 2018
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