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Comprehensive analysis of peripheral T-cell and natural killer/T-cell lymphoma in Asian patients: A multinational, multicenter, prospective registry study in Asia

Yoon SE, Song Y, Kim SJ, Yoon DH, Chen TY, Koh Y, et al.

Lancet Reg Health West Pac, 2021 May;10:100126.
PMID: 34327343 DOI: 10.1016/j.lanwpc.2021.100126

Background: Peripheral T-cell lymphomas (PTCLs) are uncommon and their frequency is regionally heterogeneous. Several studies have been conducted to evaluate the clinical features and treatment outcomes of this disease entity, but the majority of these were conducted in limited areas, making it difficult to comprehensively analyze their relative frequency and clinical features. Furthermore, no consensus treatment for PTCLs has been established. Therefore, we conducted an Asia-specific study to understand the relative frequency of PTCLs and assess treatments and their outcomes in Asian patients.
Methods: We performed a multinational, multicenter, prospective registry of adult patients with PTCLs that was named as the International Cooperative non-Hodgkin T-cell lymphoma prospective registry study where thirty-two institutes from six Asian countries and territories (Korea, China, Taiwan, Singapore, Malaysia, and Indonesia) participated.
Findings: A total of 486 patients were registered between April 2016 and February 2019, and more than a half of patients (57%) had stage III or IV. Extranodal natural killer (NK)/T- cell lymphoma was the most common subtype (n = 139,28.6%), followed by angioimmunoblastic T-cell lymphoma (AITL, n = 120,24.7%), PTCL-not otherwise specified (PTCL-NOS, n = 101,20.8%), ALK-positive anaplastic large cell lymphoma (ALCL, n = 34,6.9%), and ALK-negative ALCL (n = 30,6.2%). The median progression-free survival (PFS) and overall survival (OS) were 21.1 months (95% CI,10.6-31.6) and 83.6 months (95% CI, 56.7-110.5), respectively. Upfront use of combined treatment with chemotherapy and radiotherapy showed better PFS than chemotherapy alone in localized ENKTL whereas consolidation with upfront autologous stem cell transplantation (SCT) provided longer PFS in advance stage ENKTL. In patients with PTCLs other than ENKTL, anthracycline-containing chemotherapies were widely used, but the outcome of those regimens was not satisfactory, and upfront autologous SCT was not significantly associated with survival benefit, either. The treatment outcome of salvage chemotherapy was disappointing, and none of the salvage strategies showed superiority to one another.
Interpretation: This multinational, multicenter study identified the relative frequency of each subtype of PTCLs across Asian countries, and the survival outcomes according to the therapeutic strategies currently used.
Funding: Samsung Biomedical Research Institute.
Fulltext Percutaneous dilational tracheostomy--a 3 year experience in a general hospital in Malaysia

Tan CC, Lee HS, Balan S

Med J Malaysia, 2004 Dec;59(5):591-7.
PMID: 15889560

All percutaneous tracheostomies performed in the general intensive care unit (ICU), Hospital Sultanah Aminah, Johor Bahru, Malaysia, from July 1999 to June 2002 were studied. The tracheostomies were performed as an elective bedside technique in the ICU. A total of 352 percutaneous tracheostomies were performed. Eighty-eight percent of the tracheostomies were completed within 15 minutes. The most common complication was bleeding which occurred in 52 patients (14.7%). The rest of the complications encountered were:- transient hypoxia twelve (3.4%), inability/ difficulty to insert tracheostomy tube eight (2.3%), false passage four (1.1%), transient hypotension two (0.6%), pneumothorax two (0.6%), peristomal infection two (0.6%), subcutaneous emphysema one (0.3%), cuff rupture one (0.3%), oesophageal cannulation one (0.3%), and granuloma formation one (0.3%). Conversion to conventional tracheostomies were performed on 7 patients (2%). There was one unfortunate death related to percutaneous tracheostomy. In conclusion, percutaneous dilational tracheostomy can be used safely to manage the airway of critically ill patients.
Fulltext An outbreak of dermatitis among stevodores

Phoon WH, Lee HS, Ho SF, Ngui SJ

Med J Malaysia, 1985 Sep;40(3):220-4.
PMID: 2948100

Cement is a common cause of dermatitis. Workers affected are usually those in cement factories and at building construction sites. Cement dermatitis among port-workers is not so commonly reported. This paper describes an outbreak of dermatitis among stevodores at a port handling cement. The cement was imported in bags, and because of breakage, there was much spillage. It was also hot and dusty inside the hatch of the ship, and some of the stevodores worked bare-bodied. Cases of dermatitis began to appear in January 1983 and reached a peak in April 1983, gradually subsiding over the next few months to August 1983. This coincided with the increased tonnage of cement handled at the port. A total of 33 stevodores were reported as having dermatitis over this period. Of the 15 cases examined, 13 had eczema, and in 19 the hands and wrists were affected. However, most of the cases had multiple site involvement, including the arms, legs and abdomen.
Samples of cement showed the presence of water-soluble chromium, varying from 9.9 to 17.8pg/g. As the stevodores were reluctant to go for skin patch-testing, only four were tested, but two did not return for the reading of the results. The other two were found to have a positive reaction to dichromates. The outbreak of dermatitis was probably due to several factors which are discussed.
Prevalence of elevated body mass index condition and its associated demographic variables among adults in urban areas in Johor, Malaysia

Rozita Z, Lim MT, Lee HS

Med J Malaysia, 2019 04;74(2):145-150.
PMID: 31079126

INTRODUCTION: The prevalence of overweight and obesity is increasing at an alarming rate. It is a major factor for many other metabolic disorders. This study aimed to determine the prevalence of increase body mass index (BMI) and obesity and their associated demographic characteristics among adults in an urban area.
METHODS: A retrospective study was conducted where data was extracted from the Health Status Screening Form (BSSK) at health clinics in Johor Bahru. Using the World Health Organization (WHO), criteria for obesity, BMI≥30.0 kg/m2 was specified as obese and combination of both BMI ranges for overweight (25.0-30.0kg/m2) and obesity (≥30.0kg/m2) as elevated BMI.
RESULTS: The overall prevalence of elevated BMI and obesity was 54.6% and 20.1% respectively. Men had a higher prevalence of elevated BMI (57.4%) with odds of 1.28 higher (95%CI: 1.04-1.58). High prevalence of elevated BMI and obesity were seen among the Indians (elevated BMI - 60.2%, obesity - 19.4%) followed by Malays (elevated BMI -57.8%, obesity - 23.1%) and Chinese showed the lowest (elevated BMI - 39.0%, obesity - 8.8%). The odds of elevated BMI and obesity were lower among younger adults as compared to older adults (≥30 years old).
CONCLUSION: Using WHO criteria, about one in two adults had elevated BMI while one in five were obese. Elevated BMI and obesity disparities were evident in age and ethnicity, but sex differences were encountered in elevated BMI group.
PXR, CAR and HNF4alpha genotypes and their association with pharmacokinetics and pharmacodynamics of docetaxel and doxorubicin in Asian patients

Hor SY, Lee SC, Wong CI, Lim YW, Lim RC, Wang LZ, et al.

Pharmacogenomics J, 2008 Apr;8(2):139-46.
PMID: 17876342

Previously studied candidate genes have failed to account for inter-individual variability of docetaxel and doxorubicin disposition and effects. We genotyped the transcriptional regulators of CYP3A and ABCB1 in 101 breast cancer patients from 3 Asian ethnic groups, that is, Chinese, Malays and Indians, in correlation with the pharmacokinetics and pharmacodynamics of docetaxel and doxorubicin. While there was no ethnic difference in docetaxel and doxorubicin pharmacokinetics, ethnic difference in docetaxel- (ANOVA, P=0.001) and doxorubicin-induced (ANOVA, P=0.003) leukocyte suppression was observed, with Chinese and Indians experiencing greater degree of docetaxel-induced myelosuppression than Malays (Bonferroni, P=0.002, P=0.042), and Chinese experiencing greater degree of doxorubicin-induced myelosuppression than Malays and Indians (post hoc Bonferroni, P=0.024 and 0.025). Genotyping revealed both PXR and CAR to be well conserved; only a PXR 5'-untranslated region polymorphism (-24381A>C) and a silent CAR variant (Pro180Pro) were found at allele frequencies of 26 and 53%, respectively. Two non-synonymous variants were identified in HNF4alpha (Met49Val and Thr130Ile) at allele frequencies of 55 and 1%, respectively, with the Met49Val variant associated with slower neutrophil recovery in docetaxel-treated patients (ANOVA, P=0.046). Interactions were observed between HNF4alpha Met49Val and CAR Pro180Pro, with patients who were wild type for both variants experiencing least docetaxel-induced neutropenia (ANOVA, P=0.030). No other significant genotypic associations with pharmacokinetics or pharmacodynamics of either drug were found. The PXR-24381A>C variants were significantly more common in Indians compared to Chinese or Malays (32/18/21%, P=0.035) Inter-individual and inter-ethnic variations of docetaxel and doxorubicin pharmacokinetics or pharmacodynamics exist, but genotypic variability of the transcriptional regulators PAR, CAR and HNF4alpha cannot account for this variability.
Variability of plasma phenobarbitone concentration in Asian children in Singapore

Lee HS

Ther Drug Monit, 1984;6(2):182-8.
PMID: 6740737

In a study with 113 Asian children in which phenobarbitone was used as the sole antiepileptic drug in 75 children, including Chinese, Malays, and Indians, the mean phenobarbitone dosage required to produce a plasma level of 15 micrograms/ml was 5.2 mg/kg/day. While the mean plasma level/dose ratio varied, the differences between the three ethnic groups were not statistically significant. Also of little difference were the ratios between the male and female groups. For those patients with poor seizure control, however, the mean plasma level/dose ratio was significantly lower than in those whose seizures were controlled. Using additional anticonvulsant drugs concurrently with phenobarbitone in 40 children raised the mean plasma level/dose ratios significantly in each ethnic group. Further, the greater age level in those given additional antiepileptic drugs might have contributed slightly to a higher mean plasma level/dose ratio.
Pharmacokinetics of propofol infusion in Asian patients undergoing coronary artery bypass grafting

Lee HS, Khoo YM, Chua BC, Ng AS, Tan SS, Chew SL

Ther Drug Monit, 1995 Aug;17(4):336-41.
PMID: 7482686

The pharmacokinetics of propofol was studied in 11 Asian patients with fentanyl-isoflurane anaesthesia during cardiopulmonary bypass (CPB) and undergoing elective coronary artery bypass grafting (CABG). Instead of the usual increments of morphine and a benzodiazepine, propofol (4 mg/kg/h) was initiated at the start of CPB and ceased at CPB separation. Whole blood propofol concentrations were determined during and postinfusion using high-performance liquid chromatography with fluorescence detection. Data from four patients seemed to fit a two-compartment model, whereas those from seven patients were significantly (F test, p < 0.05) better fitted to a three-compartment model. The pharmacokinetic parameters were as follows: The mean (SD) of the initial distribution phase t1/2 pi, intermediate distribution phase t1/2 alpha, and elimination phase t1/2 beta were 2.22 (1.04) min, 42.9 (16.4) min, and 370 (138) min, respectively. The mean clearance of 1.31 (0.50) L/min was lower than those reported from other studies, whereas the mean blood concentration of 2.2 (1.0) mg/L at the 1-h infusion period was higher. The mean calculated apparent Css was 3.9 (1.5) mg/L. The low clearance is likely to be due to hemodynamic changes during CPB and CABG, thereby affecting drug distribution and blood flow to the liver.
Clinical evaluation and serum concentration of zuclopenthixol acetate in psychotic Asian patients: a single-dose preliminary study

Tan CH, Low BL, Ng LL, Khoo YM, Lee HS

Ther Drug Monit, 1993 Apr;15(2):108-12.
PMID: 8099240

Nineteen acutely disturbed psychotic Asian patients were treated with a single intramuscular injection of 50 mg of zuclopenthixol acetate in Viscoleo. Patients were assessed clinically before and after treatment using the Brief Psychiatric Rating Scale (BPRS). Serum zuclopenthixol and the inactive geometric isomer trans(E)-clopenthixol were determined by high-performance liquid chromatography after intramuscular injection. All patients improved, with the BPRS being significantly reduced (p < 0.001) at 72 h after injection. Adverse effects were generally few. The mean +/- SEM serum zuclopenthixol concentrations at 24, 48, and 72 h were 19.9 +/- 2.8, 31.5 +/- 4.5, and 17.8 +/- 2.9 micrograms/L, respectively. trans(E)-Clopenthixol concentrations ranged from negligible to 39.5 micrograms/L. This study confirms that a single intramuscular injection of 50 mg is adequate for managing severely disturbed psychotic patients for the first 3 days. The serum zuclopenthixol concentrations attained in the Asian patients were higher than those reported in Caucasian psychiatric patients. In some patients, a considerable amount of zuclopenthixol had been transformed to trans(E)-clopenthixol.
Molecular epidemiology of Newcastle disease viruses in Vietnam

Choi KS, Kye SJ, Kim JY, To TL, Nguyen DT, Lee YJ, et al.

Trop Anim Health Prod, 2014 Jan;46(1):271-7.
PMID: 24061688 DOI: 10.1007/s11250-013-0475-3

Newcastle disease virus (NDV) causes significant economic losses to the poultry industry in Southeast Asia. In the present study, 12 field isolates of NDV were recovered from dead village chickens in Vietnam between 2007 and 2012, and were characterized. All the field isolates were classified as velogenic. Based on the sequence analysis of the F variable region, two distinct genetic groups (Vietnam genetic groups G1 and G2) were recognized. Phylogenetic analysis revealed that all the 12 field isolates fell into the class II genotype VII cluster. Ten of the field isolates, classified as Vietnam genetic group G1, were closely related to VIIh viruses that had been isolated from Indonesia, Malaysia, and Cambodia since the mid-2000s, while the other two field isolates, of Vietnam genetic group G2, clustered with VIId viruses, which were predominantly circulating in China and Far East Asia. Our results indicate that genotype VII viruses, especially VIIh viruses, are predominantly responsible for the recent epizootic of the disease in Vietnam.
Cross-protective efficacy of the O1 Manisa + O 3039 bivalent vaccine and the O 3039 monovalent vaccine against heterologous challenge with FMDV O/Jincheon/SKR/2014 in pig

Kim T, Hong JK, Oem JK, Lee KN, Lee HS, Kim YJ, et al.

Vaccine, 2019 03 14;37(12):1702-1709.
PMID: 30712811 DOI: 10.1016/j.vaccine.2018.11.080

After massive foot-and-mouth disease (FMD) outbreaks originated from Jincheon County from Dec. 2014 to Apr. 2015, the effectiveness of the previous FMD vaccine containing only the O1 Manisa as the O antigen, O1 Manisa + A Malaysia 97 + Asia 1 Sharmir trivalent vaccine, was questioned in South Korea, and a change in the O antigen in FMD vaccines was demanded to control the FMD caused by FMDV O/Jincheon/SKR/2014, the O Jincheon strain. Therefore, the efficacies of O1 Manisa + O 3039 bivalent vaccine and O 3039 monovalent vaccine were studied for cross-protection against heterologous challenge with the O Jincheon strain. In this study, the efficacy of the O1 Manisa + O 3039 bivalent vaccine was better than that of the O 3039 monovalent vaccine, even though the serological relationship (r1 value) between O Jincheon and O 3039 was matched according to the OIE Terrestrial Manual. According to serological test results from vaccinated specific pathogen free pigs, virus neutralization test titers against Jincheon were good estimates for predicting protection against challenge. A field trial of the O1 Manisa + O 3039 bivalent vaccine was performed to estimate the possibility of field application in conventional pig farms, especially due to concerns about the effect of maternally derived antibodies (MDA) in field application of the FMD vaccine. According to the result of the field trial, the O1 Manisa + O 3039 bivalent vaccine was considered to overcome MDA. The results of the efficacy and field trials indicated that the O1 Manisa + O3039 vaccine could be suitable to replace previous FMD vaccines to control the FMD field situation caused by O Jincheon FMDV.
Molecular characterization of serotype A foot-and-mouth disease viruses circulating in Vietnam in 2009

Le VP, Nguyen T, Lee KN, Ko YJ, Lee HS, Nguyen VC, et al.

Vet Microbiol, 2010 Jul 29;144(1-2):58-66.
PMID: 20097490 DOI: 10.1016/j.vetmic.2009.12.033

Foot-and-mouth disease (FMD) is a major cause of endemic outbreaks in Vietnam in recent years. In this work, six serotype A foot-and-mouth disease viruses (FMDV), collected from endemic outbreaks during January and February of 2009 in four different provinces in Vietnam, were genetically characterized for their complete genome sequences. Genetic analysis based on the complete viral genome sequence indicated that they were closely related to each other and shared 99.0-99.8% amino acid (aa) identity. Genetic and deduced aa analysis of the capsid coding gene VP1 showed that the six Vietnamese strains were all classified into the genotype IX from a total of 10 major genotypes worldwide, sharing 98.1-100% aa identity each other. They were most closely related to the type A strains recently isolated in Laos (A/LAO/36/2003, A/LAO/1/2006, A/LAO/6/2006, A/LAO/7/2006, and A/LAO/8/2006), Thailand (A/TAI/2/1997 and A/TAI/118/1987), and Malaysia (A/MAY/2/2002), sharing 88.3-95.5% nucleotide (nt) identities. In contrast, Vietnamese type A strains showed low nt identities with the two old type A FMDVs, isolated in 1960 in Thailand (a15thailand iso43) and in 1975 in the Philippines (aphilippines iso50), ranging from 77.3 to 80.9% nt identity. A multiple alignment based on the deduced amino acid sequences of the capsid VP1 coding gene of type A FMDV revealed three amino acid substitutions between Vietnamese strains and the strains of other Southeast Asian countries (Laos, Thailand, Malaysia, and the Philippines). Alanine was replaced by valine at residue 24, asparagine by arginine at residue 85, and serine by threonine at residue 196. Furthermore, type A FMDV strains recently isolated in Vietnam, Laos, Thailand, and Malaysia all have one amino acid deletion at residue 140 of the capsid VP1 protein compared with the two old type A FMDV strains from Thailand and the Philippines as well as most other type A representatives worldwide. This article is the first to report on the comprehensive genetic characterization of type A FMDV circulating in Vietnam.
Molecular epidemiological investigation of velogenic Newcastle disease viruses from village chickens in Cambodia

Choi KS, Kye SJ, Kim JY, Damasco VR, Sorn S, Lee YJ, et al.

Virus Genes, 2013 Oct;47(2):244-9.
PMID: 23764918 DOI: 10.1007/s11262-013-0930-2

Three isolates of Newcastle disease virus (NDV) were isolated from tracheal samples of dead village chickens in two provinces (Phnom Penh and Kampong Cham) in Cambodia during 2011-2012. All of these Cambodian NDV isolates were categorized as velogenic pathotype, based on in vivo pathogenicity tests and F cleavage site motif sequence ((112)RRRKRF(117)). The phylogenetic analysis and the evolutionary distances based on the sequences of the F gene revealed that all the three field isolates of NDV from Cambodia form a distinct cluster (VIIh) together with three Indonesian strains and were assigned to the genotype VII within the class II. Further phylogenetic analysis based on the hyper-variable region of the F gene revealed that some of NDV strains from Malaysia since the mid-2000s were also classified into the VIIh virus. This indicates that the VIIh NDVs are spreading through Southeast Asia. The present investigation, therefore, emphasizes the importance of further surveillance of NDV in neighboring countries as well as throughout Southeast Asia to contain further spreading of these VIIh viruses.

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