Displaying publications 21 - 40 of 44 in total

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  1. Fong TS, Kim SC, Kim JE, Lee ES, Kim TW, Lee YS
    J Arthroplasty, 2019 09;34(9):1929-1937.
    PMID: 31138501 DOI: 10.1016/j.arth.2019.04.061
    BACKGROUND: This study aimed at assessing the morphometry of resected femurs in Korean patients during total knee arthroplasty (TKA) and comparing these measurements with current Western-designed femoral component dimensions.

    METHODS: This single-blind, prospective, randomized, controlled trial involved intraoperative measurements for 271 femoral component implantations from 3 contemporary TKA systems, with 2 systems offering narrow sizing options. The difference between femoral component dimensions and the resected surface of distal femur was measured in millimeters at 5 distinct zones.

    RESULTS: Overhang of standard femoral component was common in the anterior-medial condyle and anterior-lateral condyle ranging from 50.8% to 99.0% and 21.5% to 88.0%, respectively. With narrow femoral components, the rate of overhang reduced to 21.5%-30.2% and 9.2%-32.1%. Conversely, underhang rates were higher over the anterior flange width, middle medial-lateral and posterior medial-lateral zones. Standard components displayed higher underhang rates at these zones compared to narrow components. The good fit rate for femoral component was low among the 3 systems ranging from 1.0% to 56.0%. System with narrow option sizing increases the underhang rates in males, while improving the component fit among females at similar zones with rate ranging from 5.2% to 52.9%.

    CONCLUSION: Currently available TKA implant designs may not provide a perfect match for the distal femoral shape of the Korean population. The availability of implants with standard and narrow options can substantially improve the optimal fitting of femoral components in the Korean population.

  2. Gan HS, Sayuti KA, Ramlee MH, Lee YS, Wan Mahmud WMH, Abdul Karim AH
    Int J Comput Assist Radiol Surg, 2019 May;14(5):755-762.
    PMID: 30859457 DOI: 10.1007/s11548-019-01936-y
    PURPOSE: Manual segmentation is sensitive to operator bias, while semiautomatic random walks segmentation offers an intuitive approach to understand the user knowledge at the expense of large amount of user input. In this paper, we propose a novel random walks seed auto-generation (SAGE) hybrid model that is robust to interobserver error and intensive user intervention.

    METHODS: Knee image is first oversegmented to produce homogeneous superpixels. Then, a ranking model is developed to rank the superpixels according to their affinities to standard priors, wherein background superpixels would have lower ranking values. Finally, seed labels are generated on the background superpixel using Fuzzy C-Means method.

    RESULTS: SAGE has achieved better interobserver DSCs of 0.94 ± 0.029 and 0.93 ± 0.035 in healthy and OA knee segmentation, respectively. Good segmentation performance has been reported in femoral (Healthy: 0.94 ± 0.036 and OA: 0.93 ± 0.034), tibial (Healthy: 0.91 ± 0.079 and OA: 0.88 ± 0.095) and patellar (Healthy: 0.88 ± 0.10 and OA: 0.84 ± 0.094) cartilage segmentation. Besides, SAGE has demonstrated greater mean readers' time of 80 ± 19 s and 80 ± 27 s in healthy and OA knee segmentation, respectively.

    CONCLUSIONS: SAGE enhances the efficiency of segmentation process and attains satisfactory segmentation performance compared to manual and random walks segmentation. Future works should validate SAGE on progressive image data cohort using OA biomarkers.

  3. Kim JE, Won S, Jaffar MSA, Lee JI, Kim TW, Lee YS
    Knee, 2020 Jun;27(3):940-948.
    PMID: 32331827 DOI: 10.1016/j.knee.2020.04.008
    BACKGROUND: Open-wedge high tibial osteotomy (OWHTO) produces three- dimensional (3D) geometric changes. Among them, increased posterior tibial slope (PTS), and altered coronal inclination that induces unintended tibial translation may affect anterior cruciate ligament (ACL) status. The purpose of current study was to evaluate the geometric changes following OWHTO, such as increasing PTS and decreasing tibial subluxation, which may affect the status of ACL.

    METHODS: From April 2014 to December 2015, a total of 72 knees in 64 patients that underwent OWHTO, second-look arthroscopy, and magnetic resonance imaging (MRI) assessment, were enrolled. Preoperative and postoperative coronal and sagittal translation, joint line orientation angle, the distance between medial femoral notch marginal line and medial tibial spine, and PTS were evaluated. ACL status was arthroscopically graded from grade 1 (best) to 4 (worst). The MRI signal of the graft in three portions (proximal, middle, and distal) was graded from grade 1 (best) to 4 (worst).

    RESULTS: High grade (3: partial, and 4: complete rupture) was noted in 28 cases (38.9%) at the second-look arthroscopy compared with 10 cases (13.9%) at index arthroscopy. The MRI signal grade significantly increased at follow up MRI compared with preoperative MRI (P<0.01). An increased signal was commonly noted in the middle and distal portions of the graft.

    CONCLUSIONS: Geometric changes after OWHTO were related to ACL deterioration. The ACL was commonly affected at the middle and distal portions and rarely at the proximal portion. There is a possibility of impingement because of the geometric changes.

    LEVEL OF EVIDENCE: Level IV.

  4. Lee JI, Jaffar MSA, Choi HG, Kim TW, Lee YS
    J Knee Surg, 2022 Feb;35(3):299-307.
    PMID: 32659817 DOI: 10.1055/s-0040-1713898
    The purpose of this study was to evaluate the outcomes of isolated medial patellofemoral ligament (MPFL) reconstruction, regardless of the presence of predisposing factors. A total of 21 knees that underwent isolated MPFL reconstruction from March 2014 to August 2017 were included in this retrospective series. Radiographs of the series of the knee at flexion angles of 20, 40, and 60 degrees were acquired. The patellar position was evaluated using the patellar tilt angle, sulcus angle, congruence angle (CA), and Caton-Deschamps and Blackburne-Peel ratios. To evaluate the clinical outcome, the preoperative and postoperative International Knee Documentation Committee (IKDC) and Lysholm knee scoring scales were analyzed. To evaluate the postoperative outcomes based on the predisposing factors, the results were separately analyzed for each group. Regarding radiologic outcomes, 20-degree CA was significantly reduced from 10.37 ± 5.96° preoperatively to -0.94 ± 4.11° postoperatively (p = 0.001). In addition, regardless of the predisposing factors, delta values of pre- and postoperation of 20-degree CA were not significantly different in both groups. The IKDC score improved from 53.71 (range: 18-74) preoperatively to 94.71 (range: 86-100) at the last follow-up (p = 0.004), and the Lysholm score improved from 54.28 (range: 10-81) preoperatively to 94.14 (range: 86-100) at the last follow-up (p = 0.010). Isolated MPFL reconstruction provides a safe and effective treatment for patellofemoral instability, even in the presence of mild predisposing factors, such as trochlear dysplasia, increased patella height, increased TT-TG distance, or valgus alignment. This is a Level 4, case series study.
  5. Tan VM, Ooi DS, Kapur J, Wu T, Chan YH, Henry CJ, et al.
    Eur J Nutr, 2016 Jun;55(4):1573-81.
    PMID: 26160548 DOI: 10.1007/s00394-015-0976-0
    PURPOSE: There are wide inter-individual differences in glycemic response (GR). We aimed to examine key digestive parameters that influence inter-individual and ethnic differences in GR in healthy Asian individuals.
    METHODS: Seventy-five healthy male subjects (25 Chinese, 25 Malays, and 25 Asian-Indians) were served equivalent available carbohydrate amounts (50 g) of jasmine rice (JR) and basmati rice (BR) on separate occasions. Postprandial blood glucose concentrations were measured at fasting (-5 and 0 min) and at 15- to 30-min interval over 180 min. Mastication parameters (number of chews per mouth and chewing time per mouthful), saliva α-amylase activity, AMY1 gene copy numbers and gastric emptying rate were measured to investigate their relationships with GR.
    RESULTS: The GR for jasmine rice was significantly higher than for basmati rice (P 0.05).
    CONCLUSION: Mastication parameters contribute significantly to GR. Eating slowly and having larger food boluses before swallowing (less chewing), both potentially modifiable, may be beneficial in glycemic control.
  6. Lee OS, Ahn S, Ahn JH, Teo SH, Lee YS
    Arch Orthop Trauma Surg, 2018 Feb;138(2):227-236.
    PMID: 29143167 DOI: 10.1007/s00402-017-2826-4
    INTRODUCTION: The purpose of this systematic review and meta-analysis was to evaluate the efficacy of concurrent cartilage procedures during high tibial osteotomy (HTO) for medial compartment osteoarthritis (OA) by comparing the outcomes of studies that directly compared the use of HTO plus concurrent cartilage procedures versus HTO alone.

    MATERIALS AND METHODS: Results that are possible to be compared in more than two articles were presented as forest plots. A 95% confidence interval was calculated for each effect size, and we calculated the I 2 statistic, which presents the percentage of total variation attributable to the heterogeneity among studies. The random effects model was used to calculate the effect size.

    RESULTS: Seven articles were included to the final analysis. Case groups were composed of HTO without concurrent procedures and control groups were composed of HTO with concurrent procedures such as marrow stimulation procedure, mesenchymal stem cell transplantation, and injection. The case group showed a higher hospital for special surgery score and mean difference was 4.10 [I 2 80.8%, 95% confidence interval (CI) - 9.02 to 4.82]. Mean difference of the mechanical femorotibial angle in five studies was 0.08° (I 2 0%, 95% CI - 0.26 to 0.43). However, improved arthroscopic, histologic, and MRI results were reported in the control group.

    CONCLUSION: Our analysis support that concurrent procedures during HTO for medial compartment OA have little beneficial effect regarding clinical and radiological outcomes. However, they might have some beneficial effects in terms of arthroscopic, histologic, and MRI findings even though the quality of healed cartilage is not good as that of original cartilage. Therefore, until now, concurrent procedures for medial compartment OA have been considered optional. Nevertheless, no conclusions can be drawn for younger patients with focal cartilage defects and concomitant varus deformity. This question needs to be addressed separately.

  7. Rasheed ZB, Lee YS, Kim SH, Teoh T, MacIntyre DA, Bennett PR, et al.
    PMID: 36213265 DOI: 10.3389/fendo.2022.983924
    BACKGROUND: Prematurity is the leading cause of childhood death under the age of five. The aetiology of preterm birth is multifactorial; however, inflammation and infection are the most common causal factors, supporting a potential role for immunomodulation as a therapeutic strategy. 15-Deoxy-Delta-12,14-prostaglandin J2 (15dPGJ2) is an anti-inflammatory prostaglandin and has been shown to delay lipopolysaccharide (LPS) induced preterm labour in mice and improve pup survival. This study explores the immunomodulatory effect of 15dPGJ2 on the transcription factors NF-κB and AP-1, pro-inflammatory cytokines, and contraction associated proteins in human cultured myocytes, vaginal epithelial cell line (VECs) and primary amnion epithelial cells (AECs).

    METHODS: Cells were pre-incubated with 32µM of 15dPGJ2 and stimulated with 1ng/mL of IL-1β as an in vitro model of inflammation. Western immunoblotting was used to detect phosphorylated p-65 and phosphorylated c-Jun as markers of NF-κB and AP-1 activation, respectively. mRNA expression of the pro-inflammatory cytokines IL-6, IL-8, and TNF-α was examined, and protein expression of COX-2 and PGE2 were detected by western immunoblotting and ELISA respectively. Myometrial contractility was examined ex-vivo using a myograph.

    RESULTS: 15dPGJ2 inhibited IL-1β-induced activation of NF-κB and AP-1, and expression of IL-6, IL-8, TNF-α, COX-2 and PGE2 in myocytes, with no effect on myometrial contractility or cell viability. Despite inhibiting IL-1β-induced activation of NF-κB, expression of IL-6, TNF-α, and COX-2, 15dPGJ2 led to activation of AP-1, increased production of PGE2 and increased cell death in VECs and AECs.

    CONCLUSION: We conclude that 15dPGJ2 has differential effects on inflammatory modulation depending on cell type and is therefore unlikely to be a useful therapeutic agent for the prevention of preterm birth.

  8. Ho JPY, Cho JH, Nam HS, Park SY, Lee YS
    PMID: 37975939 DOI: 10.1007/s00167-023-07660-0
    PURPOSE: The aim of this study was to identify if constitutional alignment and preoperative radiologic parameters determined whether medial gap balancing was required in mechanically aligned total knee arthroplasty (TKA).

    METHODS: Two hundred and sixty three patients with 394 consecutive knees who underwent primary TKAs were retrospectively analysed in this study. Selective sequential multiple needle puncturing (MNP) was performed for medial ligament balancing when required. Constitutional alignment, which was determined using the Coronal Plane Alignment of the Knee (CPAK) classification, as well as preoperative and postoperative radiologic parameters was evaluated to identify factors which predicted the need for MNP.

    RESULTS: One hundred and fifty eight (40.1%) knees required medial ligament balancing with MNP. Patients who required MNP during surgery had significantly more constitutional varus, more varus preoperative mechanical Hip-Knee-Ankle angle (mHKA), smaller preoperative medial proximal tibial angle (MPTA) and a larger change in mHKA and MPTA after surgery than those who did not. Patients with constitutional varus also had a higher incidence of having had MNP to both anterior and posterior superficial medial collateral ligament (sMCL) fibres. There was no significant difference in preoperative lateral distal femoral angle (LDFA), posterior tibial slope (PTS) and varus-valgus difference (VVD) between groups.

    CONCLUSION: Ligament balancing using MNP was determined by constitutional alignment rather than medial soft tissue contracture. Patients with constitutional varus who had a larger medio-lateral gap difference in extension also had a higher incidence of having had MNP to both anterior and posterior sMCL fibres.

    LEVEL OF EVIDENCE: Retrospective comparative study, level IV.

  9. Ho JPY, Cho JH, Nam HS, Park SY, Lee YS
    Knee, 2023 Dec;45:65-74.
    PMID: 37852039 DOI: 10.1016/j.knee.2023.10.002
    BACKGROUND: (1) To evaluate if referencing system affects selection of implant size, position, and gap balance in total knee arthroplasty (TKA) with the use of contemporary implant designs and (2) to describe the authors' intraoperative sizing strategy using anterior referencing (AR) and posterior referencing (PR) systems.

    METHODS: This was a retrospective review of 270 consecutive patients (397 knees) who underwent primary TKA with an AR or PR system. Selection of implant size, mediolateral and anteroposterior alignment of the femoral component, as well as gaps were compared between groups.

    RESULTS: In the AR group, more patients had femoral components which were upsized or downsized compared to those in the PR group (29.5% vs 12.0% respectively) and in patients who underwent bilateral TKA, 49.4% of those in the AR group had femur component size asymmetry. The AR group had better medio-lateral (ML) fit over the distal cutting surface area, smaller change in anterior offset but higher incidence of anterior notching when compared to the PR group. Posterior condylar offset (PCO) was restored in both groups and gap differences in flexion-extension and ML were comparable. There was also no difference in clinical scores and ROM between groups at 2-years follow-up.

    CONCLUSION: In this study, conventional implications related to referencing system were not observed. In practice, AR systems can restore PCO while PR systems do not result in increased anterior notching or anterior overstuffing. Differences observed in this study are most likely related to implant design specifics and surgical technique.

  10. Ho JPY, Park SY, Nam HS, Cho JH, Lee YS
    Knee, 2023 Dec;45:35-45.
    PMID: 37774563 DOI: 10.1016/j.knee.2023.09.003
    BACKGROUND: The aims of this study were (1) to compare in vivo coverage and rotational alignment of 2 tibial component designs: anatomic and symmetrical; and (2) to determine if coronal deformity and tibial torsion were related to rotation and coverage.

    METHODS: Postoperative CT scans of 200 propensity score-matched patients who underwent TKA with either an anatomic (ATC) or symmetrical tibia component (STC) were analyzed. Rotation was measured using four axes: surgical transepicondylar axis (sTEA), Berger's protocol, medio-lateral (ML) axis and posterior borders of the tibial plateau, while coverage was assessed by measuring fit and surface area. The relationship between coronal deformity, tibial torsion, rotation, and coverage was investigated.

    RESULTS: Overall, STCs had more internal rotation when measured using the sTEA (-0.6° ± 3.5 vs 0.5° ± 3.6, p = 0.03), Berger's protocol (-21.6° ± 7.1 vs -17.9° ± 6.2, p = 0.000) and ML axes (2.9° ± 3.9 vs 8.1° ± 5.1, p = 0.000) compared to ATCs. STCs also had more posteromedial underhang (-3.3 mm ± 2.4 mm vs -1.7 mm ± 2.5 mm, p = 0.000) but smaller change in tibial torsion postoperatively (-18.4° ± 9.9° vs -13.1° ± 9.4°, p = 0.000). Tibial torsion was more pronounced in valgus than varus knees both preoperative (-25.4° ± 6.5° vs -20.2° ± 9.3°, p = 0.02) and postoperatively (-19.7° ± 7.2° vs -14.7° ± 10.3°, p = 0.04), but there was no difference in postoperative tibial torsion between ATCs and STCs in this subgroup.

    CONCLUSION: The use of an anatomic tibial baseplate optimizes coverage by reducing posterolateral overhang and posteromedial underhang. It also achieved better rotational profiles compared to STCs. However, it resulted in a larger change in tibial torsion after TKA.

  11. Lim WY, Kwek K, Chong YS, Lee YS, Yap F, Chan YH, et al.
    J Hypertens, 2014 Apr;32(4):857-64.
    PMID: 24390251 DOI: 10.1097/HJH.0000000000000096
    OBJECTIVE: Greater maternal adiposity is a potentially modifiable risk factor for elevated blood pressure during pregnancy; however, the association has been little studied in Asian populations, and no study has evaluated potential differences in the adiposity-blood pressure relation between ethnic groups or interaction with gestational diabetes.

    METHODS: We performed a cross-sectional evaluation of a Singapore mother-offspring cohort comprising 799 pregnant Chinese, Malay and Indian women. Data on body weight, height, skinfold thickness and glycaemia (oral glucose tolerance test) were collected during the 2nd trimester; peripheral SBP and DBP were measured using an oscillometric device and central pressures by noninvasive radial applanation tonometry. The associations between adiposity measures BMI and sum of skinfold thickness and blood pressure outcomes were examined by linear regression with adjustment for potential confounders.

    RESULTS: Higher maternal BMI was associated with elevated peripheral and central pressures: the increases in pressure (mmHg) for each kg/m(2) increase in BMI were 1.19 (95% confidence interval, 1.03-1.36) for peripheral SBP, 0.76 (0.63-0.89) for peripheral DBP, 1.02 (0.87-1.17) for central systolic pressure and 0.26 (0.16-0.37) for central pulse pressure. The associations were generally stronger in Chinese women (P-interaction = 0.03 for central pulse pressure) and individuals with gestational diabetes (P-interaction = 0.03 for DBP and P-interaction = 0.046 for central systolic pressure). Similar patterns of results were found when using skinfold thickness as the measure of adiposity.

    CONCLUSION: Maternal adiposity is associated with higher peripheral and central blood pressures during pregnancy. Stronger associations in Chinese women and individuals with gestational diabetes warrant further investigation.
  12. Choi EK, Lee YS, Chern AKC, Jiampo P, Chutinet A, Hanafy DA, et al.
    Open Heart, 2020 11;7(2).
    PMID: 33184127 DOI: 10.1136/openhrt-2020-001343
    BACKGROUND AND PURPOSE: Real-world data about treatment convenience and satisfaction in Asian non-valvular atrial fibrillation (NVAF) patients after switching from vitamin K antagonists (VKAs) to non-VKA oral anticoagulants were evaluated.

    METHODS: In this non-interventional study involving 49 sites across five countries in Southeast Asia and South Korea, 379 stable NVAF patients who switched from VKA therapy to dabigatran during routine clinical practice were recruited and followed up for 6 months. Treatment convenience and satisfaction were evaluated using Perception on Anticoagulant Treatment Questionnaire-2 (PACT-Q2). Through post hoc analysis, factors associated with improved treatment convenience scores at visit 2 were described.

    RESULTS: Treatment convenience and satisfaction significantly improved after switching from VKAs to dabigatran at visit 2 and visit 3 (convenience: p<0.001 each vs baseline; satisfaction: p=0.0174 (visit 2), p=0.0004 (visit 3) compared with baseline). Factors predictive of higher (>80th percentile) response on treatment convenience were female sex, younger age (<75 years), higher baseline stroke risk, higher creatinine clearance and absence of concomitant hypertension, stroke or gastrointestinal diseases.

    CONCLUSION: Dabigatran was associated with a significant improvement in treatment convenience and satisfaction after switching from VKAs when used for stroke prevention in NVAF patients from Southeast Asia and South Korea.

  13. Lee YS, Oh YS, Choi EK, Chern AKC, Jiampo P, Chutinet A, et al.
    Open Heart, 2021 12;8(2).
    PMID: 34857666 DOI: 10.1136/openhrt-2021-001745
    PURPOSE: Dabigatran is a direct thrombin inhibitor approved for stroke prophylaxis in patients with non-valvular atrial fibrillation (NVAF). Real-world data about patient preference, satisfaction and convenience in patients in Asia are not available. The study aimed to explore the perception of patients with newly diagnosed NVAF regarding dabigatran versus vitamin K antagonists (VKAs), when used for stroke prevention.

    PATIENTS AND METHODS: This was a multinational, multicentre, non-interventional study involving 49 sites across 5 countries in South East Asia and South Korea where 934 patients newly diagnosed with NVAF were initiated on either dabigatran (N=591) or VKA (N=343). Data were collected at baseline and over two follow-up visits across 6 months. Treatment satisfaction and patient convenience were evaluated using the Perception on Anticoagulant Treatment Questionnaire-2 (PACT-Q2).

    RESULTS: The mean age of the patients was 65.9±10.4 years, and 64.2% were male. Mean CHA2DS2-VASc score was 2.4±1.5, and mean HAS-BLED score was 1.2±0.9. At baseline, patients initiated on dabigatran had higher stroke risk, bleeding risk, creatinine clearance and proportion of patients with concomitant illnesses compared with patients initiated on VKAs. Treatment convenience was perceived to be significantly better with dabigatran versus VKAs at visits 2 and 3 (p=0.0423 and 0.0287, respectively). Treatment satisfaction was significantly better with dabigatran compared with VKAs at visit 3 (p=0.0300).

    CONCLUSION: In this study, dabigatran is associated with better patient perception in terms of treatment convenience and satisfaction compared with VKAs when used for stroke prevention in newly diagnosed NVAF patients from South East Asia and South Korea.

    TRIAL REGISTRATION NUMBER: NCT02849509.

    PLAIN LANGUAGE SUMMARY: Patient satisfaction with dabigatran versus VKAs in South East Asia. Patients with atrial fibrillation are at high risk of stroke and require anticoagulants for stroke prevention. Two such anticoagulants are dabigatran and VKAs. We wanted to compare the extent of satisfaction and treatment convenience among newly diagnosed patients with atrial fibrillation from the South East Asian region when they were given either dabigatran or VKAs. Consenting patients filled out a standardised questionnaire called the PACT-Q2 over three visits after they were started on either dabigatran (591 patients) or VKAs (343 patients). We found that satisfaction and convenience were significantly higher when patients received dabigatran than when they received VKAs.

  14. Ho SY, Goh CW, Gan JY, Lee YS, Lam MK, Hong N, et al.
    Zebrafish, 2014 Oct;11(5):407-20.
    PMID: 24967707 DOI: 10.1089/zeb.2013.0879
    Existing zebrafish embryonic stem (ES) cell lines are derived and maintained using feeder layers. We describe here the derivation and long-term culture of an ES cell-like line derived from zebrafish blastomeres without the use of feeder cells. This line, designated as ZES1, has been maintained for more than 800 days in defined Dulbecco's modified Eagle's medium supplemented with fetal bovine serum, zebrafish embryo extract, trout serum, and human basic fibroblast growth factor. ZES1 cells possessed a morphology typical of ES cells, being round or polygonal in shape with a large nucleus and sparse cytoplasm and were mostly diploid. The cells formed individual colonies consisting of tightly packed cells that stained positively for alkaline phosphatase. ZES1 cells also formed embryoid bodies when transferred onto uncoated wells. The pluripotent nature of ZES1 cells was confirmed when they could be induced to differentiate in vitro into several cell types, through low- or high-density culture conditions. Treatment with retinoic acid also induced the differentiation of ZES1 cells into primarily neuronal cells. Using immunostaining and real-time polymerase chain reaction, we showed that Sox2, a known pluripotent marker in mammalian ES cells, was also present in ZES1 cells. Chimera experiments revealed that fluorescent-labeled ZES1 cells microinjected into zebrafish blastulas participated in the formation of all three germ layers. Using GFP-labeled ZES1 cells, chimera germline transmission was also demonstrated at the F1 generation. In conclusion, ZES1 cells possess both in vitro and in vivo pluripotency characteristics, indicating that nonmammalian ES cells can be readily derived and maintained for a long term under feeder-free culture conditions.
  15. Yang PL, Lu Y, Khoo CM, Leow MK, Khoo EY, Teo A, et al.
    J Clin Endocrinol Metab, 2013 Nov;98(11):4516-23.
    PMID: 24037892 DOI: 10.1210/jc.2013-2454
    Chinese men in Singapore have a higher incidence of hip fractures than Malay and Indian men. We investigated whether there were corresponding ethnic differences in peak bone mineral density (BMD) in young men and whether differences in body composition influenced peak BMD.
  16. Rasheed ZBM, Lee YS, Kim SH, Rai RK, Ruano CSM, Anucha E, et al.
    Front Immunol, 2020;11:1899.
    PMID: 32983111 DOI: 10.3389/fimmu.2020.01899
    Background: Infection/inflammation is an important causal factor in spontaneous preterm birth (sPTB). Most mechanistic studies have concentrated on the role of bacteria, with limited focus on the role of viruses in sPTB. Murine studies support a potential multi-pathogen aetiology in which a double or sequential hit of both viral and bacterial pathogens leads to a higher risk preterm labour. This study aimed to determine the effect of viral priming on bacterial induced inflammation in human in vitro models of ascending and haematogenous infection. Methods: Vaginal epithelial cells, and primary amnion epithelial cells and myocytes were used to represent cell targets of ascending infection while interactions between peripheral blood mononuclear cells (PBMCs) and placental explants were used to model systemic infection. To model the effect of viral priming upon the subsequent response to bacterial stimuli, each cell type was stimulated first with a TLR3 viral agonist, and then with either a TLR2 or TLR2/6 agonist, and responses compared to those of each agonist alone. Immunoblotting was used to detect cellular NF-κB, AP-1, and IRF-3 activation. Cellular TLR3, TLR2, and TLR6 mRNA was quantified by RT-qPCR. Immunoassays were used to measure supernatant cytokine, chemokine and PGE2 concentrations. Results: TLR3 ("viral") priming prior to TLR2/6 agonist ("bacterial") exposure augmented the pro-inflammatory, pro-labour response in VECs, AECs, myocytes and PBMCs when compared to the effects of agonists alone. In contrast, enhanced anti-inflammatory cytokine production (IL-10) was observed in placental explants. Culturing placental explants in conditioned media derived from PBMCs primed with a TLR3 agonist enhanced TLR2/6 agonist stimulated production of IL-6 and IL-8, suggesting a differential response by the placenta to systemic inflammation compared to direct infection as a result of haematogenous spread. TLR3 agonism generally caused increased mRNA expression of TLR3 and TLR2 but not TLR6. Conclusion: This study provides human in vitro evidence that viral infection may increase the susceptibility of women to bacterial-induced sPTB. Improved understanding of interactions between viral and bacterial components of the maternal microbiome and host immune response may offer new therapeutic options, such as antivirals for the prevention of PTB.
  17. Lee KW, Tan SF, Omar A, Nasir NH, Ching SM, Mohd Noor MK, et al.
    Gynecol Endocrinol, 2022 Jan;38(1):55-62.
    PMID: 34636710 DOI: 10.1080/09513590.2021.1988561
    AIM: The objective of this study was to determine the effectiveness of system-based intervention in reducing the incidence of diabetes and to improve the postnatal metabolic profiles among women with gestational diabetes mellitus (GDM).

    MATERIALS AND METHODS: For women in the intervention arm (n = 130), they received one session of individualized health education at 36 gestational weeks, a booklet of diabetes prevention, five-session of postpartum booster educational program which were conducted including 1 session of dietary and exercise counseling by dietician and physiotherapist at 6 weeks postpartum. For women in the control group (n = 168), standard treatment whereby they had received group therapy on diet and physical activity modification by dietician and staff nurses during the antenatal period.

    RESULTS: There were no significant differences in baseline characteristics between groups for most of the variables examined except for educational level which the control group had a higher education than the intervention group. The women assigned to system-based intervention have a significant difference to GDM women who were assigned to the control group for LDL and HDL but not in anthropometric measurements, blood pressure, glucose index, total cholesterol, and triglyceride. In addition, it was found that the incidence of Type 2 diabetes mellitus (T2DM) 2 years after delivery was 20% in the intervention arm compared to 17% in the control arm.

    CONCLUSION: The system-based intervention was not statistically superior to the control intervention as there is no difference in terms of incidence of T2DM between the intervention and control group. We, therefore, suggested that more intensive interventions are needed to prevent GDM from developing into T2DM.

  18. Tan D, Phipps C, Hwang WY, Tan SY, Yeap CH, Chan YH, et al.
    Lancet Haematol, 2015 Aug;2(8):e326-33.
    PMID: 26688485 DOI: 10.1016/S2352-3026(15)00097-6
    BACKGROUND: Patients with relapsed or refractory peripheral T-cell lymphoma have a poor prognosis after conventional chemotherapy. Approved novel agents have only modest single-agent activity in most subtypes of peripheral T-cell lymphoma. Panobinostat is a potent oral pan-deacetylase inhibitor. Findings of many preclinical studies have shown synergistic antilymphoma activity when panobinostat is combined with the proteasome inhibitor bortezomib. We aimed to study the effect of panobinostat and bortezomib in patients with relapsed or refractory peripheral T-cell lymphoma.

    METHODS: In this open-label, multicentre phase 2 trial, we recruited patients aged 21 years or older with relapsed or refractory peripheral T-cell lymphoma who had received at least one previous line of systemic therapy from five tertiary hospitals in Singapore, Malaysia, and South Korea. Patients received 20 mg oral panobinostat three times a week and 1·3 mg/m(2) intravenous bortezomib two times a week, both for 2 of 3 weeks for up to eight cycles. The primary endpoint was the proportion of patients who achieved an objective response in accordance with the International Working Group revised response criteria; analyses were by intention to treat. The study is completed and is registered with ClinicalTrials.gov, number NCT00901147.

    FINDINGS: Between Nov 9, 2009, and Nov 26, 2013, we enrolled 25 patients with various histological subtypes of peripheral T-cell lymphoma. Of 23 patients assessable for responses, ten (43%, 95% CI 23-63) patients had an objective response, of which five were complete responses. Serious adverse events were reported in ten (40%) of 25 patients. Common treatment-related grade 3-4 adverse events included thrombocytopenia (17 [68%]), neutropenia (ten [40%]), diarrhoea (five [20%]), and asthenia or fatigue (two [8%]). We recorded peripheral neuropathy of any grade in ten (40%) patients.

    INTERPRETATION: Combined proteasome and histone deacetylase inhibition is safe and feasible and shows encouraging activity for patients with peripheral T-cell lymphoma. Our findings validate those of preclinical studies showing synergism in the combination and represent a rational way forward in harnessing the full potential of novel agents in peripheral T-cell lymphoma.

    FUNDING: Novartis Pharmaceuticals, Janssen Pharmaceuticals, and Singhealth Foundation.

  19. Chong YS, Cai S, Lin H, Soh SE, Lee YS, Leow MK, et al.
    BMC Pregnancy Childbirth, 2014 Oct 02;14:345.
    PMID: 25273851 DOI: 10.1186/1471-2393-14-345
    BACKGROUND: Universal and high-risk screening for gestational diabetes mellitus (GDM) has been widely studied and debated. Few studies have assessed GDM screening in Asian populations and even fewer have compared Asian ethnic groups in a single multi-ethnic population.

    METHODS: 1136 pregnant women (56.7% Chinese, 25.5% Malay and 17.8% Indian) from the Growing Up in Singapore Towards healthy Outcomes (GUSTO) birth cohort study were screened for GDM by 75-g oral glucose tolerance test (OGTT) at 26-28 weeks of gestation. GDM was defined using the World Health Organization (WHO) criteria. High-risk screening is based on the guidelines of the UK National Institute for Health and Clinical Excellence.

    RESULTS: Universal screening detected significantly more cases than high-risk screening [crude OR 2.2 (95% CI 1.7-2.8)], particularly for Chinese women [crude OR = 3.5 (95% CI 2.5-5.0)]. Pre-pregnancy BMI > 30 kg/m2 (adjusted OR = 3.4, 95% CI 1.5-7.9) and previous GDM history (adjusted OR = 6.6, 95% CI 1.2-37.3) were associated with increased risk of GDM in Malay women while GDM history was the only significant risk factor for GDM in Chinese women (adjusted OR = 4.7, 95% CI 2.0-11.0).

    CONCLUSION: Risk factors used in high-risk screening do not sufficiently predict GDM risk and failed to detect half the GDM cases in Asian women. Asian women, particularly Chinese, should be screened to avoid under-diagnosis of GDM and thereby optimize maternal and fetal outcomes.

  20. Parvaresh Rizi E, Teo Y, Leow MK, Venkataraman K, Khoo EY, Yeo CR, et al.
    J Clin Endocrinol Metab, 2015 11;100(11):4249-56.
    PMID: 26308293 DOI: 10.1210/jc.2015-2639
    CONTEXT: Among Asian ethnic groups, Chinese or Malays are more insulin sensitive than South Asians, in particular in lean individuals. We have further reported that body fat partitioning did not explain this ethnic difference in insulin sensitivity.

    OBJECTIVE: We examined whether adipocytokines might explain the ethnic differences in the relationship between obesity and insulin resistance among the three major ethnic groups in Singapore.

    DESIGN AND PARTICIPANTS: This was a cross-sectional study of 101 Chinese, 82 Malays, and 81 South Asian men. Insulin sensitivity index (ISI) was measured using hyperinsulinemic euglycemic clamp. Visceral (VAT) and subcutaneous adipose tissue (SAT) volumes were quantified using magnetic resonance imaging.

    MAIN OUTCOME MEASURES: Plasma total and high-molecular-weight adiponectin, leptin, visfatin, apelin, IL-6, fibroblast growth factor 21 (FGF21), retinol binding protein-4 (RBP 4), and resistin were measured using enzyme-linked immunoassays.

    RESULTS: Principle component (PC) analysis on the adipocytokines identified three PCs, which explained 49.5% of the total variance. Adiponectin loaded negatively, and leptin and FGF21 loaded positively onto PC1. Visfatin, resistin, and apelin all loaded positively onto PC2. IL-6 loaded positively and RBP-4 negatively onto PC3. Only PC1 was negatively associated with ISI in all ethnic groups. In the path analysis, SAT and VAT were negatively associated with ISI in Chinese and Malays without significant mediatory role of PC1. In South Asians, the relationship between VAT and ISI was mediated partly through PC1, whereas the relationship between SAT and ISI was mediated mainly through PC1.

    CONCLUSIONS: The relationships between abdominal obesity, adipocytokines and insulin sensitivity differ between ethnic groups. Adiponectin, leptin, and FGF21 play a mediating role in the relationship between abdominal adiposity and insulin resistance in South Asians, but not in Malays or Chinese.

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