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  1. Sivalingam SP, Yoon KH, Koh DR, Fong KY
    Tissue Antigens, 2003 Dec;62(6):498-504.
    PMID: 14617033 DOI: 10.1046/j.1399-0039.2003.00137.x
    Rheumatoid arthritis (RA) is a chronic arthritic condition that can lead to deformities and disabilities. Although numerous studies reported the association of human leukocyte antigen (HLA)-DRB1*04 and RA, other genes, e.g. cytokines genes, may contribute towards disease susceptibility. Interleukin-18 (IL-18) is a proinflammatory cytokine postulated to play a role in the acute and chronic inflammatory phases of RA. The IL-18 protein expression seems to be regulated by two single-nucleotide polymorphisms (SNPs) located at positions -607 and -137 in the promoter region of the gene. It is postulated that specific alleles may be associated with susceptibility to the development of RA. In the present study, we described the IL-18 gene promoter region genotypes and combined genotypes (-607/-137) in 106 RA patients and 273 unrelated healthy controls to evaluate the contributions of these alleles to RA predisposition in Chinese, Malays, and Indians. The genotyping were performed using sequence-specific polymerase chain reactions. Rheumatoid factors were assayed by enzyme-linked immunosorbent assay. Biodata were obtained through chart review. The controls had significantly higher frequency of AA genotype at position -607 when compared to RA patients. No significant differences were observed in the distribution of either allelic or genotypic frequencies at position -137. There was no association between the genotypes and the presence of rheumatoid factors. This study did not find evidence of a genetic susceptibility factor but demonstrated the novel finding that the AA genotype at position -607 is associated with a protective effect against development of RA in Chinese individuals. This protection may be mediated through inhibition of cyclic (Adenosine 3', 5'-cyclic monophosphate) AMP-responsive element (CRE)-binding protein by the disruption of the CRE consensus sequence.
  2. Yoon KH, Kim JS, Park JY, Park SY, Kiat RYD, Kim SG
    Orthop J Sports Med, 2021 Feb;9(2):2325967120985153.
    PMID: 33709007 DOI: 10.1177/2325967120985153
    Background: There is currently no consensus on the optimal placement of the tibial tunnel for remnant-preserving posterior cruciate ligament (PCL) reconstruction.

    Purpose/Hypothesis: The purpose of this study was to compare the clinical and radiologic outcomes of remnant-preserving PCL reconstruction using anatomic versus low tibial tunnels. We hypothesized that the outcomes of low tibial tunnel placement would be superior to those of anatomic tibial tunnel placement at the 2-year follow-up after remnant-preserving PCL reconstruction.

    Study Design: Cohort study; Level of evidence, 3.

    Methods: We retrospectively reviewed the data for patients who underwent remnant-preserving PCL reconstruction between March 2011 and January 2018 with a minimum follow-up of 2 years (N = 63). On the basis of the tibial tunnel position on postoperative computed tomography, the patients were divided into those with anatomic placement (group A; n = 31) and those with low tunnel placement (group L; n = 32). Clinical scores (International Knee Documentation Committee subjective score, Lysholm score, and Tegner activity level), range of motion, complications, and stability test outcomes at follow-up were compared between the 2 groups. Graft signal on 1-year follow-up magnetic resonance imaging scans was compared between 22 patients in group A and 17 patients in group L.

    Results: There were no significant differences between groups regarding clinical scores or incidence of complications, no between-group differences in posterior drawer test results, and no side-to-side difference on Telos stress radiographs (5.2 ± 2.9 mm in group A vs 5.1 ± 2.8 mm in group L; P = .900). Postoperative 1-year follow-up magnetic resonance imaging scans showed excellent graft healing in both groups, with no significant difference between them.

    Conclusion: The clinical and radiologic outcomes and complication rate were comparable between anatomic tunnel placement and low tibial tunnel placement at 2-year follow-up after remnant-preserving PCL reconstruction. The findings of this study suggest that both tibial tunnel positions are clinically feasible for remnant-preserving PCL reconstruction.

  3. Yoon KH, Lee HW, Park SY, Yeak RDK, Kim JS, Park JY
    Am J Sports Med, 2020 08;48(10):2370-2375.
    PMID: 32692971 DOI: 10.1177/0363546520938771
    BACKGROUND: The purpose of this study was to evaluate the clinical score and stability after meniscal allograft transplantation (MAT) after a previous anterior cruciate ligament (ACL) reconstruction.

    HYPOTHESIS: Medial MAT would improve anteroposterior stability, and lateral MAT would improve rotational stability.

    STUDY DESIGN: Cohort study; Level of evidence, 3.

    METHOD: We retrospectively investigated 31 cases of MAT after a previous total or nearly total meniscectomy and ACL reconstruction between November 2008 and June 2017. Cases were divided into medial (16 cases) and lateral (15 cases) MAT groups. The patients were assessed preoperatively and at the 2-year follow-up.

    RESULTS: In the medial MAT group, the International Knee Documentation Committee, Lysholm, Lysholm instability, and Tegner scores improved significantly at the 2-year follow-up, and there were also significant improvements in the anterior drawer, Lachman, and pivot-shift tests. In the lateral MAT group, the Lysholm and Tegner scores improved significantly at the 2-year follow-up, as had the anterior drawer and Lachman tests but not the pivot-shift test. The medial MAT group showed significant improvement in side-to-side difference on Telos stress radiographs, from 6.5 mm (preoperatively) to 3.6 mm (2-year follow-up) (P = .001), while the lateral MAT group showed no significant change. There was no progression of arthritis in either group.

    CONCLUSION: Medial MAT improved not only anteroposterior stability but also rotational stability in the meniscus-deficient ACL-reconstructed knee. Lateral MAT showed improvements in the anterior drawer and Lachman tests but not in the pivot-shift test or side-to-side difference on Telos stress radiographs in meniscus-deficient ACL-reconstructed knees. Instability and pain are indications for MAT in meniscus-deficient ACL-reconstructed knees.

  4. Yoon KH, Kim JS, Park JY, Park SY, Kiat RYD, Kim SG
    Knee Surg Sports Traumatol Arthrosc, 2021 Jun;29(6):1936-1943.
    PMID: 32914218 DOI: 10.1007/s00167-020-06266-0
    PURPOSE: To compare clinical and radiological outcomes and failure rates between anatomical and high femoral tunnels in remnant-preserving single-bundle posterior cruciate ligament (PCL) reconstruction.

    METHODS: 63 patients who underwent remnant-preserving single-bundle PCL reconstruction between 2011 and 2018 with a minimum 2-year follow-up were retrospectively reviewed. Patients were divided into two groups according to the femoral tunnel position: group A (33 patients with anatomical femoral tunnel) and group H (30 patients with high femoral tunnels). The femoral tunnel was positioned at the center (group A) or upper margin (group H) of the remnant anterolateral bundle. The position of the femoral tunnel was evaluated using the grid method on three-dimensional computed tomography. Clinical and radiological outcomes and failure rates were compared between the groups at the 2-year follow-up.

    RESULTS: The position of the femoral tunnel was significantly high in group H than in group A (87.4% ± 4.2% versus 76.1% ± 3.7%, p 

  5. Khoo CM, Deerochanawong C, Chan SP, Matawaran B, Sheu WH, Chan J, et al.
    Diabetes Obes Metab, 2021 Feb;23(2):299-317.
    PMID: 33155749 DOI: 10.1111/dom.14251
    Early onset of type 2 diabetes and a high prevalence of co-morbidities predispose the Asian population to a high risk for, and rapid progression of, diabetic kidney disease (DKD). Apart from renin-angiotensin system inhibitors, sodium-glucose co-transporter-2 (SGLT-2) inhibitors have been shown to delay renal disease progression in patients with DKD. In this review article, we consolidate the existing literature on SGLT-2 inhibitor use in Asian patients with DKD to establish contemporary guidance for clinicians. We extensively reviewed recommendations from international and regional guidelines, data from studies on Asian patients with DKD, global trials (DAPA-CKD, CREDENCE and DELIGHT) and cardiovascular outcomes trials. In patients with DKD, SGLT-2 inhibitor therapy significantly reduced albuminuria and the risk of hard renal outcomes (defined as the onset of end-stage kidney disease, substantial decline in renal function from baseline and renal death), cardiovascular outcomes and hospitalization for heart failure. In all the cardiovascular and renal outcomes trials, there was an initial decline in the estimated glomerular filtration rate (eGFR), which was followed by a slowing in the decline of renal function compared with that seen with placebo. Despite an attenuation in glucose-lowering efficacy in patients with low eGFR, there were sustained reductions in body weight and blood pressure, and an increase in haematocrit. Based on the available evidence, we conclude that SGLT-2 inhibitors represent an evidence-based therapeutic option for delaying the progression of renal disease in Asian patients with DKD and preserving renal function in patients at high risk of kidney disease.
  6. Sheu WHH, Chan SP, Matawaran BJ, Deerochanawong C, Mithal A, Chan J, et al.
    Diabetes Metab J, 2020 02;44(1):11-32.
    PMID: 32097996 DOI: 10.4093/dmj.2019.0208
    The prevalence of obesity in Asia is of epidemic proportions, with an estimated 1 billion overweight/obese individuals in the region. The majority of patients with type 2 diabetes mellitus (T2DM) are overweight/obese, which increases the risk of cardiorenal outcomes in these patients; hence, sustained reductions in body weight and visceral adiposity are important management goals. However, most of the glucose-lowering therapies such as insulin, sulfonylureas, glinides, and thiazolidinediones induce weight gain, which makes the management of overweight/obese T2DM patients challenging. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors are the only oral glucose-lowering agents that have been shown to reduce body weight and visceral adiposity. In addition, SGLT-2 inhibitors therapy reduces ectopic fat deposition and improves adipose tissue function and weight-related quality of life. In this article, we aim to consolidate the existing literature on the effects of SGLT-2 inhibitors in Asian patients with T2DM and to produce clinical recommendations on their use in overweight or obese patients with T2DM. Recommendations from international and regional guidelines, as well as published data from clinical trials in Asian populations and cardiovascular outcomes trials are reviewed. Based on the available data, SGLT-2 inhibitors represent an evidence-based therapeutic option for the management of overweight/obese patients with T2DM.
  7. Deerochanawong C, Chan SP, Matawaran BJ, Sheu WH, Chan J, Man NH, et al.
    Diabetes Obes Metab, 2019 Nov;21(11):2354-2367.
    PMID: 31264765 DOI: 10.1111/dom.13819
    Diabetes mellitus in Asia accounts for more than half of the global prevalence. There is a high prevalence of cardiovascular disease (CVD) in the region among people with type 2 diabetes mellitus (T2DM) and it is often associated with multiple risk factors including hypertension, renal disease and obesity. The early onset of T2DM and the eventual long disease duration portends an increasing proportion of the population to premature CVD. In addition to lowering blood glucose, sodium-glucose co-transporter-2 (SGLT-2) inhibitors exert favourable effects on multiple risk factors (including blood pressure, body weight and renal function) and provide an opportunity to reduce the risk of CVD in patients with T2DM. In this article, we consolidated the existing literature on SGLT-2 inhibitor use in Asian patients with T2DM and established contemporary guidance for clinicians. We extensively reviewed recommendations from international and regional guidelines, published data from clinical trials in the Asian population (dapagliflozin, canagliflozin, empagliflozin, ipragliflozin, luseogliflozin and tofogliflozin), CVD outcomes trials (EMPAREG-OUTCOME, CANVAS and DECLARE-TIMI 58) and real-world evidence studies (CVD-REAL, EASEL, CVD-REAL 2 and OBSERVE-4D). A series of clinical recommendations on the use of SGLT-2 inhibitors in Asian patients with T2DM was deliberated among experts with multiple rounds of review and voting. Based on the available evidence, we conclude that SGLT-2 inhibitors represent an evidence-based therapeutic option for the primary prevention of heart failure hospitalization and secondary prevention of CVD in patients with T2DM, and should be considered early on in the treatment algorithm for patients with multiple risk factors, or those with established CVD.
  8. Kong APS, Lew T, Lau ESH, Lim LL, Kesavadev J, Jia W, et al.
    Diabetes Obes Metab, 2020 04;22(4):669-679.
    PMID: 31903728 DOI: 10.1111/dom.13950
    AIMS: To explore the pattern of insulin use and glycaemic control in Asian people with type 2 diabetes, stratified by gender, young-onset diabetes (YOD; diagnosed before age 40 years), and diabetic kidney disease (DKD; estimated glomerular filtration rate [eGFR] 
  9. Lim LL, Lau ESH, Kong APS, Fu AWC, Lau V, Jia W, et al.
    Lancet Reg Health West Pac, 2023 Mar;32:100663.
    PMID: 36785858 DOI: 10.1016/j.lanwpc.2022.100663
    BACKGROUND: In Asia, diabetes-associated death due to cardiorenal diseases were 2-3 times higher in women than men which might be due to gender disparity in quality of care and health habits.

    METHODS: Adults with type 2 diabetes (T2D) from 11 Asian countries/areas were assessed using the same protocol (2007-2015). We compared treatment target attainment (HbA1c < 7%, blood pressure [BP] < 130/80 mmHg, risk-based LDL-cholesterol, lack of central obesity [waist circumference <90 cm in men or <80 cm in women), use of cardiorenal-protective drugs (renin-angiotensin system [RAS] inhibitors, statins), and self-reported health habits including self-monitoring blood glucose (SMBG) by gender. Analyses were stratified by countries/areas, age of natural menopause (<50 vs. ≥50 years), and comorbidities (atherosclerotic cardiovascular disease [ASCVD], heart failure, kidney impairment [eGFR < 60 mL/min/1.73 m2]).

    FINDINGS: Among 106,376 patients (53.2% men; median (interquartile range) diabetes duration: 6.0 (2.0-12.0) years; mean ± SD HbA1c 8.0 ± 1.9%; 27% insulin-treated), women were older and less likely to receive college education than men (28.9% vs. 48.8%). Women were less likely to smoke/drink alcohol and were physically less active than men. Women had lower BP (<130/80 mmHg: 29.4% vs. 25.7%), less general obesity (54.8% vs. 57.8%) but more central obesity than men (77.5% vs. 57.3%). Women were less likely to have ASCVD (12.8% vs. 17.0%) or heart failure (1.3% vs. 2.3%), but more likely to have kidney impairment (22.3% vs. 17.6%) and any-site cancer than men (2.5% vs. 1.6%). In most countries/areas, more men attained HbA1c <7% and risk-based LDL-cholesterol level than women. After adjusting for potential confounders including countries and centres, men had 1.63 odds ratio (95% CI 1.51, 1.74) of attaining ≥3 treatment targets than women.

    INTERPRETATION: Asian women with T2D had worse quality of care than men especially in middle-income countries/areas, calling for targeted implementation programs to close these care gaps.

    SPONSOR: Asia Diabetes Foundation.

    FUNDING: Nil.

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