Displaying publications 381 - 398 of 398 in total

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  1. Dillon J, Yakub MA, Kong PK, Ramli MF, Jaffar N, Gaffar IF
    J. Thorac. Cardiovasc. Surg., 2015 Mar;149(3):771-7; discussion 777-9.
    PMID: 25308120 DOI: 10.1016/j.jtcvs.2014.08.066
    Mitral valve repair is perceived to be of limited durability for advanced rheumatic disease in adults. We aim to examine the long-term outcomes of repair for rheumatic disease, identify predictors of durability, and compare with repair for degenerative disease.
    Matched MeSH terms: Registries
  2. Tan J
    Nephrology (Carlton), 2014 May;19(5):288-95.
    PMID: 24641721 DOI: 10.1111/nep.12228
    Brunei Darussalam is a small South East Asian country with a high prevalence and incidence of end stage kidney disease (ESRD). This study aims to compare key performance indicators recorded in the Brunei Dialysis and Transplant Registry and department records against international practice. Registries from the USA (USRDS), UK (UK Renal Registry), Australasia (ANZDATA), Europe (ERA-EDTA Registry) and Malaysia (MDTR) were used for comparisons.
    Matched MeSH terms: Registries
  3. Lim CC, Teo BW, Ong PG, Cheung CY, Lim SC, Chow KY, et al.
    Eur J Prev Cardiol, 2015 Aug;22(8):1018-26.
    PMID: 24857889 DOI: 10.1177/2047487314536873
    BACKGROUND: Few studies have examined the impact of chronic kidney disease (CKD) on adverse cardiovascular outcomes and deaths in Asian populations. We evaluated the associations of CKD with cardiovascular disease (CVD) and all-cause mortality in a multi-ethnic Asian population.
    DESIGN: Prospective cohort study of 7098 individuals who participated in two independent population-based studies involving Malay adults (n = 3148) and a multi-ethnic cohort of Chinese, Malay and Indian adults (n = 3950).
    METHODS: CKD was assessed from CKD-EPI estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR). Incident CVD (myocardial infarction, stroke and CVD mortality) and all-cause mortality were identified by linkage with national disease/death registries.
    RESULTS: Over a median follow-up of 4.3 years, 4.6% developed CVD and 6.1% died. Risks of both CVD and all-cause mortality increased with decreasing eGFR and increasing albuminuria (all p-trend <0.05). Adjusted hazard ratios (HR (95% confidence interval)) of CVD and all-cause mortality were: 1.54 (1.05-2.27) and 2.21 (1.67-2.92) comparing eGFR <45 vs ≥60; 2.81 (1.49-5.29) and 2.34 (1.28-4.28) comparing UACR ≥300 vs <30. The association between eGFR <60 and all-cause mortality was stronger among those with diabetes (p-interaction = 0.02). PAR of incident CVD was greater among those with UACR ≥300 (12.9%) and that of all-cause mortality greater among those with eGFR <45 (16.5%).
    CONCLUSIONS: In multi-ethnic Asian adults, lower eGFR and higher albuminuria were independently associated with incident CVD and all-cause mortality. These findings extend previously reported similar associations in Western populations to Asians and emphasize the need for early detection of CKD and intervention to prevent adverse outcomes.
    Matched MeSH terms: Registries
  4. Chew BH, Mastura I, Shariff-Ghazali S, Lee PY, Cheong AT, Ahmad Z, et al.
    Cardiovasc Diabetol, 2012;11:54.
    PMID: 22607105 DOI: 10.1186/1475-2840-11-54
    BACKGROUND: Uncontrolled blood pressure (BP) is a significant contributor of morbidity and even mortality in type 2 diabetes (T2D) patients. This study was done to determine the significant determinants of uncontrolled blood pressure in T2D patients in Malaysia.
    METHODS: Between 1st January 2009 to 31st December 2009, data from 70 889 patients with Type 2 diabetes was obtained from the Adult Diabetes Control and Management Registry for analysis; 303 centers participated in the study. Their demographic characteristics, the nature of their diabetes, their state of hypertension, treatment modalities, risk factors, and complications are described. Based on their most recent BP values, subjects were divided into controlled BP and uncontrolled BP and their clinical determinants compared. Independent determinants were identified using multivariate logistic regression.
    RESULTS: The mean age of patients at diagnosis of diabetes was 52.3 +/- 11.1 years old. Most were women (59.0 %) and of Malay ethnicity (61.9 %). The mean duration of diabetes was 5.9 +/- 5.6 years. A total of 57.4 % were hypertensive. Of the 56 503 blood pressure (BP) measured, 13 280 (23.5 %) patients had BP <130/80 mmHg. Eighteen percent was on > two anti-hypertensive agents. Health clinics without doctor, older age (>/= 50 years old), shorter duration of diabetes (< 5 years), Malay, overweight were determinants for uncontrolled blood pressure (BP >/=130/80 mmHg). Patients who were on anti-hypertensive agent/s were 2.7 times more likely to have BP >/=130/80 mmHg. Type 2 diabetes patients who had ischaemic heart disease or nephropathy were about 20 % and 15 % more likely to have their blood pressure treated to target respectively.
    CONCLUSIONS: Major independent determinants of uncontrolled BP in our group of T2D patients were Malay ethnicity, older age, recent diagnosis of diabetes, overweight and follow-up at health clinics without a doctor and possibly the improper use of anti hypertensive agent. More effort, education and resources, especially in the primary health care centres are needed to improve hypertensive care among our patients with diabetes.
    Matched MeSH terms: Registries
  5. Chew BH, Ismail M, Lee PY, Taher SW, Haniff J, Mustapha FI, et al.
    Diabetes Res Clin Pract, 2012 Jun;96(3):339-47.
    PMID: 22305940 DOI: 10.1016/j.diabres.2012.01.017
    Numerous studies with compelling evidence had shown a clear relationship between dyslipidaemia and cardiovascular (CV) events in patients with diabetes mellitus. This was an observational study based on secondary data from the online registry database Adult Diabetes Control and Management (ADCM) looking into the determinants of uncontrolled dyslipidaemia in type 2 diabetes mellitus patients. Independent predictors were identified using multivariate logistic regression. A total of 303 centres (289 health clinics, 14 hospitals) contributed a total of 70,889 patients (1972 or 2.8% patients were from hospital). About thirty eight percent were reported to have dyslipidaemia. There were 40.7% patients on lipid-lowering agents and of those above age 40 years old, only 38.1% of them were on a statin. Malay ethnicity and younger age groups (<50 years old) were two major determinants of uncontrolled LDL-C, TG and HDL-C. Female gender and uncontrolled blood pressure were determinants of uncontrolled LDL-C, and poor glycaemic control was related independently to high TG. This study has highlighted the suboptimal management of diabetic dyslipidaemia in Malaysia. Pharmacological treatment of dyslipidaemia could be more effective. Healthcare stakeholders in this country, especially in the primary care, have to recognize these shortfalls and take immediate remedial measures.
    Matched MeSH terms: Registries
  6. ESRD Incidence Study Group, Stewart JH, McCredie MR, Williams SM
    Nephrol Dial Transplant, 2006 Aug;21(8):2178-83.
    PMID: 16595584
    Only unbiased estimates of end-stage renal disease (ESRD) incidence and trends are useful for disease control-identification of risk factors and measuring the effect of intervention.
    Matched MeSH terms: Registries
  7. Lauridsen TK, Park L, Tong SY, Selton-Suty C, Peterson G, Cecchi E, et al.
    Circ Cardiovasc Imaging, 2015 Jul;8(7):e003397.
    PMID: 26162783 DOI: 10.1161/CIRCIMAGING.114.003397
    Staphylococcus aureus left-sided native valve infective endocarditis (LNVIE) has higher complication and mortality rates compared with endocarditis from other pathogens. Whether echocardiographic variables can predict prognosis in S aureus LNVIE is unknown.
    Matched MeSH terms: Registries
  8. Venkatason P, Zubairi YZ, Wan Ahmad WA, Hafidz MI, Ismail MD, Hadi MF, et al.
    BMJ Open, 2019 05 05;9(5):e025734.
    PMID: 31061031 DOI: 10.1136/bmjopen-2018-025734
    OBJECTIVES: Cardiogenic shock (CS) complicating ST-elevation myocardial infarction (STEMI) carries an extremely high mortality. The clinical pattern of this life threatening complication has never been described in Malaysian setting. This study is to investigate the incidence, clinical characteristics and outcome of STEMI patients with CS in our population.

    DESIGN: A retrospective analysis of STEMI patients from 18 hospitals across Malaysia contributing to the Malaysian National Cardiovascular Database-acute coronary syndrome) registry (NCVD-ACS) year 2006-2013.

    PARTICIPANTS: 16 517 patients diagnosed of STEMI from 18 hospitals in Malaysia from the year 2006 to 2013.

    PRIMARY OUTCOME MEASURES: In-hospital and 30 day post-discharge mortality.

    RESULTS: CS complicates 10.6% of all STEMIs in this study. They had unfavourable premorbid conditions and poor outcomes. The in-hospital mortality rate was 34.1% which translates into a 7.14 times mortality risk increment compared with STEMI without CS. Intravenous thrombolysis remained as the main urgent reperfusion modality. Percutaneous coronary interventions (PCI) in CS conferred a 40% risk reduction over non-invasive therapy but were only done in 33.6% of cases. Age over 65, diabetes mellitus, hypertension, chronic lung and kidney disease conferred higher risk of mortality.

    CONCLUSION: Mortality rates of CS complicating STEMI in Malaysia are high. In-hospital PCI confers a 40% mortality risk reduction but the rate of PCI among our patients with CS complicating STEMI is still low. Efforts are being made to increase access to invasive therapy for these patients.

    Matched MeSH terms: Registries
  9. King TL, Tiong LL, Kaman Z, Zaw WM, Abdul Aziz Z, Chung LW
    J Stroke Cerebrovasc Dis, 2020 Sep;29(9):105012.
    PMID: 32807427 DOI: 10.1016/j.jstrokecerebrovasdis.2020.105012
    BACKGROUND: Located on the Borneo Island, Sarawak is the largest state of Malaysia and has a population distinctive from Peninsular Malaysia. The ischaemic stroke data in Sarawak had not been reported despite the growing number of patients annually. We aimed to investigate patient characteristics, management, and outcomes of ischaemic stroke in Sarawak and benchmark the results with national and international published data.

    METHODS: We included ischaemic stroke cases admitted to Sarawak General Hospital between June 2013 and August 2018 from Malaysia National Stroke Registry. We performed descriptive analyses on patient demographics, cardiovascular risk factors, prior medications, smoking status, arrival time, thrombolysis rate, Get With The Guidelines (GWTG)-Stroke measures, and outcomes at discharge. We also numerically compared the results from Sarawak with the published data from selected national and international cohorts.

    RESULTS: We analysed 1435 ischaemic stroke cases. The mean age was 60.1±13.2 years old; 64.9% were male; median baseline National Institute of Health Stroke Scale was seven points. Hypertension was the most prevalent risk factor of ischaemic stroke; 12.7% had recurrent stroke; 13.7% were active smokers. The intravenous thrombolysis rate was 18.8%. We achieved 80-90% in three GWTG-Stroke performance measures and 90-98% in four additional quality measures in our ischaemic stroke management. At discharge, 57% had modified Rankin Scale of 0-2; 6.7% died during hospitalisation. When compared with selected national and international data, patients in Sarawak were the youngest; Sarawak had more male and more first-ever stroke. Thrombolysis rate in Sarawak was higher compared with most studies in the comparison. Functional outcome at discharge in Sarawak was better than national cohort but still lagging behind when compared with the developed countries. In-hospital mortality rate in Sarawak was slightly lower than the national data but higher when compared with other countries.

    CONCLUSION: Our study described characteristics, management, and outcomes of ischaemic stroke in Sarawak. We achieved high compliance with most of GTWG-Stroke performance and quality indicators. Sarawak had better outcomes than the national results on ischaemic stroke. However, there is still room for improvement when compared with other countries. Actions are needed to reduce the cardiovascular burdens for stroke prevention, enhance healthcare resources for stroke care, and improve intravenous thrombolysis treatment in Sarawak.

    Matched MeSH terms: Registries
  10. Montefusco A, De Filippo O, Gili S, Mancone M, Calcagno S, Cirillo P, et al.
    Coron Artery Dis, 2020 01;31(1):27-34.
    PMID: 31658146 DOI: 10.1097/MCA.0000000000000790
    AIMS: To assess the long-term outcomes of patients treated with sirolimus-eluting Stentys stent in a real-life setting.

    BACKGROUND: Few data regarding the safety and effectiveness of self-apposing sirolimus-eluting Stentys stent are available.

    METHODS: 278 patients (30% stable coronary artery disease, 70% acute coronary syndromes, and 54% on unprotected left main) treated with sirolimus eluting Stentys stent were retrospectively included in the self-aPposing, bAlloon-delivered, siRolimus-eluting stent for the Treatment of the coronary Artery disease multicenter registry. Major adverse cardiovascular events (MACE, a composite of cardiac death, myocardial infarction, target lesion revascularization, stent thrombosis) were the primary end-point, single components of MACE were the secondary ones.

    RESULTS: After 13 months (interquartile range 5-32), MACE was 14%. Stent thrombosis occurred in 3.9% of the patients (2.5% definite stent thrombosis and 1.4% probable stent thrombosis), 66% of them presenting with ST-segment elevation myocardial infarction (STEMI) at admission. Cardiovascular death, target lesion revascularization and myocardial infarction was 4.7%, 8.3%, and 7.2%, respectively. At multivariate analysis, risk of MACE was increased by diabetes (hazard ratios 4.76; P = 0.002) but was not affected by the indication leading to sirolimus-eluting Stentys stent implantation (marked vessel tapering vs. coronary ecstasies, hazard ratios 0.74, P = 0.71).

    CONCLUSION: Sirolimus-eluting Stentys stent may represent a potential solution for specific coronary anatomies such as bifurcation, ectasic, or tapered vessels. Risk of stent thrombosis appears related to clinical presentation with STEMI and to anatomic features, stressing the importance of the use of intracoronary imaging for self-expandable stents implantation.

    Matched MeSH terms: Registries
  11. Chew BH, Lee PY, Cheong AT, Ismail M, Shariff-Ghazali S, Goh PP
    Prim Care Diabetes, 2016 10;10(5):383-6.
    PMID: 27459893 DOI: 10.1016/j.pcd.2016.07.003
    A persistent and increasing prevalence of diagnosed and undiagnosed diabetes mellitus has recently been reported in the National Health and Morbidity Survey 2015. This commentary recapitulates the relevant and valuable lessons in the Malaysian national diabetes registries to inform the healthcare stakeholders and policy makers on potential areas of clinical practice improvement and future researches. Under performance of the process measures and sub-optimal control of HbA1c, blood pressure and lipids profile were prevalent (<40% achieved treatment targets). Although these had improved slightly from 2009 to 2012, diabetes co-morbidities (hypertension and dyslipidaemia) and complications had also increased. Prevalence of insulin use had doubled, and lipid lowering agent use had increased about 50% in 2012 compared to 2009. We identified six clinical areas for urgent attention and improvement, and three potential areas for future research.
    Matched MeSH terms: Registries
  12. Montefusco A, D'Ascenzo F, Gili S, Smolka G, Chieffo A, Baumbach A, et al.
    Catheter Cardiovasc Interv, 2019 02 01;93(2):208-215.
    PMID: 30298593 DOI: 10.1002/ccd.27809
    OBJECTIVES: To compare the effectiveness and safety of self-expandable, sirolimus-eluting Stentys stents (SES) and second-generation drug-eluting stents (DES-II) for the treatment of the unprotected left main (ULM).

    BACKGROUND: SES may provide a valuable option to treat distal ULM, particularly when significant caliber gaps with side branches are observed.

    METHODS: Patients from the multicenter SPARTA (clinicaltrials.gov: NCT02784405) and FAILS2 registries were included. Propensity-score with matching was performed to account for the lack of randomization. Primary end-point was the rate of major adverse cardiovascular events (MACE, a composite of all cause death, myocardial infarction, target lesion revascularization [TLR], unstable angina and definite stent thrombosis [ST]). Single components of MACE were the secondary end-points.

    RESULTS: Overall, 151 patients treated with SES and 1270 with DES-II were included; no differences in MACE rate at 250 days were observed (9.8% vs. 11.5%, P = 0.54). After propensity score with matching, 129 patients treated with SES and 258 with DES-II, of which about a third of female gender, were compared. After a follow-up of 250 days, MACE rate did not differ between the two groups (9.9% vs. 8.5%, P = 0.66), as well as the rate of ULM TLR (1.6% vs. 3.1%, P = 0.36) and definite ST (0.8% vs. 1.2%, P = 0.78). These results were consistent also when controlling for the treatment with provisional vs. 2-stents strategies for the ULM bifurcation.

    CONCLUSION: SES use for ULM treatment was associated with a similar MACE rate compared to DES-II at an intermediate-term follow-up. SES might represent a potential option in this setting.

    Matched MeSH terms: Registries
  13. Pang J, Chan DC, Hu M, Muir LA, Kwok S, Charng MJ, et al.
    J Clin Lipidol, 2019 01 25;13(2):287-300.
    PMID: 30797720 DOI: 10.1016/j.jacl.2019.01.009
    BACKGROUND: There is a lack of information on the health care of familial hypercholesterolemia (FH).

    OBJECTIVE: The objective of this study was to compare the health care of FH in countries of the Asia-Pacific region and Southern Hemisphere.

    METHODS: A series of questionnaires were completed by key opinion leaders from selected specialist centers in 12 countries concerning aspects of the care of FH, including screening, diagnosis, risk assessment, treatment, teaching/training, and research; the United Kingdom (UK) was used as the international benchmark.

    RESULTS: The estimated percentage of patients diagnosed with the condition was low (overall <3%) in all countries, compared with ∼15% in the UK. Underdetection of FH was associated with government expenditure on health care (ϰ = 0.667, P 

    Matched MeSH terms: Registries
  14. Krackhardt F, Rosli MA, Leschke M, Schneider A, Sperling C, Heang TM, et al.
    Catheter Cardiovasc Interv, 2018 06;91(7):1221-1228.
    PMID: 28944613 DOI: 10.1002/ccd.27306
    OBJECTIVE: The objective of this study was to compare the safety and efficacy of a polymer-free sirolimus coated, ultrathin strut drug eluting stent (PF-SES) to its uncoated bare-metal stent (BMS) platform of identical stent architecture.

    BACKGROUND: Recently published randomized trials comparing BMS to DES with a focus on shortened dual-antiplatelet therapy reported incidences of stent thrombosis (ST) and bleeding complications (LEADERS FREE) in favor of drug eluting stents (DES).

    METHODS: Data of previously published large-sale, international, single-armed, multicenter, observational studies of ultra-thin PF-SES, and BMS were propensity score (PS) matched for selected lesion morphological and cardiovascular risk factors to compare target lesion revascularization (TLR), myocardial infarction, cardiac death, major adverse cardiac events (MACE), bleeding complications and ST rates. Primary endpoint in both studies was TLR at 9 months.

    RESULTS: At 9 months the rates of TLR was significantly lower in the PF-SES group as compared with patients treated with the BMS analogue of identical stent design (1.4% vs. 4.6%, P = 0.005). Likewise the 9-month MACE rates were lower in the PF-SES group (3.2% vs. 8.7%, P = 0.001) whereas there were no differences in the accumulated ST rates (0.5% vs. 1.5%, P = 0.109). Overall accumulated bleeding incidences (BARC 1-5) were not significantly different between PF-SES and BMS patients (1.8% vs. 2.7%, p = 0.388).

    CONCLUSIONS: PF-SES are superior over analogue BMS of identical stent architecture in daily clinical routine with lower rates of TLR and MACE in a PS-matched, unselected patient population without differences in accumulated ST rates and bleeding frequencies given the currently favored postprocedural comedication (ClinicalTrials.gov Identifier NCT02629575).

    Matched MeSH terms: Registries
  15. Lim LL, Fu AWC, Lau ESH, Ozaki R, Cheung KKT, Ma RCW, et al.
    Nephrol Dial Transplant, 2019 Aug 01;34(8):1320-1328.
    PMID: 29939305 DOI: 10.1093/ndt/gfy154
    BACKGROUND: Early detection and risk factor control prevent chronic kidney disease (CKD) progression. Evaluation of peripheral autonomic dysfunction may detect incident cardiovascular-renal events in type 2 diabetes (T2D).

    METHODS: SUDOSCAN, a non-invasive tool, provides an age-adjusted electrochemical skin conductance (ESC) composite score incorporating hands/feet ESC measurements, with a score ≤53 indicating sudomotor dysfunction. A consecutive cohort of 2833 Chinese adults underwent structured diabetes assessment in 2012-13; 2028 participants without preexisting cardiovascular disease (CVD) and CKD were monitored for incident cardiovascular-renal events until 2015.

    RESULTS: In this prospective cohort {mean age 57.0 [standard deviation (SD) 10.0] years; median T2D duration 7.0 [interquartile range (IQR) 3.0-13.0] years; 56.1% men; 72.5% never-smokers; baseline ESC composite score 60.7 (SD 14.5)}, 163 (8.0%) and 25 (1.2%) participants developed incident CKD and CVD, respectively, after 2.3 years of follow-up. The adjusted hazard ratios (aHRs) per 1-unit decrease in the ESC composite score for incident CKD, CVD and all-cause death were 1.02 [95% confidence interval (CI) 1.01-1.04], 1.04 (1.00-1.07) and 1.04 (1.00-1.08), respectively. Compared with participants with an ESC composite score >53, those with a score ≤53 had an aHR of 1.56 (95% CI 1.09-2.23) for CKD and 3.11 (95% CI 1.27-7.62) for CVD, independent of common risk markers. When added to clinical variables (sex and duration of diabetes), the ESC composite score improved discrimination of all outcomes with appropriate reclassification of CKD risk.

    CONCLUSIONS: A low ESC composite score independently predicts incident cardiovascular-renal events and death in T2D, which may improve the screening strategy for early intervention.

    Matched MeSH terms: Registries
  16. Navarrete-Muñoz EM, Wark PA, Romaguera D, Bhoo-Pathy N, Michaud D, Molina-Montes E, et al.
    Am J Clin Nutr, 2016 Sep;104(3):760-8.
    PMID: 27510540 DOI: 10.3945/ajcn.116.130963
    BACKGROUND: The consumption of sweet beverages has been associated with greater risk of type 2 diabetes and obesity, which may be involved in the development of pancreatic cancer. Therefore, it has been hypothesized that sweet beverages may increase pancreatic cancer risk as well.

    OBJECTIVE: We examined the association between sweet-beverage consumption (including total, sugar-sweetened, and artificially sweetened soft drink and juice and nectar consumption) and pancreatic cancer risk.

    DESIGN: The study was conducted within the European Prospective Investigation into Cancer and Nutrition cohort. A total of 477,199 participants (70.2% women) with a mean age of 51 y at baseline were included, and 865 exocrine pancreatic cancers were diagnosed after a median follow-up of 11.60 y (IQR: 10.10-12.60 y). Sweet-beverage consumption was assessed with the use of validated dietary questionnaires at baseline. HRs and 95% CIs were obtained with the use of multivariable Cox regression models that were stratified by age, sex, and center and adjusted for educational level, physical activity, smoking status, and alcohol consumption. Associations with total soft-drink consumption were adjusted for juice and nectar consumption and vice versa.

    RESULTS: Total soft-drink consumption (HR per 100 g/d: 1.03; 95% CI: 0.99, 1.07), sugar-sweetened soft-drink consumption (HR per 100 g/d: 1.02; 95% CI: 0.97, 1.08), and artificially sweetened soft-drink consumption (HR per 100 g/d: 1.04; 95% CI: 0.98, 1.10) were not associated with pancreatic cancer risk. Juice and nectar consumption was inversely associated with pancreatic cancer risk (HR per 100 g/d: 0.91; 95% CI: 0.84, 0.99); this association remained statistically significant after adjustment for body size, type 2 diabetes, and energy intake.

    CONCLUSIONS: Soft-drink consumption does not seem to be associated with pancreatic cancer risk. Juice and nectar consumption might be associated with a modest decreased pancreatic cancer risk. Additional studies with specific information on juice and nectar subtypes are warranted to clarify these results.

    Matched MeSH terms: Registries
  17. Sazlina SG, Mastura I, Ahmad Z, Cheong AT, Adam BM, Jamaiyah H, et al.
    Geriatr Gerontol Int, 2014 Jan;14(1):130-7.
    PMID: 23581598 DOI: 10.1111/ggi.12070
    The aims of the present study were to assess the control of glycemia and other cardiovascular disease risk factors, and the association between age and these controls among older adults with type 2 diabetes in Malaysia.
    Matched MeSH terms: Registries
  18. Masir N, Akhter A, Roshan TM, Florence CS, Abdul-Rahman F, Tumian NR, et al.
    J Clin Pathol, 2019 Sep;72(9):630-635.
    PMID: 31189540 DOI: 10.1136/jclinpath-2019-205837
    AIMS: Heightened B-cell receptor (BCR) activity in diffuse large B-cell lymphoma (DLBCL) is well established, and a subset of patients with relapsed DLBCL can benefit from BCR-targeted therapies. Universal outreach of such emerging therapies mandates forming a global landscape of BCR molecular signalling in DLBCL, including Southeast Asia.

    METHODS: 79 patients with DLBCL (nodal, 59% and extranodal, 41%) treated with rituximab combined with cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) therapy were selected. Expression levels of BCR and linked signalling pathway molecules were inter-related with Lymph2Cx-based cell of origin (COO) types and overall survival (OS).

    RESULTS: Activated B-cell (ABC) type DLBCL constituted 49% (39/79) compared with germinal centre B-cell (GCB) type DLBCL (29/79; 37%) and revealed poor prognosis (p=0.013). In ABC-DLBCL, high BTK expression exerted poor response to R-CHOP, while OS in ABC-DLBCL with low BTK expression was similar to GCB-DLBCL subtype (p=0.004). High LYN expression coupled with a poor OS for ABC-DLBCL as well as GCB-DLBCL subtypes (p=0.001). Furthermore, high coexpression of BTK/LYN (BTKhigh/LYNhigh) showed poor OS (p=0.019), which linked with upregulation of several genes associated with BCR repertoire and nuclear factor-kappa B pathway (p<0.01). In multivariate analysis, high BTK and LYN expression retained prognostic significance against established clinical predictive factors such as age, International Prognostic Index and COO (p<0.05).

    CONCLUSIONS: Our data provide a clear association between high BCR activity in DLBCL and response to therapy in a distinct population. Molecular data provided here will pave the pathway for the provision of promising novel-targeted therapies to patients with DLBCL in Southeast Asia.

    Matched MeSH terms: Registries
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