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Adverse pregnancy outcomes among multi-ethnic systemic lupus erythematosus patients in Malaysia

Shaharir SS, Maulana SA, Shahril NS, Mohd R, Mustafar R, Said MSM, et al.

Lupus, 2020 Sep;29(10):1305-1313.
PMID: 32660312 DOI: 10.1177/0961203320938871

BACKGROUND: Despite the improvement in the live birth rate among patients with systemic lupus erythematosus (SLE), they are still at an increased risk of adverse pregnancy outcomes (APOs).
OBJECTIVE: To determine the prevalence and factors associated with APOs in the multi-ethnic SLE populations in Malaysia.Methodology: This was a retrospective review of the consecutive SLE patients who attended the outpatient clinic in two major rheumatology centres from January 2016 until December 2019 with complete pre-pregnancy, antenatal and intra-partum records. APOs include pregnancy loss, prematurity, pre-eclampsia, intra-uterine growth restriction (IUGR) and maternal death. Univariate and multivariable logistic regression with generalised estimating equation (GEE) analyses were performed to determine the factors associated with APOs.
RESULTS: A total of 153 patients with 240 pregnancies were included and the majority of the patients were Malay (69.9%), followed by Chinese (24.2%) and Indian (5.9%). The prevalence of APOs was 61.7% with the commonest complication being prematurity (28.3%), followed by pregnancy loss (24.6%) and pre-eclampsia (21.8%). Logistic regression model-based GEE analysis revealed that the independent predictors of APOs were active haematological system during pregnancy, pre-pregnancy active disease, Indian patients and positive lupus anticoagulant. Hydroxychloroquine use was associated with lower APOs including pre-eclampsia, prematurity and IUGR in the univariate analyses but it was no longer significant in the GEE analysis.
CONCLUSION: The prevalence of APOs was high particularly among the Indian patients. Positive lupus anticoagulant and pre-pregnancy active disease were the factors strongly associated with APOs in our multi-ethnic cohort. Hydroxychloroquine may protect against APOs but further larger studies are needed to confirm this.
Factors associated with increased white matter hyperintense lesion (WMHI) load in patients with systemic lupus erythematosus (SLE)

Shaharir SS, Osman SS, Md Rani SA, Sakthiswary R, Said MSM

Lupus, 2018 Jan;27(1):25-32.
PMID: 28467290 DOI: 10.1177/0961203317707062

Introduction White matter hyperintense (WMHI) lesions are the most common finding in magnetic resonance imaging (MRI) of the brain in patients with systemic lupus erythematosus (SLE). Objective The objective of this article is to determine the clinical factors associated with an increase in WMHI lesion load among SLE patients. Method A total of 83 SLE patients with MRI of the brain from National University of Malaysia Medical Centre were included. The WMHI lesion load was determined using the Scheltens score and Fazekas scale, and their distribution was divided into the deep white matter (DWMHI) and periventricular (PVH) regions. The clinical correlates of WMHI lesions were initially determined using univariate analyses and subsequently multivariable regression analyses were performed to determine the independent factors of increased WMHI lesion load. Results MRI of the brain of 46 patients who had WMHI lesions were compared with 37 patients with normal MRI. We found significant association between the presence of WMHI lesions and age, presence of cerebral infarcts, positive antiphospholipid antibody (aPL), active disease, neuropsychiatric lupus (NPSLE) and disease damage. Age, SLEDAI scores, cerebral infarcts and disease damage were significantly associated with higher DWMHI and PVH Scheltens scores. Meanwhile, patients with active lupus nephritis (LN), lower serum albumin and more severe proteinuria were associated with larger Fazekas WMHI lesions. Multivariable regression analysis revealed that the independent factors associated with presence of WMHI lesions were positive aPL and SLEDAI scores ( p
Fulltext Periodontal disease in seropositive rheumatoid arthritis: scoping review of the epidemiological evidence

Nik-Azis NM, Mohd N, Baharin B, Said MSM, Fadzilah FM, Haflah NHM

Germs, 2021 Jun;11(2):266-286.
PMID: 34422698 DOI: 10.18683/germs.2021.1263

The link between periodontal disease (PD) and rheumatoid arthritis (RA) has been hypothesized to lie in the anti-cyclic citrullinated protein antibody (ACPA) molecules present in seropositive RA. This review aimed to discuss how RA and specifically ACPA-positive RA link to PD, and appraise the epidemiological evidence on the relationship between ACPA-positive RA and PD. Articles were searched following the PRISMA guideline across the MEDLINE, Web of Science, Scopus and Cochrane Library databases. A total of 21 articles met the inclusion criteria of reporting the epidemiological data on the different ACPA status of the subjects with RA and PD (or periodontitis) parameters. A discrepancy is noted in the epidemiological evidence on the difference in the prevalence and severity of PD between ACPA-positive and ACPA-negative RA patients. Although the link between RA and PD is mostly discussed in terms of ACPA, reports on the different manifestations of PD between the two RA subsets remains inconclusive.
RUNX1/ETO regulates reactive oxygen species (ROS) levels in t(8,21) acute myeloid leukaemia via FLT3 and RAC1

Azlan A, Khor KZ, Rajasegaran Y, Rosli AA, Said MSM, Yusoff NM, et al.

Med Oncol, 2023 Jun 21;40(7):208.
PMID: 37341821 DOI: 10.1007/s12032-023-02075-w

Reactive oxygen species (ROS) homeostasis is crucial for leukaemogenesisand deregulation would hamper leukaemic progression. Although the regulatory effects of RUNX1/ETO has been extensively studied, its underlying molecular mechanims in ROS production in t(8,21) AML is yet to be fully elucidated. Here, we report that RUNX1/ETO could directly control FLT3 by occupying several DNA elements on FLT3 locus. The possible hijacking mechanism by RUNX1/ETO over FLT3 mediated ROS modulation in AML t(8;21) was made apparent when suppression of RUNX1/ETO led to decrement in ROS levels and the direct oxidative marker FOXO3 but not in FLT3 and RAC1 suppressed t(8,21) AML cell line Furthermore, nuclear import of RUNX1/ETO was aberrated following RUNX1/ETO and RAC1 suppression suggesting association in ROS control. A different picture was depicted in non t(8;21) cells where suppression of RAC1 and FLT3 led to decreased levels of FOXO3a and ROS. Results alltogether indicate a possible dysregulation of ROS levels by RUNX1/ETO in t(8,21) AML.
Knowledge and Awareness of Stroke in Rural and Urban Communities in Indonesia

Ambarika R, Said MSM, Adiutama NM, Anggraini NA, Poddar S, Abdullah BF

Enferm Clin (Engl Ed), 2024 Apr 17.
PMID: 38641005 DOI: 10.1016/j.enfcle.2024.04.004

INTRODUCTION: The average stroke morbidity rate, especially in rural communities, is higher when compared to the national average.
OBJECTIVE: Identify the profile of knowledge and awareness of stroke in rural and urban communities and analyze the differences between the two.
METHOD: Respondents who met the requirements answered a questionnaire containing a total of 41 items regarding knowledge and awareness of stroke. Characteristic data obtained includes age, gender, education, occupation, and ethnicity. Differences in characteristics were analyzed using Mann-Whitney, and the profiles of knowledge and awareness of stroke in rural and urban groups were analyzed using independent t tests to see differences between the two.
RESULT: Differences in the characteristics of rural and urban groups were only in education (p = 0.036) and occupation (p = 0.021). The mean score of the knowledge domain for the rural group was 72.53 (SD = 11.04), for the urban group it was 81.06 (SD = 11.12). The mean score awareness of stroke domain in the rural group was 72.18 (SD = 11.01), the urban group was 85.51 (SD = 11.67). The profile of knowledge and awareness of stroke in rural communities was significantly lower than in urban communities. The significance value was (p = 0.004) for knowledge and (p = 0.002) for awareness of stroke.
CONCLUSION: Based on the findings, it is reasonable to suspect that educational and occupational factors contribute to differences in the profile of knowledge and awareness of stroke in the two groups. Therefore, the stroke awareness campaign strategy for rural communities needs to be specifically designed by emphasizing/considering educational and occupational factors.
Fulltext Risk factors for symptomatic Avascular Necrosis (AVN) in a multi-ethnic Systemic Lupus Erythematosus (SLE) cohort

Shaharir SS, Chua SH, Mohd R, Mustafar R, Noh MM, Shahril NS, et al.

PLoS One, 2021;16(3):e0248845.
PMID: 33739994 DOI: 10.1371/journal.pone.0248845

Avascular necrosis of bone (AVN) is increasingly being recognized as a complication of SLE and causes significant disability due to pain and mobility limitations. We studied the prevalence and factors associated with avascular necrosis (AVN) in a multiethnic SLE cohort. SLE patients who visited the outpatient clinic from October 2017 to April 2019 were considered eligible. Their medical records were reviewed to identify patients who developed symptomatic AVN, as confirmed by either magnetic resonance imaging or plain radiography. Subsequently, their SLE disease characteristics and treatment were compared with the characteristics of patients who did not have AVN. Multivariable logistic regression analyses were performed to determine the independent factors associated with AVN among the multiethnic SLE cohort. A total of 390 patients were recruited, and the majority of them were females (92.6%); the patients were predominantly of Malay ethnicity (59.5%), followed by Chinese (35.9%) and Indian (4.6%). The prevalence of symptomatic AVN was 14.1%, and the mean age of AVN diagnosis was 37.6 ± 14.4 years. Both univariate and multivariable logistic regression analyses revealed that a longer disease duration, high LDL-C (low density lipoprotein cholesterol), positive anti-cardiolipin (aCL) IgG and anti-dsDNA results, a history of an oral prednisolone dose of more than 30 mg daily for at least 4 weeks and osteoporotic fractures were significantly associated with AVN. On the other hand, hydroxychloroquin (HCQ), mycophenolate mofetil (MMF) and bisphosphonate use were associated with a lower risk of AVN. No associations with ethnicity were found. In conclusion, several modifiable risk factors were found to be associated with AVN, and these factors may be used to identify patients who are at high risk of developing such complications. The potential protective effects of HCQ, MMF and bisphosphonates warrant additional studies.