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Association of dengue serotypes and its complications: a retrospective cohort study

Lau Q, Lee ZM, Shunmugarajoo A, Tan CY, Azmel A, Yap SY

Med J Malaysia, 2023 May;78(3):372-378.
PMID: 37271848

INTRODUCTION: Dengue fever is an arthropod-borne disease and has a wide clinical spectrum. It is hypothesised that dengue serotypes could be a possible factor for such phenomena and therefore be a possible predictor for the development of severe dengue.
METHOD: A retrospective cohort study was done to explore the association between dengue serotypes and the various complications. All patients who underwent dengue serotyping from 1st January to 31st December 2018 in Tengku Ampuan Rahimah Hospital were selected. Serotypes were randomly done for admitted dengue patients. Notes were then retrieved for data collection. Secondary outcomes like length of stay and highest lactate level were also studied. Data analysis was done using SPSS version 20.
RESULT: A total of 193 patient records were included in the analysis. Chi-square test for independence indicated that the proportion of dengue complications between male and female were significantly different (χ2(1) = 11.37, p = 0.001). Dengue serotype was not associated with the development of dengue complications, total number of dengue complications, length of admission, lactate level and survival among the serotypes. Results of the binary logistic regression showed that men have thrice the odds (AOR = 3.3, 95% CI: 1.6 6.7) for developing dengue complications. One patient was found to be co-infected with serotype 2 and 3.
CONCLUSION: Our study did not reveal any association between the different dengue virus serotypes and its complications. Therefore, all dengue infection should be approached with equal meticulousness. There are possibilities that apart from serotype, dengue genotype and lineage would determine clinical outcome. However, more studies are required to study such associations.
Clinical characteristics and computed tomographical features of pulmonary thromboembolic disease associated with COVID-19 infection: A tertiary hospital analysis

Tan TL, Illa NE, Ting SY, Hwong PL, Azmel A, Shunmugarajoo A, et al.

Med J Malaysia, 2023 Mar;78(2):155-162.
PMID: 36988524

INTRODUCTION: The co-existence of coronavirus disease 2019 (COVID-19) and pulmonary thromboembolic (PTE) disease poses a great clinical challenge. To date, few researches have addressed this important clinical issue among the South-East Asian populations. The objectives of this study were as follow: (1) to describe the clinical characteristics and computed tomographical (CT) features of patients with PTE disease associated with COVID-19 infection and (2) to compare these parameters with those COVID-19 patients without PTE disease.
MATERIALS AND METHODS: This cross-sectional study with retrospective record review was conducted in Hospital Tengku Ampuan Rahimah, Selangor, Malaysia. We included all hospitalised patients with confirmed COVID-19 infection who had undergone CT pulmonary angiogram (CTPA) examinations for suspected PTE disease between April 2021 and May 2021. Clinical data and laboratory data were extracted by trained data collectors, whilst CT images retrieved were analysed by a senior radiologist. Data analysis was performed using Statistical Package for the Social Sciences (SPSS) version 20.
RESULTS: We studied 184 COVID-19 patients who were suspected to have PTE disease. CTPA examinations revealed a total of 150 patients (81.5%) suffered from concomitant PTE disease. Among the PTE cohort, the commonest comorbidities were diabetes mellitus (n=78, 52.0%), hypertension (n=66, 44.0%) and dyslipidaemia (n=25, 16.7%). They were generally more ill than the non-PTE cohort as they reported a significantly higher COVID-19 disease category during CTPA examination with p=0.042. Expectedly, their length of both intensive care unit stays (median number of days 8 vs. 3; p=0.021) and hospital stays (median number of days 14.5 vs. 12; p=0.006) were significantly longer. Intriguingly, almost all the subjects had received either therapeutic anticoagulation or thromboprophylactic therapy prior to CTPA examination (n=173, 94.0%). Besides, laboratory data analysis identified a significantly higher peak C-reactive protein (median 124.1 vs. 82.1; p=0.027) and ferritin levels (median 1469 vs. 1229; p=0.024) among them. Evaluation of CT features showed that COVID-19 pneumonia pattern (p<0.001) and pulmonary angiopathy (p<0.001) were significantly more profound among the PTE cohort. To note, the most proximal pulmonary thrombosis was located in the segmental (n=3, 2.0%) and subsegmental pulmonary arteries (n=147, 98.0%). Also, the thrombosis predominantly occurred in bilateral lungs with multilobar involvement (n=95, 63.3%).
CONCLUSION: Overall, PTE disease remains prevalent among COVID-19 patients despite timely administration of thromboprophylactic therapy. The presence of hyperinflammatory activities, unique thrombotic locations as well as concurrent pulmonary parenchyma and vasculature aberrations in our PTE cohort implicate immunothrombosis as the principal mechanism of this novel phenomenon. We strongly recommend future researchers to elucidate this important clinical disease among our post- COVID vaccination populations.
The clinical utility of CD163 in viral diseases

Yap YJ, Wong PF, AbuBakar S, Sam SS, Shunmugarajoo A, Soh YH, et al.

Clin Chim Acta, 2023 Feb 15;541:117243.
PMID: 36740088 DOI: 10.1016/j.cca.2023.117243

Macrophage activation and hypercytokinemia are notable presentations in certain viral infections leading to severe disease and poor prognosis. Viral infections can cause macrophage polarization into the pro-inflammatory M1 or anti-inflammatory M2 phenotype. Activated M1 macrophages usually restrict viral replication whereas activated M2 macrophages suppress inflammation and promote tissue repair. In response to inflammatory stimuli, macrophages polarize to the M2 phenotype expressing hemoglobin scavenger CD163 surface receptor. The CD163 receptor is shed as the soluble form, sCD163, into plasma or tissue fluids. sCD163 causes detoxification of pro-oxidative hemoglobin which produces anti-inflammatory metabolites that promote the resolution of inflammation. Hence, increased CD163 expression in tissues and elevated circulatory levels of sCD163 have been associated with acute and chronic inflammatory diseases. CD163 and other macrophage activation markers have been commonly included in the investigation of disease pathogenesis and progression. This review provides an overview of the involvement of CD163 in viral diseases. The clinical utility of CD163 in viral disease diagnosis, progression, prognosis and treatment evaluation is discussed.
Fulltext A 3D Microfluidic ELISA for the Detection of Severe Dengue: Sensitivity Improvement and Vroman Effect Amelioration by EDC-NHS Surface Modification

Maeno H, Wong PF, AbuBakar S, Yang M, Sam SS, Jamil-Abd J, et al.

Micromachines (Basel), 2021 Nov 30;12(12).
PMID: 34945351 DOI: 10.3390/mi12121503

Serum is commonly used as a specimen in immunoassays but the presence of heterophilic antibodies can potentially interfere with the test results. Previously, we have developed a microfluidic device called: 3D Stack for enzyme-linked immunosorbent assay (ELISA). However, its evaluation was limited to detection from a single protein solution. Here, we investigated the sensitivity of the 3D Stack in detecting a severe dengue biomarker-soluble CD163 (sCD163)-within the serum matrix. To determine potential interactions with serum matrix, a spike-and-recovery assay was performed, using 3D Stacks with and without surface modification by an EDC-NHS (N-ethyl-N'-(3-(dimethylamino)propyl)carbodiimide/N-hydroxysuccinimide) coupling. Without surface modification, a reduced analyte recovery in proportion to serum concentration was observed because of the Vroman effect, which resulted in competitive displacement of coated capture antibodies by serum proteins with stronger binding affinities. However, EDC-NHS coupling prevented antibody desorption and improved the sensitivity. Subsequent comparison of sCD163 detection using a 3D Stack with EDC-NHS coupling and conventional ELISA in dengue patients' sera revealed a high correlation (R = 0.9298, p < 0.0001) between the two detection platforms. Bland-Altman analysis further revealed insignificant systematic error between the mean differences of the two methods. These data suggest the potentials of the 3D Stack for further development as a detection platform.