Pulmonary thromboembolic disease associated with COVID-19 infection: a comparison between geriatric and non-geriatric populations.

INTRODUCTION: The magnitude of Coronavirus Disease 2019 (COVID-19) infection among the elderly population is expected to rise. Our study compares the clinical and computed tomographical (CT) features of pulmonary thromboembolic (PTE) disease associated with COVID-19 infection in geriatric and non-geriatric cases, and explores the 60-day mortality rate in these two groups. MATERIALS AND METHODS: We conducted this retrospective cross-sectional study in Hospital Tengku Ampuan Rahimah, Selangor, Malaysia. Patients admitted in April 2021 and May 2021 with concomitant COVID-19 infection and PTE disease were included. Demographic, clinical and laboratory data were retrieved, whilst CTPA images were analysed by a senior radiologist. RESULTS: A total of 150 patients were recruited, comprising 45 geriatric patients and 105 non-geriatric patients. The prevalence rate of hypertension, diabetes mellitus and dyslipidaemia were higher among the geriatric cohort. Evidently, the percentage of patients with fever and diarrhoea were significantly higher among the non-geriatric cohort. The geriatric cohort also recorded a significantly lower absolute lymphocyte count at presentation and albumin level during admission. Despite earlier presentation, the geriatric cohort suffered from more severe diseases. Analysis of the CT features demonstrated that the most proximal pulmonary thrombosis specifically limited to the segmental and subsegmental pulmonary arteries in both cohorts. The elderly suffered from a significantly higher inhospital mortality rate and their cumulative probability of survival was significantly lower. CONCLUSION: Typical COVID-19 symptoms may be absent among the elderly, prompting a lower threshold of suspicion during the COVID-19 pandemic. Additionally, the elderly demonstrated a higher probability of adverse outcomes despite earlier presentation and treatment.

Clinical characteristics and computed tomographical features of pulmonary thromboembolic disease associated with COVID-19 infection: A tertiary hospital analysis.

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.

Factors related to prehospital delay and decision delay among acute stroke patients in a district hospital, Malaysia.

INTRODUCTION: Time is the greatest challenge in stroke management. This study aimed to examine factors contributing to prehospital delay and decision delay among stroke patients. MATERIALS AND METHODS: A cross-sectional study involving acute stroke patients admitted to Seri Manjung Hospital was conducted between August 2019 and October 2020 via faceto- face interview. Prehospital delay was defined as more than 120 minutes taken from recognition of stroke symptoms till arrival in hospital, while decision delay was defined as more than 60 minutes taken from recognition of stroke symptoms till decision was made to seek treatment. RESULTS: The median prehospital delay of 102 enrolled patients was 364 minutes (IQR 151.5, 1134.3) while the median for decision delay was 120 minutes (IQR 30.0, 675.0). No history of stroke (adj. OR 4.15; 95% CI 1.21, 14.25; p=0.024) and unaware of thrombolysis service (adj. OR 17.12; 95% CI 1.28, 229.17; p=0.032) were associated with higher odds of prehospital delay, while Indian ethnicity (adj. OR 0.09; 95% CI 0.02, 0.52; p=0.007) was associated with lower odds of prehospital delay as compared to Malay ethnicity. On the other hand, higher National Institutes of Health Stroke Scale (NIHSS) score (adj. OR 0.86; 95% CI 0.78, 0.95; p=0.002) was associated with lower odds of decision delay. CONCLUSION: Public awareness is crucial to shorten prehosital delay and decision delay for better patients' outcomes in stroke. Various public health campaigns are needed to improve the awareness for stroke.

Metabolic adaptation via regulated enzyme degradation in the pathogenic yeast Candida albicans.

The virulence of Candida albicans is dependent upon fitness attributes as well as virulence factors. These attributes include robust stress responses and metabolic flexibility. The assimilation of carbon sources is important for growth and essential for the establishment of infections by C. albicans. Previous studies showed that the C. albicans ICL1 genes, which encode the glyoxylate cycle enzymes isocitratelyase are required for growth on non-fermentable carbon sources such as lactate and oleic acid and were repressed by 2% glucose. In contrast to S. cerevsiae, the enzyme CaIcl1 was not destabilised by glucose, resulting with its metabolite remaining at high levels. Further glucose addition has caused CaIcl1 to lose its signal and mechanisms that trigger destabilization in response to glucose. Another purpose of this study was to test the stability of the Icl1 enzyme in response to the dietary sugars, fructose, and galactose. In the present study, the ICL1 mRNAs expression was quantified using Quantitative Real Time PCR, whereby the stability of protein was measured and quantified using Western blot and phosphoimager, and the replacing and cloning of ICL1 ORF by gene recombination and ubiquitin binding was conducted via co-immuno-precipitation. Following an analogous experimental approach, the analysis was repeated using S. cerevisiaeas a control. Both galactose and fructose were found to trigger the degradation of the ICL1 transcript in C. albicans. The Icl1 enzyme was stable following galactose addition but was degraded in response to fructose. C. albicans Icl1 (CaIcl1) was also subjected to fructose-accelerated degradation when expressed in S. cerevisiae, indicating that, although it lacks a ubiquitination site, CaIcl1 is sensitive to fructose-accelerated protein degradation. The addition of an ubiquitination site to CaIcl1 resulted in this enzyme becoming sensitive to galactose-accelerated degradation and increases its rate of degradation in the presence of fructose. It can be concluded that ubiquitin-independent pathways of fructose-accelerated enzyme degradation exist in C. albicans.