The outcome of 12-week corticosteroid therapy in COVID-19-related diffuse interstitial lung abnormalities.

INTRODUCTION: The efficacy of long-course corticosteroid therapy in treating COVID-19-related diffuse interstitial lung abnormalities (DILA) needs to be better understood. We aimed to investigate the benefits of 12-week corticosteroid treatment in COVID-19-related DILA by evaluating computed tomography (CT) lung severity scores. MATERIALS AND METHODS: This retrospective, single-centre observational study included patients aged 18 years or older admitted with moderate to severe COVID-19 pneumonia who received 12 weeks of oral prednisolone between January 2021 and December 2021. We recorded clinical parameters, baseline CT scores and post-treatment, modified Medical Research Council (mMRC) dyspnoea scale and pulmonary function tests. RESULTS: A total of 330 patients were analysed. The mean (standard deviation, SD) age was 54.6 (14.2) years, and 43% were females. Three-point nine per cent (3.9%) require noninvasive ventilation (NIV), while 14.6% require mechanical ventilation (MV). On follow-up at 12 weeks, the CT patterns showed improvement in ground-glass opacities, perilobular density and consolidation. There was an improvement in the mean (SD) CT score before and after prednisolone therapy, with values of 17.3 (5.3) and 8.6 (5.5), respectively (p<0.001). The median mMRC was 1 (IQR 0-1), and 98.8% had a radiological response. The common side effects of prednisolone therapy were weight gain (13.9%), hyperglycaemia (1.8%) and cushingoid habitus (0.6%). CONCLUSION: A 12-week treatment with prednisolone showed significant improvement in CT scores with minimal residual dyspnoea and was relatively safe. Longer duration of steroids may be beneficial in moderate to severe COVID-19- related DILA.

Non-bacteremia liver abscess caused by Burkholderia pseudomallei from a tertiary teaching hospital in Malaysia: a case report and literature review.

Melioidosis is endemic in Southeast Asia, including Malaysia. Liver abscess is not uncommon in melioidosis, but it is usually associated with bacteremia. We presented a case of a 55-year-old gentleman with underlying end-stage renal failure who presented with non-specific abdominal pain for three months. Initial blood investigations showed leukocytosis and increased C-reactive protein. Computed tomography (CT) of the abdomen revealed multiple hypodense lesions in the liver and spleen. The culture of the liver specimen obtained through the ultrasound-guided isolated Burkholderia pseudomallei. He was given an adjusted dose of intravenous ceftazidime due to underlying renal failure. Melioidosis serology also returned positive for IgM with titer >1:1280. His blood cultures were reported negative three times. Despite on antibiotics for five weeks, there was no significant improvement of the liver abscesses was observed. He was unfortunately infected with the SARS-CoV-2 virus during his admission and passed away due to severe COVID-19 pneumonia.

Non-bacteremia liver abscess caused by Burkholderia pseudomallei from a tertiary teaching hospital in Malaysia: a case report and literature review

@#Melioidosis is endemic in Southeast Asia, including Malaysia. Liver abscess is not uncommon in melioidosis, but it is usually associated with bacteremia. We presented a case of a 55-year-old gentleman with underlying end-stage renal failure who presented with non-specific abdominal pain for three months. Initial blood investigations showed leukocytosis and increased C-reactive protein. Computed tomography (CT) of the abdomen revealed multiple hypodense lesions in the liver and spleen. The culture of the liver specimen obtained through the ultrasound-guided isolated Burkholderia pseudomallei. He was given an adjusted dose of intravenous ceftazidime due to underlying renal failure. Melioidosis serology also returned positive for IgM with titer >1:1280. His blood cultures were reported negative three times. Despite on antibiotics for five weeks, there was no significant improvement of the liver abscesses was observed. He was unfortunately infected with the SARS-CoV-2 virus during his admission and passed away due to severe COVID-19 pneumonia.

A case of lupus nephritis flare-up in severe COVID-19 infection.

The novel Coronavirus disease 2019 (COVID-19) had rapidly spread and became a worldwide pandemic since its detection in Wuhan, China. The disease has caused significant morbidity and mortality, particularly among patients with comorbidities. The current treatment involves supportive management alongside antiviral therapy and immunosuppressant therapy in severely affected patients. We describe a case of a patient with underlying lupus nephritis (LN) who presented with severe COVID-19 infection and concomitant LN flare with acute kidney injury (AKI). The patient was treated with antiviral therapy, Favipiravir, considering his risk of developing severe COVID-19 infection. As the patients would usually have AKI alongside LN flare, we administered initial steroid therapy at a lower dose (Methylprednisolone 50mg daily) and oral hydroxychloroquine despite the initial concerns on immunosuppressant usage in COVID-19 infections. Although our patient recovered relatively well from COVID- 19 infection, he continued to have positive reverse transcriptase-polymerase chain reaction (RT-PCR) nasopharyngeal swab for COVID-19 up to 29 days of illness. His kidney function stabilised despite having persistent nephrotic range proteinuria. Hence, the attending team decided to pulse the patient with a high dose steroid (IV Methylprednisolone 250mg OD for three days) after two weeks of illness despite the persistent positive swab. The patient's condition continued to improve, and this case illustrates an approach in treating COVID-19 with concomitant active immune-mediated glomerulonephritis. We find that it is safe to institute high dose immunosuppressant in recovered COVID-19 patients two weeks after the illness.

Understanding of Coronavirus Disease 2019 (COVID-19) and the practice of preventive measures among doctors and nurses in a university teaching hospital- A cross-sectional study.

INTRODUCTION: Knowledge and adequate practice of preventive measures among health care workers (HCWs) are important to reduce the risk of COVID-19 transmission. METHODS: A cross-sectional study was conducted among doctors and nurses in the medical department in Pusat Perubatan Universiti Kebangsaan Malaysia between November 18, 2020 and December 18, 2020 during the third wave of COVID-19 epidemic in Malaysia. We studied the knowledge and practice of preventive measures of COVID-19 among doctors and nurses in the COVID-19 or sudden acute respiratory infection (SARI) wards and general medical wards. Data was collected using a validated self-designed google form online-questionnaire. RESULTS: A total of 407 subjects completed the study and 80.8% were females; 55.8% were aged between 30-39 years; 46.4% were medical doctors. The main source of COVID-19 knowledge was the Ministry of Health Malaysia (MOH) website (35.1%). Majority (97%) had sufficient knowledge and 82% practiced proper preventive measures. Doctors had a higher mean knowledge score compared to nurses (p < 0.001). HCWs working in COVID-19 or SARI wards scored higher in knowledge questions compared to those in the general medical wards (p = 0.020). Nurses practiced better preventive measures (p < 0.001). Good knowledge could not be predicted based on professions (OR: 0.222, 95% CI: 0.048 - 1.028, p = 0.054). Majority were unable to recall the proper steps of donning (85.8%) and doffing (98.5%). CONCLUSIONS: Although majority had good knowledge and practiced proper preventive measures, there was a poor recall in donning and doffing steps regardless of place of practice. The MOH website is a useful platform for tailored continuous medical education and regular updates on COVID-19. Regular training and retraining on donning and doffing of PPE is needed to bridge this gap.

A descriptive study of the psychological experience of health care workers in close contact with a person with COVID-19.

BACKGROUND: COVID-19 has the potential to affect the mental health of health care workers (HCWs). It is known that HCWs who serve as front-liners during the COVID-19 pandemic experience stress and have the fear of contracting the infection. Little is known of how being a positive contact affects HCWs. OBJECTIVE: We examined the experience of HCWs who were quarantined following a close unprotected contact with a COVID-19 positive colleague and explore the psychological impact especially as the timing of the quarantine coincided with the Eid (annual Muslim festival) celebration in Malaysia. METHODS: This was a cross-sectional on-line questionnaire study, involving HCWs exposed to a COVID-19 positive colleague in Universiti Kebangsaan Malaysia Medical Centre, a teaching hospital. Data on demographics, levels of depression, anxiety and stress using a validated depression, anxiety, and stress scale (DASS-21) questionnaire, aspects of quarantine, wearing of masks, hand hygiene practice and swab experience were collected. RESULTS: Twenty-two HCWs participated. Eighteen (81.8%) were between 30-39 years and 17 (77.3%) were women. Majority 19 (86.3%) were Malays. There were twelve (54.5%) medical officers, 5 (22.7%) specialists and 5(22.7%) allied health staff. Eighteen out of 22 (81.8%) felt they were able to do home quarantine adequately. All tested negative with a mean (Standard Deviation) hour of contact of 2.56±2.38 hours. Eighteen reported their biggest concern was infecting their families. CONCLUSION: HCWs undergoing contact swabbing and quarantine are vulnerable to depression, anxiety and stress. The ability of the HCW to adequately home quarantine should not be taken for granted. Psychological support should be offered to HCWs who are positive contacts.

COVID-19 detected from targeted contact tracing, attempting to see the pattern in random happenings: early lessons in Malaysia.

The world feels strange as we face what is for most of us our first ever pandemic. The number of newly diagnosed cases rises daily in many parts of the world, and we are faced with the reality that there are still many things to learn about this new disease. We share here our experience of treating our first 199 COVID-19 patients in the Hospital Canselor Tuanku Muhriz, Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM).

Lung computed tomography patterns of a cluster of asymptomatic young males with COVID-19 admitted to a teaching hospital in Kuala Lumpur.

BACKGROUND AND OBJECTIVE: Coronavirus Disease 2019 (COVID- 19) was first reported in Malaysia in March 2020. We describe here the clinical characteristics and computed tomography (CT) patterns in asymptomatic young patients who had laboratory-confirmed COVID-19. METHODS: This is a retrospective observational study where 25 male in-patients with laboratory-confirmed COVID-19 in Hospital Canselor Tuanku Muhriz. Demographics, clinical data and CT images of these patients were reviewed by 2 senior radiologists. RESULTS: In total there were 25 patients (all males; mean age [±SD], 21.64±2.40 years; range, 18-27 years). Patients with abnormal chest CT showed a relatively low normal absolute lymphocytes count (median: 2.2 x 109/L) and absolute monocyte count (median: 0.5 x 109/L). Lactate dehydrogenase was elevated in 5 (20%) of the patients. The procalcitonin level was normal while elevated levels of alanine aminotransferase, total bilirubin, platelet and C-reactive protein were common. Baseline chest CT showed abnormalities in 6 patients. The distribution of the lesions were; upper lobe 3 (12%) lower lobe 3 (12%) with peripheral distribution 4 (16%). Of the 25 patients included, 4 (16%) had ground glass opacification (GGO), 1 (4%) had a small peripheral subpleural nodule, and 1 (4%) had a dense solitary granuloma. Four patients had typical CT features of COVID-19. CONCLUSION: We found that the CT imaging showed peripheral GGO in our patients. They remained clinically stable with no deterioration of their respiratory symptoms suggesting stability in lung involvement. We postulate that rapid changes in CT imaging may not be present in young, asymptomatic, non-smoking COVID-19 patients. Thus the use of CT thoraxfor early diagnosis may be reserved for patients in the older agegroups, and not in younger patients.

The crucial role of molecular testing to facilitate the diagnosis of pneumocystis pneumonia during pregnancy.

Pneumocystis pneumonia is an important human immunodeficiency virus (HIV)-associated opportunistic infection, and especially so in pregnant HIV-positive patients. We report a case of a 40-year-old woman in her first trimester of pregnancy who initially presented with acute gastroenteritis symptoms but due to a history of high-risk behaviour and the observation of oral thrush, she was worked up for HIV infection. Her retroviral status was positive and her CD4+ T cell count was only 8 cells/µL. She was also worked up for pneumocystis pneumonia due to the presence of mild resting tachypnoea and a notable drop in oxygen saturation (from 100% to 88%) following brief ambulation. Her chest radiograph revealed bilaterally symmetrical lower zone reticular opacities and Giemsa staining of her bronchoalveolar lavage (BAL) was negative for Pneumocystis jirovecii cysts. However, real-time P. jirovecii polymerase chain reaction (PCR) testing on the same BAL specimen revealed the presence of the organism. A course of oral co-trimoxazole plus prednisolone was commenced and her clinical condition improved.

Diagnosis of disseminated microsporidiosis: Detection of circulating Enterocytozoon bieneusi DNA in blood of HIV/AIDS patients.

Disseminated microsporidiosis among HIV/AIDS patients is life-threatening. The incidence may be actually higher than what has been reported. This is due to non-specific presentations of the disseminated cases and also the insensitivity of routine diagnostic technique which contribute to delay in the treatment of the disease. In the present study, we report the use of blood specimens to detect circulating microsporidia DNA, which has not been reported for diagnosis of disseminated microsporidiosis. Blood samples from HIV/AIDSpositive patients were collected over a period of one year. These samples were subjected to PCR assay using species-specific primer EBIEF1/EBIER1. Out of 100 patients, seven were confirmed positive for E. bieneusi by PCR. A fragment of 607 bp was successfully amplified. Identification of circulating microsporidia DNA in blood samples may aid in early diagnosis, thereby allows timely administration of anti-parasitic treatment.

Distinct Effect of TCF4 on the NFκB Pathway in Human Primary Chondrocytes and the C20/A4 Chondrocyte Cell Line.

OBJECTIVE: Previous studies indicated a difference in crosstalk between canonical WNT pathway and nuclear factor-κB (NFκB) signaling in human and animal chondrocytes. To assess whether the differences found were dependent on cell types used, we tested the effect of WNT modulation on NFκB signaling in human primary articular chondrocytes in comparison with the immortalized human costal chondrocyte cell line C20/A4. DESIGN: We used gene expression analysis to study the effect of WNT modulation on IL1ß-induced matrix metalloproteinase (MMP) expression as well as on WNT and NFκB target gene expression. In addition, we tested the involvement of RelA and TCF4 on activation of the WNT and NFκB pathway by TCF/LEF and NFκB reporter experiments, respectively. RESULTS: We found an inhibitory effect of both induction and inhibition of WNT signaling on IL1ß-induced MMP mRNA expression in primary chondrocytes, whereas WNT modulation did not affect MMP expression in C20/A4 cells. Furthermore, TCF/LEF and NFκB reporter activation and WNT and NFκB target gene expression were regulated differentially by TCF4 and RelA in a cell type-dependent manner. Additionally, we found significantly higher mRNA and protein expression of TCF4 and RelA in C20/A4 cells in comparison with primary chondrocytes. CONCLUSIONS: We conclude that WNT modulation of NFκB is, at least in part, cell type dependent and that the observed differences are likely because of impaired sensitivity of the NFκB pathway in C20/A4 cells to modulations in WNT signaling. This might be caused by higher basal levels of TCF4 and RelA in C20/A4 cells compared to primary chondrocytes.

Nocardiosis in a patient with rheumatoid arthritis treated with rituximab and a summary of reported cases.

Rituximab is a B-cell-depleting monoclonal anti-CD20 antibody. It is widely used in haematology and rheumatology. However, usage of rituximab in immunosupressed patient has been associated with various opportunistic infections. The authors reported a case of refractory rheumatoid arthritis treated with rituximab, which later presented with non-resolving pneumonia with pulmonary nodule. Percutaneous computer tomogram guided lung biopsy was arranged to confirm the suspicion of tuberculosis, but did not yield conclusive results. Later, she presented left-chest abscess and underwent incision and drainage. The pus culture and sensitivity confirmed pulmonary nocardiosis with chest wall dissemination. She was treated with 2-week course of trimethoprim sulfamethoxazole and responded. The authors also reviewed published cases of nocardiosis post-rituximab.

Steven Johnson syndrome in a patient with Cushing's disease.

Cushing's syndrome is a pathological condition associated with excessive cortisol production, the commonest etiology being Cushing's disease. Corticosteroids in high doses have been used in the management of Steven Johnson Syndrome (SJS) with favourable outcome. We describe a patient with Cushing's disease who developed SJS, one week after taking sperulina a product from sea-weed while waiting for transphenoidal surgery.

Synthesis of 3-(2-pyridyl)-2-substituted-quinazolin-4(3H)-ones as new analgesic and anti-inflammatory agents.

A new series of 3-(2-pyridyl)-2-substituted-quinazolin-4(3H)-ones were synthesized by reacting the amino group of 2-hydrazino-3-(2-pyridyl)-quinazolin-4(3H)-one with a variety of aldehydes and ketones. The starting material 2-hydrazino-3-(2-pyridyl)-quinazolin-4(3H)-one was synthesized from 2-aminopyridine. The title compounds were investigated for analgesic, anti-inflammatory and ulcerogenic index activities. While the test compounds exhibited significant activity, compound 2-(1-ethylpropylidene)-hydrazino-3-(2-pyridyl)-quinazolin-4(3H)-one (AS2) showed moderate analgesic activity and compound 2-(1-methylbutylidene)-hydrazino-3-(2-pyridyl)-quinazolin-4(3H)-one (AS3) showed realistic anti-inflammatory activity when compared to the reference standard diclofenac sodium. Interestingly the test compounds showed only mild ulcerogenic side effect when compared to aspirin.