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  1. Fulltext Cerebral venous thrombosis as an initial manifestation of acute myeloid leukemia
    Tang ASO, Yeo ST, Law WC, Chew LP
    Oxf Med Case Reports, 2019 Jan;2019(1):omy118.
    PMID: 30697435 DOI: 10.1093/omcr/omy118
    Cancer-associated thromboembolism is not an uncommon complication in patients with malignancies. No study has reported the occurrence of thromboembolism prior to the diagnosis of acute myeloid leukemia (AML). Most reports are anectodal and data are scarce on this subject. In this report, we present a case of extensive cerebral venous thrombosis (CVT) that was detected a few weeks before the diagnosis of AML, in which case the patient responded well to chemotherapy and anticoagulation.
  2. Fulltext Successful Non-surgical Treatment of an Acute Calculous Cholecystitis in a Myeloma Patient with Covid-19: Case Report
    Tang ASO, Leong TS, Chew LP, Chua HH
    SN Compr Clin Med, 2021;3(2):666-669.
    PMID: 33554049 DOI: 10.1007/s42399-021-00785-8
    COVID-19 has a wide spectrum of clinical phenotypes. While fever and cough are the most common symptoms, abdominal pain is rarely reported. We report the first case of COVID-19 pneumonia in an elderly patient with multiple myeloma (MM), complicated by acute calculous cholecystitis (ACC). A 73-year-old gentleman with underlying IgG kappa MM, presented with fever, cough and dyspnoea. His nasopharyngeal swab was positive for SARS-CoV-2. Piperacillin/tazobactam and oral hydroxychloroquine were started in addition to granulocyte colony-stimulating factor (GCSF) support due to neutropenia. Patient deteriorated on day 5, requiring high flow oxygen support. Dexamethasone, low molecular weight heparin prophylaxis and one dose of intravenous immunoglobulin were given. Despite negative swab on day 10, he developed ACC on day 17. With antibiotics and supportive care, patient showed full recovery without any surgical intervention. It remains elusive whether the gallbladder might be vulnerable to COVID-19, necessitating further validation via prospective studies.
  3. Diagnostic and Treatment Challenges in Cerebral Tuberculoma in a Patient with Morbid Obesity
    Wong QY, Tang ASO, Loh WH, Yong XM, Samuel D, Law WC, et al.
    Am J Case Rep, 2021 Jul 10;22:e932852.
    PMID: 34244464 DOI: 10.12659/AJCR.932852
    BACKGROUND Tuberculosis is prevalent, especially in low-income countries. The most devastating manifestation of tuberculosis is central nervous system (CNS) involvement, albeit rare. CASE REPORT We report a rare case of a 26-year-old woman with morbid obesity and hepatitis C who had cerebral tuberculoma and was treated with an extended duration of anti-tuberculosis multi-drug therapy. This patient was initially diagnosed with disseminated tuberculosis of the lungs, liver, and peritoneum. After 4 months of anti-tuberculosis treatment, she developed new right temporal hemianopia and new cerebral tuberculoma, which was identified on repeated magnetic resonance imaging (MRI) and was attributed to tuberculosis-immune reconstitution inflammatory syndrome. The anti-tuberculosis treatment was continued; however, she gained large amounts of weight, which resulted in the failure of the anti-tuberculosis treatment of the cerebral tuberculoma. We decided to adjust the anti-tuberculosis drug dosage using her total body weight, and she responded well, with a decrease in size of the cerebral tuberculoma. The anti-tuberculosis treatment was subsequently stopped after 3 years because of clinical and imaging improvement. CONCLUSIONS This case illustrates the challenges faced in the treatment of cerebral tuberculoma, which, in this case, included a high body mass index affecting drug dosage and confounding an inadequate treatment response as seen on interim MRI, resulting in prolonged duration of anti-tuberculosis treatment. Persistent enhancement seen on brain MRI does not equate to treatment failure.
  4. Subcutaneous mycosis presenting as a non- healing left calf ulcer in an immunocompromised patient
    Tang ASO, Yong KY, Wong J, Chua HH, Chew LP
    Med J Malaysia, 2017 04;72(2):122-123.
    PMID: 28473676
    This is a case report of subcutaneous mycosis presenting as a non-healing left calf ulcer in an immunocompromised patient. Traumatic inoculation of the causative agent is the most likely route of infection. The diagnosis requires a detailed history and high clinical suspicion, confirmed by histopathological examination. The management requires a multidisciplinary team approach involving surgeon, pathologist, physician sub-specialised in infectious disease, wound care nursing team as well as social support services. The literature review recommended that the treatment of choice for such infection is surgical debridement in addition to optimal antifungal therapy.
  5. Fulltext Disseminated AIDS-related Kaposi's sarcoma
    Tang ASO, Teh YC, Chea CY, Yeo ST, Chua HH
    Oxf Med Case Reports, 2018 Dec;2018(12):omy107.
    PMID: 30487992 DOI: 10.1093/omcr/omy107
    We present a case of disseminated Kaposi's sarcoma with both cutaneous and extracutaneous involvement in an HIV-infected patient with a relatively high CD4 count of 369 cell/mm3. He developed chronic diarrhea, constitutional symptoms, worsening bilateral pleural effusion with respiratory distress, and progression of skin lesions distributed over his chest and extremities. The temporal relationship between rapid clinical progression and initiation of HAART suggested the possibility of Kaposi's sarcoma-associated immune reconstitution inflammatory syndrome, which eventually resulted in the death of this patient.
  6. Fulltext The mystery of 'saturation gap': a case of dapsone-induced methaemoglobinemia in a pregnant mother with leprosy
    Tang ASO, Yeo ST, Teh YC, Kho WM, Chew LP, Muniandy P
    Oxf Med Case Reports, 2019 Jan;2019(1):omy111.
    PMID: 30697428 DOI: 10.1093/omcr/omy111
    Limited data regarding methemoglobinemia in pregnancy, particularly secondary to dapsone is available up to date. We report a case of dapsone-induced methemoglobinemia in a pregnant mother with multibacillary leprosy who presented with fever, productive cough and cyanosis of 2 days duration 2 weeks after multidrug therapy was commenced. On examination, she had central cyanosis with low oxygen saturation (SpO2 = 84-88%). Arterial blood gas analysis showed PO2 of 111 mmHg and SO2 of 98 mmHg. Patient was administered 100% oxygen inhalation, but there was no improvement in cyanosis. Vitamin C (1000 mg/day) was prescribed. Dapsone was replaced by ofloxacin 200 mg twice daily. There was a gradual increase in SpO2 level. She delivered a healthy baby. In conclusion, clinicians should be aware of the side effects of dapsone and know how to promptly manage any undesirable events. Ofloxacin is a safe and feasible alternative in replacement of dapsone in pregnancy.
  7. Fulltext Cost of Treatment for Myelofibrosis Patients in Ministry of Health Hospitals in Sarawak, Malaysia
    Tang ASO, Leong TS, Ong JHL, Goh A, Chew LP
    Asian Pac J Cancer Prev, 2023 Mar 01;24(3):733-736.
    PMID: 36974524 DOI: 10.31557/APJCP.2023.24.3.733
    OBJECTIVE: Primary myelofibrosis is a rare type of myeloproliferative neoplasm with an annual incidence rate of 0.47 per 100,000. A retrospective, observational study was conducted to determine the disease evolution and costs of treatment for myelofibrosis (MF) patients managed in 4 Ministry of Health (MOH) hospitals in Sarawak, Malaysia.

    METHODS: The estimation of treatment cost was a planned analysis of the Real World Evidence (RWE) study which included retrospective chart review of adult MF patients treated in Sarawak General, Sibu, Bintulu and Miri Hospitals. The study was approved by Sarawak General Hospital HRRC and MREC. The current study was conducted to estimate the cost of out-patient visits, hospitalisation, transfusion and medication from the perspective of MOH. Out-patient visits and hospitalisation costs were calculated using current unit costs for full fee-paying charges of MOH hospitals. Transfusion costs were estimated for packed cell and platelet transfusions. Medication costs were calculated using drug prices from IQVIA database for MOH hospital sub-sector in 2021. Unit costs were standardised to index year of 2021.

    RESULT: Data from 63 patients was available for analysis. Mean annual health resource utilisation (HRU) was 6.13 clinic visits, 9.47 days of hospitalisation and 1.61 transfusions per patient per year. Mean HRU cost was RM23,320 (USD5,217) per patient per year, comprised of RM19,122 (USD4,278) in drug costs, RM3,030 (USD678) for hospitalisation, RM799 (USD178) for transfusions and RM368 (USD82) for outpatient cost.

    CONCLUSION: The present analysis suggests that medication and hospitalisation were the main drivers of costs for MF treatment in Sarawak MOH hospitals. This study provides the first RWE estimate of the cost of MF in Malaysia and may provide insight into unmet clinical needs and a guide for further health economic research into the treatment of MF.

  8. Fulltext Acquired C1-inhibitor deficiency in chronic lymphocytic leukaemia: a case report
    Tang ASO, Wong QY, Yeo ST, Lee JTH, Leong TS, Chew LP
    Hong Kong Med J, 2022 Oct;28(5):403-405.
    PMID: 38232966 DOI: 10.12809/hkmj219478
  9. Demographics and outcome of patients with congenital haemophilia in Sarawak, Malaysia
    Tang ASO, Wong QY, Tan YY, Chieng CH, Ko CT, Ong GB, et al.
    Med J Malaysia, 2021 Jan;76(1):51-55.
    PMID: 33510109
    INTRODUCTION: Sarawak has a population that is geographically and characteristically widely varied. This study aimed to determine the demographic profile of patients in Sarawak, Malaysia. Materials and Methods - A cross-sectional study was conducted in 2019 at four major haemophilia treatment centres in Kuching, Sibu, Bintulu and Miri Hospitals, Sarawak. Demographic and clinical data were collected with consents from patients.

    RESULTS AND DISCUSSION: Ninety-six haemophilia patients were identified - 79(82.3%) haemophilia A(HA) and 17(17.7%) haemophilia B(HB). Severe haemophilia patients were noted in 45.6% (36/79) of HA and 64.7% (11/17) of HB. In all 44.3% of the HA and 52.9% of the HB population had no identifiable family history of haemophilia. Two-thirds of the patients with severe HA were on prophylaxis [24/36 (66.7%)] and only onethird [4/11 (36.4%)] in severe HB. Inhibitors developed in 9/79 (11.4%) of the HA population [3/79 (3.8%) high responders]. The median inhibitor titre was not significantly different between the different treatment groups - on demand versus prophylaxis (1.0BU versus 2.0BU; z statistic -1.043, p-value 0.297, Mann-Whitney test). None of the patients developed inhibitory alloantibodies to factor IX. Four HA patients (5.1%) underwent immune tolerance induction where one case had a successful outcome. Three severe HA patients received emicizumab prophylaxis and showed remarkable reduction in bleeding events with no thromboembolic events being reported. One female moderate HA patient received PEGylated recombinant anti-haemophilic factor. Eleven patients underwent radiosynovectomy. One mild HB patient succumbed to traumatic intracranial bleeding. Our data reported a prevalence (per 100,000 males) of 5.40 cases for all severities of HA, 2.46 cases for severe HA; 1.16 cases for all severities of HB, and 0.75 cases for severe HB. The overall incidence of HA and HB was 1 in 11,500 and 1 in 46,000, respectively.

    CONCLUSION: This study outlines the Sarawakian haemophilia landscape and offers objective standards for forward planning. Shared responsibilities among all parties are of utmost importance to improve the care of our haemophilia population.

  10. Fulltext First 2 Fabry Cases with Novel Mutation and Their Associated Clusters in Malaysia
    Tang ASO, Wong QY, Pao Lin Ting I, Selvesten P, Yeo ST, Chew LP, et al.
    Am J Case Rep, 2021 Aug 06;22:e932923.
    PMID: 34354036 DOI: 10.12659/AJCR.932923
    BACKGROUND No cases of Fabry disease (FD) have been reported thus far in Malaysia. We aimed to report the demographic characteristics, clinical manifestations, molecular results, and treatment outcomes of 2 FD cases. This study was a retrospective review of 2 family clusters of FD on follow-up in Sarawak, Malaysia. CASE REPORT Two index patients were confirmed to have FD. Index patient 1, who had nephrotic-range proteinuria and cornea verticillata, carried a variant within exon 4 of the GLA gene: c.610 T>C (p.Trp204Arg). Agalsidase beta (Fabrazyme®) enzyme replacement therapy was initiated, with the absence of neutralizing antibody after 24 months. No hypersensitivity or adverse reactions were reported. The patient's proteinuria and renal function remained stable. Other family members who carried the same mutation were asymptomatic. Index patient 2, who had residual activity of alpha-galactosidase A and a normal globotriaosylsphingosine level, carried a novel GLA mutation of c.548-5T>A. He was diagnosed with end-stage renal disease on regular dialysis and had nonspecific headache with 1 episode of seizure a few years prior to FD genetic screening. One brother had chronic neuropathic pain but refused further investigations. Other family members who had the same mutation were asymptomatic. This mutation has never been reported in literature, and its pathogenicity warrants further studies. CONCLUSIONS It is of utmost importance to increase awareness of FD among clinicians, so that appropriate screening may be done to determine its true prevalence and prompt treatment can be initiated early.
  11. Fulltext Immunodeficiency and Thymoma: A Case Report on Good Syndrome, a Diagnosis Frequently Missed and Forgotten
    Tang ASO, Loh WH, Wong QY, Yeo ST, Ng WL, Teoh PI, et al.
    Am J Case Rep, 2021 Mar 13;22:e928659.
    PMID: 33712551 DOI: 10.12659/AJCR.928659
    BACKGROUND Good syndrome (thymoma with immunodeficiency) is a frequently missed and forgotten entity. It is a rare cause of combined B and T cell immunodeficiency in adults. To date, fewer than 200 patients with Good syndrome have been reported in the literature. CASE REPORT We report a case of type AB Masaoka-Koga stage I thymoma which predated the evidence of immune dysregulation by 5 years, manifesting as bilateral cytomegalovirus retinitis, multiple bouts of pneumonia, and bronchiectasis in a HIV-seronegative 55-year-old man. Intravitreal ganciclovir was administered in addition to intravenous systemic ganciclovir, which resulted in severe neutropenic sepsis. A thorough immunodeficiency workup confirmed the presence of hypogammaglobulinemia with complete absence of B cells and reduced CD4/CD8 ratio. The patient responded well to monthly intravenous immunoglobulin replacement therapy, with no further episodes of infection since then. The immunoglobulin level doubled after 1 year of treatment. However, as the patient refused further intravitreal and CMV-targeted treatment, his vision did not recover. CONCLUSIONS Clinicians should be aware that thymoma can precede the onset of immunodeficiency. Clinical suspicion should be heightened in at-risk patients who present with multiple bouts of infection, particularly in thymoma cases with adult-onset immune dysfunction. It is of paramount importance to follow up those patients with annual clinical reviews and immunodeficiency screening.
  12. Fulltext Central nervous system melioidosis in systemic lupus erythematosus: A clinical vignette
    Cheok LH, Tang ASO, Desmond S, Wong YL, Cheong YK, Ng SC, et al.
    IDCases, 2021;26:e01255.
    PMID: 34458097 DOI: 10.1016/j.idcr.2021.e01255
    Central nervous system melioidosis is an uncommon presentation of melioidosis infection. We report a case of a disseminated melioidosis infection with central nervous system, pulmonary, spleen, bone and cutaneous involvement in a patient with underlying systemic lupus erythematous. The diagnosis was confirmed based on positive blood and cerebrospinal fluid cultures coupled with radiological findings. Agriculture contact and underlying immunocompromised state were the predisposing risk factors for melioidosis infection in this case. Our patient was successfully treated with 10 weeks of intensive antibiotics therapy and 1 year of eradication antibiotics therapy with significant clinical and radiological improvement.
  13. Fulltext The Sarawak Myelofibrosis (SaMy) experience: Demographics and outcome of myelofibrosis patients in Sarawak, Malaysia
    Tang ASO, Leong TS, Wong QY, Tan XY, Ko CT, Ngew KY, et al.
    SAGE Open Med, 2023;11:20503121231194433.
    PMID: 37705719 DOI: 10.1177/20503121231194433
    Introduction: Myelofibrosis is a rare disease. There is currently no published data reporting the demographics and outcome of myelofibrosis patients in Malaysia. We aimed to study the demographics, clinical characteristics, and outcome of our patients in Sarawak. Materials and methods: This non-interventional, retrospective, and multi-center study was conducted on secondary data of medical records collected at four Sarawak Public Hospitals. All adult myelofibrosis patients diagnosed between January 2001 and December 2021 were included. Results: A total of 63 patients (male 31) with myelofibrosis were included-47 (74.6%) primary and 16 (25.4%) secondary myelofibrosis. Eleven had antecedent polycythaemia vera, whereas five transformed from essential thrombocythaemia. The combined annual incidence rate was 0.182 per 100,000 population. The period prevalence per 100,000 population over the entire study duration was 2.502. The median age was 59.0 years (33.0-93.0). Majority had high-risk (34/63(54.0%)) and intermediate-2 risk disease (19/63(30.2%)). JAK2V617F mutation was identified in 52 patients (82.5%), followed by CALR mutation in 6 (9.5%) and negative for both mutations in 5 (7.9%). Hydroxyurea was used as first-line therapy in 41/63 (65.1%), followed by interferon (8/63(12.7%)) and ruxolitinib (4/63(6.3%)). Out of 46 patients who received second-line therapy, 18 (39.1%) were switched to ruxolitinib and 9 (19.6%) to interferon. The median age of survival for overall patients was 6.8 years. The use of ruxolitinib in myelofibrosis patients showed a better overall 5-year survival compared to the no ruxolitinib arm, despite no statistical significance (p = 0.34). Patients who had good performance status had lower hazard of death than patients who had poor performance status (high-risk (95% confidence intervals): 0.06(0.013-0.239), p 
  14. Fulltext Challenges in Managing a Lepromatous Leprosy Patient Complicated with Melioidosis Infection, Dapsone-Induced Methemoglobinemia, Hemolytic Anemia, and Lepra Reaction
    Tang ASO, Wong QY, Yeo ST, Ting IPL, Lee JTH, Fam TL, et al.
    Am J Case Rep, 2021 May 26;22:e931655.
    PMID: 34038399 DOI: 10.12659/AJCR.931655
    BACKGROUND Leprosy is an infection caused by Mycobacterium leprae. An extensive literature search did not reveal many reports of melioidosis in association with leprosy. CASE REPORT A 22-year-old woman, who was diagnosed with multibacillary leprosy, developed dapsone-induced methemoglobinemia and hemolytic anemia, complicated by melioidosis. Methemoglobinemia was treated with methylene blue and vitamin C. Two weeks of ceftazidime was initiated to treat melioidosis, and the patient was discharged on amoxicillin/clavulanic acid and doxycycline as melioidosis eradication therapy. However, she developed drug-induced hypersensitivity. Trimethoprim/sulfamethoxazole, as an alternative treatment for melioidosis eradication, was commenced and was successfully completed for 12 weeks. During the fifth month of multidrug therapy, the patient developed type II lepra reaction with erythema nodosum leprosum reaction, which was treated with prednisolone. Leprosy treatment continued with clofazimine and ofloxacin, and complete resolution of skin lesions occurred after 12 months of therapy. CONCLUSIONS Our case highlighted the challenges posed in managing a patient with multibacillary leprosy with multiple complications. Clinicians should be aware that dapsone-induced methemoglobinemia and hemolysis might complicate the treatment of leprosy. Our case also highlighted the safety and efficacy of combining ofloxacin and clofazimine as a leprosy treatment regimen in addition to gradual steroid dose titration in the presence of type II lepra reaction.
  15. The magnitude of tyrosine kinase inhibitor induced cytopaenia on normal haematopoietic tissues in chronic myeloid leukaemia patients
    Kuan JW, Ng SY, Hon SL, Lim SM, Chai AJM, Teo HG, et al.
    Int J Lab Hematol, 2023 Feb;45(1):e1-e5.
    PMID: 35896146 DOI: 10.1111/ijlh.13940
  16. Fulltext Plasma Cell Leukemia with Successful Upfront Venetoclax in Combination with Allogeneic Transplantation
    Tang ASO, Ahmad Asnawi AW, Koh AZY, Chong SL, Liew PK, Selvaratnam V, et al.
    Am J Case Rep, 2023 Mar 08;24:e938868.
    PMID: 36882990 DOI: 10.12659/AJCR.938868
    BACKGROUND Plasma cell leukemia (PCL) is an aggressive form of plasma cell neoplasm. We report the first case of primary PCL successfully treated with upfront novel agents consisting of Venetoclax and daratumumab in combination with intensive chemotherapy and allogeneic transplantation. CASE REPORT A 59-year-old woman presented with epistaxis, gum bleeding, and blurred vision. On examination, she appeared pale, with multiple petechiae and hepatomegaly. Fundoscopy revealed retinal hemorrhages. Laboratory investigations revealed bicytopenia and leukocytosis, with mild coagulopathy and hypofibrinogenemia. Elevated globulin and calcium levels were also observed. Serum protein electrophoresis demonstrated IgG lambda paraproteinemia, with a serum-free light chain kappa-to-lambda ratio of 0.074. A skeletal survey revealed the presence of lytic lesions. Bone marrow investigations confirmed the presence of lambda-light-chain-restricted clonal plasma cells. FISH detected t(11;14) and 17p13.1 deletion. Therefore, a final diagnosis of primary PCL was made. The patient received 1 cycle of bortezomib, cyclophosphamide, and dexamethasone (VCD) and 5 cycles of Venetoclax-VCD, followed by an unsuccessful stem cell mobilization. One cycle of daratumumab in combination with bortezomib, lenalidomide, and dexamethasone (VRD) was then given. The patient achieved complete remission. She underwent allogeneic stem cell transplantation of an HLA-matched sibling donor. Post-transplant marrow assessment showed disease remission and absence of t(11;14) and 17p deletions. She was administered pamidronate and lenalidomide maintenance. She remained clinically well with a good performance status and no active graft-versus-host disease 18 months after transplant. CONCLUSIONS The success of our patient in achieving complete remission has highlighted the efficacy and safety of this novel therapy in the front-line management of PCL.
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