Demographics and outcome of patients with congenital haemophilia in Sarawak, Malaysia.

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.

Thrombotic thrombocytopenic purpura-like syndrome associated with arcanobacterium pyogenes endocarditis in a post-transplant patient: A case report.

Systemic Arcanobacterium pyogenes is a rare bacterial infection in humans.1The diagnosis of thrombotic thrombocytopenic purpura (TTP)-like syndrome and infective endocarditis (IE) is often elusive. We report a case of TTP-like syndrome associated with A. pyogenes endocarditis in a post-allogenic transplant patient.

Thrombocytopenia and CD34 expression is decoupled from α-granule deficiency with mutation of the first growth factor-independent 1B zinc finger.

Essentials The phenotypes of different growth factor-independent 1B (GFI1B) variants are not established. GFI1B variants produce heterogeneous clinical phenotypes dependent on the site of mutation. Mutation of the first non-DNA-binding zinc-finger causes a mild platelet and clinical phenotype. GFI1B regulates the CD34 promoter; platelet CD34 expression is an indicator of GFI1B mutation. SUMMARY: Background Mutation of the growth factor-independent 1B (GFI1B) fifth DNA-binding zinc-finger domain causes macrothrombocytopenia and α-granule deficiency leading to clinical bleeding. The phenotypes associated with GFI1B variants disrupting non-DNA-binding zinc-fingers remain uncharacterized. Objectives To determine the functional and phenotypic consequences of GFI1B variants disrupting non-DNA-binding zinc-finger domains. Methods The GFI1B C168F variant and a novel GFI1B c.2520 + 1_2520 + 8delGTGGGCAC splice variant were identified in four unrelated families. Phenotypic features, DNA-binding properties and transcriptional effects were determined and compared with those in individuals with a GFI1B H294 fs mutation of the fifth DNA-binding zinc-finger. Patient-specific induced pluripotent stem cell (iPSC)-derived megakaryocytes were generated to facilitate disease modeling. Results The DNA-binding GFI1B variant C168F, which is predicted to disrupt the first non-DNA-binding zinc-finger domain, is associated with macrothrombocytopenia without α-granule deficiency or bleeding symptoms. A GFI1B splice variant, c.2520 + 1_2520 + 8delGTGGGCAC, which generates a short GFI1B isoform that lacks non-DNA-binding zinc-fingers 1 and 2, is associated with increased platelet CD34 expression only, without quantitative or morphologic platelet abnormalities. GFI1B represses the CD34 promoter, and this repression is attenuated by different GFI1B zinc-finger mutations, suggesting that deregulation of CD34 expression occurs at a direct transcriptional level. Patient-specific iPSC-derived megakaryocytes phenocopy these observations. Conclusions Disruption of GFI1B non-DNA-binding zinc-finger 1 is associated with mild to moderate thrombocytopenia without α-granule deficiency or bleeding symptomatology, indicating that the site of GFI1B mutation has important phenotypic implications. Platelet CD34 expression appears to be a common feature of perturbed GFI1B function, and may have diagnostic utility.

Subcutaneous mycosis presenting as a non- healing left calf ulcer in an immunocompromised patient.

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.

Epidemiology of Culture-positive Infection in Adult Patients with Haematological Malignancies in Sarawak.

No abstract available.

Outbreak of chikungunya in Johor Bahru, Malaysia: clinical and laboratory features of hospitalized patients.

In 2008, an outbreak of chikungunya infection occurred in Johor. We performed a retrospective review of all laboratory confirmed adult chikungunya cases admitted to Hospital Sultanah Aminah, Johor Bahru from April to August 2008, looking into clinical and laboratory features. A total of 18 laboratory confirmed cases of chikungunya were identified with patients presenting with fever, joint pain, rash and vomiting. Haemorrhagic signs were not seen. Lymphopenia, neutropenia, thrombocytopenia, raised liver enzymes and deranged coagulation profile were the prominent laboratory findings. We hope this study can help guide physician making a diagnosis of chikungunya against other arborviruses infection.

Fast detection of common geometric substructure in proteins.

We consider the problem of identifying common three-dimensional substructures between proteins. Our method is based on comparing the shape of the alpha-carbon backbone structures of the proteins in order to find three-dimensional (3D) rigid motions that bring portions of the geometric structures into correspondence. We propose a geometric representation of protein backbone chains that is compact yet allows for similarity measures that are robust against noise and outliers. This representation encodes the structure of the backbone as a sequence of unit vectors, defined by each adjacent pair of alpha-carbons. We then define a measure of the similarity of two protein structures based on the root mean squared (RMS) distance between corresponding orientation vectors of the two proteins. Our measure has several advantages over measures that are commonly used for comparing protein shapes, such as the minimum RMS distance between the 3D positions of corresponding atoms in two proteins. A key advantage is that this new measure behaves well for identifying common substructures, in contrast with position-based measures where the nonmatching portions of the structure dominate the measure. At the same time, it avoids the quadratic space and computational difficulties associated with methods based on distance matrices and contact maps. We show applications of our approach to detecting common contiguous substructures in pairs of proteins, as well as the more difficult problem of identifying common protein domains (i.e., larger substructures that are not necessarily contiguous along the protein chain).

Unit-vector RMS (URMS) as a tool to analyze molecular dynamics trajectories.

The Unit-vector RMS (URMS) is a new technique to compare protein chains and to detect similarities of chain segments. It is limited to comparison of C(alpha) chains. However, it has a number of unique features that include exceptionally weak dependence on the length of the chain and efficient detection of substructure similarities. Two molecular dynamics simulations of proteins in the neighborhood of their native states are used to test the performance of the URMS. The first simulation is of a solvated myoglobin and the second is of the protein MHC. In accord with previous studies the secondary structure elements (helices or sheets) are found to be moving relatively rigidly among flexible loops. In addition to these tests, folding trajectories of C peptides are analyzed, revealing a folding nucleus of seven amino acids.