Displaying all 2 publications

Abstract:
Sort:
  1. Collopy LC, Walne AJ, Cardoso S, de la Fuente J, Mohamed M, Toriello H, et al.
    Blood, 2015 Jul 09;126(2):176-84.
    PMID: 26024875 DOI: 10.1182/blood-2015-03-633388
    Dyskeratosis congenita (DC) and related diseases are a heterogeneous group of disorders characterized by impaired telomere maintenance, known collectively as the telomeropathies. Disease-causing variants have been identified in 10 telomere-related genes including the reverse transcriptase (TERT) and the RNA component (TERC) of the telomerase complex. Variants in TERC and TERT can impede telomere elongation causing stem cells to enter premature replicative senescence and/or apoptosis as telomeres become critically short. This explains the major impact of the disease on highly proliferative tissues such as the bone marrow and skin. However, telomerase variants are not always fully penetrant and in some families disease-causing variants are seen in asymptomatic family members. As a result, determining the pathogenic status of newly identified variants in TERC or TERT can be quite challenging. Over a 3-year period, we have identified 26 telomerase variants (16 of which are novel) in 23 families. Additional investigations (including family segregation and functional studies) enabled these to be categorized into 3 groups: (1) disease-causing (n = 15), (2) uncertain status (n = 6), and (3) bystanders (n = 5). Remarkably, this process has also enabled us to identify families with novel mechanisms of inheriting human telomeropathies. These include triallelic mutations, involving 2 different telomerase genes, and an epigenetic-like inheritance of short telomeres in the absence of a telomerase mutation. This study therefore highlights that telomerase variants have highly variable functional and clinical manifestations and require thorough investigation to assess their pathogenic contribution.
  2. Trieu HT, Vuong NL, Hung NT, Nguyen Minh T, Nguyen Van VC, Phan TQ, et al.
    BMJ Glob Health, 2025 Mar 11;10(3).
    PMID: 40068930 DOI: 10.1136/bmjgh-2024-017538
    INTRODUCTION: The pathognomonic feature of dengue shock syndrome (DSS) is a transient capillary leak syndrome resulting in profound intravascular volume depletion. WHO management guidelines recommend particular parenteral fluid regimens during the critical leakage phase, including synthetic colloid solutions in certain circumstances. We set out to describe the actual fluid management strategies employed in different settings and to investigate relationships with clinical outcomes.

    METHODS: We performed a retrospective review of paediatric DSS cases managed at seven hospitals across Malaysia, Myanmar and Vietnam. We explored the effects of both initial resuscitation (crystalloid alone or mixed crystalloid/colloid in the first 2 hours) and general management: group 1 (conservative-colloid, crystalloid only), group 2 (intermediate-colloid, colloid for 1-4 hours) or group 3 (liberal-colloid, continuous colloid for more than 4 hours) categorised according to the fluid given over the first 6 hours in clinically stable patients. We incorporated an inverse probability weighting score to adjust for potential differences in baseline severity.

    RESULTS: Among all 691 patients, respiratory compromise (HR 2.08, p=0.022), requirement for nasal continuous positive airway pressure (NCPAP)/ventilation (OR 2.34, p<0.045) and days in hospital after DSS onset (risk ratio, RR 1.33, p=0.032) were significantly worse for mixed crystalloid/colloid versus crystalloid-only initial resuscitation regimens, after adjusting for baseline severity. Among the 547/691 children who stabilised within 2 hours, although a liberal-colloid general management strategy (group 3) was associated with a reduction in recurrent shock episodes (RR 0.13, p=0.043) when compared with a conservative-colloid strategy (group 1), the risks for respiratory compromise (OR 8.84, p<0.001) and requirement for NCPAP/ventilation (OR 8.16, p<0.001) were markedly increased. Additionally, the respective costs for group 3 vs group 1 were significantly higher.

    CONCLUSIONS: The study highlights the potential benefits and risks of using colloid solutions in children with DSS. Formal randomised trials could help determine the most effective and safe parenteral fluid regimens for paediatric DSS. In the meantime, prolonged use of colloid solutions may be inappropriate, especially in settings without access to respiratory support.

Related Terms
Filters
Contact Us

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links