A synopsis of current haemophilia care in Hong Kong

Objective To provide a synopsis of current haemophilia care in Hong Kong. Design Retrospective survey. Setting All haematology units of the Hospital Authority in Hong Kong. Patients All patients with haemophilia A and haemophilia B. Results To date, there were 222 mild-to-severe haemophilia patients (192 type A, 30 type B) under regular public care in Hong Kong (43% were considered severe, 33% moderate, and 24% mild), which gave a crude prevalence of 6.8/100 000 male inhabitants. A total of 12.8 million units of Factor VIII and 3 million units of Factor IX were prescribed annually. This amounts to 1.83 units of FVIII per capita of the population, which is comparable to that of other developed countries. Leading causes of mortality were human immunodefciency virus-related complications (10 cases) and cerebral bleeding (2 cases). The life expectancy of patients with severe haemophilia in Hong Kong is improving; currently the oldest patient is 60 years old. Such improved survival may be due to enhanced factor availability, prompt treatment of bleeding episodes at home, safer factor products, and better antiviral treatment. Primary prophylaxis is the accepted standard of care for severe and moderate cases, and "Factor First" has become hospital policy. However, 12 patients continue to present treatment challenges, due to the documented presence of factor inhibitors. In all, 28,100, and 14 cases respectively were positive for human immunodefciency virus, hepatitis C virus, and hepatitis B virus; the youngest patients with the corresponding infections being 28,13, and 22 years old. Comprehensive care with dedicated physiotherapy, surgical support, and radionucleotide synovectomy may reduce morbidity further. Conclusion A multidisciplinary approach can further improve the future care for haemophilia patients in Hong Kong.published_or_final_versio

A synopsis of current care of thalassaemia major patients in Hong Kong

OBJECTIVE: To provide a synopsis of current thalassaemia major patient care in Hong Kong. DESIGN: Retrospective study. SETTING: All haematology units of the Hospital Authority in Hong Kong. PATIENTS: All patients with thalassaemia major with regular transfusion. RESULTS: To date, there were 363 thalassaemia major patients under the care of the Hospital Authority. Prenatal diagnosis has helped to reduce the number of indigenous new cases, but in recent years immigrant cases are appearing. The patients have a mean age of 23 (range, 1-52) years, and 78% of them are adults. In 2009, they received 18 782 units of blood. This accounted for 9.5% of all blood consumption from the Hong Kong Red Cross. In the past, cardiac iron overload was the major cause of death (65%) and few patients survived beyond the age of 45 years. The availability of cardiac iron assessment by magnetic resonance imaging (T2 MRI) to direct the use of oral deferiprone chelation has reduced the prevalence of heart failure and cardiac haemosiderosis, which should reduce mortality and improve life expectancy. CONCLUSION: The future for thalassaemia care in Hong Kong is bright. With better transfusion and chelation, it should be possible to avoid growth and endocrine deficiencies in younger patients.published_or_final_versio

Prognostic significance of CD26 in patients with colorectal cancer

Background: CD26, dipeptidyl peptidase IV, was discovered firstly as a membrane-associated peptidase on the surface of leukocyte. We previously demonstrated that a subpopulation of CD26+ cells were associated with the development of distant metastasis, enhanced invasiveness and chemoresistance in colorectal cancer (CRC). In order to understand the clinical impact of CD26, the expression was investigated in CRC patient's specimens. This study investigated the prognostic significance of tumour CD26 expression in patients with CRC. Examination of CD26+ cells has significant clinical impact for the prediction of distant metastasis development in colorectal cancer, and could be used as a selection criterion for further therapy. Methods: Tumour CD26 expression levels were studied by immunohistochemistry using Formalin-fixed paraffin embedded (FFPE) tissues in 143 patients with CRC. Tumour CD26 expression levels were correlated with clinicopathological features of the CRC patients. The prognostic significance of tumour tissue CD26 expression levels was assessed by univariate and multivariate analyses. Result: CD26 expression levels in CRC patients with distant metastasis were significantly higher than those in non-metastatic. High expression levels of CD26 were significantly associated with advanced tumour staging. Patients with a high CD26 expression level had significantly worse overall survival than those with a lower level (p<0.001). Conclusions: The expression of CD26 was positively associated with clinicopathological correlation such as TNM staging, degree of differentiation and development of metastasis. A high CD26 expression level is a predictor of poor outcome after resection of CRC. CD26 may be a useful prognostic marker in patients with CRC. © 2014 Lam et al.published_or_final_versio

A Lyapunov-type condition for robust feedback stability of delay control systems

In this paper, we show that a delay control system can be robustly stabilized by certain closed-loop feedback if a Lyapunov-type condition is fulfilled. Copyright 2006 Oxford University Press.link_to_subscribed_fulltex

Somatic mosaicism of PIK3CA mutation in PIK3CA-related overgrowth disorders

Oral Free Paper SessionOutstanding Oral PresentationBackground and aims Somatic mosaicism of phosphatidylinositol-4,5-bisphosphate 3-kinase (PIK3CA) mutation, one of the genes involved in the PI3K/AKT/mTOR pathway, is associated with a group of rare asymmetrical overgrowth syndrome that is collectively named as PIK3CA-related overgrowth disorder. This group of disorder includes CLOVES syndrome, fibroadipose hyperplasia, and facial infiltrating lipomatosis. The general abnormalities associated with somatic mutation of PIK3CA include abnormal overgrowth of skeletal and fibroadipose tissues, vascular malformations and skin abnormalities. The PI3K/AKT/mTOR pathway is an intracellular signaling pathway which is involved in cellular processes like cell proliferation and apoptosis, and mutations of components of this pathway result in overactivation the pathway, leading to various overgrowth- related diseases such as tuberous sclerosis and cancers. Mutation of PIK3CA also over-activates the PI3K/AKT/mTOR pathway, therefore leading to abnormal overgrowth in patients. We identify seven suspected cases of PIK3CA-related overgrowth disorder, including three suspected cases of CLOVES syndrome, one with cystic hygroma, one with isolated macrodactyly, one with asymmetric limb overgrowth, and one with multiple lipomatosis. We aim to identify the mutations of PIK3CA in each case. Methods For the cases with fresh tissues, tissue DNA extraction was performed by QIAamp DNA Mini (Qiagen) according to the manufacturer's protocol. For cases with formalin-fixed, paraffin-embedded (FFPE) fixed tissues, DNA extraction was performed by QIAamp DNA FFPE Tissue (Qiagen). Since four mutation hotspots have been identified in patients of PIK3CA-related overgrowth disorder, we carried out sanger sequencing on these mutation hotspots. Results In one suspected case of CLOVES syndrome, somatic mosaicism of PIK3CA c.3297A>G (p.His1047Arg) mutation was identified in the patient's affected cartilage and affected lipomatous tissues, whereas mutation was not found in her unaffected skin tissue. Molecular analysis of the other suspected PIK3CA-related overgrowth disorders is in progress. Conclusion Somatic muation of PIK3CA is the cause of PIK3CA-related overgrowth disorder, where mutations can only be found in affected tissues but not in unaffected tissues, suggesting somatic mosaicism. This implies that when genetic test is considered, the correct choice of tissues is important for molecular confirmation of the disease. Further experiment will be carried out on identifying the mutation on other cases, and also quantifying the percentage of somatic mosaicism using pyrosequencing

AAV-CRISPR-Cas13 eliminates human enterovirus and prevents death of infected mice

10.1016/j.ebiom.2023.104682eBioMedicine93104682