Genomic medicine and precision medicine initiatives have taken centre stage in scientific, clinical, as well as health economics and utility research on the global scene for the past decade. It is ...clear the important role genomic advancement has played in enhancing diagnostic rate, streamlining personalised treatment, and improving efficacy of the overall clinical management of undiagnosed, rare, and common diseases for humankind. The Hong Kong Genome Institute (HKGI) was established in May 2020 within the Food and Health Bureau, Hong Kong Special Administrative Region, to integrate genomic medicine into mainstream healthcare. The main goals of setting up HKGI are to (1) improve the diagnostic rate and future care for individuals affected by undiagnosed diseases and hereditary cancers using whole genome sequencing; (2) advance research in genomic science; (3) nurture talents in genomic medicine; and (4) enhance public genomic literacy and overall engagement through the launching of the Hong Kong Genome Project (HKGP). In this paper, we review the current landscape and specific challenges encountered during the construction of the infrastructure and implementation of the pilot phase of HKGP. Through reviewing what has been achieved and established to date, and the potentials and prospects that have emerged in the process, this paper will provide insights into planning the main phase of HKGP, and considerations for our international counterparts when building similar projects.
Hydatidiform mole (HM) is classified into partial (PHM) and complete (CHM) subtypes according to histopathologic and genetic criteria. Traditionally, it is believed that PHM carries a better ...prognosis and rarely develops metastasis. However, making a distinction between PHM and CHM using histologic criteria alone may be difficult.
The authors used fluorescent microsatellite genotyping following laser-capture microdissection and chromosome in situ hybridization (CISH) to perform a genetic analysis of six patients with histologically diagnosed PHM who subsequently developed metastatic gestational trophoblastic neoplasia.
Patients ranged in age from 25 years to 44 years (mean, 33.2 years). The gestational age of the molar pregnancies varied from 6 weeks to 20 weeks. All six patients had pulmonary metastases, with additional liver metastasis in two patients. Among the six patients with histologically diagnosed PHM, it was found that four patients had a diploid karyotype and no maternal alleles; thus, their neoplasms actually were CHM. Maternal genome was detected in the remaining two patients consistent with a biparental origin, and these patients had a triploid karyotype. CISH findings in all patients correlated with the genotyping findings. Triploid HM had maternally derived alleles, whereas diploid HMs were purely androgenetic.
In the current study, which may be the largest series of genetically analyzed metastatic PHMs to date, the difficulty of histologic distinction between PHM and CHM was confirmed. Molecular analysis may help to refine the classification of HM. Although the current findings support the belief that most aggressive trophoblastic diseases are derived from CHM, a small number of PHMs do progress to metastatic disease. Thus, the current study reaffirmed that all patients with HM should be followed closely irrespective of histologic subclassification.
We describe a 72-year-old Chinese man who developed fulminant Bacillus cereus endophthalmitis 36 h after an uneventful surgery for cataract extraction. Clinical progression of disease was extremely ...rapid, in spite of early vitrectomy and intravitreal injection of antibiotics. Results of Gram staining showed gram-positive bacilli, and the culture was positive for B. cereus. Endophthalmitis is rare after cataract surgery (cumulative probability within 1 year, ∼0.08%), and cases caused by B. cereus are even less common. The prognosis and plan of treatment are discussed.
Introduction: Real-world management of patients with hepatocellular carcinoma (HCC) is crucially challenging in the current rapidly evolving clinical environment which includes the need for ...respecting patient preferences and autonomy. In this context, regional/national treatment guidelines nuanced to local demographics have increasing importance in guiding disease management. We report here real-world data on clinical outcomes in HCC from a validation of the Consensus Guidelines for HCC at the National Cancer Centre Singapore (NCCS). Method: We evaluated the NCCS guidelines using prospectively collected real-world data, comparing the efficacy of treatment received using overall survival (OS) and progression-free survival (PFS). Treatment outcomes were also independently evaluated against 2 external sets of guidelines, the Barcelona Clinic Liver Cancer (BCLC) and Hong Kong Liver Cancer (HKLC). Results: Overall treatment compliance to the NCCS guidelines was 79.2%. Superior median OS was observed in patients receiving treatment compliant with NCCS guidelines for early (nonestimable vs. 23.5 months p < 0.0001), locally advanced (28.1 vs. 22.2 months p = 0.0216) and locally advanced with macrovascular invasion (10.3 vs. 3.3 months p = 0.0013) but not for metastatic HCC (8.1 vs. 6.8 months p = 0.6300), but PFS was similar. Better clinical outcomes were seen in BCLC C patients who received treatment compliant with NCCS guidelines than in patients with treatment only allowed by BCLC guidelines (median OS 14.2 vs. 7.4 months p = 0.0002; median PFS 6.1 vs. 4.0 months p = 0.0286). Clinical outcomes were, however, similar for patients across all HKLC stages receiving NCCS-recommended treatment regardless of whether their treatment was allowed by HKLC. Conclusion: The high overall compliance rate and satisfactory clinical outcomes of patients managed according to the NCCS guidelines confirm its validity. This validation using real-world data considers patient and treating clinician preferences, thus providing a realistic analysis of the usefulness of the NCCS guidelines when applied in the clinics.
Aim: To assess the efficacy and safety of percutaneous transhepatic cholecystostomy (PTC) in treatment for acute cholecystitis in high surgical risk patients.
Patients and methods: A retrospective ...review was carried out from January 1999 to June 2007 on 23 patients, 11 males and 12 females, who underwent PTC for the management of acute cholecystitis at the Department of Surgery, Queen Mary Hospital, Hong Kong, China. The mean age of the patients was 83. They all had either clinical or radiological evidence of acute cholecystitis and had significant pre‐morbid diseases. The median follow‐up period on them was 35 months.
Results: All the PTCs performed were technically successful. One patient died from procedure‐related haemoperitoneum, while 87% (n= 20) of all the patients had clinical resolution of sepsis by 20 h after PTC. Eight patients underwent elective cholecystectomy afterwards (62.5% with the laparoscopic approach). Eight patients had dislodgement of the PTC catheter and one of them developed recurrent acute cholecystitis 3 months after PTC. That patient was treated conservatively. Four patients died from their pre‐morbid conditions during the follow‐up period.
Conclusion: PTC was a safe and effective alternative for treating acute cholecystitis in this group of patients. Thirteen of them without elective cholecystectomy performed did not have recurrent acute cholecystitis after a single session of PTC. It may be considered as a definitive treatment for this group of patients.
Abstract While deletion of chromosome 17p13.3 (encompassing PAFAH1B1 and YWHAE genes) is known to result in Miller–Dieker syndrome (OMIM 247200), 17p13.3 microduplication gives rise to a condition ...commonly associated with developmental delay and autism spectrum disorder. We report a Chinese newborn presenting with dysmorphic features, microcephaly and valvar aortic stenosis, who was confirmed to have a 790 kb microduplication in chromosome 17p13.3 by array comparative genomic hybridization (aCGH). The patient passed away at 4 months of age with presumably life-threatening event associated with his cardiac condition. From literature review, congenital heart diseases of various kinds were identified in up to 20% of patients with 17p13.3 microduplication. We propose cardiac assessment should be part of the comprehensive evaluation of these patients.
Initiated chemical vapor deposition of polymers (iCVD) is a process similar to hot-wire CVD (HWCVD) in which a free-radical initiating species is employed to greatly increase the growth rate while ...decreasing the required energy input. In general, iCVD allows for the deposition of linear polymer, copolymer and/or crosslinked films with a wide range of functions. Surveyed examples include antimicrobial, superhydrophobic, superhydrophilic, and other functional thin polymer films and coatings.
Background. Cytogenetically normal acute myeloid leukaemia (CN-AML) occurs in 50% adult AML and is a group of diseases with diverse mutations and distinct clinical outcome. CEBPα, NPM1 and FLT3 ...mutations that are commonly seen in CN-AML have been incorporated into risk stratification. However, prognostic impacts of other gene mutations and their combinations in this AML subtype have remained unclear. In this study, we examined a cohort of young adults with de novo CN-AML who have received uniform treatment protocol in Hong Kong and identified a mutation pentad that might define their clinical outcome.
Methodology. Young adults (18-60 years old) with de novo CN-AML, diagnosed from 1st August 2003 to 7th August 2018 in 8 regional hospitals in Hong Kong, were included. They received standard “7+3” induction (Daunorubicin 60-90 mg/m2 and Cytarabine 100 mg/m2) followed by up to 4 courses of high dose cytarabine consolidation (Cytarabine 3 gram/m2 for 4-6 doses). Decision on allogeneic haematopoietic stem cell transplantation (HSCT) was based on clinical grounds and gene mutations according to ELN recommendations. Next generation sequencing (NGS) was performed in diagnostic bone marrow (BM) in 362 patients for 36 recurrent mutated genes and analyzed by in-house bioinformatics pipelines. Relapse-free survival (RFS) was defined by the time from first complete remission (CR) to relapse or death and overall survival (OS) by the time from diagnosis to death. Patients were censored at last follow up. Survivals were evaluated by Kaplan-Meier analysis and compared by log-rank test. Multivariate analyses of clinical and genetic parameters were analyzed by Cox-regression. P-values of <0.05 were considered statistically significant.
Results. A total of 436 patients (Male=189; Female=247) were recruited. Their median age of onset was 49 years old (Range 18-60); median presenting white cell counts (WCC) was 21.85x109/L (range 0.25-411x109/L), median circulating blast % was 46% (range 1-99). 416 patients received induction of whom 90.1% achieved CR or CRi (N=375) after 1 (N=268), 2 (N=78) or ≥ 3 courses of induction (N=29). One hundred and sixty three patients received allogeneic HSCT at CR1 (N=102), CR2 (N=51), ≥ CR3 (N=2) and relapsed state (N=8). Eight mutations with ≥ 10% prevalence occurred in 79.8% patients (Figure 1). Univariate analyses showed that mutations of CEBPα, TET2, IDH2-R172K and RAS were not associated with treatment outcome and survival. Five genetic subgroups based on NPM1, FLT3 and DNMT3A mutations could be identified: NPM1 mutation only; NPM1 mutation and FLT3-ITD; All wildtype; FLT3-ITD only; DNMT3A irrespective of NPM1 and FLT3-ITD status. These subgroups showed distinct RFS and OS (Figure 2). Impacts of IDH1-R132 and IDH2-R140Q mutations were evaluated in these 5 subgroups. Interestingly, adverse impacts of IDH1-R132 on RFS and OS were only significant in the all wildtype subgroup and the adverse impact of IDH2-R140Q was only significant for RFS in the NPM1 mutation only subgroup.
Conclusion. A mutation pentad comprising NPM1, FLT3, DNMT3A, IDH1-R132 and IDH2-R140Q seemed to define distinct prognostic subgroups in young adults with de novo CN-AML. A limited gene panel based on this pentad using conventional PCR may provide a practical and cost-effective means to guide post-remission therapy in these patients, especially in places where NGS may not be readily available.
Acknowledgements: SK Yee Medical Foundation; Li Shu Fan Medical Foundation, LKS Faculty of Medicine, University of Hong Kong, Hong Kong Blood Cancer Foundation
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Leung:Curegenix: Research Funding; Servier: Research Funding; Merck: Research Funding; Pfizer: Research Funding.
The kinetics of the degradation of an LH-RH antagonist, RS-26306,1, in aqueous solution from pH 1 to pH 11 were studied by reverse-phase HPLC. The pH-rate profiles at 50, 60, and 80 degrees C were ...U-shaped with the rate law of kobs = kHaH + kw + kOHaOH. The predicted 25 degrees C shelf life at the pH of maximum stability, pH approximately 5, is greater than 10 years. The products from the degradation were analyzed by HPLC-MS using thermospray ionization. Below pH 3, the primary product, 2, forms from the acid-catalyzed deamidation of the C-terminal amide. Above pH 7, epimerization of the individual amino acids is the principal reaction. Between pH 4 and pH 6, intramolecular serine-catalyzed peptide hydrolysis becomes important, yielding a tripeptide, 3, and a heptapeptide, 4. At the pH of maximum stability all three pathways for degradation are observed.
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