Evaluating the Health-Related Quality of Life of the Rare Disease Population in Hong Kong Using EQ-5D 3-Level.

OBJECTIVES: This study aimed to establish a normative profile of health-related quality of life (HRQOL) of the rare disease (RD) population in Hong Kong (HK) and identify potential predictors. METHODS: Between March 2020 and October 2020, patients with RD and caregivers were recruited through Rare Disease Hong Kong, the largest RD patient group alliance in HK. HRQOL was derived using the EQ-5D 3-Level with reference to the established HK value set. Utility scores were stratified according to demographics and disease-related information. Multiple linear regression was performed to explore the associations between patient characteristics and HRQOL. RESULTS: A total of 286 patients, covering 107 unique RDs, reported a mean utility score of 0.53 (SD 0.36). Thirty patients (10.5%) reported negative utility scores, indicating worse-than-death health states. More problems were recorded in the "usual activities" and "self-care" dimensions. Univariate analyses revealed that neurologic diseases, high out-of-pocket expenditure, home modification, and living in public housing or subdivided flats/units were significantly associated with lower HRQOL. A total of 99 caregivers reported a mean utility score of 0.78 (SD 0.17), which was significantly associated with the utility score of patients they took care of (r = 0.32; P = .001). CONCLUSIONS: The normative profile of the RD population was established, which revealed lower HRQOL in the RD population than other chronic disease groups and general population in HK. Findings were corroborated by evidence from other cohorts using EQ-5D, combined as part of a meta-analysis. Identifying predictors highlight areas that should be prioritized to improve HRQOL of RD population through clinical and psychosocial dimensions.

Perception of personalized medicine, pharmacogenomics, and genetic testing among undergraduates in Hong Kong.

BACKGROUND: The global development and advancement of genomic medicine in the recent decade has accelerated the implementation of personalized medicine (PM) and pharmacogenomics (PGx) into clinical practice, while catalyzing the emergence of genetic testing (GT) with relevant ethical, legal, and social implications (ELSI). RESULTS: The perception of university undergraduates with regards to PM and PGx was investigated, and 80% of undergraduates valued PM as a promising healthcare model with 66% indicating awareness of personal genome testing companies. When asked about the curriculum design towards PM and PGx, compared to undergraduates in non-medically related curriculum, those studying in medically related curriculum had an adjusted 7.2 odds of perceiving that their curriculum was well-designed for learning PGx (95% CI 3.6-14.6) and a 3.7 odds of perceiving that PGx was important in their study (95% CI 2.0-6.8). Despite this, only 16% of medically related curriculum undergraduates would consider embarking on future education on PM. When asked about their perceptions on GT, 60% rated their genetic knowledge as "School Biology" level or below while 76% would consider undergoing a genetic test. As for ELSI, 75% of undergraduates perceived that they were aware of ethical issues of GT in general, particularly on "Patient Privacy" (80%) and "Data Confidentiality" (68%). Undergraduates were also asked about their perceived reaction upon receiving an unfavorable result from GT, and over half of the participants perceived that they would feel "helpless or pessimistic" (56%), "inadequate or different" (59%), and "disadvantaged at job seeking" (59%), while older undergraduates had an adjusted 2.0 odds of holding the latter opinion (95% CI 1.1-3.5), compared to younger undergraduates. CONCLUSION: Hong Kong undergraduates showed a high awareness of PM but insufficient genetic knowledge and low interest in pursuing a career towards PM. They were generally aware of ethical issues of GT and especially concerned about patient privacy and data confidentiality. There was a predominance of pessimistic views towards unfavorable testing results. This study calls for the attention to evaluate education and talent development on genomics, and update existing legal frameworks on genetic testing in Hong Kong.

Cyanuric chloride as the basis for compositionally diverse lipids.

Cyanuric chloride has been utilized in the development of new synthetic lipid compounds using two differing schemes. The resulting lipids, presented in this manuscript, were characterized and evaluated for their ability to form nanoparticles and subsequently tested for their utility in various biological applications, including gene delivery and immunization. Of the 12 lipids synthesized, 8 formed nanoparticles that remained stable, based on dynamic light scattering, for at least one month. The compounds were then assessed for their toxicity, and subsequently tested for their ability to encapsulate drugs, genes and peptides. While the compounds did not seem to encapsulate carboxyfluorescein, we demonstrate that these lipids are capable of plasmid delivery in vitro, and inducing antibody profiles similar to other hydrophobic anchors in liposomal peptide vaccines. This strategy for accessing diverse lipid compounds offers a way to easily optimize lipid-based therapeutics for research in an expedited manner.

A Meta-Analysis of Rupture Risk for Intracranial Aneurysms 10 mm or Less in Size Selected for Conservative Management Without Repair.

BACKGROUND: Small unruptured intracranial aneurysms (UIAs) are considered to have low risk of rupture. The proportion of UIAs measuring 10 mm or less in size that rupture when selected for conservative management without repair is not well known. The aim of this study is to determine the proportion of UIAs that rupture by size threshold from ≤10 to ≤3 mm when selected for management without repair and to determine the level of precision and sources of heterogeneity in the rupture risk estimate. METHODS: This study was prospectively registered with the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42019121522). The Ovid MEDLINE, EMBASE, Web of Science Core Collection, and the Cochrane Central Register of Controlled Trials were searched (inception to August 2020). Studies with longitudinal follow-up of patients with UIAs ( ≤10 mm to ≤3 mm) without endovascular or neurosurgical repair were eligible. We included studies, which provided details of aneurysm size and in which UIA rupture was reported as an outcome. The primary outcome of the pooled proportion of UIA rupture during follow-up was synthesized with random-effects meta-analysis; heterogeneity was explored using meta-regression. RESULTS: A total of 31 studies that included 13,800 UIAs ≤10 mm in size were eligible for data synthesis. The pooled proportion of ≤10 mm UIAs that ruptured when managed without repair was 1.1% (95% CI 0.8-1.5; I 2 = 52.9%) over 3.7 years. Findings were consistent in sensitivity analyses at all the size stratified thresholds including ≤5 and ≤3 mm; rupture occurred in 1.0% (95% CI 0.8-1.3; I 2 = 0%) of 7,280 ≤5 mm UIAs and 0.8% (95% CI 0.4-1.5; I 2 = 0%) of 1,228 ≤3 mm UIAs managed without repair. In higher quality studies with lower risk of bias, rupture occurred in 1.8% (95% CI 1.5-2.0; I 2 = 0%) over 3.9 years. In meta-regression, aneurysm size, shape, anatomical location, and exposure to prior subarachnoid hemorrhage were not identified as sources of heterogeneity. CONCLUSION: For every 1,000 UIAs that are 10 mm or less in size and selected for conservative management without repair, between 8 and 15 UIAs are estimated to rupture over 3.7 years. When stratified by size, these pooled rupture risk estimates are consistent and clinically applicable for ≤5 mm UIAs selected for management without repair. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/, identifier: CRD42019121522.

The Destructive Fungal Pathogen Botrytis cinerea-Insights from Genes Studied with Mutant Analysis.

Botrytis cinerea is one of the most destructive fungal pathogens affecting numerous plant hosts, including many important crop species. As a molecularly under-studied organism, its genome was only sequenced at the beginning of this century and it was recently updated with improved gene annotation and completeness. In this review, we summarize key molecular studies on B. cinerea developmental and pathogenesis processes, specifically on genes studied comprehensively with mutant analysis. Analyses of these studies have unveiled key genes in the biological processes of this pathogen, including hyphal growth, sclerotial formation, conidiation, pathogenicity and melanization. In addition, our synthesis has uncovered gaps in the present knowledge regarding development and virulence mechanisms. We hope this review will serve to enhance the knowledge of the biological mechanisms behind this notorious fungal pathogen.

A Bioengineered Neuregulin-Hydrogel Therapy Reduces Scar Size and Enhances Post-Infarct Ventricular Contractility in an Ovine Large Animal Model.

The clinical efficacy of neuregulin (NRG) in the treatment of heart failure is hindered by off-target exposure due to systemic delivery. We previously encapsulated neuregulin in a hydrogel (HG) for targeted and sustained myocardial delivery, demonstrating significant induction of cardiomyocyte proliferation and preservation of post-infarct cardiac function in a murine myocardial infarction (MI) model. Here, we performed a focused evaluation of our hydrogel-encapsulated neuregulin (NRG-HG) therapy's potential to enhance cardiac function in an ovine large animal MI model. Adult male Dorset sheep (n = 21) underwent surgical induction of MI by coronary artery ligation. The sheep were randomized to receive an intramyocardial injection of saline, HG only, NRG only, or NRG-HG circumferentially around the infarct borderzone. Eight weeks after MI, closed-chest intracardiac pressure-volume hemodynamics were assessed, followed by heart explant for infarct size analysis. Compared to each of the control groups, NRG-HG significantly augmented left ventricular ejection fraction (p = 0.006) and contractility based on the slope of the end-systolic pressure-volume relationship (p = 0.006). NRG-HG also significantly reduced infarct scar size (p = 0.002). Overall, using a bioengineered hydrogel delivery system, a one-time dose of NRG delivered intramyocardially to the infarct borderzone at the time of MI in adult sheep significantly reduces scar size and enhances ventricular contractility at 8 weeks after MI.

Platelet Function Testing in Neurovascular Procedures: Tool or Gimmick?

BACKGROUND: Platelet inhibitors are used to prevent thromboembolic complications related to neurovascular stenting (NVS) procedures. Despite substantial inter-individual variability of functional platelet inhibition, the value of platelet function tests (PFT) to assess inhibition remains controversial. OBJECTIVE: This study was conducted to compare differences in thromboembolic complication rates associated with NVS in platelet-inhibited patients with and without PFT. Clinical neurological outcomes were assessed by differences in the modified Rankin Scale (mRS). MATERIALS AND METHODS: One hundred seventeen consecutive patients underwent elective NVS procedures within a 7-year period. All patients received aspirin and clopidogrel 8 days before the procedure. Fifty-two patients were treated without assessment of platelet inhibition, and 65 patients were tested for clopidogrel resistance. When clopidogrel resistance was revealed, corresponding patients were converted to ticagrelor. Changes in mRS and thromboembolic event rates were compared between the 2 cohorts. RESULTS: Thirty-five percent of patients from the cohort subjected to PFT tests showed inadequate platelet inhi-bition under clopidogrel and were converted to ticagrelor. Compared to the non-PFT test -cohort, neurological deficits were significantly reduced (12 vs. 0%; p = 0.009) and a lower number of thromboembolic events was found (12 vs. 3%; p > 0.05) within the test cohort. CONCLUSION: PFT appears to identify patients with clopidogrel resistance prior to NVS procedures. When non-responders are converted to alternative platelet inhibitors, neurological outcomes and thromboembolic complication rates may improve. Consequently, this study provides preliminary evidence that PFT may be a useful clinical tool to enhance procedural safety and improve clinical outcomes in NVS procedures.

Residuals, recurrences and re-treatment after endovascular repair of intracranial aneurysms: A retrospective methodological comparison.

OBJECTIVE: Incomplete aneurysm occlusions and re-treatment rates of 52 and 10-30%, respectively, have been reported following endovascular treatment of intracranial aneurysms, raising clinical concerns regarding procedural efficacy. We compare residual, recurrence and re-treatment rates subject to different endovascular techniques in both ruptured and unruptured intracranial aneurysms at a comprehensive state-wide tertiary neurovascular centre in Australia. METHODS: Medical records, procedural and follow-up imaging studies of all patients who underwent endovascular treatment for intracranial aneurysms between July 2010 and July 2017 were reviewed retrospectively. Residuals, recurrences and re-treatment rates were assessed regarding initial aneurysm rupture status and applied endovascular technique: primary coiling, balloon- and stent-assisted coiling and flow diversion. RESULTS: Among 233 aneurysms, residual, recurrence and re-treatment rates were 27, 11.2 and 9.4%, respectively. Compared with unruptured aneurysms, similar residual and recurrence (p > .05), but higher re-treatment rates (4.5% vs. 19%; p < .001) were found for ruptured aneurysms. Residual, recurrence and re-treatment rates were: 13.3, 16 and 12% for primary coiling; 12, 12 and 10.7% for balloon-assisted coiling; 14.9, 7.5 and 4.5% for stent-assisted coiling; 91.9, 0 and 5.4% for flow diversion. Stent-assistance and flow-diversion were associated with lower recurrence and re-treatment rates, when compared with primary- and balloon-assisted coiling (p < .05). CONCLUSIONS: Residuals and recurrences after endovascular treatment of intracranial aneurysms are less common than previously reported. Stent assistance and flow diversion seem associated with reduced recurrence- and re-treatment rates, when compared with primary- and balloon-assisted coiling. Restrained use of stents in ruptured aneurysms may be a contributing factor for higher recurrence/retreatment rates compared to unruptured aneurysms.

Radiation exposure, and procedure and fluoroscopy times in endovascular treatment of intracranial aneurysms: a methodological comparison.

BACKGROUND: Limited data are available for radiation exposure, and procedure and fluoroscopy times in neuroendovascular treatment (NET) strategies. OBJECTIVE: This study establishes and compares related parameters between coil embolization (COIL), balloon assisted coil embolization (BAC), stent assisted coil embolization (SAC), and flow diverting technology (FDT) in NET of intracranial aneurysms. MATERIALS AND METHODS: Between 2010 and 2017, 249 consecutive intracranial aneurysms underwent NET at a single center, all performed by the same operator. Dose area products (DAP), and procedure and fluoroscopy times were recorded and compared between COIL, BAC, SAC, and FDT techniques. Differences in parameters between cohorts were analyzed for significance using the Mann-Whitney U test, unpaired t test and χ2test. Additional subgroup analysis was performed for emergency and elective cases. RESULTS: 83 aneurysms were treated with COIL (33%), 72 with BAC (29%), 61 with SAC (25%), and 33 with FDT (13%). Baseline characteristics were largely similar within these groups (P>0.05). Among COIL, BAC, and FDT cohorts, no significant difference was found for mean DAP, or procedure and fluoroscopy times (P>0.05). However, compared with all other cohorts, SAC was associated with a significantly higher DAP and longer procedure and fluoroscopy times (P<0.005). No significant difference was recorded for emergency and elective case subgroups. CONCLUSION: Compared with other NET strategies, SAC was associated with a significantly higher DAP, and longer procedure and fluoroscopy times. This study provides an initial dataset regarding radiation exposure, and procedure and fluoroscopy times for common NET, and may assist ALARA (As Low As Reasonably Achievable) principles to reduce radiation risks.

Long-term follow-up of aneurysms treated electively with woven stent-assisted coiling.

BACKGROUND: Preliminary short-term results for stent-assisted coil embolization (SACE) using woven/braided stents have been promising. However, evidence supporting mid- to long-term efficacy and durability is lacking. OBJECTIVE: To report the long-term results for the durability of elective intracranial aneurysms treated with woven stents. MATERIALS AND METHODS: Between May 2012 and May 2015, 98 consecutive patients with 103 aneurysms underwent elective woven SACE across three Australian neurovascular centres. All patients had immediate, 6- and 18-month clinical and radiological follow-up. Radiological assessment was performed with modified Raymond-Roy occlusion scores based on angiography results, while clinical assessment was based on the modified Rankin Scale. RESULTS: Six-month follow-up was available in 100 aneurysms, and an 18-month follow-up in 97 aneurysms. Total occlusion rates of 82% were achieved at inception, 82% at 6 months, and 90% at 18 months. Satisfactory occlusion with small neck remnants was present in 17% at inception, 16% at 6 months, and 9% at 18 months. Good neurological outcomes were achieved in 95% at 18 months. Intraprocedural thromboembolic events were recorded in 3% and delayed events in 1% (all in patients taking clopidogrel). Aneurysm recurrence occurred in one patient (1%). Technical complications occurred in 5%. The total complication rate was 10%. CONCLUSIONS: Woven SACE is safe, efficacious, and durable at long-term 18-month follow-up, with very low recurrence and re-treatment rates. Preliminary results appear better than those for traditional laser-cut stents.

Long term follow-up of bifurcation aneurysms treated with braided stent assisted coiling and complex T- and Y- stent constructs.

BACKGROUND: Stent assisted coil embolization (SACE) of bifurcation aneurysms is challenging. Heterogeneous results have been achieved to date, but largely for laser cut stents. While braided stents offer multiple technical advantages, their long term efficacy has yet to be validated. OBJECTIVE: To report the first long term 18 month results for the durability of bifurcation aneurysms treated with braided stents. MATERIALS AND METHODS: Over a 4 year period, 59 consecutive patients with 60 bifurcation aneurysms underwent elective braided SACE across three Australian neurovascular centers. 17 of these aneurysms underwent T- or Y-shaped stent constructs. All patients had immediate, 6 month and 18 month clinical and radiological follow-up. Radiological assessment was made on modified Raymond-Roy occlusion scores while clinical assessment was based on the modified Rankin Scale. Subgroup analysis of 17 aneurysms treated with multi-stent constructs was conducted. RESULTS: 6 month follow-up data were available for 59 aneurysms and 18 month follow-up data for 58 aneurysms. Satisfactory aneurysm occlusion was achieved in 97% at inception and at 6 months, and 98% at 18 months. Good neurological outcomes were achieved in 95% at 18 months. Similar satisfactory results were achieved with the multi-stent construct cohort. Intraprocedural thromboembolic events were recorded in 5% and delayed events in 2%. Technical complications were found in 5%. All complication rate was 13%. CONCLUSION: Braided SACE was safe, efficacious, and durable at the long term 18 month follow-up, including for multi-stent constructs. Preliminary results indicate favorable clinical and radiological outcomes compared with laser cut stents.

Long-term follow-up of minimal-access and open posterior lumbar interbody fusion for spondylolisthesis.

BACKGROUND: Although posterior lumbar interbody fusion (PLIF) is regarded as an effective treatment for spondylolisthesis, few studies have reported comprehensive, long-term outcome data, and none has investigated the incidence of deterioration of outcomes. OBJECTIVE: To determine and compare the success rates and long-term stability of outcomes of open PLIF and minimal-access PLIF in the treatment of radicular pain and back pain in patients with spondylolisthesis. METHODS: Forty-three patients were followed for a minimum of 3 years. They completed a Short-Form Health Survey and visual analog scores for back pain and leg pain and underwent lumbar spine radiography. Outcomes were compared with baseline data and 12-month data. RESULTS: Surgery succeeded in reducing listhesis and increasing disc height, but had little effect on lumbar lordosis or the angulation of the segment treated. At 12 months after surgery, listhesis was reduced, disc height was increased, leg pain was reduced or eliminated, and physical functioning restored. Back pain was less often relieved. These outcomes were largely maintained over the ensuing 2 years. Only 5% to 10% of patients reported deterioration in their relief of pain. Depending on the definition adopted for success, the long-term success rate of PLIF may be as high as 70%. CONCLUSION: For the relief of leg pain, the success rates of open PLIF (70%) and minimal-access PLIF (67%) for spondylolisthesis are high and durable in the long-term. PLIF is less often successful in relieving back pain, but the outcomes are maintained. The outcomes of open PLIF and minimal-access PLIF were statistically indistinguishable. ABBREVIATIONS: MCIC, minimally clinically important changeMPLIF, minimal-access posterior lumbar interbody fusionOPLIF, open-access posterior lumbar interbody fusionPLIF, posterior lumbar interbody fusionSF-36, Short-Form Health Survey.

Rapid onset aggressive vertebral haemangioma.

INTRODUCTION: Vertebral haemangiomas are generally benign asymptomatic vascular tumours seen commonly in the adult population. Presentations in paediatric populations are extremely rare, which can result in rapid onset of neurological symptoms. We present a highly unusual case of an aggressive paediatric vertebral haemangioma causing significant cord compression. CASE REPORT: A 13-year-old boy presented with only 2 weeks duration of progressive gait disturbance, truncal ataxia and loss of bladder control. Magnetic resonance imaging (MRI) of the spine revealed a large vascular epidural mass extending between T6 and T8 vertebral bodies. Associated displacement and compression of the spinal cord was present. A highly vascular bony lesion was found during surgery. Histopathology identified this tumour to be a vertebral haemangioma. DISCUSSION: We present an extremely unusual acute presentation of a paediatric vertebral haemangioma. This study highlights the need for early diagnosis, MRI for investigation and urgent surgical management.