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Background: Spinal metastasis is a rare complication of supratentorial glioblastoma. We report the clinical features and prognosis of this phenomenon and review the relevant literature. Methods: This is a territory-wide, multicentre, retrospective review using data from the Hong Kong High-grade Glioma Registry from 2006 to 2023. Data of consecutive adult patients diagnosed with supratentorial glioblastoma and spinal metastasis were extracted and analyzed. Results: Among the 1342 patients with supratentorial glioblastoma, 15 were diagnosed to have spinal metastasis (1.1%). The median time to spinal metastasis from the initial diagnosis of glioblastoma was 38.7 weeks (IQR: 15.1–57.6). Multi-level spinal involvement was present in 60% (9/15) of patients. Neither the topographical location of the tumor in relation to the subventricular zone, extent of resection, occurrence of intraoperative ventricular entry, nor methylguanine methyltransferase (MGMT) promoter methylation status predicted the time to spinal metastasis. The median overall survival was 44.1 weeks (IQR: 29.9–80.2), and the median post-spinal metastasis survival was 12.6 weeks (IQR: 5.0–15.0). Two-thirds of patients received spinal radiotherapy, 26.7% had systemic therapy (chemotherapy, targeted therapy, and/or immunotherapy), and 13.3% underwent surgical spinal decompression. No significant survival improvement was observed among patients who received spinal radiotherapy (HR: 0.61; 95% CI: 0.17–2.23) or systemic therapy (HR: 0.94; 95% CI: 0.20–4.39). Conclusions: This case series illustrates the management practices and clinical course of glioblastoma patients with spinal metastasis. No treatment modality was proven to be superior. Treatment remains largely palliative and should be tailored on an individual basis.

To investigate the association between obesity and airway inflammation and spirometric parameters in local children. Cross-sectional and observational study. Paediatric clinics of a university-affiliated teaching hospital in Hong Kong. Chinese subjects aged 6 to 18 years were recruited from the paediatric clinics. Obesity was defined as being 120% or more of the median weight-for-height. Airway inflammation assessed by exhaled nitric oxide concentration; lung function evaluated by measuring forced expiratory flow in 1-second and forced vital capacity using spirometry; and peak expiratory flow rate measured by using a mini-Wright peak flow meter. Fifty-five subjects were recruited into four groups as follows: 13 non-obese controls, 16 obese non-asthmatics, 15 non-obese asthmatics, and 11 obese asthmatics. The median (interquartile range) exhaled nitric oxide concentrations of these groups were 17.6 (14.4-20.9), 33.3 (26.1-75.4), 65.7 (32.0-110.0) and 49.2 (41.1-82.6) parts per billion, respectively (P=0.001 for trend). Post-hoc analysis revealed higher exhaled nitric oxide concentration in the latter three groups (obese and/or asthmatic subjects) than controls (P< or =0.002). Exhaled nitric oxide concentration did not differ among obese non-asthmatics, non-obese asthmatics, and obese asthmatics (P>0.1 for all). In non-asthmatics, exhaled nitric oxide concentration correlated positively with age (P=0.048), weight-for-height z-score (P=0.001), and forced vital capacity (P=0.009). Weight-for-height z-score correlated positively with forced vital capacity (P=0.041), but inversely with the forced expiratory flow in 1-second/forced vital capacity ratio (P=0.049). Such correlations were not observed in asthmatic children. Increased airway inflammation as revealed by exhaled nitric oxide concentration was found in obese non-asthmatic children. Weight-for-height z-score as an indicator of childhood obesity correlated with exhaled nitric oxide concentration and spirometric parameters in children without asthma. Nonetheless, concomitant obesity does not influence exhaled nitric oxide concentration in asthmatic children. Further studies are needed to identify the pathophysiologic mechanisms for such associations.

High prevalence of anxiety symptoms has been reported globally in the university students. Cognitive behavioral therapy (CBT) is the recognized treatment for anxiety and is traditionally conducted face-to-face (f-CBT). The efficacy of internet-based CBT (i-CBT) for anxiety has been extensively studied, yet evidence on its cost-effectiveness is scarce. We aimed to evaluate the cost-effectiveness of guided low-intensity i-CBT for university students with mild anxiety symptoms from the societal perspective of Hong Kong. A 5-year Markov model was designed to compare outcomes of guided i-CBT and f-CBT in a hypothetical cohort of university students with mild anxiety symptoms. Model inputs of cost and healthcare resources associated with anxiety were retrospectively collected from a cohort of university students with anxiety symptoms. Clinical and utility model inputs were retrieved from published literature. Model outcome measures were anxiety-related total cost (including direct medical and indirect costs) and quality-adjusted life-year (QALY). Sensitivity analyses were performed to examine the robustness of base-case results. In base-case analysis, i-CBT gained higher QALYs (2.9956 versus 2.9917) at lower total cost (US$6,101 versus US$6,246) than f-CBT. In one-way sensitivity analysis, the QALY gained by i-CBT was sensitive to the relative patient acceptance and adherence to CBT. In probabilistic sensitivity analysis, i-CBT was cost-effective in 90.9% of the time at the willingness-to-pay threshold of 138,210 per QALY (3× GDP per capita in Hong Kong). The probability of i-CBT to be cost-effective was 99.9% at a willingness-to-pay threshold of zero. Guided i-CBT appears to be cost-saving and effective for management of university students with mild symptoms of anxiety from the societal perspective of Hong Kong. The cost-effectiveness of i-CBT is highly subject to the individual acceptance and adherence of CBT delivered by the internet platform.

ObjectiveThe impact of faecal microbiota transplantation (FMT) on microbiota engraftment in patients with metabolic syndrome is uncertain. We aimed to study whether combining FMT with lifestyle modification could enhance the engraftment of favourable microbiota in obese patients with type 2 diabetes mellitus (T2DM).DesignIn this double-blind, randomised, placebo-controlled trial, 61 obese subjects with T2DM were randomly assigned to three parallel groups: FMT plus lifestyle intervention (LSI), FMT alone, or sham transplantation plus LSI every 4 weeks for up to week 12. FMT solution was prepared from six healthy lean donors. Faecal metagenomic sequencing was performed at baseline, weeks 4, 16 and 24. The primary outcome was the proportion of subjects acquiring ≥20% of microbiota from lean donors at week 24.ResultsProportions of subjects acquiring ≥20% of lean-associated microbiota at week 24 were 100%, 88.2% and 22% in the FMT plus LSI, FMT alone, and sham plus LSI groups, respectively (p<0.0001). Repeated FMTs significantly increased the engraftment of lean-associated microbiota (p<0.05). FMT with or without LSI increased butyrate-producing bacteria. Combining LSI and FMT led to increase in Bifidobacterium and Lactobacillus compared with FMT alone (p<0.05). FMT plus LSI group had reduced total and low-density lipoprotein cholesterol and liver stiffness at week 24 compared with baseline (p<0.05).ConclusionRepeated FMTs enhance the level and duration of microbiota engraftment in obese patients with T2DM. Combining lifestyle intervention with FMT led to more favourable changes in recipients’ microbiota and improvement in lipid profile and liver stiffness.Trial registration number NCT03127696.

Internet-based cognitive behavioral therapy (CBT) provides psychological interventions to individuals with mild depressive symptoms. This study aimed to examine the potential cost-effectiveness of internet-based guided-CBT in university students with mild depressive symptoms from the perspective of service providers in Hong Kong. The outcomes of low-intensity guided internet-based CBT and in-person CBT in a hypothetical cohort of university students with mild depressive symptoms were examined using a 5-year decision-analytic model. Model inputs were obtained from published literature and local data. Model outcomes included direct medical cost, school dropouts, and quality-adjusted life years (QALYs). Sensitivity analyses were conducted on all model parameters. Compared to the in-person group, the internet group gained higher QALYs by 0.0211 QALYs, lowered school dropouts by 0.052%, and saved US $249 in the base-case analysis. In one-way sensitivity analysis, the internet group gained higher QALYs at a lower cost than the in-person group throughout the variation of all model inputs. Probabilistic sensitivity analysis showed that the internet group was cost-effective (at willingness-to-pay threshold was US $48,119/QALY) in 99.7% of the 10,000 Monte Carlo simulations. Internet-based CBT appears to be the cost-effective option when compared to in-person CBT for university students with mild depressive symptoms from the perspective of service providers in Hong Kong.

Cryptococcus neoformans is a pathogenic basidiomycetous yeast responsible for more than 600,000 deaths each year. It occurs as two serotypes (A and D) representing two varieties (i.e. grubii and neoformans, respectively). Here, we sequenced the genome and performed an RNA-Seq-based analysis of the C. neoformans var. grubii transcriptome structure. We determined the chromosomal locations, analyzed the sequence/structural features of the centromeres, and identified origins of replication. The genome was annotated based on automated and manual curation. More than 40,000 introns populating more than 99% of the expressed genes were identified. Although most of these introns are located in the coding DNA sequences (CDS), over 2,000 introns in the untranslated regions (UTRs) were also identified. Poly(A)-containing reads were employed to locate the polyadenylation sites of more than 80% of the genes. Examination of the sequences around these sites revealed a new poly(A)-site-associated motif (AUGHAH). In addition, 1,197 miscRNAs were identified. These miscRNAs can be spliced and/or polyadenylated, but do not appear to have obvious coding capacities. Finally, this genome sequence enabled a comparative analysis of strain H99 variants obtained after laboratory passage. The spectrum of mutations identified provides insights into the genetics underlying the micro-evolution of a laboratory strain, and identifies mutations involved in stress responses, mating efficiency, and virulence.

Human Recombinant ACE2 Reduces the Progression of Diabetic Nephropathy Gavin Y. Oudit 1 , 2 , George C. Liu 3 , JiuChang Zhong 1 , 2 , Ratnadeep Basu 1 , 2 , Fung L. Chow 1 , 2 , Joyce Zhou 3 , Hans Loibner 4 , Evelyne Janzek 4 , Manfred Schuster 4 , Josef M. Penninger 5 , Andrew M. Herzenberg 6 , Zamaneh Kassiri 2 , 7 and James W. Scholey 3 1 Division of Cardiology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada; 2 Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada; 3 Division of Nephrology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada; 4 Apeiron Biologics, Vienna, Austria; 5 Institute for Molecular Biotechnology of the Austrian Academy of Sciences, Vienna, Austria; 6 Department of Laboratory Medicine and Pathology, University of Toronto, Toronto, Ontario, Canada; 7 Department of Physiology, University of Alberta, Edmonton, Alberta, Canada. Corresponding author: Gavin Y. Oudit, gavin.oudit{at}ualberta.ca . Abstract OBJECTIVE Diabetic nephropathy is one of the most common causes of end-stage renal failure. Inhibition of ACE2 function accelerates diabetic kidney injury, whereas renal ACE2 is downregulated in diabetic nephropathy. We examined the ability of human recombinant ACE2 (hrACE2) to slow the progression of diabetic kidney injury. RESEARCH DESIGN AND METHODS Male 12-week-old diabetic Akita mice ( Ins2 WT/C96Y ) and control C57BL/6J mice ( Ins2 WT/WT ) were injected daily with placebo or with rhACE2 (2 mg/kg, i.p.) for 4 weeks. Albumin excretion, gene expression, histomorphometry, NADPH oxidase activity, and peptide levels were examined. The effect of hrACE2 on high glucose and angiotensin II (ANG II)–induced changes was also examined in cultured mesangial cells. RESULTS Treatment with hrACE2 increased plasma ACE2 activity, normalized blood pressure, and reduced the urinary albumin excretion in Akita Ins2 WT/C96Y mice in association with a decreased glomerular mesangial matrix expansion and normalization of increased α-smooth muscle actin and collagen III expression. Human recombinant ACE2 increased ANG 1–7 levels, lowered ANG II levels, and reduced NADPH oxidase activity. mRNA levels for p47 phox and NOX2 and protein levels for protein kinase Cα (PKCα) and PKCβ1 were also normalized by treatment with hrACE2. In vitro, hrACE2 attenuated both high glucose and ANG II–induced oxidative stress and NADPH oxidase activity. CONCLUSIONS Treatment with hrACE2 attenuates diabetic kidney injury in the Akita mouse in association with a reduction in blood pressure and a decrease in NADPH oxidase activity. In vitro studies show that the protective effect of hrACE2 is due to reduction in ANG II and an increase in ANG 1–7 signaling. Footnotes The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Received August 17, 2009. Accepted October 31, 2009. © 2010 by the American Diabetes Association.

Noncommunicable diseases (NCDs) have become the leading contributors to morbidity and mortality worldwide, responsible for 74% of all deaths. The major risk factors that substantially contribute to and significantly increase the risk of dying from NCDs include tobacco and alcohol use, unhealthy diet, and physical inactivity. Proactive prevention strategies are vital in reducing the burden. Presenting at the emergency department (ED) can be an excellent “teachable moment” to intervene for unhealthy behaviors because people seeking medical treatment from doctors at EDs may be more motivated to adopt healthy lifestyles. We aim to examine the effectiveness of a general health promotion intervention based on self-determination theory in helping ED attendees adopt a healthy lifestyle. A randomized clinical trial will be conducted on Chinese adults aged ≥18 years attending the EDs of five major acute care hospitals in Hong Kong. Participants will be randomized 1:1 into intervention and control groups (n = 586 per group). Intervention group will receive a brief telephone intervention using the AWARD (Ask, Warn, Advise, Refer and Do-it-again) model, weekly personalized instant messages and four 1-minute videos focused on the desired behaviors via WeChat/WhatsApp, and follow-up assessments of behavior changes at 3, 6, and 12 months. While control group will receive similar brief intervention which only advises them to adopt a healthy lifestyle, similar number of SMS messages containing only general health advice, and follow-up assessments at same schedule with the intervention group. Outcome measures include the composite event rate of adopting at least one of the four healthy lifestyles at 6 (primary outcome) and 12 months measured by a behavioral risk-factor questionnaire and improvement in health-related quality of life at 6 and 12 months measured by the EuroQoL 5-Dimension 5-level (EQ-5D-5L) questionnaire. Ethical approval has been obtained. This trial is registered at ClinicalTrials.gov on March 17, 2025: NCT06889792.

The novel interleukin (IL)-1 family cytokine IL-33 has been shown to activate T helper 2 (Th2) lymphocytes, mast cells and basophils to produce an array of proinflammatory cytokines, as well as to mediate blood eosinophilia, IgE secretion and hypertrophy of airway epithelium in mice. In the present study, we characterized the activation of human eosinophils by IL-33, and investigated the underlying intracellular signaling mechanisms. IL-33 markedly enhanced eosinophil survival and upregulated cell surface expression of the adhesion molecule intercellular adhesion molecule (ICAM)-1 on eosinophils, but it suppressed that of ICAM-3 and L-selectin. In addition, IL-33 mediates significant release of the proinflammatory cytokine IL-6 and the chemokines CXCL8 and CCL2. We found that IL-33-mediated enhancement of survival, induction of adhesion molecules, and release of cytokines and chemokines were differentially regulated by activation of the nuclear factor (NF)-κB, p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase (ERK) pathways. Furthermore, we compared the above IL-33 activities with two structurally and functionally related cytokines, IL-1β and IL-18. IL-1β, but not IL-18, markedly upregulated cell surface expression of ICAM-1. IL-1β and IL-18 also significantly enhanced eosinophil survival, and induced the release of IL-6 and chemokines CXCL8 and CCL2 via the activation of the NF-κB, p38 MAPK and ERK pathways. Synergistic effects on the release of IL-6 were also observed in combined treatment with IL-1β, IL-18 and IL-33. Taken together, our findings provide insight into IL-33-mediated activation of eosinophils via differential intracellular signaling cascades in the immunopathogenesis of allergic inflammation.

This study aimed to assess the discriminatory ability and calibration performance of the European System for Cardiac Operative Risk Evaluation (EuroSCORE) II, a widely used risk prediction tool, in predicting postoperative mortality among patients undergoing cardiac surgery at Prince of Wales Hospital (PWH) in Hong Kong. Complete data from 4180 patients who underwent cardiac surgery at PWH between 2013 and 2023 were available for validation of EuroSCORE II and comparison of its discriminatory ability with the logistic EuroSCORE. Discriminatory performance was primarily assessed using the area under the receiver operating characteristic curve (AUROC). Calibration was evaluated using the Hosmer-Lemeshow test, coefficient of determination (R2), and normalised root mean square error (NRMSE). EuroSCORE II demonstrated strong discrimination and good calibration for predicting 30-day mortality in the overall cohort (AUROC=0.829; Hosmer-Lemeshow P=0.155) and key subgroups: isolated coronary artery bypass grafting (CABG) [AUROC=0.847; P=0.113], isolated valve surgery (AUROC=0.810; P=0.162), and aortic surgery (AUROC=0.735; P=0.549). More than 85% of the variation in 30-day mortality (R ) was explained across these groups. Compared with the logistic EuroSCORE, EuroSCORE II showed improved discrimination and calibration, with higher AUROC values and lower NRMSE. EuroSCORE II demonstrates strong discriminatory ability and good calibration for predicting 30-day mortality among patients undergoing cardiac surgery and within key subgroups-isolated CABG, isolated valve surgery, and aortic surgery-in this cohort.