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Background Ganciclovir (GCV) is widely used in solid organ and haematopoietic stem cell transplant patients for prophylaxis and treatment of cytomegalovirus. It has long been considered a mutagen and carcinogen. However, the contribution of GCV to cancer incidence and other factors that influence its mutagenicity remains unknown. Methods This retrospective cohort study analysed genomics data for 121,771 patients who had undergone targeted sequencing compiled by the Genomics Evidence Neoplasia Information Exchange (GENIE) or Foundation Medicine (FM). A statistical approach was developed to identify patients with GCV-associated mutational signature (GCV sig ) from targeted sequenced data of tumour samples. Cell line exposure models were further used to quantify mutation burden and DNA damage caused by GCV and other antiviral and immunosuppressive drugs. Results Mutational profiles from 22 of 121,771 patient samples in the GENIE and FM cohorts showed evidence of GCV sig . A diverse range of cancers was represented. All patients with detailed clinical history available had previously undergone solid organ transplantation and received GCV and mycophenolate treatment. RAS hotspot mutations associated with GCV sig were present in 9 of the 22 samples, with all samples harbouring multiple GCV-associated protein-altering mutations in cancer driver genes. In vitro testing in cell lines showed that elevated DNA damage response and GCV sig are uniquely associated with GCV but not acyclovir, a structurally similar antiviral. Combination treatment of GCV with the immunosuppressant, mycophenolate mofetil (MMF), increased the misincorporation of GCV in genomic DNA and mutations attributed to GCV sig in cell lines and organoids. Conclusions In summary, GCV can cause a diverse range of cancers. Its mutagenicity may be potentiated by other therapies, such as mycophenolate, commonly co-prescribed with GCV for post-transplant patients. Further investigation of the optimal use of these drugs could help reduce GCV-associated mutagenesis in post-transplant patients.

Background: Detection of measurable residual disease (MRD) is becoming the standard of care in the prognostication of acute myeloid leukaemia post-chemotherapy, but its role in early post-haematopoietic stem cell transplantation (HSCT) is less defined. Objectives: This study aims to examine the role of MRD detection by molecular tools in early post-HSCT settings and its significance in prognostication among other clinicopathologic factors. Design: It is a retrospective cohort study. Methods: We examined MRD early post-HSCT (median: 26 days) in patients receiving allogeneic HSCT at complete remission by droplet digital PCR or next-generation sequencing targeting leukaemia-associated mutations. The effect of MRD positivity and other clinicopathologic variables on post-HSCT leukaemia-free survival (LFS), overall survival (OS) and cumulative incidence of relapse (CIR) were investigated. Results: One hundred fifty-nine patients were included, and the median follow-up time was 6 years. Early post-HSCT MRD positivity was observed in 36% patients and was associated with higher CIR (37.1% vs 13.2% at third year, p = 0.0005), inferior LFS (median: 3.8 years vs not reached, p = 0.002) and OS (median: 10.6 years vs not reached, p = 0.019). It was the only significant factor associated with inferior post-HSCT LFS, CIR and OS in both univariate and multivariate analyses. Conclusion: This study demonstrated that early MRD positivity was predictive of a higher risk of relapse, and inferior LFS and OS post-HSCT. This information laid the foundation for designing MRD-guided strategies early post-HSCT to prevent haematological relapse.

Merging neutron stars offer an excellent laboratory for simultaneously studying strong-field gravity and matter in extreme environments. We establish the physical association of an electromagnetic counterpart (EM170817) with gravitational waves (GW170817) detected from merging neutron stars. By synthesizing a panchromatic data set, we demonstrate that merging neutron stars are a long-sought production site forging heavy elements by r-process nucleosynthesis. The weak gamma rays seen in EM170817 are dissimilar to classical short gamma-ray bursts with ultrarelativistic jets. Instead, we suggest that breakout of a wide-angle, mildly relativistic cocoon engulfing the jet explains the low-luminosity gamma rays, the high-luminosity ultraviolet-optical-infrared, and the delayed radio and x-ray emission. We posit that all neutron star mergers may lead to a wide-angle cocoon breakout, sometimes accompanied by a successful jet and sometimes by a choked jet.

We aimed to determine the effect of semaglutide on patients with acute large vessel occlusion (LVO) receiving endovascular therapy (EVT). In this phase 2, investigator-initiated, multicenter, prospective, randomized, open-label, blinded endpoint trial conducted in China, we recruited patients with disabling LVO undergoing EVT. Patients were randomized to semaglutide therapy (0.5 mg subcutaneous semaglutide before and 1 week after EVT) or standard therapy. The primary outcome was defined as favorable neurological recovery (modified Rankin Scale 0–2 at 90 days). Between August 2023 and July 2024, 140 patients were randomized to semaglutide ( n  = 69) or standard therapy ( n  = 71). The primary outcome occurred in 39 (56.5%) in the semaglutide group and 39 (54.9%) in the standard therapy group (adjusted RR 1.05, 95% CI 0.95–1.15, p  = 0.37). We observed treatment effect modification by intravenous thrombolysis (IVT) on semaglutide therapy ( p interaction = 0.02); thus we performed the following exploratory analyses: The primary outcome occurred in 22 (64.7%) in the semaglutide group and 15 (44.1%) in the standard therapy group (adjusted RR 1.18, 95% CI 1.02–1.36) in the no-IVT stratum ( n  = 68). The primary outcome was similar between two groups in the IVT-stratum. No severe adverse event was attributed to semaglutide treatment. This phase 2 trial suggested semaglutide was safe in patients with LVO and was associated with an improved neurological outcome in patients not receiving IVT. These preliminary observations should be confirmed in a phase 3 randomized trial (ClinicalTrials.gov Identifier: NCT05920889). Semaglutide, a GLP-1 receptor agonist, may offer neuroprotective benefits after stroke, but its effects in large vessel occlusion (LVO) are unknown. Here the authors show, in a phase 2 randomized trial, that semaglutide is safe after endovascular therapy and may improve recovery in patients not receiving intravenous thrombolysis.

Nirmatrelvir-ritonavir (NMV-r) and molnupiravir (MOL) were developed as out-patient anti-viral for mild COVID-19. There was limited data on their role in treating COVID-19 for hospitalized patients, especially among adult patients who are unvaccinated and had chronic respiratory diseases. A territory-wide retrospective study was conducted in Hong Kong to compare the efficacy of NMV-r and MOL against COVID-19 in unvaccinated adult patients with asthma, chronic obstructive pulmonary disease, bronchiectasis and interstitial lung diseases presenting with moderate COVID-19 from 16th February 2022 to 15th March 2023. A total of 1354 patients were included, 738 received NMV-r and 616 received MOL. NMV-r was more effective in reducing 90-day mortality with adjusted hazard ratios (aHR) of 0.508 (95% confidence interval [CI] = 0.314-0.822, p = 0.006). Patients who received NMV-r also had significantly shorter length of stay (LOS) than those receiving MOL, with median LOS of 4 (Interquartile range [IQR] = 2-7) for NMV-r and 6 (IQR = 3-10) for MOL (p-value < 0.001). There was no statistically significant difference in the development of respiratory failure and severe respiratory failure in the two groups. NMV-r was more effective than MOL among unvaccinated adults with chronic respiratory diseases who were hospitalized for moderate COVID-19 without hypoxaemia on admission.

Cardiovascular disease (CVD) is a major contributor to the global burden of disease. Berberine, a long-standing, widely used, traditional Chinese medicine, is thought to have beneficial effects on CVD risk factors and in women with polycystic ovary syndrome. The mechanisms and effects, specifically in men, possibly via testosterone, have not been examined previously. To assess the effect of berberine on CVD risk factors and any potential pathway via testosterone in men, we conducted a randomized, double-blind, placebo-controlled, parallel trial in Hong Kong. In total, 84 eligible Chinese men with hyperlipidemia were randomized to berberine (500 mg orally, twice a day) or placebo for 12 weeks. CVD risk factors (lipids, thromboxane A2, blood pressure, body mass index and waist–hip ratio) and testosterone were assessed at baseline, and 8 and 12 weeks after intervention. We compared changes in CVD risk factors and testosterone after 12 weeks of intervention using analysis of variance, and after 8 and 12 weeks using generalized estimating equations (GEE). Of the 84 men randomized, 80 men completed the trial. Men randomized to berberine had larger reductions in total cholesterol (−0.39 mmol/L, 95% confidence interval (CI) −0.70 to −0.08) and high-density lipoprotein cholesterol (−0.07 mmol/L, 95% CI −0.13 to −0.01) after 12 weeks. Considering changes after 8 and 12 weeks together, berberine lowered total cholesterol and possibly low-density lipoprotein-cholesterol (LDL-c), and possibly increased testosterone. Changes in triglycerides, thromboxane A2, blood pressure, body mass index and waist–hip ratio after the intervention did not differ between the berberine and placebo groups. No serious adverse event was reported. Berberine is a promising treatment for lowering cholesterol. Berberine did not lower testosterone but instead may increase testosterone in men, suggesting sex-specific effects of berberine. Exploring other pathways and assessing sex differences would be worthwhile, with relevance to drug repositioning and healthcare.

We report the use of a pericapsular nerve group (PENG) cryoneurolysis for longer-term analgesia in a patient with a hip fracture and severe medical comorbidities as an alternative to hip fracture surgery. A frail but lucid and fully autonomous 97-yr-old female from an assisted living facility sustained a subcapital fracture of her right proximal femur following a ground level fall. She had significant comorbidities including end-stage respiratory disease. An attempt was made to proceed with a hemiarthroplasty; however, following a spinal anesthetic with 2 mL of 0.5% isobaric bupivacaine, she suffered significant respiratory compromise resulting in abortion of the surgical procedure. A multidisciplinary shared decision was made for palliative nonoperative management (P-NOM), and PENG cryoneurolysis was successfully performed. This significantly reduced the patient's pain on movement, which greatly enhanced and facilitated nursing care for the patient. She no longer required any opioid analgesia for the remainer of her stay, and residual pain was managed with regular acetaminophen. She was able to get up to standing with the help of the physiotherapist or nursing staff, who commented favourably on her improvement after cryoneurolysis. She continued to do well and was discharged to an assisted living facility seven days later. Our case report shows that PENG cryoneurolysis can be used as an option for P-NOM in hip fracture surgery to provide significant and durable pain relief for those patients who may not be suitable for anesthesia and surgery.

•A total of 977 hair samples from a population of ketamine users in Hong Kong were investigated.•Ketamine and its metabolite norketamine in hair were analyzed by LC–MS/MS method.•The cut-off value for ketamine in hair was proposed to be 400pg/mg. Ketamine is one of the most frequent abused drugs in Hong Kong and South-East Asia, and the cases of ketamine abused have been reported worldwide. Hair has been commonly used as a specimen for the proof of chronic drug abused because of its non-invasiveness and long detection windows. The determinations of ketamine in hair with varieties of state-of-the-art instruments and detection methods have been developed in the past decade; however, the cut-off value for ketamine abuser has not been developed according to the international guidelines. The aim of this study is to propose a cut-off value for ketamine in hair by analyzing ketamine and its metabolite norketamine by LC–MS/MS method in a population of ketamine users in Hong Kong. The limit of detection (LOD) and limit of quantification (LOQ) for ketamine and norketamine were 20pg/mg and 100pg/mg, respectively. From 977 ketamine abusers, the cut-off value for ketamine in hair was proposed to be 400pg/mg of hair. This proposed cut-off value is the concentration of hair ketamine when over 90% of samples are being detected with the presence of norketamine, which is a proof of ketamine abuse. This value could be applied as a screening or occupational cut-off for reference.

Evidence supports the effectiveness of serious games in health education, but little is known about their effects on the psychosocial well-being of children in the general population. This study aimed to investigate the potential of a mobile game-based safety education program in improving children's safety and psychosocial outcomes. Safe City is a mobile roleplaying game specifically designed to educate children in Hong Kong about safety. This randomized controlled trial included 340 children in grades 4 through 6. Intervention arm participants (n=170) were instructed to play the Safe City mobile game for 4 weeks, whereas control arm participants (n=170) received a safety booklet. All participants completed a survey on safety knowledge and behaviors and psychosocial problems at baseline (T1), 1 month postintervention (T2), and 3 months postintervention (T3). Cumulative game scores and mini-game performance were analyzed as a proxy for the extent of exposure to the game. Outcome data were analyzed using 2-sample 2-tailed t tests to compare mean change from T1 to T2 and to T3 for intervention versus control arm participants. The association of game use with outcome changes postintervention was analyzed using generalized additive models. No significant differences were found in mean changes between the intervention and control arms. However, use analyses showed that higher game scores were associated with improvements in safe behavior (P=.03) and internalizing problems (P=.01) at T3. Matching and Spot the Danger mini-game performance significantly predicted improvements in safety knowledge at T2 and T3. Analysis of use has shown that playing the Safe City mobile game can result in significant improvements in safety knowledge and reductions in unsafe behavior and internalizing problems. These findings provide evidence for the positive impact of serious games on psychological and social well-being, highlighting the potential of technology-driven interventions to assist children in learning about safety and preventing injuries. ClinicalTrials.org NCT04096196; https://clinicaltrials.gov/show/NCT04096196. RR2-10.2196/17756.

The number of teaching assistants (TAs) working in mainstream schools has soared in recent years as students with special educational needs (SEN) are integrated into regular classrooms. However, research on TAs is rare. This study investigated whether and how work engagement mediates the relationship between self-efficacy and job satisfaction among 292 Chinese TAs working in Hong Kong mainstream schools. Survey data were analyzed using partial least squares structural equation modeling (PLS-SEM). Supported by the social cognitive theory of self-efficacy and self-determination theory of work engagement, our results showed that TAs’ self-efficacy is positively related to their job satisfaction through the mediation of work engagement. Implications for an appropriate focus on enhancing TAs’ self-efficacy through classroom experiences and training courses are discussed.