Absence of neurotoxicity with perineural injection of ultrasound gels: assessment using an animal model

BACKGROUND: Ultrasound gels may contain propylene glycol and glycerol, which are neurotoxic in high concentrations. If the needle passes through gel during regional anesthesia, gel may be injected near the nerve. It is unknown if this practice poses a risk for neurotoxicity. Using an animal model, we assessed the histological changes of perineural propylene glycol on nerves. We then assessed three commonly used sterile gels for evidence of neurotoxicity. METHODS: Micro-ultrasound guided perineural sciatic nerve injections were performed in mice. Propylene glycol (PG) 2.5%, 10%, 35%, 70% (v/v) or saline was injected. Nerves were assessed after three days for evidence of neurotoxicity. Aquasonic® 100 Ultrasound Gel, K-Y® Lubricating Jelly, and PDI® Lubricating Jelly were also studied against saline controls. RESULTS: Confluent areas of axonal degeneration and intraneural inflammation occurred in 5 of 9 specimens injected with 70% PG. At 35%, 2 of 8 specimens showed patchy changes not present at lower concentrations. No degeneration occurred with Aquasonic® 100 or PDI® Lubricating Jelly. In the K-Y® group, one gel and one saline specimen demonstrated confluent degenerative changes. CONCLUSIONS: Similar to glycerol, 70% PG may cause confluent areas of axon and myelin degeneration with associated intraneural inflammation. The concentration of PG present in ultrasound gels is unlikely to cause neurotoxicity. Aquasonic® 100 and PDI® Lubricating Jelly did not cause neurotoxicity. The results for K-Y® Lubricating Jelly are inconclusive. There is no evidence that passing the needle through the studied gels during regional anesthesia procedures is harmful

Papillary tumour of the pineal region

Papillary tumour of the pineal region (PTRR) is one of the new tumour entities to be included in the latest World Health Organization classification of central nervous system tumours. We report two illustrative patients, a 25-year-old female who presented following a head injury sustained from a fall due to gait disturbances, and a 42-year-old man who presented with headaches. Histology of both cases showed distinct papillary growth patterns with lining of the papillae by multi-layered cuboidal to columnar cells, prominent perivascular rosette and focal true rosette formation. Immunohistochemistry exhibited strong cytokeratin immunoreactivity in addition to CD56, focal S100, glial fibrillary acidic protein and neuron specific enolase positivity which supported a diagnosis of PTPR in both patients. Postoperatively, both patients underwent courses of adjuvant radiation therapy. One patient reported local recurrence of the tumour 23 months after surgery. While PTPR may have been misdiagnosed in the past, clear and consistent characteristics are beginning to be elucidated in the published reports and literature, which have been reviewed. As a relatively new distinct clinicopathological entity, prognostic data are limited and guidelines for treatment protocols are still being investigated in view of its propensity for local recurrence

Factors influencing school connectedness: Chinese adolescents' perspectives

Abstract This study explored the concept of school connectedness and the factors that may influence its development with a sample of Chinese adolescents. Six focus groups involving 52 high school students were conducted using a set of predetermined discussion topics. Results indicated that the students fully understood the notion of school connectedness and could identify a number of key influences affecting its development. These factors could be grouped under several domains including teacher care, peer relations, broader school relationships, school disciplinary policies and practices, activities within the school's guidance and counseling program, and opportunities for talent development. The students were also able to suggest practical strategies that schools might introduce to enhance and strengthen students' acquisition of connectedness to school. The implications from the findings are discussed with particular reference to implementing comprehensive school guidance and counseling program in Hong Kong

Enactment of apology legislation in Hong Kong: Report and second round consultation

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Integrated genomic and transcriptomic analysis of human brain metastases identifies recurrently altered pathways of potential clinical significance

Treatment options for patients with brain metastases (BMs) have limited efficacy and the mortality rate is virtually 100%. Targeted therapy is critically under-utilized, and our understanding of mechanisms underpinning metastatic outgrowth in the brain is limited. To address these deficiencies, we investigated the genomic and transcriptomic landscapes of 36 BMs from breast, lung, melanoma and oesophageal cancers, using DNA copy-number analysis and exome- and RNA-sequencing. The key findings were as follows. (a) Identification of novel candidates with possible roles in BM development, including the significantly mutated genes DSC2, ST7, PIK3R1 and SMC5, and the DNA repair, ERBB-HER signalling, axon guidance and protein kinase-A signalling pathways. (b) Mutational signature analysis was applied to successfully identify the primary cancer type for two BMs with unknown origins. (c) Actionable genomic alterations were identified in 31/36 BMs (86%); in one case we retrospectively identified ERBB2 amplification representing apparent HER2 status conversion, then confirmed progressive enrichment for HER2-positivity across four consecutive metastatic deposits by IHC and SISH, resulting in the deployment of HER2-targeted therapy for the patient. (d) In the ERBB/HER pathway, ERBB2 expression correlated with ERBB3 (r = 0.496; p < 0.0001) and HER3 and HER4 were frequently activated in an independent cohort of 167 archival BM from seven primary cancer types: 57.6% and 52.6% of cases were phospho-HER3 or phospho-HER4 membrane-positive, respectively. The HER3 ligands NRG1/2 were barely detectable by RNAseq, with NRG1 (8p12) genomic loss in 63.6% breast cancer-BMs, suggesting a microenvironmental source of ligand. In summary, this is the first study to characterize the genomic landscapes of BM. The data revealed novel candidates, potential clinical applications for genomic profiling of resectable BMs, and highlighted the possibility of therapeutically targeting HER3, which is broadly over-expressed and activated in BMs, independent of primary site and systemic therapy

Characterising frailty, metrics of continuous glucose monitoring, and mortality hazards in older adults with type 2 diabetes on insulin therapy (HARE):a prospective, observational cohort study

Summary Background: To our knowledge, no previous study has examined the inter-relationship between frailty, dysglycaemia, and mortality in frail older adults with type 2 diabetes who are on insulin therapy. We used continuous glucose monitors (CGMs) to profile this patient population and determine the prognostic value of CGM metrics. We hypothesised that incremental frailty was associated with increased hypoglycaemia or time below range (TBR). Methods: HARE was a multicentre, prospective, observational cohort study with mortality hazard analysis carried out in four hospitals in Hong Kong. Eligible participants were community-living adults aged 70 years and older; had had type 2 diabetes for 5 years or more; were on insulin therapy; were frail; and were not hospitalised at the time of frailty assessment and CGM recording. Glucose control was characterised according to the Advanced Technologies and Treatments for Diabetes 2019 international consensus clinical targets. Frailty index was computed, and comprehensive frailty assessments and targeted serum metabolic profiling were performed. The Jonckheere-Terpstra test for trend was used to analyse frailty index tertiles and variables. Inter-relationships between CGM metrics and frailty, glycated haemoglobin A1c (HbA1c), and serum albumin were characterised using adjusted regression models. Survival analysis and Cox proportional hazard modelling were performed. Findings: Between July 25, 2018, and Sept 27, 2019, 225 participants were recruited, 222 of whom had CGMs fitted and 215 of whom had analysable CGM data (190 were frail, 25 were not frail). Incremental frailty was associated with older age, greater HbA1c, worse renal function, and history of stroke. Eight of 11 CGM metrics were significantly associated with frailty. Decreased time in range (TIR; glucose concentration 3·9–10·0 mmol/L) and increased time above range (TAR) metrics were strongly correlated with increased frailty and hyperglycaemia, whereas TBR metrics were marginally or not different between frailty levels. Glucose-lowering agents did not significantly affect regression estimates. In patients with HbA1c of 7·5% or more, reduced serum albumin was associated with level 2 TAR (glucose concentration &gt;13·9 mmol/L) and dysglycaemia. During a median follow-up of 28·0 months (IQR 25·3–30·4), increased level 2 TAR was predictive of mortality explainable by frailty in the absence of detectable interaction. Each 1% increment of level 2 TAR was associated with 1·9% increase in mortality hazard. Interpretation: In older adults with type 2 diabetes who are on insulin therapy, incremental frailty was associated with increased dysglycaemia and hyperglycaemia rather than hypoglycaemia. Mortality hazard was increased with severe hyperglycaemia. Future clinical studies and trials targeting actionable CGM metrics highlighted in this study could translate into improved care and outcomes. Funding: Health and Medical Research Fund, Food and Health Bureau, The Government of the Hong Kong Special Administrative Region of China