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Eric LK Chan,1 Chengfei Zhang,2 Gary SP Cheung2 1Department of Health, Government of Hong Kong SAR, Hong Kong, Special Administrative Region; 2Comprehensive Dental Care (Endodontics), Faculty of Dentistry, University of Hong Kong, Hong Kong Special Administrative Region of the People's Republic of China Purpose: The aim of this study was to evaluate the cytotoxic effect of a novel nano-silver particle (25.2±6.5 nm) endodontic irrigant (0.2 mM) and compare it with 3% sodium hypochlorite. Materials and methods: Two cell types, mouse fibroblast National Institutes of Health 3T3 (NIH 3T3) and primary human periodontal ligament stem cell (hPDLSCs) were used in a test for the effect of direct and indirect (by separating the agent and cell with a layer of agar) exposure to the two solutions. In the direct exposure experiment, ten groups of cell cultures were exposed to one dilution (3:1, 2:1, 1:1, 1:2, 1:3, 1:4, 1:5, 1:6 or 1:7) of a nano-silver irrigant for 48 hours; the concentration-response function was estimated by determining the number of viable cells in each group by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The 50% lethal dose of the testing irrigant for NIH3T3 and hPDLSCs were estimated. In the second part of the experiment, a modified agar overlaying technique was applied. Twelve culture wells (6-well plate) were divided into three groups (n=4). The cell lysis zone (cytotoxic range) created by the stock nano-silver solution, 3% sodium hypochlorite, and an isotonic phosphate buffering saline (control) was measured by two double blinded observers (Kappa score =100%). The cytotoxic score of specific irrigant was derived by modified Sjögren's method. Results: The 50% lethal doses of the testing nano silver irrigant for NIH 3T3 and hPDLSCs after 48 hours of direct exposure were 0.58 and 0.608 dilution of stock solution, respectively.The cytotoxic scores of nano-silver irrigant and control (phosphate buffered saline) on NIH 3T3 were 0.25 (95% confidence interval [CI] =0 to 1.04) and 0 (95% CI =0 to 0); and on hPDLSCs were 0.13 (95% CI =0 to 0.52) and 0.25 (95% CI =0 to 1.04), respectively. Toxicity of the test and control group on both mouse fibroblasts (P>0.05) and hPDLSCs (P=1.00) was not statistically different. Conclusion: Our results showed that the nano-silver irrigant was non-cytotoxic to both NIH 3T3 and hPDLSCs. Keywords: root canal irrigant, biocompatibility, hPDLSC, agar overlay, MTT

Background: Physical rehabilitation of critically ill patients may improve physical outcomes; however, the relative benefits and risks with patients requiring vasoactive drugs is currently unknown. A feasibility study is needed to inform the design of a future trial required to address this issue., Methods: A two-phase exploratory observational feasibility study was carried out: A retrospective study to clarify the current practice of rehabilitation with patients receiving vasoactive drugs to inform future trial interventions and design.A prospective study exploring recruitment and outcome measurement. Intensive care patients receiving vasoactive drugs were recruited and asked about the acceptability of a future trial. The feasibility of using an adverse event tool was measured during rehabilitation. Patients were followed up after 60 days to describe the feasibility of measuring outcomes for a future trial., Results: Retrospective study (n = 78): Twenty-one percent of patients took part in physical rehabilitation whilst receiving vasoactive drugs. Of 321 days with vasoactive drugs administered, physical rehabilitation occurred on 27 days (8%). Prospective study (n = 40): Eighty-one percent of participants indicated acceptability of being recruited into a future trial (n = 37). Eighty-eight percent of clinicians found it acceptable to randomise patients into either early rehabilitation or standard care. The adverse event tool was implemented by researchers with 2% loss of information. Finally, a 100% follow-up rate at day 60 was achieved for mortality outcomes. Follow-up rates were 70% for the EQ-5D (5 level), 65% for the World Health Organisation's Disability Assessment Schedule 2.0 and RAND 36-item Health Survey 1.0 and 26% for the 6-minute walk test., Conclusions: This study found a low frequency of physical rehabilitation occurring with intensive care patients receiving vasoactive drugs. A high proportion of clinicians and patients found a future RCT within this patient group acceptable. Mortality and patient-reported outcomes were the most feasible to measure., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: HRW reports personal lecture fees from Brunel University and the University of East London., (Copyright: © 2025 Woodbridge et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Head-and-neck cancer (HNC) can present with life.threatening symptoms in the emergency department. Patients can sometimes be misdiagnosed with pulmonary disease due to similar signs and symptoms, ultimately leading to delayed diagnosis and potentially devastating consequences. Reasons for this include lack of awareness of patient risk factors and knowledge of the myriad of presenting complaints in the disease process among physicians working in primary care and in the emergency department. This article explores the contemporary risk factors and common presenting symptoms and discusses initial management for a patient with potential head-and-neck malignancy. Emergency presentations of HNC are wide ranging and can overlap with common respiratory pathologies. Clinician awareness of this can assist the team in deciding what appropriate examination and investigations are required to reduce the risk of delaying diagnosis and further treatment., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Emergencies, Trauma, and Shock.)

Purpose: The combination of talimogene laherparepvec (T-VEC) and pembrolizumab previously demonstrated an acceptable safety profile and an encouraging complete response rate (CRR) in patients with advanced melanoma in a phase Ib study. We report the efficacy and safety from a phase III, randomized, double-blind, multicenter, international study of T-VEC plus pembrolizumab (T-VEC-pembrolizumab) versus placebo plus pembrolizumab (placebo-pembrolizumab) in patients with advanced melanoma., Methods: Patients with stage IIIB-IVM1c unresectable melanoma, naïve to antiprogrammed cell death protein-1, were randomly assigned 1:1 to T-VEC-pembrolizumab or placebo-pembrolizumab. T-VEC was administered at ≤ 4 × 10 6 plaque-forming unit (PFU) followed by ≤ 4 × 10 8 PFU 3 weeks later and once every 2 weeks until dose 5 and once every 3 weeks thereafter. Pembrolizumab was administered intravenously 200 mg once every 3 weeks. The dual primary end points were progression-free survival (PFS) per modified RECIST 1.1 by blinded independent central review and overall survival (OS). Secondary end points included objective response rate per mRECIST, CRR, and safety. Here, we report the primary analysis for PFS, the second preplanned interim analysis for OS, and the final analysis., Results: Overall, 692 patients were randomly assigned (346 T-VEC-pembrolizumab and 346 placebo-pembrolizumab). T-VEC-pembrolizumab did not significantly improve PFS (hazard ratio, 0.86; 95% CI, 0.71 to 1.04; P = .13) or OS (hazard ratio, 0.96; 95% CI, 0.76 to 1.22; P = .74) compared with placebo-pembrolizumab. The objective response rate was 48.6% for T-VEC-pembrolizumab (CRR 17.9%) and 41.3% for placebo-pembrolizumab (CRR 11.6%); the durable response rate was 42.2% and 34.1% for the arms, respectively. Grade ≥ 3 treatment-related adverse events occurred in 20.7% of patients in the T-VEC-pembrolizumab arm and in 19.5% of patients in the placebo-pembrolizumab arm., Conclusion: T-VEC-pembrolizumab did not significantly improve PFS or OS compared with placebo-pembrolizumab. Safety results of the T-VEC-pembrolizumab combination were consistent with the safety profiles of each agent alone.

Transforming growth factor-β (TGF-β) signaling is an important pathway for promoting the pathogenesis of inflammatory diseases, including cancer. The roles of TGF-β signaling are heterogeneous and versatile in cancer development and progression, both anticancer and protumoral actions are reported. Interestingly, increasing evidence suggests that TGF-β enhances disease progression and drug resistance via immune-modulatory actions in the tumor microenvironment (TME) of solid tumors. A better understanding of its regulatory mechanisms in the TME at the molecular level can facilitate the development of precision medicine to block the protumoral actions of TGF-β in the TME. Here, the latest information about the regulatory mechanisms and translational research of TGF-β signaling in the TME for therapeutic development had been summarized., Competing Interests: The authors declare that they have no conflicts of interest., (© The Author(s) 2023.)

Blunt chest trauma is a rare cause of acute coronary syndrome and can be masked by other injuries in polytrauma patients. It can have devastating consequences due to damage to the myocardial tissue if left un-recognized. Myocardial injury can result in life-threatening arrhythmias and complications such as systolic and diastolic dysfunction. This can significantly affect patients' quality of life. A 34-year-old man involved in a paragliding incident in Kazakhstan. His equipment failed at 30 meters height and result him to be propelled at high velocity to the ground. He sustained multiple injuries including spinal fractures, lung contusions and a mediastinal haematoma. He was transported to a local hospital and noted to have ST segment elevation on his admission electrocardiogram (ECG). He underwent an angiogram that showed sub-occlusion of his left anterior descending (LAD) artery. This resulted in a time-critical Percutaneous Coronary Intervention (PCI). He was stabilized and repatriated to the UK to manage of remaining injuries., Competing Interests: None declared.

The winter 2018/19 influenza season in Hong Kong has been predominated by influenza A(H1N1)pdm09 as at January 2019. We enrolled 2,016 children in three public hospitals in Hong Kong between 2 September 2018 and 11 January 2019. Using the test-negative approach, we estimated high early season effectiveness of inactivated influenza vaccine against influenza A or B of 90% (95% confidence interval (CI): 80-95%) and 92% (95% CI: 82-96%) against influenza A(H1N1)pdm09.

Tyrosine kinase inhibitors are effective treatments for cancers. Knowing the specific kinase mutants that drive the underlying cancers predict therapeutic response to these inhibitors. Thus, the current protocol for personalized cancer therapy involves genotyping tumors in search of various driver mutations and subsequently individualizing the tyrosine kinase inhibitor to the patients whose tumors express the corresponding driver mutant. While this approach works when known driver mutations are found, its limitation is the dependence on driver mutations as predictors for response. To complement the genotype approach, we hypothesize that a phosphoarray platform is equally capable of personalizing kinase inhibitor therapy. We selected head and neck squamous cell carcinoma as the cancer model to test our hypothesis. Using the receptor tyrosine kinase phosphoarray, we identified the phosphorylation profiles of 49 different tyrosine kinase receptors in five different head and neck cancer cell lines. Based on these results, we tested the cell line response to the corresponding kinase inhibitor therapy. We found that this phosphoarray accurately informed the kinase inhibitor response profile of the cell lines. Next, we determined the phosphorylation profiles of 39 head and neck cancer patient derived xenografts. We found that absent phosphorylated EGFR signal predicted primary resistance to cetuximab treatment in the xenografts without phosphorylated ErbB2. Meanwhile, absent ErbB2 signaling in the xenografts with phosphorylated EGFR is associated with a higher likelihood of response to cetuximab. In summary, the phosphoarray technology has the potential to become a new diagnostic platform for personalized cancer therapy., (© 2017 UICC.)

In this work, Direct Numerical Simulations (DNS) of a pendular liquid bridge formed between two relatively moving particles are performed to evaluate the normal component of the viscous force exerted on the particles. The viscous force obtained are non-dimensionalised in order to clarify the parameters which can affect the dimensionless force. The DNS results are compared with the viscous force models in literature which are commonly used in DEM simulations. It is found that these models cannot be used with large inter-particle separation distance. A new and more accurate viscous force model is proposed from the DNS results which can be directly implemented in the DEM framework., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: New information about antiepileptic drugs has arisen since the publication of the Hong Kong Epilepsy Guideline in 2009. This article set out to fill the knowledge gap between 2007 and 2016 on the use of antiepileptic drugs in Hong Kong., Participants: Between May 2014 and April 2016, four consensus meetings were held in Hong Kong, where a group comprising 15 professionals (neurologists, paediatricians, neurosurgeons, radiologists, and clinical psychologists) from both public and private sectors aimed to review the best available evidence and update all practising physicians on a range of clinical issues including drug-related matters. All participants were council members of The Hong Kong Epilepsy Society., Evidence: A literature review of the clinical use of antiepileptic drugs as monotherapy suggested Level A evidence for levetiracetam and Level B evidence for lacosamide. No change in the level of evidence was found for oxcarbazepine (Level A evidence) or pregabalin (undesignated), and no evidence was found for perampanel. A literature review on the clinical use of antiepileptic drugs as adjunctive therapy suggested Level A evidence for both lacosamide and perampanel. No change to the level of evidence was found for levetiracetam (Level A evidence), oxcarbazepine (Level A evidence), or pregabalin (Level A evidence). A literature search on the use of generic antiepileptic drugs suggested Level A evidence for the use of lamotrigine in generic substitution., Consensus Process: Three lead authors of the Subcommittee drafted the manuscript that consisted of two parts-part A: evidence on new antiepileptic drugs, and part B: generic drugs. The recommendations on monotherapy/adjunctive therapy were presented during the meetings. The pros and cons for our health care system of generic substitution were discussed. The recommendations represent the 'general consensus' of the participants in keeping with the evidence found in the literature., Conclusions: Recommendations for the use of levetiracetam, lacosamide, oxcarbazepine, pregabalin, and perampanel were made. The consensus statements may provide a reference to physicians in their daily practice. Controversy exists over the use of generic products among patients who are currently taking brand medications. In this regard, approvals from prescriber and patient are pivotal. Good communication between doctors and patients is essential, as well as enlisting the assistance of doctors, nurses, and pharmacists, therapeutic blood monitoring if available, and the option of brand antiepileptic drug as a self-financed item. The physical appearance of generic drugs should be considered as it may hamper drug compliance. Support from medical services is recommended. In the longer term, the benefit of flexibility and the options to have a balance between the generic and brand drug market may need to be addressed by institutions and regulatory bodies.

From 1 September 2015 through 31 January 2016, we enrolled 2068 children 6 months to 17 years of age admitted to hospital with a febrile acute respiratory infection in our test-negative study. Information on receipt of 2015-16 northern hemisphere inactivated influenza vaccination was elicited from parents or legal guardians. Using conditional logistic regression adjusting for age and matching on calendar time, we estimated influenza vaccine effectiveness against hospitalization with influenza A or B to be 79.2% (95% confidence interval: 42.0%-92.4%). Annual influenza vaccination should be more widely used in children in Hong Kong., (© 2016 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.)

Objective: To examine the effect of acceleration and deceleration distance (0, 1, 2 and 3 m) on the comfortable and maximum walking speeds in: (i) the 5-m walk test (5mWT); and (ii) the 10-m walk test (10mWT) in people with chronic stroke., Design: Cross-sectional study., Setting: University-based rehabilitation centre., Subjects: Thirty individuals with chronic stroke., Methods: Timed walking at comfortable and maximum walking speeds in the 5mWT and 10mWT with different acceleration and deceleration distances (0, 1, 2 and 3 m)., Results: The comfortable walking speed in the 5mWT with 0 m acceleration and deceleration distance was significantly slower than that with 1, 2 or 3 m acceleration and deceleration distances (p < 0.0083), but there was no significant difference among 1, 2 and 3 m acceleration and deceleration distances. No significant difference was found in the maximum walking speed in the 5mWT, or in the comfortable and maximum walking speeds of the 10mWT., Conclusion: Adoption of 1 m acceleration and deceleration distance is recommended when measuring the comfortable walking speed in the 5mWT in people with stroke. Neither acceleration nor deceleration distance is needed when measuring the maximum walking speed in the 5mWT, the comfortable walking speed or the maximum walking speed in the 10mWT.

Unlabelled: EGFR is a popular therapeutic target for many cancers. EGFR inhibitors have been tested in children with refractory neuroblastoma. Interestingly, partial response or stable disease was observed in a few neuroblastoma patients. As EGFR mutations are biomarkers for response to anti-EGFR drugs, primary neuroblastoma tumors and cell lines were screened for mutations. A novel EGFR extracellular domain deletion mutant, EGFRΔ768, was discovered and the biologic and biochemical properties of this mutant were characterized and compared with wild-type and EGFRvIII receptors. EGFRΔ768 was found to be constitutively active and localized to the cell surface. Its expression conferred resistance to etoposide and drove proliferation as well as invasion of cancer cells. While EGFRΔ768 had similarity to EGFRvIII, its biologic and biochemical properties were distinctly different from both the EGFRvIII and wild-type receptors. Even though erlotinib inhibited EGFRΔ768, its effect on the mutant was not as strong as that on wild-type EGFR and EGFRvIII. In addition, downstream signaling of EGFRΔ768 was different from that of the wild-type receptor. In conclusion, this is the first study to demonstrate that neuroblastoma express not only EGFRvIII, but also a novel EGFR extracellular domain deletion mutant, EGFRΔ768. The EGFRΔ768 also possesses distinct biologic and biochemical properties which might have therapeutic implications for neuroblastoma as well as other tumors expressing this novel mutant., Implications: Neuroblastoma expressed a novel EGFR mutant which possesses distinct biologic and biochemical properties that might have therapeutic implications. Mol Cancer Res; 14(8); 740-52. ©2016 AACR., (©2016 American Association for Cancer Research.)

Background: We estimated vaccine effectiveness (VE) against pediatric influenza B hospitalizations in Hong Kong year round between November 2001 and October 2014., Methods: We conducted a test-negative year-round study, enrolling children 6 months to 17 years of age admitted to two hospitals in Hong Kong with a febrile acute respiratory infection. Children were tested for influenza A and B. Conditional logistic regression was used to estimate overall and lineage-specific vaccine effectiveness comparing influenza vaccination history of the trivalent influenza vaccine (TIV) among patients testing positive for influenza B versus negative for influenza A and B, adjusting for age and sex and matching by calendar week of recruitment., Results: Of the 6013 children included in the analysis, 262 tested positive for influenza B. Vaccination coverage was low: 6.5% in the influenza B positive children when compared with 8.8% in children who tested negative for both influenza A and B (p=0.248). Overall, VE was 47.6% (95% CI: 10.0, 69.4%) against influenza B hospitalization despite variable co-circulation of both lineages in all years. VE for Victoria-like virus calculated from 3 years when the vaccine was lineage-matched was 59.1% (95% CI: 6.2, 82.2%). Lineage-matched VE for Yamagata-like virus was -8.8% (95% CI: -215.4, 62.5%) in a clade mismatch season. With wide confidence intervals, we were unable to demonstrate cross-lineage protection: VE against the mismatched B/Yamagata-like virus was 9.5% (95% CI: -240.4, 76.0%) in 2011/12 and against mismatched B/Victoria-like virus in 2013/14 was 42.7% (95% CI: -368.6, 93.0%)., Conclusions: TIV conferred an overall VE of 47.6% (95% CI: 10.0, 69.4%) against influenza B hospitalization in children despite variable co-circulation of both lineages in all years. Lineage-matched VE for Yamagata-like virus was poor and may be related to clade mismatch. Cross-lineage protection was not observed., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objectives: We sought to document the incidence of pediatric hospitalization for bacterial pneumonia before universal childhood conjugate pneumococcal vaccination using two different methods of diagnosis., Methods: By following the World Health Organization (WHO) chest radiography (CXR) protocol, two radiologists independently read the CXRs of a cohort of systematically recruited children younger than 5 years. The children had acute respiratory infections and were admitted to one of two hospitals that care for 72.5% of all pediatric admissions on Hong Kong Island. Medical records were reviewed for clinical manifestation and to identify bacterial pneumonia diagnosed by pediatricians., Results: In children younger than 5 years, the incidences of bacterial pneumonia, as diagnosed by pediatricians and by the WHO CXR standard, were 775.7 per 100,000 population [95% confidence interval (CI, 591.8-998.3)] and 439.5 per 100,000 population (95% CI, 304.6-614.5), respectively. The study period was from 2002 to 2004., Conclusion: This study provided a reliable baseline estimate of the hospitalization burden of pneumococcal pneumonia in Hong Kong children before the advent of universal conjugate pneumococcal vaccination., (Copyright © 2014. Published by Elsevier B.V.)

We investigated differences in outcomes between 68 children hospitalized with macrolide-sensitive Mycoplasma pneumoniae pneumonia (MSMP group) and 25 children hospitalized with macrolide-resistant M. pneumoniae pneumonia (MRMP group). In the MRMP group, 19 children received macrolides and clinical failure occurred in six of which five had pneumonia progression during therapy., (Copyright © 2014. Published by Elsevier B.V.)

The proto-oncogenic ALK is a druggable receptor tyrosine kinase for cancer treatment. Two small molecule inhibitors of ALK, crizotinib and ceritinib, have been recently approved for the treatment of metastatic non-small-cell lung cancer, with marked improvement of progression-free survival of patients. Independent case reports also indicate their potential therapeutic activity in other ALK-rearranged cancers. Numerous single-agent and combination therapy trials are ongoing in lung and many other cancers. Results of these trials are greatly anticipated. Here, we summarize our current understanding of ALK signaling, genomic aberrations in cancer and emerging mechanisms of drug resistance. We will also provide a timely review on all ALK inhibitors and their current status of development in clinical settings.

Background: The level of patient safety and outcomes accomplished depends on the quality of care provided. Previous studies found that nurse-to-patient ratio, practice environment, and nursing education were significant predictors of patient outcomes. However, the outcomes measured in previous studies were mainly inpatient mortality and failure-to-rescue rates. Few nurse-sensitive patient outcomes have been measured that quantify nurses' contribution to patient care. Selecting appropriate outcomes that reflect the clinically relevant effect of nursing care is important. Moreover previous studies were largely cross-sectional and retrospective. These research designs are limited in their ability to explain the casual links between the variables examined. This study is aimed at determining the associations among staffing levels, skill mix of baccalaureate-prepared registered nurses, and practice environment on nurse-sensitive outcomes for medical and surgical patients in public hospitals in Hong Kong., Method/designs: A multi-method research design will be adopted. The sample includes all medical and surgical wards of four major public hospitals that offer 24-h accident and emergency services. Multiple responses from registered nurses who work in the study wards will be collected over 12 months to examine their individual characteristics and perceptions of the practice environment. A 12-month prospective observational study will be performed to determine the association between nurse staffing levels, the practice environment, and nurse-sensitive patient outcomes including pressure ulcers, falls and restraint prevalence, urinary catheter-associated urinary tract infections, and central line catheter-associated bloodstream infections. Multilevel Cox proportional hazards models will be employed to examine the association between these patient outcomes and the explanatory nursing factors of primary interest (nurse staffing levels, education composition, and practice environment), with adjustment for all patient-, ward- and hospital-level potential confounders (age, sex, diagnosis, comorbidities, level of surgical invasiveness, mortality, length of stay, and type of admission)., Discussion: It is anticipated that knowledge of the association between nurse staffing levels, the practice environment, and nurse-sensitive outcomes will inform the provision of quality and timely patient care. This study will provide a landmark report that is of relevance and importance to patients and to hospital stakeholders and managers, health policy makers, nurses, and educators who advocate patient benefits., Trial Registration: Clinical Trials Registry CCTCTR CUHK&#95;CCT00460 . Date of trial registration: 02 July 2015.