Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 52
Filtrar
Mais filtros

Base de dados
País/Região como assunto
Tipo de documento
Intervalo de ano de publicação
1.
Am J Emerg Med ; 77: 39-45, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38096638

RESUMO

OBJECTIVE: Patients with dizziness commonly present to Emergency Departments (ED) and 6% of these patients will be diagnosed with acute stroke. The TriAGe+ score comprises of eight clinical parameters and stratifies patients into four risk groups. The Japanese authors reported that the tool performed well, so our aim was to validate this diagnostic tool in our ED in Hong Kong. MATERIALS AND METHODS: A single-center retrospective observational study was conducted in the ED of our university hospital in Hong Kong. The primary outcome was the diagnosis of an acute cerebrovascular event. Receiver operator characteristic (ROC) analysis was performed to determine the best cut-off score. Secondary outcomes included univariable and multivariable analyses of stroke predictors. RESULTS: 455 patients aged 18 years or above with dizziness or vertigo at ED triage were recruited between 19 July and 30 September 2021. The overall prevalence of stroke was 11.9%. The median TriAGe+ score was 7 (IQR = 4-9). The AUC was 0.9. At a cut-off >5, sensitivity was 96.4% (95%CI: 87.3-99.5) and the negative likelihood ratio was 0.09 (95%CI: 0.02-0.3). At a cut-off >10, specificity was 99.8% (95%CI: 98.6-100.0), and the positive likelihood ratio was 237.6 (95%CI: 33.1-1704). On multivariable analyses, atrial fibrillation, blood pressure, gender, dizziness (not vertigo) and no history of dizziness, vertigo or labyrinth/vestibular disease were found to be positively associated with stroke outcomes significantly. CONCLUSION: The TriAGe+ score is an efficient stroke prediction score for patients presenting to the ED with dizziness.


Assuntos
Tontura , Acidente Vascular Cerebral , Humanos , Tontura/diagnóstico , Tontura/epidemiologia , Serviço Hospitalar de Emergência , Hong Kong/epidemiologia , Hospitais Universitários , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Triagem , Vertigem/diagnóstico , Vertigem/epidemiologia , Estudos Retrospectivos
2.
Postgrad Med J ; 2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38679808

RESUMO

BACKGROUND: Low back pain (LBP) is a leading cause of disability worldwide and has posed numerous health and socioeconomic challenges. This study compared whether nonsteroidal anti-inflammatory drugs (NSAIDs) in combination with tramadol, tizanidine or placebo would be the best treatment regime to improve the Roland Morris Disability Questionnaire (RMDQ) scores at 1 week. METHODS: This was a multi-center, double-blind, randomized, and placebo-controlled trial including adult patients with acute LBP and sciatica in three emergency departments in Hong Kong. Patients were randomized to the receive tramadol 50 mg, tizanidine 2 mg, or placebo every 6 hours for 2 weeks in a 1:1:1 ratio. The RMDQ and other secondary outcomes were measured at baseline, Day 2, 7, 14, 21, and 28. Data were analyzed on an intention to treat basis. Crude and adjusted mean differences in the changes of RMDQ and NRS scores from baseline to Day 7 between tizanidine/tramadol and placebo were determined with 95% confidence intervals. RESULTS: Two hundred and ninety-one patients were analyzed with the mean age of 47.4 years and 57.7% were male. The primary outcome of mean difference in RMDQs on Day 7 (compared with baseline) was non-significant for tizanidine compared with placebo (adjusted mean difference - 0.56, 95% CI -2.48 to 1.37) and tramadol compared with placebo (adjusted mean difference - 0.85, 95% CI -2.80 to 1.10). Only 23.7% were fully compliant to the treatment allocated. Complier Average Causal Effect analysis also showed no difference in the primary outcome for the tizanidine and tramadol versus placebo. CONCLUSION: Among patients with acute LBP and sciatica presenting to the ED, adding tramadol or tizanidine to diclofenac did not improve functional recovery.

3.
Am J Emerg Med ; 60: 73-77, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35908299

RESUMO

BACKGROUND: A key component of trauma system evaluation is the Injury Severity Score (ISS). The ISS is dependent on the AIS, and as AIS versions are updated this effects the number of patients within a health system which are considered severely injured (ISS >15). This study aims to analyse the changes comparing AIS1998 and AIS2015, and its impact on injury severity scoring and survival prediction model in a major trauma centre. METHODS: This retrospective study reviewed all blunt trauma admissions from 1 January 2020 to 31 December 2020 from the trauma registry of Prince of Wales Hospital, Hong Kong. Patients were manually double coded with AIS1998 and AIS2015 by the same experienced trauma nurse who have completed both AIS 1998 and AIS 2015 Courses. AIS patterns and Injury Severity Scores (ISS) derived from AIS 1998 and 2015 were compared using the Wilcoxon Signed Rank Test. The area under the receiving operator curve (AUROC) was compared based on the Trauma and Injury Severity Score (TRISS) model using AIS 1998 and AIS 2015. RESULTS: 739 patients were included. There were 34 deaths within 30 days (30-day mortality rate 4.6%). Patients coded with AIS2015 compared with AIS1998 had significant reductions in the classification of serious, severe and critical categories of AIS, with a substantial increase in the mild and moderate categories. The largest reduction was observed in the head and neck region (Z = -11.018, p < 0.001), followed by the chest (Z = -6.110, p < 0.001), abdomen (Z = -4.221, p < 0.001) and extremity regions (Z = -4.252, p < 0.001). There was a 27% reduction in number of cases with ISS >15 in AIS2015 compared with AIS1998. Rates of 30-day mortality, ICU admission, emergency operation and trauma team activation of ISS > 15 using AIS 1998 were similar to the cut off for New Injury Severity Score (NISS) >12 using AIS 2015. The AUROC from the TRISS (AIS2015) was 0.942, and not different from the AUROC for TRISS (AIS1998) of 0.936. The sensitivity and specificity were 93.9% and 82.1% for TRISS (AIS2015), and 93.9% and 76.0% for TRISS (AIS1998). CONCLUSION: Trauma centres should be aware of the impact of the AIS2015 update on the benchmarking of trauma care, and consider the need for updating the ISS cut off for major trauma definitions.


Assuntos
Centros de Traumatologia , Ferimentos e Lesões , Escala Resumida de Ferimentos , Humanos , Escala de Gravidade do Ferimento , Sistema de Registros , Estudos Retrospectivos , Índices de Gravidade do Trauma
4.
Cancer Immunol Immunother ; 70(12): 3525-3540, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33903974

RESUMO

Immune checkpoint inhibitors (ICIs) have emerged as promising therapies for the treatment of cancer. However, existing ICIs, namely PD-(L)1 and CTLA-4 inhibitors, generate durable responses only in a subset of patients. TIGIT is a co-inhibitory receptor and member of the DNAM-1 family of immune modulating proteins. We evaluated the prevalence of TIGIT and its cognate ligand, PVR (CD155), in human cancers by assessing their expression in a large set of solid tumors. TIGIT is expressed on CD4+ and CD8+ TILs and is upregulated in tumors compared to normal tissues. PVR is expressed on tumor cells and tumor-associated macrophages from multiple solid tumors. We explored the therapeutic potential of targeting TIGIT by generating COM902, a fully human anti-TIGIT hinge-stabilized IgG4 monoclonal antibody that binds specifically to human, cynomolgus monkey, and mouse TIGIT, and disrupts the binding of TIGIT with PVR. COM902, either alone or in combination with a PVRIG (COM701) or PD-1 inhibitor, enhances antigen-specific human T cell responses in-vitro. In-vivo, a mouse chimeric version of COM902 in combination with an anti-PVRIG or anti-PD-L1 antibody inhibited tumor growth and increased survival in two syngeneic mouse tumor models. In summary, COM902 enhances anti-tumor immune responses and is a promising candidate for the treatment of advanced malignancies.


Assuntos
Anticorpos Monoclonais/imunologia , Antígeno B7-H1/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Receptores de Superfície Celular/imunologia , Receptores Imunológicos/imunologia , Transdução de Sinais/imunologia , Animais , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Feminino , Humanos , Imunoglobulina G/imunologia , Imunoterapia/métodos , Células Jurkat , Macaca fascicularis , Camundongos , Camundongos Endogâmicos BALB C
5.
BMC Health Serv Res ; 21(1): 474, 2021 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-34011321

RESUMO

BACKGROUND: Truly patient-centred care needs to be aligned with what patients consider important, and is highly desirable in the first 24 h of an acute admission, as many decisions are made during this period. However, there is limited knowledge on what matters most to patients in this phase of their hospital stay. The objective of this study was to identify what mattered most to patients in acute care and to assess the patient perspective as to whether their treating doctors were aware of this. METHODS: This was a large-scale, qualitative, flash mob study, conducted simultaneously in sixty-six hospitals in seven countries, starting November 14th 2018, ending 50 h later. One thousand eight hundred fifty adults in the first 24 h of an acute medical admission were interviewed on what mattered most to them, why this mattered and whether they felt the treating doctor was aware of this. RESULTS: The most reported answers to "what matters most (and why)?" were 'getting better or being in good health' (why: to be with family/friends or pick-up life again), 'getting home' (why: more comfortable at home or to take care of someone) and 'having a diagnosis' (why: to feel less anxious or insecure). Of all patients, 51.9% felt the treating doctor did not know what mattered most to them. CONCLUSIONS: The priorities for acutely admitted patients were ostensibly disease- and care-oriented and thus in line with the hospitals' own priorities. However, answers to why these were important were diverse, more personal, and often related to psychological well-being and relations. A large group of patients felt their treating doctor did not know what mattered most to them. Explicitly asking patients what is important and why, could help healthcare professionals to get to know the person behind the patient, which is essential in delivering patient-centred care. TRIAL REGISTRATION: NTR (Netherlands Trial Register) NTR7538 .


Assuntos
Hospitalização , Projetos de Pesquisa , Adulto , Humanos , Tempo de Internação , Países Baixos , Pesquisa Qualitativa
6.
J Immunol ; 200(6): 2025-2037, 2018 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-29431694

RESUMO

The B7-like protein family members play critical immunomodulatory roles and constitute attractive targets for the development of novel therapies for human diseases. We identified Ig-like domain-containing receptor (ILDR)2 as a novel B7-like protein with robust T cell inhibitory activity, expressed in immune cells and in immune-privileged and inflamed tissues. A fusion protein, consisting of ILDR2 extracellular domain with an Fc fragment, that binds to a putative counterpart on activated T cells showed a beneficial effect in the collagen-induced arthritis model and abrogated the production of proinflammatory cytokines and chemokines in autologous synovial-like cocultures of macrophages and cytokine-stimulated T cells. Collectively, these findings point to ILDR2 as a novel negative regulator for T cells, with potential roles in the development of immune-related diseases, including autoimmunity and cancer.


Assuntos
Antígenos B7/imunologia , Proteínas de Membrana/imunologia , Linfócitos T/imunologia , Animais , Células Cultivadas , Citocinas/imunologia , Humanos , Domínios de Imunoglobulina/imunologia , Fragmentos Fc das Imunoglobulinas/imunologia , Ativação Linfocitária/imunologia , Macrófagos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C
7.
Am J Emerg Med ; 37(3): 450-456, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30041911

RESUMO

BACKGROUND: With the aging population, the number of older patients with multiple injuries is increasing. The aim of this study was to understand the patterns and outcomes of older patients admitted to a major trauma centre in Hong Kong from 2006 to 2015, and investigate the performance of the trauma team activation (TTA) criteria for these elderly patients. METHODS: This was a retrospective cohort study from a university hospital major trauma centre in Hong Kong from 2006 to 2015. Patients aged 55 or above who entered the trauma registry were included. Patients were divided into those aged 55-70, and above 70. To test the performance of the TTA criteria, we defined injured patients with severe outcomes as those having any of the following: death within 30 days; the need for surgery; or the need for intensive care unit (ICU) care. RESULTS: 2218 patients were included over the 10 year period. The 30-day mortality was 7.5% for aged 55-70 and 17.7% for those aged above 70. The sensitivity of TTA criteria for identifying severe outcomes for those aged 55 or above was 35.6%, with 91.6% specificity. The under-triage rate was 59% for age 55-70, and 69.1% for those aged above 70. CONCLUSION: There is a need to consider alternative TTA criteria for our geriatric trauma population, and to more clearly define the process and standards of care in Hong Kong.


Assuntos
Centros de Traumatologia , Triagem/normas , Ferimentos e Lesões/mortalidade , Idoso , Idoso de 80 Anos ou mais , Feminino , Hong Kong/epidemiologia , Hospitais Universitários , Humanos , Escala de Gravidade do Ferimento , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Estudos Retrospectivos , Sensibilidade e Especificidade , Triagem/estatística & dados numéricos
8.
Prehosp Emerg Care ; 21(6): 709-714, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28467148

RESUMO

OBJECTIVE: Studies done in the 1990's suggested nursing home residents with cardiac arrest had minimal chance of survival and resuscitation was not recommended. More recent studies showed opposing results. In Hong Kong, the proportion of elderly living in the residential care homes for the elderly is increasing. There is no study of out-of-hospital cardiac arrest outcomes in this population. This study aimed at evaluating the prognosis of out-of-hospital cardiac arrest occurring in the residential care homes for the elderly. It is hoped that the findings may inform the local emergency medical service concerning the issue of futility of resuscitating the residents with cardiac arrest in the residential care homes. METHODS: This study was a retrospective analysis of a database of all patients aged 65 years or above with atraumatic out-of-hospital cardiac arrest and who were attended by the emergency medical service in a 12-month period. Data in the database were prospectively collected by the emergency medical service. The characteristics of patients and cardiac arrests, timeliness of the emergency medical service, and survival were analyzed. Comparison was made between elderly living in and not living in the residential care homes. Predictors of survival were evaluated with logistic regression. RESULTS: 3919 patients aged ≥ 65 years were analyzed. There were 1506 cases of cardiac arrest occurring in the residential care homes for the elderly. Resuscitation was discontinued at the emergency department in over 70% of these cases. The survival to hospital admission rate and the 30-day survival rate were 9.6% and 0.3% respectively. Both were lower than patients not residing in the residential care homes. Younger age, witnessed arrest, bystander defibrillation, and shorter call to ED interval were associated with higher chance of surviving to hospital admission. CONCLUSION: Elderly suffering from cardiac arrest in residential care homes had a poor chance of survival. Except age, witnessed arrest, bystander defibrillation, and call to ED interval are modifiable predictors of survival. It is inappropriate to declare that resuscitating elderly in residential care homes is futile unless those factors have been fully addressed.


Assuntos
Parada Cardíaca Extra-Hospitalar/mortalidade , Instituições Residenciais , Idoso , Idoso de 80 Anos ou mais , Reanimação Cardiopulmonar , Bases de Dados Factuais , Cardioversão Elétrica , Serviços Médicos de Emergência , Serviço Hospitalar de Emergência , Feminino , Hong Kong , Hospitalização , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Parada Cardíaca Extra-Hospitalar/etiologia , Parada Cardíaca Extra-Hospitalar/terapia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
10.
J Emerg Med ; 51(6): 677-679, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27687174

RESUMO

BACKGROUND: Injection of botulinum toxin type A for cosmetic purposes is common. It is believed to be safe, but adverse reactions have been reported, including dysphagia, generalized paralysis, respiratory depression, and death caused by focal injection of the toxin. Early administration of antitoxin in patients with adverse reactions is the mainstay of management, but the time window for its clinical efficacy is not well defined. CASE REPORTS: Two female adult patients with clinical botulism after botulinum toxin type A injection are described. Both patients had received intramuscular injection of botulinum toxin type A in their calves at beauty shops for cosmetic reasons. They developed clinical botulism about 3 days postinjection. They presented late to the emergency department. Monovalent type A botulinum antitoxin was administered 7 and 9 days from symptom onset, respectively. Both patients showed clinical improvement after the antitoxin treatment. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Patients may present to the emergency department with systemic effects of botulinum toxin type A after cosmetic injection. Clinical efficacy of botulinum antitoxin treatment was observed in two patients who were given the drug 7 and 9 days after the occurrence of symptoms of botulism after cosmetic injection of botulinum toxin type A. It may be worthwhile to commence antitoxin treatment even if patients present late.


Assuntos
Antitoxina Botulínica/uso terapêutico , Toxinas Botulínicas Tipo A/efeitos adversos , Botulismo/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Fármacos Neuromusculares/efeitos adversos , Adulto , Botulismo/etiologia , Técnicas Cosméticas/efeitos adversos , Transtornos de Deglutição/induzido quimicamente , Feminino , Humanos , Debilidade Muscular/induzido quimicamente , Distúrbios da Fala/induzido quimicamente , Tempo para o Tratamento
12.
Pediatr Surg Int ; 31(1): 83-8, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25348879

RESUMO

INTRODUCTION: Data on laparoscopic Nissen fundoplication for gastro-oesophageal reflux disease (GERD) in infants remain limited. We describe our experience with this operation in children and in particular, infants younger than 12 months old. MATERIALS AND METHODS: Medical records of all paediatric patients who had laparoscopic fundoplication done for GERD from 1998 to 2013 were reviewed. Patients were divided into two groups based on age: group I: 0-12 months, and group II >12 months. Data on indications, patient's demographics, operative time, blood loss, conversions, complications, recurrences and duration of hospitalization were studied. RESULTS: A total of 86 patients were reviewed (group I, n = 21; group II, n = 65). While the mean age and body weight for group I were 8 ± 2.99 months and 6 ± 1.96 kg, the values for group II were 98 ± 65 months and 18 ± 9.6 kg, respectively. All patients had concurrent laparoscopic gastrostomy for feeding difficulties. The mean operative time was shorter in group I (157 ± 55 vs 169 ± 52 min, p = 0.66). Both groups had minimal blood loss only. The surgical outcomes in both groups were comparable in terms of recurrence (0 vs 3 %, p = 0.105) and complications (9.5 vs 6 %, p = 0.275). The median follow-up duration for group I and group II was 23 and 40 months, respectively. Sixteen (76 %) patients in group I and 45 (67 %) patients in group II did not develop pneumonia post fundoplication. CONCLUSION: Laparoscopic Nissen fundoplication can be safely performed in infants with outcomes comparable to older patients and a shorter operative duration. Low recurrence rate (up to 3 %) is shown by our long term follow-up data. We recommend laparoscopic Nissen fundoplication to be considered in managing infants with GERD.


Assuntos
Fundoplicatura/métodos , Refluxo Gastroesofágico/cirurgia , Laparoscopia/métodos , Feminino , Humanos , Lactente , Masculino , Complicações Pós-Operatórias , Resultado do Tratamento
13.
Pediatr Surg Int ; 31(3): 249-54, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25616564

RESUMO

INTRODUCTION: Tracheobronchial obstruction, although uncommon in the pediatric age group, remains a challenging problem. We review the long-term outcome of endoscopic metallic stenting in infants with tracheobronchial obstruction. MATERIALS AND METHODS: Medical records of all pediatric surgical patients who underwent tracheobronchial metallic stenting in our center were reviewed retrospectively from 1996 to 2014. Patients' demographic data, including etiology, associated anomalies and nature of obstruction were reviewed. Outcome measures include complications such as re-stenosis, granulation tissue, stent migration, fractured stent, maximal tracheal diameter achieved, weaning of ventilator and growth at interval follow-up. RESULTS: Twelve balloon-expandable metallic stents were placed in the trachea (n = 10) and/or bronchi (n = 2) of 5 patients with a median age of 13 months (range 5-30 months). Etiology of the airway obstruction included congenital tracheal stenosis (n = 4), giant cervical and superior mediastinal lymphatic malformation with tracheobronchomalacia (n = 1). Seven complications were reported (3 patients developed granulation tissue, 2 patients had re-stenosis, 1 stent migrated, 1 stent fractured). All patients survived and were in good condition with a median follow-up of 16 years (range 11-18 years). Three patients weaned off ventilator and oxygen. CONCLUSIONS: Endoscopic stenting with metallic stent has satisfactory long-term outcome in treating infants with tracheobronchial obstruction.


Assuntos
Obstrução das Vias Respiratórias/terapia , Constrição Patológica/terapia , Stents , Traqueia/anormalidades , Obstrução das Vias Respiratórias/congênito , Brônquios/cirurgia , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Estudos Retrospectivos , Traqueia/cirurgia , Resultado do Tratamento
14.
Chin J Traumatol ; 18(3): 137-40, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26643238

RESUMO

PURPOSE: To evaluate the performance of a prehospital trauma diversion system in Hong Kong, China. METHODS: A retrospective analysis of prospectively collected data in the trauma registry of Queen Mary Hospital, Hong Kong from 1 January 2009 to 31 December 2013 was done. All adult patients aged 18 years or above, either primarily or secondarily diverted to Queen Mary Hospital according to the trauma patient diversion protocol, were recruited. Need for trauma center level of care was based on a consensus-based criterion standard published in 2014. Performance of the protocol in terms of over- diversion and under-diversion was determined. RESULTS: A total of 209 patients were included for analysis. About 30% of the patients required trauma center level of care. The most common reason was the need for vascular, neurologic, abdominal, thoracic, pelvic, spine or limb-conserving surgery within 24 h of presentation. The over-diversion rate and under- diversion rate were 69.6% and 19.7% respectively. CONCLUSION: The trauma patient diversion protocol currently in use in Hong Kong is not accurate enough. Further revision and refinement is needed.


Assuntos
Serviços Médicos de Emergência , Centros de Traumatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Hong Kong , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
15.
J Transl Med ; 12: 184, 2014 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-24965603

RESUMO

BACKGROUND: Homologous recombination repair (HRR) pathway deficiencies have significant implications for cancer predisposition and treatment strategies. Improved quantitative methods for functionally characterizing these deficiencies are required to accurately identify patients at risk of developing cancer and to identify mechanisms of drug resistance or sensitivity. METHODS: Flow cytometry-based single cell network profiling (SCNP) was used to measure drug-induced activation of DNA damage response (DDR) proteins in cell lines with defined HRR pathway mutations (including ATM-/-, ATM+/-, BRCA1+/-, BRCA2-/-) and in primary acute myeloid leukemia (AML) samples. Both non-homologous end joining (NHEJ) and HRR pathways were examined by measuring changes in intracellular readouts (including p-H2AX, p-ATM, p-DNA-PKcs, p-53BP1, p-RPA2/32, p-BRCA1, p-p53, and p21) in response to exposure to mechanistically distinct genotoxins. The cell cycle S/G2/M phase CyclinA2 marker was used to normalize for proliferation rates. RESULTS: Etoposide induced proliferation-independent DNA damage and activation of multiple DDR proteins in primary AML cells and ATM +/+but not ATM -/- cell lines. Treatment with the PARPi AZD2281 +/- temozolomide induced DNA damage in CyclinA2+ cells in both primary AML cells and cell lines and distngiushed cell lines deficient (BRCA2-/-) or impaired (BRCA1+/-) in HRR activity from BRCA1+/+ cell lines based on p-H2AX induction. Application of this assay to primary AML samples identified heterogeneous patterns of repair activity including muted or proficient activation of NHEJ and HRR pathways and predominant activation of NHEJ in a subset of samples. CONCLUSIONS: SCNP identified functional DDR readouts in both NHEJ and HRR pathways, which can be applied to identify cells with BRCA1+/- haploinsuffiency and characterize differential DDR pathway functionality in primary clinical samples.


Assuntos
Dano ao DNA , Reparo do DNA , Análise de Célula Única/métodos , Adulto , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Proteína BRCA1/metabolismo , Proteína BRCA2/metabolismo , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Criança , Ciclina A2/metabolismo , Quebras de DNA de Cadeia Dupla/efeitos dos fármacos , Reparo do DNA/efeitos dos fármacos , Dacarbazina/análogos & derivados , Dacarbazina/farmacologia , Inibidores Enzimáticos/farmacologia , Etoposídeo/farmacologia , Haploinsuficiência/efeitos dos fármacos , Histonas/metabolismo , Recombinação Homóloga/efeitos dos fármacos , Humanos , Mutagênicos/toxicidade , Fosforilação/efeitos dos fármacos , Inibidores de Poli(ADP-Ribose) Polimerases , Poli(ADP-Ribose) Polimerases/metabolismo , Reprodutibilidade dos Testes , Temozolomida
16.
J Pathol ; 225(4): 525-34, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21661123

RESUMO

Aberrant activation of Hedgehog (Hh) signalling has been implicated in the pathogenesis of human cancers. However, the cognate molecular mechanisms contributing to this disregulated pathway are incompletely understood. In this study, we showed that Zic2 was frequently over-expressed and associated with high-grade cervical cancer (p = 0.032), high levels of Gli1 (p < 0.001) and CyclinD1 (p < 0.001) by immunohistochemical and quantitative RT-PCR analyses. Further biochemical studies using luciferase reporter, co-immunoprecipitation, subcellular fractionation and immunofluorescence analyses demonstrated that Zic2 can physically interact with Gli1 and retain it in the nucleus, which in turn increases Gli-mediated transcriptional activity. Gain- and loss-of-function analyses of Zic2 showed that Zic2 could increase Hh signalling activity, cell proliferation and anchorage-independent growth ability in cervical cancer cells. Conversely, deletion of the zinc finger domain at C-terminus of Zic2 significantly abrogated its interaction with Gli1, the retention of Gli1 in the nucleus, effects on Hh signalling activity and oncogenic properties in cervical cancer cells. Our findings suggest that Zic2 is a positive modulator increasing Gli1 transcriptional and oncogenic activity by retaining Gli1 in the nucleus of cervical cancer cells.


Assuntos
Adenocarcinoma/metabolismo , Núcleo Celular/metabolismo , Proteínas Nucleares/metabolismo , Fatores de Transcrição/metabolismo , Neoplasias do Colo do Útero/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/patologia , Linhagem Celular Transformada , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica , Proteínas Hedgehog/genética , Proteínas Hedgehog/metabolismo , Humanos , Proteínas Nucleares/genética , RNA Mensageiro/metabolismo , Transdução de Sinais , Fatores de Transcrição/genética , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia , Proteína GLI1 em Dedos de Zinco
18.
Chin J Traumatol ; 15(5): 273-8, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23069097

RESUMO

OBJECTIVE: Focused Abdominal Sono-graphy for Trauma (FAST) is widely used for the detection of intraperitoneal free fluids in patients suffering from blunt abdominal trauma (BAT). This study aimed at assessing the diagnostic accuracy of this investigation in a designated trauma centre. METHODS: This was a retrospective study of BAT patients over a 6 year period seen in a trauma centre in Hong Kong. FAST findings were compared with laparotomy, abdominal computed tomography or autopsy findings, which served as the gold standard for presence of intraperitoneal free fluids. The patients who did not have FAST or gold standard confirmatory test performed, had preexisting peritoneal fluid, died at resuscitation or had imcomplete documentation of FAST findings were excluded. The performance of FAST was expressed as sensitivity, specificity, predictive values (PV), likelihood ratios (LR) and accuracy. RESULTS: FAST was performed in 302 patients and 153 of them were included in this analysis. The sensitivity, specificity, positive PV, negative PV, positive LR, negative LR and accuracy for FAST were respectively 50.0%, 97.3%, 87.0%, 84.6%, 18.8, 0.5 and 85.0%. FAST was found to be more sensitive in less severely injured patients and more specific in more severely injured patients. CONCLUSION: FAST is a reliable investigation in the initial assessment of BAT patients. The diagnostic values of FAST could be affected by the severity of injury and staff training is needed to further enhance its effective use. Key words: Laparotomy; Autopsy; Tomography, X-ray computed; Tomography, spiral computed; Ultrasonography.


Assuntos
Traumatismos Abdominais , Centros de Traumatologia , Traumatismos Abdominais/diagnóstico , Hong Kong , Humanos , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Ferimentos não Penetrantes/diagnóstico
19.
Eur J Trauma Emerg Surg ; 48(2): 1417-1426, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34086062

RESUMO

PURPOSE: The purpose was to investigate long-term health impacts of trauma and the aim was to describe the functional outcome and health status up to 7 years after trauma. METHODS: We conducted a prospective, multi-centre cohort study of adult trauma patients admitted to three regional trauma centres with moderate or major trauma (ISS ≥ 9) in Hong Kong (HK). Patients were followed up at regular time points (1, 6 months and 1, 2, 3, 4, 5, 6, and 7 years) by telephone using extended Glasgow Outcome Scale (GOSE) and the Short-Form 36 (SF36). Observed annual mortality rate was compared with the expected mortality rate estimated using the HK population cohort. Linear mixed model (LMM) analyses examined the changes in SF36 with subgroups of age ≥ 65 years, ISS > 15, and GOSE ≥ 5 over time. RESULTS: At 7 years, 115 patients had died and 48% (138/285) of the survivors responded. The annual mortality rate (AMR) of the trauma cohort was consistently higher than the expected mortality rate from the general population. Forty-one percent of respondents had upper good recovery (GOSE = 8) at 7 years. Seven-year mean PCS and MCS were 45.06 and 52.06, respectively. LMM showed PCS improved over time in patients aged < 65 years and with baseline GOSE ≥ 5, and the MCS improved over time with baseline GOSE ≥ 5. Higher mortality rate, limited functional recovery and worse physical health status persisted up to 7 years post-injury. CONCLUSION: Long-term mortality and morbidity should be monitored for Asian trauma centre patients to understand the impact of trauma beyond hospital discharge.


Assuntos
Nível de Saúde , Centros de Traumatologia , Adulto , Estudos de Coortes , Hong Kong/epidemiologia , Humanos , Estudos Prospectivos
20.
Eur J Trauma Emerg Surg ; 48(2): 1093-1100, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33900416

RESUMO

PURPOSE: Hong Kong (HK) trauma registries have been using the Trauma and Injury Severity Score (TRISS) for audit and benchmarking since their introduction in 2000. We compare the mortality prediction model using TRISS and Revised Injury Severity Classification, version II (RISC II) for trauma centre patients in HK. METHODS: This was a retrospective cohort study with all five trauma centres in HK. Adult trauma patients with Injury Severity Score (ISS) > 15 suffering from blunt injuries from January 2013 to December 2015 were included. TRISS models using the US and local coefficients were compared with the RISC II model. The primary outcome was 30-day mortality and the area under the receiver operating characteristic curve (AUC) for tested models. RESULTS: 1840 patients were included, of whom 1236/1840 (67%) were male. Median age was 59 years and median ISS was 25. Low falls were the most common mechanism of injury. The 30-day mortality was 23%. RISC II yielded a superior AUC of 0.896, compared with the TRISS models (MTOS: 0.848; PATOS: 0.839; HK: 0.858). Prespecified subgroup analyses showed that all the models performed worse for age ≥ 70, ASA ≥ III, and low falls. RISC II had a higher AUC compared with the TRISS models in all subgroups, although not statistically significant. CONCLUSION: RISC II was superior to TRISS in predicting the 30-day mortality for Hong Kong adult blunt major trauma patients. RISC II may be useful when performing future audit or benchmarking exercises for trauma in Hong Kong.


Assuntos
Ferimentos e Lesões , Ferimentos não Penetrantes , Adulto , Hong Kong/epidemiologia , Humanos , Escala de Gravidade do Ferimento , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Índices de Gravidade do Trauma
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA