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1.
Proc Natl Acad Sci U S A ; 116(4): 1370-1377, 2019 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-30622177

RESUMO

Breast cancers enduring treatment with chemotherapy may be enriched for cancer stem cells or tumor-initiating cells, which have an enhanced capacity for self-renewal, tumor initiation, and/or metastasis. Breast cancer cells that express the type I tyrosine kinaselike orphan receptor ROR1 also may have such features. Here we find that the expression of ROR1 increased in breast cancer cells following treatment with chemotherapy, which also enhanced expression of genes induced by the activation of Rho-GTPases, Hippo-YAP/TAZ, or B lymphoma Mo-MLV insertion region 1 homolog (BMI1). Expression of ROR1 also enhanced the capacity of breast cancer cells to invade Matrigel, form spheroids, engraft in Rag2-/-[Formula: see text] mice, or survive treatment with paclitaxel. Treatment of mice bearing breast cancer patient-derived xenografts (PDXs) with the humanized anti-ROR1 monoclonal antibody cirmtuzumab repressed expression of genes associated with breast cancer stemness, reduced activation of Rho-GTPases, Hippo-YAP/TAZ, or BMI1, and impaired the capacity of breast cancer PDXs to metastasize or reengraft Rag2-/-[Formula: see text] mice. Finally, treatment of PDX-bearing mice with cirmtuzumab and paclitaxel was more effective than treatment with either alone in eradicating breast cancer PDXs. These results indicate that targeting ROR1 may improve the response to chemotherapy of patients with breast cancer.


Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , Receptores Órfãos Semelhantes a Receptor Tirosina Quinase/metabolismo , Adenosina Trifosfatases/metabolismo , Animais , Anticorpos Monoclonais , Mama/efeitos dos fármacos , Mama/metabolismo , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Xenoenxertos , Humanos , Camundongos , Células NIH 3T3 , Proteínas Nucleares/metabolismo , Paclitaxel/farmacologia , Complexo Repressor Polycomb 1/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Fatores de Transcrição/metabolismo
2.
J Oral Maxillofac Surg ; 79(5): 1026.e1-1026.e8, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33515506

RESUMO

PURPOSE: Our study fills the vacancy of litigation research related to trigeminal neuralgia management, giving health care providers the information needed to understand the potential litigious outcomes that follow treatment methods. METHODS: We queried the Westlaw database to identify litigation cases related to trigeminal neuralgia management. Key variables extracted included medical complaints, trial outcomes, and demographics. Continuous variables were compared between cases in favor of defendant and cases in favor of plaintiff using t-test or Wilcoxon rank sum test. Categorial variables were compared using χ2 or Fisher exact test. RESULTS: About 49 cases met the inclusion criteria-for those cases surgical complications (42.9%) were cited as the most common reasons for malpractice claims. Cranial nerve deficits (34.7%) were the most frequent postoperative complaints. Verdicts ruled in favor of the plaintiff in 26.5% of cases with a mean payout of $1,982,428.46. Dentists were included in the most cases, 63.3%, and the average payout was $415,908, whereas neurosurgeons were involved in 20.4% of cases with an average payout of $618,775. Cases with verdicts in favor of the plaintiff were more likely to be older than cases with verdicts in favor of the defendant (P = .03). CONCLUSIONS: Over one-half of cases resulted in verdicts in favor of the defendant with surgical complications cited as the most common reason for litigation. Dentistry was the most common individual clinical specialty for defendants, whereas neurosurgery contributed to the largest average payout based on specialty (for n > 1). Cranial nerve deficits were the most common plaintiff postoperative complaints. These analyses may help doctor teams involved in management of trigeminal neuralgia to have a more informed discussion with the patient at every visit so that such litigations may be avoided.


Assuntos
Imperícia , Neuralgia do Trigêmeo , Bases de Dados Factuais , Pessoal de Saúde , Humanos , Neuralgia do Trigêmeo/cirurgia
3.
Neurosurg Focus ; 49(5): E22, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33130607

RESUMO

OBJECTIVE: Among medical practices, surgical fields, including neurosurgery, are at a high risk for medical malpractice litigation. With meningiomas contributing to 10% of the total neurosurgery litigation cases, the aim of this study was to identify demographic characteristics, reasons for litigation, and surgical complications commonly reported in these cases. This analysis serves to increase neurosurgeons' awareness of factors associated with medical malpractice litigation. METHODS: The online legal database Westlaw was utilized to query public litigation cases related to the medical management of meningiomas between December 1985 and May 2020. Variables extracted included the following: plaintiff and defendant demographics, litigation category, plaintiff medical complaints, and trial outcomes. The authors compared these characteristics between cases with decisions in favor of the defendant and those with decisions in favor of the plaintiff. RESULTS: A total of 47 cases met the inclusion criteria. Failure to diagnose (68.1%) was the most common type of malpractice claim, and surgical complications (19.1%), motor weakness (33%), and financial loss (33%) were cited as the most common postoperative complaints. Individual specialties that most often required defense due to malpractice claims were radiology (21.7%) and neurosurgery (19.6%). The jury verdict was in favor of the defense in 51.1% of cases and in favor of the plaintiff in 27.7% of cases. A settlement was reached in 19.1% of cases. The mean payout for a verdict in favor of the plaintiff was $3,409,650.22, while the mean payout for settlements was $867,555.56. The greatest average payout for specialties was in neurosurgery at $3,414,400, followed by radiology at $3,192,960. Cases with a verdict in favor of the plaintiff were more likely to involve an internal medicine physician as a defendant (p = 0.007). CONCLUSIONS: Over one-half of the cases resulted in a defendant's verdict with failure to diagnose cited as the most common reason for litigation. Radiology and neurosurgery were the most common specialties for legal cases and also had some of the largest average payouts based on specialty. Motor weakness and financial loss were the most common plaintiff postoperative complaints. These findings may inform surgeons on active measures to take, such as increasing focus on diagnostic accuracy and reducing specific postoperative complaints, such as motor weakness, through risk management and prophylactic measures, to reduce unfavorable legal outcomes.


Assuntos
Imperícia , Neoplasias Meníngeas , Meningioma , Bases de Dados Factuais , Humanos , Neoplasias Meníngeas/diagnóstico por imagem , Neoplasias Meníngeas/cirurgia , Meningioma/diagnóstico por imagem , Meningioma/cirurgia , Neurocirurgiões
4.
Biol Blood Marrow Transplant ; 22(3): 536-41, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26721209

RESUMO

Allogeneic hematopoietic stem cell transplantation (HSCT) can potentially cure human immunodeficiency virus (HIV) by eliminating infected recipient cells, particularly in the context of technologies that may confer HIV resistance to these stem cells. But, to date, the Berlin patient remains the only case of HIV cure despite multiple attempts to eradicate infection with HSCT. One approach to improve this is to administer virus-specific T cells, a strategy that has proven success in preventing other infections after transplantation. Although we have reported that broadly HIV-specific T cells can be expanded from HIV+ patients, allogeneic transplantations only contain virus-naïve T cells. Modifying this approach for the allogeneic setting requires a robust, reproducible platform that can expand HIV-specific cells from the naïve pool. Hence, we hypothesized that HIV-specific T cells could be primed ex vivo from seronegative individuals to effectively target HIV. Here, we show that ex vivo-primed and expanded HIV-specific T cells released IFNγ in response to HIV antigens and that these cells have enhanced ability to suppress replication in vitro. This is the first demonstration of ex vivo priming and expansion of functional, multi-HIV antigen-specific T cells from HIV-negative donors, which has implications for use of allogeneic HSCT as a functional HIV cure.


Assuntos
Antígenos Virais/imunologia , Epitopos de Linfócito T/imunologia , HIV-1/imunologia , Transplante de Células-Tronco Hematopoéticas , Transfusão de Linfócitos , Produtos do Gene gag do Vírus da Imunodeficiência Humana/imunologia , Produtos do Gene nef do Vírus da Imunodeficiência Humana/imunologia , Aloenxertos
5.
Mol Ther ; 23(2): 387-95, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25366030

RESUMO

Antiretroviral therapy (ART) is unable to eradicate human immunodeficiency virus type 1 (HIV-1) infection. Therefore, there is an urgent need to develop novel therapies for this disease to augment anti-HIV immunity. T cell therapy is appealing in this regard as T cells have the ability to proliferate, migrate, and their antigen specificity reduces the possibility of off-target effects. However, past human studies in HIV-1 infection that administered T cells with limited specificity failed to provide ART-independent, long-term viral control. In this study, we sought to expand functional, broadly-specific cytotoxic T cells (HXTCs) from HIV-infected patients on suppressive ART as a first step toward developing cellular therapies for implementation in future HIV eradication protocols. Blood samples from seven HIV+ patients on suppressive ART were used to derive HXTCs. Multiantigen specificity was achieved by coculturing T cells with antigen-presenting cells pulsed with peptides representing Gag, Pol, and Nef. All but two lines were multispecific for all three antigens. HXTCs demonstrated efficacy as shown by release of proinflammatory cytokines, specific lysis of antigen-pulsed targets, and the ability to suppress HIV replication in vitro. In conclusion, we are able to generate broadly-specific cytotoxic T cell lines that simultaneously target multiple HIV antigens and show robust antiviral function.


Assuntos
Epitopos de Linfócito T/imunologia , Antígenos HIV/imunologia , Infecções por HIV/imunologia , HIV-1/imunologia , Especificidade do Receptor de Antígeno de Linfócitos T/imunologia , Linfócitos T Citotóxicos/imunologia , Células Apresentadoras de Antígenos/imunologia , Células Apresentadoras de Antígenos/metabolismo , Terapia Antirretroviral de Alta Atividade , Técnicas de Cultura Celular por Lotes , Citocinas/metabolismo , Infecções por HIV/terapia , Infecções por HIV/virologia , Humanos , Memória Imunológica , Imunofenotipagem , Imunoterapia , Fenótipo , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Linfócitos T Citotóxicos/metabolismo
6.
J Tissue Viability ; 25(3): 167-74, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27161952

RESUMO

INTRODUCTION: Foot blisters are a common injury, which can impact on activity and lead to infection. Increased skin surface hydration has been identified as a risk factor for blister formation, indicating that a reduction in hydration could reduce the risk of blister. METHOD: Thirty healthy adults were randomised into 3 groups, each receiving a preventative foot blister treatment (2Toms(®) Blister Shield(®); Flexitol(®) Blistop and Boots Anti-Perspirant Foot Spray). Cycles of compression and shear loads where applied to heel skin using a mechanism driven by compressed air. Temperature changes were measured during load application using a thermal imaging camera (FLIR Systems Inc. and Therm CAM™ Quick Report). Near surface hydration of the skin was measured using a Corneometer(®) (C & K, Germany). RESULTS: There was no significant difference in the rate of temperature change of the skin between the three groups compared to not using products (p = 0.767, p = 0.767, p = 0.515) or when comparing each product (p = 0.551). There was a significant decrease in near surface skin hydration, compared to baseline, after the application of powder (-8.53 AU, p = 0.01). There was no significant difference in hydration after the application of film former and antiperspirant (-1.47 AU, p = 0.26; -1.00 AU, p = 0.80, respectively). CONCLUSION: With the application of external load we found no significant difference in the effect of the three products on temperature change. The powder product demonstrated an effect on reducing the risk of blister. It is postulated that powder may have a barrier effect.


Assuntos
Vesícula/prevenção & controle , , Adulto , Fricção , Humanos
7.
J Infect Dis ; 212(2): 258-63, 2015 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-25589335

RESUMO

Enhanced human immunodeficiency virus (HIV)-specific immunity may be required for HIV eradication. Administration of autologous, ex vivo expanded, virus-specific, cytotoxic T-lymphocytes derived from HIV-infected patients on suppressive antiretroviral therapy (HXTCs) are a powerful tool for proof-of-concept studies. Broadly specific, polyclonal HXTCs resulting from ex vivo expansion demonstrated improved control of autologous reservoir virus compared to bulk CD8(+) T cells in viral inhibition assays. Furthermore, patient-derived HXTCs were able to clear latently infected autologous resting CD4(+) T cells following exposure to the latency-reversing agent, vorinostat. HXTCs will be ideal reagents to administer with precise control in future in vivo studies in combination with latency-reversing agents.


Assuntos
Infecções por HIV/imunologia , HIV-1/imunologia , Linfócitos T Citotóxicos/imunologia , Fármacos Anti-HIV/farmacologia , Fármacos Anti-HIV/uso terapêutico , Células Cultivadas , Técnicas de Cocultura , Infecções por HIV/tratamento farmacológico , Humanos , Ácidos Hidroxâmicos/farmacologia , Ácidos Hidroxâmicos/uso terapêutico , Linfócitos T Citotóxicos/virologia , Vorinostat
8.
Blood ; 122(17): 2965-73, 2013 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-24030379

RESUMO

Autologous T cells expressing a CD19-specific chimeric antigen receptor (CD19.CAR) are active against B-cell malignancies, but it is unknown whether allogeneic CD19.CAR T cells are safe or effective. After allogeneic hematopoietic stem cell transplantation (HSCT), infused donor-derived virus-specific T cells (VSTs) expand in vivo, persist long term, and display antiviral activity without inducing graft-vs-host disease; therefore, we determined whether donor VSTs, engineered to express CD19.CAR, retained the characteristics of nonmanipulated allogeneic VSTs while gaining antitumor activity. We treated 8 patients with allogeneic (donor-derived) CD19.CAR-VSTs 3 months to 13 years after HSCT. There were no infusion-related toxicities. VSTs persisted for a median of 8 weeks in blood and up to 9 weeks at disease sites. Objective antitumor activity was evident in 2 of 6 patients with relapsed disease during the period of CD19.CAR-VST persistence, whereas 2 patients who received cells while in remission remain disease free. In 2 of 3 patients with viral reactivation, donor CD19.CAR-VSTs expanded concomitantly with VSTs. Hence CD19.CAR-VSTs display antitumor activity and, because their number may be increased in the presence of viral stimuli, earlier treatment post-HSCT (when lymphodepletion is greater and the incidence of viral infection is higher) or planned vaccination with viral antigens may enhance disease control.


Assuntos
Antígenos CD19/imunologia , Linfócitos B/imunologia , Transplante de Células-Tronco Hematopoéticas , Leucemia Linfocítica Crônica de Células B/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Linfócitos T/transplante , Adenoviridae/imunologia , Adulto , Antígenos CD19/genética , Antineoplásicos/uso terapêutico , Linfócitos B/patologia , Criança , Citomegalovirus/imunologia , Feminino , Expressão Gênica , Herpesvirus Humano 4/imunologia , Humanos , Leucemia Linfocítica Crônica de Células B/imunologia , Leucemia Linfocítica Crônica de Células B/patologia , Leucemia Linfocítica Crônica de Células B/virologia , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/virologia , Engenharia de Proteínas , Recidiva , Linfócitos T/imunologia , Linfócitos T/virologia , Transplante Homólogo
9.
Skin Res Technol ; 20(2): 246-53, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24645912

RESUMO

BACKGROUND: Friction blister research has focused on prevention and treatment approaches rather than exploring the pathophysiology of the friction blister. Increased skin hydration has been purported to be a key risk factor in friction blister development. This study aimed to test the effect of increased skin surface hydration on the risk of friction blister creation. METHODS: The skin on one foot was hydrated by soaking the foot in water. Intermittent loading was carried out until an observable change of 3°C was evident using infrared thermography. The contra lateral foot acted as a control. Skin hydration and elasticity was measured using electrical capacitance and negative pressure respectively. RESULTS: The rate of temperature change of the hydrated group was significantly greater than that of the non-hydrated foot group (P = 0.001) and showed a strong positive correlation (r = 0.520) with skin surface hydration. Weak negative correlations were seen between skin elasticity and rate of temperature change in response to load application (r = -0.166) and skin surface hydration and elasticity at baseline (r = -0.195). CONCLUSION: In controlled experimental conditions increased skin surface hydration increases the rate of temperature change of the skin in response to load application and consequently increases the risk of blister creation.


Assuntos
Vesícula/etiologia , Vesícula/fisiopatologia , Água Corporal/metabolismo , Calcanhar/lesões , Calcanhar/fisiopatologia , Estimulação Física , Água/farmacologia , Adolescente , Adulto , Vesícula/prevenção & controle , Módulo de Elasticidade , Dermatoses do Pé/fisiopatologia , Dermatoses do Pé/prevenção & controle , Fricção , Humanos , Masculino , Fatores de Risco , Absorção Cutânea , Temperatura Cutânea , Propriedades de Superfície , Adulto Jovem
11.
Eur J Pharm Sci ; 194: 106693, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38184016

RESUMO

Inhalation enables the delivery of drugs directly to the lung, increasing the retention for prolonged exposure and maximizing the therapeutic index. However, the differential regional lung exposure kinetics and systemic pharmacokinetics are not fully known, and their estimation is critical for pulmonary drug delivery. The study evaluates the pharmacokinetics of hydroxychloroquine in different regions of the respiratory tract for multiple routes of administration. We also evaluated the influence of different inhaled formulations on systemic and lung pharmacokinetics by identifying suitable nebulizers followed by early characterization of emitted aerosol physicochemical properties. The salt- and freebase-based formulations required different nebulizers and generated aerosol with different physicochemical properties. An administration of hydroxychloroquine by different routes resulted in varied systemic and lung pharmacokinetics, with oral administration resulting in low tissue concentrations in all regions of the respiratory tract. A nose-only inhalation exposure resulted in higher and sustained lung concentrations of hydroxychloroquine with a lung parenchyma-to-blood ratio of 386 after 1440 min post-exposure. The concentrations of hydroxychloroquine in different regions of the respiratory tract (i.e., nasal epithelium, larynx, trachea, bronchi, and lung parenchyma) varied over time, indicating different retention kinetics. The spatiotemporal distribution of hydroxychloroquine in the lung is different due to the heterogeneity of cell types, varying blood perfusion rate, clearance mechanisms, and deposition of inhaled aerosol along the respiratory tract. In addition to highlighting the varied lung physiology, these results demonstrate the ability of the lung to retain increased levels of inhaled lysosomotropic drugs. Such findings are critical for the development of future inhalation-based therapeutics, aiming to optimize target site exposure, enable precision medicine, and ultimately enhance clinical outcomes.


Assuntos
Hidroxicloroquina , Nebulizadores e Vaporizadores , Ratos , Animais , Hidroxicloroquina/metabolismo , Distribuição Tecidual , Aerossóis , Administração por Inalação , Pulmão/metabolismo , Sistemas de Liberação de Medicamentos
12.
BMC Public Health ; 13: 487, 2013 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-23688320

RESUMO

BACKGROUND: Colorectal cancer is the second most common cancer and cancer-killer in Hong Kong with an alarming increasing incidence in recent years. The latest World Cancer Research Fund report concluded that foods low in fibre, and high in red and processed meat cause colorectal cancer whereas physical activity protects against colon cancer. Yet, the influence of these lifestyle factors on cancer outcome is largely unknown even though cancer survivors are eager for lifestyle modifications. Observational studies suggested that low intake of a Western-pattern diet and high physical activity level reduced colorectal cancer mortality. The Theory of Planned Behaviour and the Health Action Process Approach have guided the design of intervention models targeting a wide range of health-related behaviours. METHODS/DESIGN: We aim to demonstrate the feasibility of two behavioural interventions intended to improve colorectal cancer outcome and which are designed to increase physical activity level and reduce consumption of a Western-pattern diet. This three year study will be a multicentre, randomised controlled trial in a 2x2 factorial design comparing the "Moving Bright, Eating Smart" (physical activity and diet) programme against usual care. Subjects will be recruited over a 12-month period, undertake intervention for 12 months and followed up for a further 12 months. Baseline, interim and three post-intervention assessments will be conducted.Two hundred and twenty-two colorectal cancer patients who completed curative treatment without evidence of recurrence will be recruited into the study. Primary outcome measure will be whether physical activity and dietary targets are met at the end of the 12-month intervention. Secondary outcome measures include the magnitude and mechanism of behavioural change, the degree and determinants of compliance, and the additional health benefits and side effects of the intervention. DISCUSSION: The results of this study will establish the feasibility of targeting the two behaviours (diet and physical activity) and demonstrate the magnitude of behaviour change. The information will facilitate the design of a further larger phase III randomised controlled trial with colorectal cancer outcome as the study endpoint to determine whether this intervention model would reduce colorectal cancer recurrence and mortality. TRIAL REGISTRATION: ClinicalTrials.gov No: NCT01708824.


Assuntos
Neoplasias Colorretais/prevenção & controle , Dieta , Terapia por Exercício , Recidiva Local de Neoplasia/prevenção & controle , Adulto , Feminino , Hong Kong , Humanos , Masculino , Sobreviventes , Resultado do Tratamento
13.
Pharmacy (Basel) ; 11(1)2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36827659

RESUMO

BACKGROUND: As roles have evolved over time, changes in workplace environments have created higher patient expectations creating stressful conditions for pharmacists. AIM: To evaluate pharmacists' perceptions of their working conditions, work dissatisfaction, and psychological distress; determine their predictors in New Zealand (NZ); and compare results with Canadian studies and historic NZ data. METHODS: A cross-sectional online survey was distributed to registered pharmacists in NZ. The survey included demographics, work satisfaction, psychological distress, and perceptions of their working conditions (six statements with agreement rated on a 5-point Likert scale). Comparisons were made with surveys from Canada and NZ. Chi-square, t-tests, and non-parametric statistics were used to make comparisons. RESULTS: The response rate was 24.7% (694/2815) with 73.1% practicing in a community pharmacy (45.8% independent, 27.3% chains). Pharmacists disagreed on having adequate time for breaks and tasks, while the majority contemplated leaving the profession and/or not repeating their careers again if given the choice. Working longer hours and processing more prescriptions per day were predictive factors for poorer job satisfaction. More NZ pharmacists perceived their work environment to be conducive to safe and effective primary care (57% vs. 47%, p < 0.001) and reported that they had enough staff (45% vs. 32%, p = 0.002) as compared to Canadian pharmacists. Pharmacists' job satisfaction and psychological distress have not improved compared to the assessment 20 years prior. CONCLUSIONS: NZ pharmacists perceive working conditions to be sub-optimal yet had higher satisfaction than their Canadian counterparts. Work dissatisfaction and psychological distress are high and have not improved over the last two decades.

14.
Cureus ; 15(12): e50860, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38249271

RESUMO

Background Traumatic acute subdural hematoma (ASDH) is a surgical emergency and has been associated with high morbidity and mortality. However, it is not known whether mortality from ASDH occurs more frequently in a particular season. Methodology We queried the American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP) from 2016 to 2019. They were identified in the NSQIP using the International Classification of Diseases (ICD-10) code S06.5 to capture all admissions with a primary diagnosis of traumatic subdural hematoma. Mortality rates were reviewed per season, defined as three consecutive months in the year. Demographics such as age, race, ethnicity, height, and weight were reviewed. Comorbidities such as diabetes, risk factors, including smoking history, and hospitalization characteristics, such as admission year, operation year, and inpatient/outpatient treatment type, were also reviewed. Results A total of 1,656 patients were included in this study. The mean age of all participants was 70.6 years, with 37% (604/1,656) being female. The mortality rate was highest in January, February, and March at 24.5% (104/425, P = 0.045) of admitted patients compared to mortality rates of 18.8% (70/373) in April to June, 18.4% (81/441) in July to September, and 17.5% (73/417) in October to December. Conclusions Mortality is significantly greater during the winter months of January, February, and March among patients with ASDH. Despite better survival rates of ASDH over the past two decades, postoperative mortality rates still remain high.

15.
Nat Cancer ; 4(4): 485-501, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36997747

RESUMO

To enhance the therapeutic index of T-cell engagers (TCEs), we engineered masked, precision-activated TCEs (XPAT proteins), targeting a tumor antigen (human epidermal growth factor receptor 2 (HER2) or epidermal growth factor receptor (EGFR)) and CD3. Unstructured XTEN polypeptide masks flank the N and C termini of the TCE and are designed to be released by proteases in the tumor microenvironment. In vitro, unmasked HER2-XPAT (uTCE) demonstrates potent cytotoxicity, with XTEN polypeptide masking providing up to 4-log-fold protection. In vivo, HER2-XPAT protein induces protease-dependent antitumor activity and is proteolytically stable in healthy tissues. In non-human primates, HER2-XPAT protein demonstrates a strong safety margin (>400-fold increase in tolerated maximum concentration versus uTCE). HER2-XPAT protein cleavage is low and similar in plasma samples from healthy and diseased humans and non-human primates, supporting translatability of stability to patients. EGFR-XPAT protein confirmed the utility of XPAT technology for tumor targets more widely expressed in healthy tissues.


Assuntos
Neoplasias , Linfócitos T , Animais , Humanos , Antígenos de Neoplasias/metabolismo , Receptores ErbB , Imunoterapia/efeitos adversos , Neoplasias/tratamento farmacológico , Microambiente Tumoral , Complexo CD3/metabolismo
16.
J Am Geriatr Soc ; 69(7): 1906-1915, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33891712

RESUMO

BACKGROUND/OBJECTIVES: To examine the association between white matter hyperintensities (WMH) and cognitive domains such as memory and executive function (EF) across different clinical and biomarker categories of Alzheimer's disease (AD). DESIGN: Cross-sectional study. SETTING: Alzheimer's Disease Neuroimaging Initiative. PARTICIPANTS: A total of 216 cognitively normal (CN) participants and 407 participants with mild cognitive impairment (MCI) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) at baseline. MEASUREMENTS: Based on the 2018 research framework, participants were classified using AT(N) (amyloid-ß deposition [A], pathologic tau [T], and neurodegeneration [(N)]) biomarkers into one of three categories: biomarker negative [A - T- (N)-], amyloid negative but other biomarker positive [A - T ± (N)+ or A - T + (N)±] or amyloid positive [A + T ± (N)±]. Linear regression models were then used to examine the association between WMH and memory composite scores and EF composite scores. RESULTS: Higher WMH burden was associated with worse EF in both CN and MCI subgroups while a significant association between WMH and memory was only found in the MCI subgroup. Furthermore, WMH was associated with EF in the group with A - T ± (N)+ or A - T + (N)± biomarker category, but not for A - T - (N)- (normal biomarker) and A + T ± (N) ± (AD pathology). The association between higher WMH and worse memory was independent of amyloid levels in individuals with MCI with evidence of AD pathology. CONCLUSION: Vascular disease, as indexed by WMH, independent of AD pathology affects cognitive function in both CN and MCI subgroups. Future studies using the AT(N) research framework should consider white matter lesions as a key biomarker contributing to the clinical presentation of AD.


Assuntos
Doença de Alzheimer/diagnóstico , Cognição , Disfunção Cognitiva/patologia , Leucoaraiose/patologia , Substância Branca/patologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/análise , Disfunção Cognitiva/diagnóstico por imagem , Estudos Transversais , Função Executiva , Feminino , Humanos , Leucoaraiose/psicologia , Modelos Lineares , Masculino , Memória , Transtornos da Memória/patologia , Transtornos da Memória/psicologia , Neuroimagem , Doenças Vasculares/patologia , Doenças Vasculares/psicologia , Substância Branca/diagnóstico por imagem
17.
Cureus ; 13(5): e14973, 2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-34123669

RESUMO

OBJECTIVE: Hemorrhage transformation (HT) is a known complication of arterial ischemic stroke (AIS). In addition, it is known that the increase of proinflammatory immune cells in the brain tissue after AIS predict worse outcomes. However, it is not clear whether inflammation due to preceding or post-stroke infections affect outcomes and moreover, if systemic inflammatory markers could be useful as a clinical prediction tool for HT post-stroke. Therefore, our objective was to assess the association between systemic pro-inflammatory profile in AIS patients with HT and in-hospital mortality that did not course with acute infections during hospitalization. METHODS: This study was conducted using the 2016 and 2017 National Inpatient Sample (NIS) with International Classification of Diseases (ICD-10) codes. Multivariate logistic regression was used to examine the association between HT and in-hospital mortality with pro-inflammatory anomalies of white blood cells (WBCs) in AIS patients. Exclusion criteria comprised patients with under 18 years old, and with a diagnosis of gastrointestinal, urogenital, respiratory infection, bacteremia, viral infection, sepsis, or fever. RESULTS: A total of 212,356 patients with AIS were included in the analysis. 422 (0.2%) patients had a HT and 10,230 (4.8%) patients died during hospitalization. The most common WBC pro-inflammatory marker was leukocytosis with 6.9% (n=29/422) of HT and 5.5% (n=560/10,230) of patients that died during hospitalization. After adjusting for socio-demographic, comorbidities and treatment factors, leukocytosis was found to be an independent risk factor for both outcomes, HT [OR = 1.5, 95% CI: 1-2.3, p=0.024] and, in-hospital mortality [OR = 1.5, 95% CI: 1.3-1.6, p < 0.001]. CONCLUSION: Sterile leukocytosis is a potential clinical prediction tool to determine which patients are at higher risk of developing HT and die during hospitalization.

18.
BMJ Open ; 11(8): e051052, 2021 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-34433608

RESUMO

OBJECTIVES: This is a qualitative study which aims to understand the lived experience of dietary changes among Chinese survivors of colorectal cancer who participated in a dietary intervention. SETTING: The surgical and oncological departments of four public hospitals in Hong Kong. PARTICIPANTS: Fifty-five Chinese colorectal cancer survivors who were aged 18 years or above and had received potentially curative treatment in the surgical and oncological departments in Hong Kong were examined. Participants' mean age was 64 years, with 29 (53%) males. INTERVENTION: A 12-month dietary intervention delivered via face-to-face motivational interviews, fortnightly motivational phone calls, monthly electronic pamphlets, quarterly newsletters and quarterly group meeting. OUTCOME MEASURE: We adopted the qualitative approach to capture participants' perspectives and to apply the understanding pragmatically in everyday life. Content analysis was conducted. RESULTS: We identified themes of motives to changes of dietary practices including (1) individual commitment to dietary change; (2) adaptive strategies in interpersonal contexts and (3) working with healthcare professionals during the journey. CONCLUSIONS: The findings demonstrated how Chinese custom and culture posing unique challenges to colorectal cancer survivors and the need of having dietary advice from healthcare professionals. Participants were motivated to change their eating habits by support from family, friends and healthcare professionals. Our findings could help healthcare professionals provide specific dietary advice and guidance to Chinese colorectal cancer survivors. TRIAL REGISTRATION NUMBER: NCT01708824.


Assuntos
Sobreviventes de Câncer , Neoplasias Colorretais , China , Hong Kong , Humanos , Masculino , Pessoa de Meia-Idade , Sobreviventes
19.
Artigo em Inglês | MEDLINE | ID: mdl-32570770

RESUMO

The urban forest is a green infrastructure system that delivers multiple environmental, economic, social and health services, and functions in cities. Environmental benefits of urban trees are well understood, but no review to date has examined how urban trees affect human health. This review provides a comprehensive summary of existing literature on the health impacts of urban trees that can inform future research, policy, and nature-based public health interventions. A systematic search used keywords representing human health, environmental health, and urban forestry. Following screening and appraisal of several thousand articles, 201 studies were conceptually sorted into a three-part framework. Reducing Harm, representing 41% of studies, includes topics such as air pollution, ultraviolet radiation, heat exposure, and pollen. Restoring Capacities, at 31%, includes attention restoration, mental health, stress reduction, and clinical outcomes. Building Capacities, at 28%, includes topics such as birth outcomes, active living, and weight status. The studies that were reviewed show substantial heterogeneity in purpose and method yet indicate important health outcomes associated with people's exposure to trees. This review will help inform future research and practice, and demonstrates why urban forest planning and management should strategically promote trees as a social determinant of public health.


Assuntos
Florestas , Árvores , Raios Ultravioleta , Saúde da População Urbana , Cidades , Agricultura Florestal , Humanos
20.
J Cancer Surviv ; 14(4): 424-433, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32072434

RESUMO

PURPOSE: To assess the effects of dietary and physical activity (PA) interventions on generic and cancer-specific quality of life (QoL), anxiety, and depression levels among adult Chinese colorectal cancer (CRC) survivors. METHODS: Two-hundred twenty-three adult CRC survivors within 1 year of completion of primary cancer treatment were randomized to receive dietary, PA or combined intervention, or usual care for a 12 monthduration, under a 2 (diet vs usual care) × 2 (PA vs usual care) factorial design. Generic and cancer-specific QoL was assessed using a Chinese version 12-Item Short Form Health Survey (SF-12) and the Functional Assessment of Cancer Therapy-Colorectal (FACT-C) scale, respectively. Anxiety and depression was assessed using the Hospital Anxiety and Depression Scale at baseline, 6, 12, 18, and 24 months. Linear mixed models were used for examining the intervention effects. RESULTS: Participants receiving dietary intervention experienced a significant improvement in the generic measure of QoL (SF-6D utility scores, mean difference 0.042, 95%CI 0.03 to 0.081) at 12 months, the cancer-specific QoL scores (mean difference 3.09, 95%CI 0.13 to 6.04), and levels of depression (P = 0.015) at both 12 and 24 months follow-up. Participants receiving PA intervention only demonstrated a significant improvement in SF-6D utility index (mean difference 0.039, 95%CI 0.002 to 0.077) and physical functioning (mean difference 2.85, 95%CI 1.00 to 4.70) at 6 months. CONCLUSIONS: Dietary intervention improved the generic and cancer-specific QoL and depression in CRC survivors. TRIAL REGISTRATION: The study was prospectively registered on 17 October 2012 at ClinicalTrials.gov (NCT01708824). IMPLICATIONS FOR CANCER SURVIVORS: CRC survivors can benefit from dietary interventions in alleviating depression and improving overall health-related QoL.


Assuntos
Ansiedade/terapia , Sobreviventes de Câncer/psicologia , Neoplasias Colorretais/terapia , Depressão/terapia , Dieta/psicologia , Exercício Físico/psicologia , Qualidade de Vida/psicologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sobreviventes
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