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1.
Laryngoscope ; 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38822697

RESUMEN

Liposarcomas are the most common soft tissue sarcoma in adults, whereas liposarcomas of the head and neck, particularly the hypopharynx, are incredibly rare - with approximately 50 cases reported in the literature. We present a case of an otherwise healthy and asymptomatic 42-year-old male who presented dramatically after vomiting up a large soft tissue mass. The lesion was surgically removed via transoral approach with blue laser, and diagnosis of well-differentiated liposarcoma was made via MDM2 gene amplification by FISH. Oral extrusion is a rare feature of this disease. This is the first documented case of an orally extruded liposarcoma to present in an otherwise asymptomatic and healthy patient, demonstrating how this entity may be indolent until initial presentation. Laryngoscope, 2024.

2.
Sci Adv ; 10(22): eadm6761, 2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38809986

RESUMEN

The quantum approximate optimization algorithm (QAOA) is a leading candidate algorithm for solving optimization problems on quantum computers. However, the potential of QAOA to tackle classically intractable problems remains unclear. Here, we perform an extensive numerical investigation of QAOA on the low autocorrelation binary sequences (LABS) problem, which is classically intractable even for moderately sized instances. We perform noiseless simulations with up to 40 qubits and observe that the runtime of QAOA with fixed parameters scales better than branch-and-bound solvers, which are the state-of-the-art exact solvers for LABS. The combination of QAOA with quantum minimum finding gives the best empirical scaling of any algorithm for the LABS problem. We demonstrate experimental progress in executing QAOA for the LABS problem using an algorithm-specific error detection scheme on Quantinuum trapped-ion processors. Our results provide evidence for the utility of QAOA as an algorithmic component that enables quantum speedups.

3.
Med Care Res Rev ; 81(3): 245-258, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38270374

RESUMEN

Surge management is important to hospital operations, yet surge literature has mostly focused on the addition of resources (e.g., 25% more beds) during events like pandemics. Such views are limiting, as meeting surge demands requires hospitals to engage in practices tailored to a surge's unique contingencies. We argue that a dynamic view of surge management should include surge management capability, which refers to how resources are deployed to respond to surge contingencies. To understand this capability, we qualitatively studied five hospital systems experiencing multiple surges due to COVID-19 between April 2020 and March 2022. We develop a framework showing that managing surges involves preserving capacity, expanding capacity, smoothing capacity demand, and enabling surge management. We contribute to surge literature by identifying practices hospitals can adopt to address surges and offering a better understanding of surge conditions (e.g., degree of novelty) that make some surge management practices more appropriate than others.


Asunto(s)
COVID-19 , Capacidad de Reacción , Humanos , COVID-19/terapia , COVID-19/epidemiología , SARS-CoV-2 , Pandemias , Administración Hospitalaria
4.
Health Care Manage Rev ; 48(3): 274-281, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37170401

RESUMEN

BACKGROUND: A large volume of literature identifies positive, rejuvenating benefits associated with giving compassion to others. However, the relationship between giving compassion and feelings of exhaustion remains underexplored. Understanding when giving compassion can potentially lead to feelings of emotional exhaustion is particularly important for nurses who are called upon to provide high levels of compassion to suffering patients in their daily work. We suggest that by engaging in transformational leadership behaviors, frontline supervisors can help nurses realize the positive benefits associated with giving compassion. PURPOSE: The aim of this study was to examine the impact of nurses' perceptions of transformational leadership offered by their supervisors on the relationship between the levels of compassionate behaviors nurses report engaging in with patients and feelings of emotional exhaustion and job satisfaction. METHODOLOGY/APPROACH: A time-lagged field survey was conducted across two waves of 112 full-time employed inpatient nurses within the United States. RESULTS: Providing high levels of compassionate behavior to patients was associated with reduced (increased) perceptions of emotional exhaustion and increased (decreased) job satisfaction when supervisors engaged in higher (lower) levels of transformational leadership. DISCUSSION: Transformational leadership serves as an important resource to help caregivers such that nurses feel invigorated and satisfied, as opposed to drained or fatigued, when engaging in high levels of compassionate behaviors toward suffering patients. PRACTICE IMPLICATIONS: For nurses to fully reap the established positive benefits associated with providing compassion to patients, frontline supervisors should be encouraged to engage in behaviors reflective of transformational leadership.


Asunto(s)
Liderazgo , Personal de Enfermería en Hospital , Humanos , Empatía , Personal de Enfermería en Hospital/psicología , Satisfacción en el Trabajo , Pacientes Internos , Encuestas y Cuestionarios
5.
Health Care Manage Rev ; 48(3): 260-273, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37158406

RESUMEN

BACKGROUND: Health care organizations are constantly creating new work to achieve evolving goals such as digitalization, equity, value, or well-being. However, scholars have paid less attention to how such work becomes "work" in the first place, despite implications for the design, quality, and experience of work and, consequently, employee and organizational outcomes. PURPOSE: The aim of this study was to investigate how new work becomes enacted in health care organizations. METHODOLOGY: A longitudinal, qualitative case study on the enactment of entrance screening-a new operation in response to COVID-19-in a multihospital academic medical center was performed. RESULTS: Entrance screening comprised four tasks, whose design was initially influenced by institutional guidelines (e.g., Centers for Disease Control and Prevention recommendations) and clinical experts. Organizational-level influences (e.g., resource availability) then became more prominent, necessitating multiple feedback-response loops to calibrate the performance of entrance screening. Finally, entrance screening was integrated into existing operations of the organization to ensure operational sustainability. The treatment of entrance screening as an operation changed over time-initially seen as infection control work, it eventually bifurcated into patient care and clerical work. CONCLUSION: The enactment of new work is constrained by the fit between resources and its intended output. Furthermore, the schema of work influences how and when organizational actors calibrate this fit. PRACTICE IMPLICATIONS: Health care leaders and managers should continuously update their schemas of work so that they can develop more sufficient and accurate representations of the employee capabilities that are required for the performance of new work.


Asunto(s)
COVID-19 , Humanos , Pandemias , Atención a la Salud
6.
Plast Reconstr Surg ; 152(3): 540e-546e, 2023 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-36790792

RESUMEN

BACKGROUND: The development of simulation, particularly low-cost models, has become a focus of interest within plastic surgery education. Current simulators for Mohs reconstruction are either expensive or not reusable. The authors hypothesize that using a Styrofoam head model during an interactive teaching session will positively affect plastic surgery trainee comfort in designing Mohs reconstructive options. METHODS: A cohort of integrated plastic surgery residents at a single institution performed a preactivity questionnaire to obtain baseline comfort in defect assessment and design for five Mohs defects. They subsequently underwent an interactive learning session and were instructed to design flaps on life-size Styrofoam heads with feedback from the senior author (M.L.B.). A postactivity questionnaire was completed to assess improvement in comfort in defect assessment and flap design. Three attending surgeons then compared trainee designs with the senior author's design to assess accuracy. All surveys were based on a five-point Likert scale. RESULTS: When analyzing all defects, average postactivity scores increased by 0.63 (SD, ±0.24) ( P = 0.008). Junior residents ( n = 8) had a greater increase in average score responses [mean, 1.07 (0.5 to 1.75)] compared with senior residents ( n = 9) [mean, 0.27 (0 to 1)] ( P < 0.001). When assessed by senior-level surgeons, senior residents had significantly greater accuracy in design for each defect ( P < 0.05) except cheek advancement flap ( P = 0.08). CONCLUSION: Participation in an interactive educational activity using a Styrofoam head model demonstrated significant improvements in trainee assessment and design of reconstructive options for Mohs defects.


Asunto(s)
Internado y Residencia , Procedimientos de Cirugía Plástica , Cirugía Plástica , Humanos , Colgajos Quirúrgicos , Cirugía de Mohs/métodos
7.
Otolaryngol Head Neck Surg ; 168(4): 761-768, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-35503657

RESUMEN

OBJECTIVE: We aim to more accurately characterize the current distribution and rates of squamous cell carcinoma (SCC) cases across various oral cavity subsites in the United States. STUDY DESIGN: Retrospective cohort. SETTING: Database study evaluating cancer incidence in the United States from 2001 to 2017. METHODS: We utilized the US Cancer Statistics Public Use Database, which includes deidentified cancer data reported to the Centers for Disease Control and Prevention's National Program of Cancer Registries and the National Cancer Institute's SEER (Surveillance, Epidemiology, and End Results), capturing 97% of newly diagnosed cancers. We restricted our analysis to SCC arising from oral cavity subsites from 2001 to 2017. We calculated trends in annual cancer incidence rates using SEER*Stat, as well as annual and average annual percentage change and joinpoints with the National Cancer Institute's Joinpoint program. RESULTS: Most oral cavity SCC cases arise from the oral tongue (41.7%), followed equally by lip and floor of mouth (each 16.5%), gingival (10.6%), buccal (6.7%), retromolar trigone (5.6%), and hard palate (2.3%) involvement. The overall incidence of oral tongue SCC continues to rise with an average annual percentage change of 1.8% (95% CI, 1.6%-2.1%; P < .001), with a 2.3% increase among women. This increase is seen among males and females of all age groups. Cancers involving the gum, buccal mucosa, and hard palate were also found to be increasing in rate, albeit to a lesser degree and with substantially lower incidence. CONCLUSIONS: The tongue is the most frequently involved subsite of oral cavity SCC and is increasing in incidence among males and females of all ages.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Masculino , Humanos , Femenino , Estados Unidos/epidemiología , Estudios Retrospectivos , Programa de VERF , Neoplasias de la Boca/epidemiología , Neoplasias de la Boca/patología , Carcinoma de Células Escamosas/epidemiología , Carcinoma de Células Escamosas/patología , Lengua/patología , Carcinoma de Células Escamosas de Cabeza y Cuello , Incidencia
8.
J Exp Psychol Learn Mem Cogn ; 49(1): 1-32, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-35549441

RESUMEN

A fundamental aspect of decision making is the speed-accuracy tradeoff (SAT): slower decisions tend to be more accurate, but because time is a scarce resource people prefer to conclude decisions more quickly. The current research adds to the SAT literature by documenting two previously unrecognized influences on the SAT: perception shifts and goal activation. Decision makers' perceptions of what constitutes a fast or a slow decision, and what constitutes an accurate or inaccurate decision, are based on prior experience, and these perceptions influence decision speed. Similarly, previous experience in a decision context associates the context with a particular decision goal. Thus, in later decisions the decision context will activate this goal, and influence decision speed. Both of these mechanisms contribute to a specific decision bias: decision speeds are biased toward original decision speeds in a decision context. Four experiments provide evidence for the bias and the two contributing mechanisms. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Asunto(s)
Toma de Decisiones , Objetivos , Humanos , Toma de Decisiones/fisiología , Percepción
9.
Ear Nose Throat J ; : 1455613221134428, 2022 Oct 14.
Artículo en Inglés | MEDLINE | ID: mdl-36240145

RESUMEN

Objective: To determine if postponement of elective pediatric otorhinolaryngology surgeries results in a change in overall healthcare utilization and if there is any commensurate impact on disease progression. Methods: We identified patients ≤18 years of age whose surgeries were postponed at the onset of the COVID-19 pandemic-related shutdown. We then tracked patients' rate of and patterns of rescheduling surgery. Surveys were also sent to caregivers to better characterize his/her decision regarding moving forward with his/her child's surgery during COVID-19. Results: A total of 1915 pediatric patients had elective surgeries canceled, of which 992 (51.8%) were rescheduled within 4 months. No difference in rates of rescheduling was identified based on race or ethnicity. Patients who were scheduled for tonsillectomies and/or adenoidectomies were 1.22 times more likely to reschedule compared to those patients with other planned procedures (CI: 1.02-1.46). A total of 95 caregivers at two hospitals completed surveys: 44 (47.4%) rescheduled their child's surgery. Most caregivers who rescheduled were concerned their child's disease could impact their future (n = 14, 32%). Conclusions: Just over half of patients who had pediatric otolaryngologic surgery canceled during a period of social distancing went on to have surgery within a 4-month timeframe. This reflects the dependence of pediatric otolaryngologic surgery on environmental exposures and may represent a potential target for prevention and management of some pediatric otolaryngology diseases.

10.
PLoS One ; 17(10): e0276047, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36240209

RESUMEN

Mutation in the CTNNB1 gene, leading to a deregulation of the WTN/ß-catenin pathway, is a common feature of desmoid tumors (DTs). Many ß-catenin inhibitors have recently been tested in clinical studies; however, BC2059 (also referred as Tegavivint), a selective inhibitor of nuclear ß-catenin that works through binding TBL-1, is the only one being evaluated in a clinical study, specifically for treatment of desmoid tumor patients. Preclinical studies on BC2059 have shown activity in multiple myeloma, acute myeloid leukemia and osteosarcoma. Our preclinical studies provide data on the efficacy of BC2059 in desmoid cell lines, which could help provide insight regarding antitumor activity of this therapy in desmoid tumor patients. In vitro activity of BC2059 was evaluated using desmoid tumor cell lines. Ex vivo activity of BC2059 was assessed using an explant tissue culture model. Pharmacological inhibition of the nuclear ß-catenin activity using BC2059 markedly inhibited cell viability, migration and invasion of mutated DT cells, but with lower effect on wild-type DTs. The decrease in cell viability of mutated DT cells caused by BC2059 was due to apoptosis. Treatment with BC2059 led to a reduction of ß-catenin-associated TBL1 in all mutated DT cells, resulting in a reduction of nuclear ß-catenin. mRNA and protein levels of AXIN2, a ß-catenin target gene, were also found to be downregulated after BC2059 treatment. Taken together, our results demonstrate that nuclear ß-catenin inhibition using BC2059 may be a novel therapeutic strategy for desmoid tumor treatment, especially in patients with CTNNB1 mutation.


Asunto(s)
Neoplasias Óseas , Fibromatosis Agresiva , Fibromatosis Agresiva/patología , Humanos , Mutación , ARN Mensajero/genética , Vía de Señalización Wnt , beta Catenina/metabolismo
12.
Plast Reconstr Surg ; 150(2): 317-324, 2022 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-35666161

RESUMEN

SUMMARY: Patient demand for nonsurgical and minimally invasive cosmetic treatments has increased in recent years, resulting in a growing market that is particularly vulnerable to specialty creep. Despite this growing demand, nonsurgical cosmetic training for plastic surgery residents is often inconsistent and challenging. To ensure the continued safe and effective delivery of nonsurgical cosmetic care by board-certified plastic surgeons, it is critical to implement standardized training models for plastic surgery residents. In this Special Topic article, the authors describe their experience with a resident-run clinic training model that incorporates graduated autonomy, volunteer patient recruitment, and grant-based industry support that has been successfully implemented at their institution for the past 6 years. The article provides a framework for a resident educational model and addresses common obstacles in resident cosmetic training. The authors also provide recommendations for patient recruitment, optimizing clinic workflow, and the management of patient complications.


Asunto(s)
Internado y Residencia , Procedimientos de Cirugía Plástica , Clínica Administrada por Estudiantes , Cirujanos , Cirugía Plástica , Humanos , Procedimientos de Cirugía Plástica/educación , Cirugía Plástica/educación
13.
Aesthetic Plast Surg ; 46(5): 2573-2579, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35545704

RESUMEN

BACKGROUND: An aesthetic surgery offering within academic programs has positive financial and educational implications. To compete with private practices, academic institutions must view their website as integral to patient recruitment. OBJECTIVE: This study examines the aesthetic surgery websites of academic and private practices to compare objective website characteristics. METHODS: Integrated plastic surgery programs with an aesthetic surgery website were matched with nearby private practices offering cosmetic surgery. Data was collected from websites, including information about procedures, media, surgeon characteristics, design, reputation, finances, and readability, and compared using Chi-square and T tests. RESULTS: The websites of 68 academic institutions (AP) and 68 location-matched private practices (PP) were examined. Fourteen (17.07%) programs did not have a website. Private practice websites provided information about a greater number of procedures (mean AP 21.82, PP 27.04, p = 0.013), preparation for surgery (AP 52.94%, PP 83.82%, p < 0.001), and expectations after surgery (AP 70.59%, PP 88.24%, p = 0.01). Board certification was listed more frequently for private practices (AP 87%, PP 98%, p = 0.01). Academic websites were more likely to discuss research (AP 76%, PP 57.35%, p = 0.02). There was no significant difference in the readability of AP and PP websites (mean SMOG AP 7.70, PP 7.19, p = 0.06). CONCLUSIONS: This work demonstrates a significant content gap between private and academic aesthetic websites and serves as an action item for institutions to enhance their online presence. In a field traditionally associated with high overhead costs, website modifications represent a cost-effective way for academic practices to increase their appeal in the cosmetic surgery market. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Asunto(s)
Procedimientos de Cirugía Plástica , Cirugía Plástica , Humanos , Esmog , Cirugía Plástica/métodos , Estética , Procedimientos de Cirugía Plástica/métodos , Práctica Privada
14.
Am J Emerg Med ; 54: 257-262, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35219011

RESUMEN

AIM: This study aimed to describe the prevalence of hypoxic-ischemic brain injury (HIBI) on head CT (HCT) obtained within two hours of return of spontaneous circulation (ROSC) care in the Emergency Department following out-of-hospital cardiac arrest (OHCA) and evaluate the association between early HIBI and neurologic outcome. METHODS: Retrospective single center observational study of post-OHCA patients between 2009 and 2017. Two cohorts were analyzed: those who underwent non-contrast HCT within two hours of ROSC and all others who survived to ICU admission. HIBI was defined as the presence of cerebral edema and/or abnormal gray-white matter differentiation in the HCT interpretation by a neuroradiologist. The primary outcomes were the prevalence of HIBI on early HCT and the magnitude of the association between HIBI and survival with good neurologic outcome using multivariable logistic regression. RESULTS: Following OHCA, 333 of 520 patients (64%) underwent HCT within two hours of ROSC and HIBI was present in 96 of 333 patients (29%). Of the early HCT cohort, those with HIBI had a significantly lower hospital survival (2%) and favorable neurologic outcome (1%). In those without HIBI on imaging, 88 of 237 patients (37%) had a favorable outcome. After adjustment for confounding variables, HIBI on early HCT was independently associated with a decreased likelihood of good neurologic outcome (aOR 0.015, 95% CI 0.002-0.12). CONCLUSION: HIBI was present on 29% of HCTs obtained within 2 h of ROSC in the patients selected for early imaging by emergency physicians and was strongly and inversely associated with survival with a good neurologic outcome.


Asunto(s)
Lesiones Encefálicas , Reanimación Cardiopulmonar , Hipoxia-Isquemia Encefálica , Paro Cardíaco Extrahospitalario , Humanos , Hipoxia-Isquemia Encefálica/complicaciones , Hipoxia-Isquemia Encefálica/diagnóstico por imagen , Hipoxia-Isquemia Encefálica/epidemiología , Paro Cardíaco Extrahospitalario/diagnóstico por imagen , Paro Cardíaco Extrahospitalario/terapia , Estudios Retrospectivos , Tomografía Computarizada por Rayos X
15.
Arch Plast Surg ; 48(6): 651-659, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34818713

RESUMEN

BACKGROUND: Many surgical specialties have had pioneering influences from plastic surgeons. However, many of these areas of practice have evolved to include surgeons from diverse training backgrounds. This raises the question as to whether the prominence of other specialties in clinical practice translates to greater research productivity in these areas. The objective of this paper is to investigate the publication volumes of plastic surgeons in selected areas of practice compared to surgeons from other disciplines. METHODS: PubMed was used to examine publication trends in areas associated with plastic surgery. Searches for the following topics were performed: head and neck reconstruction, hand surgery, breast reconstruction, ventral hernia repair, abdominal component separation, brachial plexus injury, craniofacial surgery, and aesthetic surgery. Affiliation tags were used to examine contributions from nine specialties. Web of Science was used to identify the top cited articles for the last 10 years in each area. RESULTS: Articles by non-plastic surgeons comprise the majority of the literature for all areas of practice studied except for breast reconstruction and aesthetic surgery. Despite this, plastic surgeons contributed the greatest number of top cited articles over the last 10 years for five of the areas of practice. CONCLUSIONS: While plastic surgeons do not contribute the greatest proportion of articles published each year in several of the selected areas of practice, they do publish a larger number of articles that are the most cited. Plastic surgeons remain the dominant academic force in terms of volume and citations for both breast and aesthetic surgery.

16.
J Urol ; 205(4): 1159-1168, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33079618

RESUMEN

PURPOSE: Clinical trials require significant resources, but benefits are only realized after trial completion and dissemination of results. We comprehensively assessed early discontinuation, registry results reporting, and publication by trial sponsor and subspecialty in urology trials. MATERIALS AND METHODS: We assessed trial registrations from 2007 to 2019 on ClinicalTrials.gov and publication data from PubMed®/MEDLINE®. Associations between sponsor or subspecialty with early discontinuation were assessed using Cox proportional hazards and results reporting or publication with logistic regression at 3 years after completion. RESULTS: Of 8,636 trials 3,541 (41.0%) were completed and 999 (11.6%) were discontinued. Of completed trials 26.9% reported results and 21.6% were published. Sponsors included academic institutions (53.1%), industry (37.1%) and the U.S. government (9.8%). Academic-sponsored (adjusted HR 0.81, 95% CI 0.69-0.96, p=0.012) and government-sponsored trials (adjusted HR 0.62, 95% CI 0.49-0.78, p <0.001) were less likely than industry to discontinue early. Government-sponsored trials were more likely to report (adjusted OR 1.72, 95% CI 1.17-2.54, p=0.006) and publish (adjusted OR 1.89, 95% CI 1.23-2.89, p=0.004). Academic-sponsored trials were less likely to report (adjusted OR 0.65, CI:0.48-0.88, p=0.006) but more likely to publish (adjusted OR 1.72, 95% CI 1.25-2.37, p <0.001). These outcomes were similar across subspecialties. However, endourology was more likely to discontinue early (adjusted HR 2.00, 95% CI 1.53-2.95, p <0.001), general urology was more likely to report results (adjusted OR 1.54, 95% CI 1.13-2.11, p=0.006) and andrology was less likely to publish (adjusted OR 0.53, 95% CI 0.35-0.81, p=0.003). CONCLUSIONS: Sponsor type is significantly associated with trial completion and dissemination. Government-sponsored trials had the best performance, while industry and academic-sponsored trials lagged in completion and results reporting, respectively. Subspecialty played a lesser role. Lack of dissemination remains a problem for urology trials.


Asunto(s)
Ensayos Clínicos como Asunto , Urología , Bases de Datos Factuales , Humanos , Difusión de la Información , Publicaciones Periódicas como Asunto , Edición , Sistema de Registros , Estados Unidos
17.
Plast Reconstr Surg Glob Open ; 8(5): e2838, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-33133899

RESUMEN

With the shift in public opinion and legalization of cannabis for therapeutic and recreational use, cannabis consumption has become more common. This trend will likely continue as decriminalization and legalization of marijuana and associated cannabinoids expand. Despite this increase in use, our familiarity with this drug and its associated effects remains incomplete. The aim of this review is to describe the physiologic effects of marijuana and its related compounds, review current literature related to therapeutic applications and consequences, discuss potential side effects of marijuana in surgical patients, and provide recommendations for the practicing plastic surgeon. Special attention is given to areas that directly impact plastic surgery patients, including postoperative pain, nausea and vomiting and wound healing. Although the literature demonstrates substantial support for marijuana in areas such as chronic pain and nausea and vomiting associated with chemotherapy, the data supporting its use for common perioperative problems are lacking. Its use for treating perioperative problems, such as pain and nausea, is poorly supported and requires further research.

18.
J Natl Cancer Inst ; 111(11): 1216-1227, 2019 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-30793158

RESUMEN

BACKGROUND: The Wnt/ß-catenin pathway is closely associated with osteosarcoma (OS) development and metastatic progression. We investigated the antitumor activity of Tegavivint, a novel ß-catenin/transducin ß-like protein 1 (TBL1) inhibitor, against OS employing in vitro, ex vivo, and in vivo cell line and patient-derived xenograft (PDX) models that recapitulate high risk disease. METHODS: The antitumor efficacy of Tegavivint was evaluated in vitro using established OS and PDX-derived cell lines. Use of an ex vivo three-dimensional pulmonary metastasis assay assessed targeting of ß-catenin activity during micro- and macrometastatic development. The in vivo activity of Tegavivint was evaluated using chemoresistant and metastatic OS PDX models. Gene and protein expression were quantified by quantitative Reverse transcription polymerase chain reaction or immunoblot analysis. Bone integrity was determined via microCT. All statistical tests were two-sided. RESULTS: Tegavivint exhibited antiproliferative activity against OS cells in vitro and actively reduced micro- and macrometastatic development ex vivo. Multiple OS PDX tumors (n = 3), including paired patient primary and lung metastatic tumors with inherent chemoresistance, were suppressed by Tegavivint in vivo. We identified that metastatic lung OS cell lines (n = 2) exhibited increased stem cell signatures, including enhanced concomitant aldehyde dehydrogenase (ALDH1) and ß-catenin expression and downstream activity, which were suppressed by Tegavivint (ALDH1: control group, mean relative mRNA expression = 1.00, 95% confidence interval [CI] = 0.68 to 1.22 vs Tegavivint group, mean = 0.011, 95% CI = 0.0012 to 0.056, P < .001; ß-catenin: control group, mean relative mRNA expression = 1.00, 95% CI = 0.71 to 1.36 vs Tegavivint group, mean = 0.45, 95% CI = 0.36 to 0.52, P < .001). ALDH1high PDX-derived lung OS cells, which demonstrated enhanced metastatic potential compared with ALDHlow cells in vivo, were sensitive to Tegavivint. Toxicity studies revealed decreased bone density in male Tegavivint-treated mice (n = 4 mice per group). CONCLUSIONS: Tegavivint is a promising therapeutic agent for advanced stages of OS via its targeting of the ß-catenin/ALDH1 axis.


Asunto(s)
Aldehído Deshidrogenasa/antagonistas & inhibidores , Antineoplásicos/farmacología , Resistencia a Antineoplásicos/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Neoplasias Pulmonares/tratamiento farmacológico , Osteosarcoma/tratamiento farmacológico , beta Catenina/antagonistas & inhibidores , Animales , Apoptosis , Biomarcadores de Tumor/metabolismo , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/metabolismo , Neoplasias Óseas/patología , Proliferación Celular , Inhibidores Enzimáticos/farmacología , Femenino , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundario , Masculino , Ratones , Ratones Endogámicos NOD , Ratones SCID , Osteosarcoma/metabolismo , Osteosarcoma/patología , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto , beta Catenina/metabolismo
20.
J Heart Valve Dis ; 26(4): 472-480, 2017 07.
Artículo en Inglés | MEDLINE | ID: mdl-29302948

RESUMEN

BACKGROUND AND AIM OF THE STUDY: Xenograft conduits have been used successfully to repair congenital heart defects, but are prone to failure over time. Hence, in order to improve patient outcomes, better xenografts are being developed. When evaluating a conduit's performance and safety it must first be compared against a clinically available control in a large animal model. The study aim was to evaluate a clinically available xenograft conduit used in right ventricular outflow tract (RVOT) reconstruction in a sheep model. METHODS: RVOT reconstruction was performed in 13 adult and juvenile sheep, using the Medtronic Hancock® Bioprosthetic Valved Conduit (Hancock conduit). The method had previously been used on patients, and a newly modified variant termed 'RVOT Extraction' was employed to facilitate the surgical procedure. Animals were monitored over predetermined terms of 70 to 140 days. Serial transthoracic echocardiography, intracardiac pressure measurements and angiography were performed. On study completion the animals were euthanized and necropsies performed. RESULTS: Two animals died prior to their designated study term due to severe valvular stenosis and distal conduit narrowing, respectively. Thus, 11 animals survived the study term, with few or no complications. Generally, maximal and mean transvalvular pressure gradients across the implanted conduits were increased throughout the postoperative course. Among 11 full-term animals, seven conduits were patent with mild or no pseudointimal proliferation and with flexible leaflets maintaining the hemodynamic integrity of the valve. CONCLUSIONS: RVOT reconstruction using the Hancock conduit was shown to be successful in sheep, with durable and efficient performances. With its extensive clinical use in patients, and ability for long-term use in sheep (as described in the present study) it can be concluded that the Hancock conduit is an excellent control device for the evaluation of new xenografts in future preclinical studies.


Asunto(s)
Bioprótesis , Implantación de Prótesis Vascular/instrumentación , Prótesis Vascular , Implantación de Prótesis de Válvulas Cardíacas/instrumentación , Prótesis Valvulares Cardíacas , Ventrículos Cardíacos/cirugía , Arteria Pulmonar/cirugía , Válvula Pulmonar/cirugía , Animales , Implantación de Prótesis Vascular/efectos adversos , Ecocardiografía Doppler en Color , Estudios de Factibilidad , Implantación de Prótesis de Válvulas Cardíacas/efectos adversos , Ventrículos Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/fisiopatología , Xenoinjertos , Ensayo de Materiales , Modelos Animales , Tereftalatos Polietilenos , Diseño de Prótesis , Arteria Pulmonar/diagnóstico por imagen , Arteria Pulmonar/fisiopatología , Circulación Pulmonar , Válvula Pulmonar/diagnóstico por imagen , Válvula Pulmonar/fisiopatología , Oveja Doméstica , Factores de Tiempo , Función Ventricular Derecha
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