Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 334
Filtrar
1.
Nat Mater ; 23(8): 1138-1149, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38965405

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is characterized by its fibrotic and stiff extracellular matrix. However, how the altered cell/extracellular-matrix signalling contributes to the PDAC tumour phenotype has been difficult to dissect. Here we design and engineer matrices that recapitulate the key hallmarks of the PDAC tumour extracellular matrix to address this knowledge gap. We show that patient-derived PDAC organoids from three patients develop resistance to several clinically relevant chemotherapies when cultured within high-stiffness matrices mechanically matched to in vivo tumours. Using genetic barcoding, we find that while matrix-specific clonal selection occurs, cellular heterogeneity is not the main driver of chemoresistance. Instead, matrix-induced chemoresistance occurs within a stiff environment due to the increased expression of drug efflux transporters mediated by CD44 receptor interactions with hyaluronan. Moreover, PDAC chemoresistance is reversible following transfer from high- to low-stiffness matrices, suggesting that targeting the fibrotic extracellular matrix may sensitize chemoresistant tumours. Overall, our findings support the potential of engineered matrices and patient-derived organoids for elucidating extracellular matrix contributions to human disease pathophysiology.


Assuntos
Carcinoma Ductal Pancreático , Resistencia a Medicamentos Antineoplásicos , Matriz Extracelular , Organoides , Neoplasias Pancreáticas , Humanos , Organoides/metabolismo , Organoides/patologia , Organoides/efeitos dos fármacos , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/tratamento farmacológico , Matriz Extracelular/metabolismo , Ácido Hialurônico/metabolismo , Ácido Hialurônico/química , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico
2.
J Urol ; 212(1): 165-174, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38700226

RESUMO

PURPOSE: Urodynamic testing (UDS) is an important tool in the management of pediatric lower urinary tract conditions. There have been notable efforts to standardize pediatric UDS nomenclature and technique, but no formal guidelines exist on essential elements to include in a clinical report. We sought to identify ideal structure and elements of a pediatric UDS assessment based on expert consensus. MATERIALS AND METHODS: Pediatric urologists regularly performing UDS were queried using a Delphi process. Participants were invited representing varied geographic, experience, and societal involvement. Participants underwent 3 rounds of questionnaires between November 2022 and August 2023 focusing on report organization, elements, definitions, and automated electronic health record clinical decision support. Professional billing requirements were also considered. Consensus was defined as 80% agreeing either in favor of or against a topic. Elements without consensus were discussed in subsequent rounds. RESULTS: A diverse sample of 30 providers, representing 27 institutions across 21 US states; Washington, District of Columbia; and Canada completed the study. Participants reported interpreting an average number of 5 UDS reports per week (range 1-22). The finalized consensus report identifies 93 elements that should be included in a pediatric UDS report based on applicable study conditions and findings. CONCLUSIONS: This consensus report details the key elements and structure agreed upon by an expert panel of pediatric urologists. Further standardization of documentation should aid collaboration and research for patients undergoing UDS. Based on this information, development of a standardized UDS report template using electronic health record implementation principles is underway, which will be openly available for pediatric urologists.


Assuntos
Consenso , Técnica Delphi , Urodinâmica , Humanos , Criança , Urologia/normas , Pediatria/normas , Masculino , Inquéritos e Questionários
3.
J Gen Intern Med ; 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38662283

RESUMO

Food is Medicine (FIM) programs to improve the accessibility of fruits and vegetables (FVs) or other healthy foods among patients with low income and diet-related chronic diseases are promising to improve food and nutrition security in the United States (US). However, FIM programs are relatively new and implementation guidance for healthcare settings using an implementation science lens is lacking. We used a narrative review to describe the evidence base on barriers and facilitators to FIM program integration in US healthcare settings following the Exploration, Preparation, Implementation, and Sustainment (EPIS) Framework. Evidence surrounding the EPIS Inner Context was a focus, including constructs Leadership, Organizational Characteristics, Quality and Fidelity Monitoring and Support, Organizational Staffing Processes, and Individual Characteristics. Peer-reviewed and grey literature about barriers and facilitators to FIM programs were of interest, defined as programs that screen and refer eligible patients with diet-related chronic disease experiencing food insecurity to healthy, unprepared foods. Thirty-one sources were included in the narrative review, including 22 peer-reviewed articles, four reports, four toolkits, and one thesis. Twenty-eight sources (90%) described EPIS Inner Context facilitators and 26 sources (84%) described FIM program barriers. The most common barriers and facilitators to FIM programs were regarding Quality and Fidelity Monitoring and Support (e.g., use of electronic medical records for tracking and evaluation, strategies to support implementation) and Organizational Staffing Processes (e.g., clear delineation of staff roles and capacity); although, barriers and facilitators to FIM programs were identified among all EPIS Inner Context constructs. We synthesized barriers and facilitators to create an EPIS-informed implementation checklist for healthcare settings for use among healthcare organizations/providers, partner organizations, and technical assistance personnel. We discuss future directions to align FIM efforts with implementation science terminology and theories, models, and frameworks to improve the implementation evidence base and support FIM researchers and practitioners.

4.
Ear Hear ; 45(2): 511-516, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38047764

RESUMO

OBJECTIVES: A method for stimulating the cochlear apex using perimodiolar electrode arrays is described. This method involves implanting an electrode (ECE1) into the helioctrema in addition to standard cochlear implant placement. One objective is to verify a suitable approach for implanting ECE1 in the helicotrema. Another is to determine how placement of ECE1 reshapes electric fields. DESIGN: Two cadaveric half-heads were implanted, and electric voltage tomography was measured with ECE1 placed in many positions. RESULTS: An approach for placing ECE1 was identified. Changes in electric fields were only observed when ECE1 was placed into the fluid in the helicotrema. When inside the helicotrema, electric voltage tomography modeling suggests an increased current flow toward the apex. CONCLUSIONS: Placement of ECE1 into the cochlear apex is clinically feasible and has the potential to reshape electric fields to stimulate regions of the cochlea more apical than those represented by the electrode array.


Assuntos
Implante Coclear , Implantes Cocleares , Humanos , Eletrodos Implantados , Implante Coclear/métodos , Cóclea/cirurgia
5.
Graefes Arch Clin Exp Ophthalmol ; 262(5): 1545-1552, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38095689

RESUMO

PURPOSE: To assess the accuracy of intraoperative wavefront aberrometry (IWA) versus modern intraocular lens formulas in post-myopic laser vision correction (LVC) patients undergoing cataract surgery with capsular tension ring placement. METHODS: This is a retrospective chart review conducted at an academic outpatient center. All post-myopic LVC eyes undergoing cataract surgery with IWA from a single surgeon from 05/2017 to 12/2019 were included. All patients received a capsular tension ring (CTR). Mean numerical error (MNE), median numerical error (MedNE), and percentages of prediction error within 0.50D, 0.75D, and 1.00D were calculated for the above formulas. RESULTS: Twenty-seven post-myopic LVC eyes from 18 patients were included. In post-myopic LVC, MNE with Optiwave Refractive Analysis (ORA), Barrett True K (BTK), Haigis, Haigis-L, Shammas, SRK/T, Hill-RBF v3.0, and W-K AL-adjusted Holladay 1 were + 0.224, - 0.094, + 0.193, - 0.231, - 0.372, + 1.013, + 0.860, and + 0.630 (F = 8.49, p < 0.001). MedNE were + 0.125, - 0.145, + 0.175, + 0.333, + 0.333, + 1.100, + 0.880, and + 0.765 (F = 7.89, p < 0.001), respectively. BTK provided improved accuracy in both MNE (p < 0.001) and MedNE (p = .033) when compared to ORA in pairwise analysis. If the ORA vs. BTK-suggested IOL power were routinely selected, 30% and 15% of eyes would have projected hyperopic outcomes, respectively (p = 0.09). CONCLUSIONS: Our study suggests that in post-myopic LVC eyes undergoing cataract surgery with CTRs, BTK performed more accurately than ORA with regard to accuracy and yielded a lower percentage of eyes with hyperopic outcomes. Haigis, Haigis-L, and Shammas yielded similar results to ORA with regard to accuracy and percentage of eyes with hyperopic outcomes. On average, Shammas and Haigis-L suggested IOLs that would yield outcomes more myopic than expected when compared to BTK.

6.
J Urol ; 210(2): 352-359, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37195856

RESUMO

PURPOSE: Testosterone administration prior to hypospadias repair is common practice among pediatric urologists; however, its impact on surgical outcomes remains controversial. We hypothesize that testosterone administration prior to distal hypospadias repair with urethroplasty significantly decreases postoperative complications. MATERIALS AND METHODS: We queried our hypospadias database for primary distal hypospadias repairs with urethroplasty from 2015 to 2021. Patients undergoing repair without urethroplasty were excluded. We collected information on patient age, procedure type, testosterone administration status, initial visit and intraoperative glans width, urethroplasty length, and postoperative complications. To determine the role of testosterone administration on incidence of complications, a logistic regression adjusting for initial visit glans width, urethroplasty length, and age was performed. RESULTS: A total of 368 patients underwent distal hypospadias repair with urethroplasty. One hundred thirty-three patients received testosterone and 235 did not. Initial visit glans width was significantly larger in the no-testosterone vs testosterone group (14.5 mm vs 13.1 mm, P = .001). Testosterone patients had significantly larger glans width at the time of surgery (17.1 mm vs 14.6 mm [no-testosterone group], P = .001). On multivariable logistic regression analysis after controlling for age at surgery, preoperative glans width, testosterone status, and urethroplasty length, testosterone administration did show significant association with reduced odds of postoperative complications (OR 0.4, P = .039). CONCLUSIONS: This retrospective review of patients shows that on multivariable analysis there is significant association between testosterone administration and decreased incidence of complications in patients undergoing distal hypospadias repair with urethroplasty. Future studies on testosterone administration should focus on specific cohorts of patients with hypospadias as benefits of testosterone may be more evident in some subgroups than others.


Assuntos
Hipospadia , Procedimentos de Cirurgia Plástica , Masculino , Humanos , Criança , Lactente , Hipospadia/cirurgia , Hipospadia/complicações , Testosterona , Uretra/cirurgia , Procedimentos de Cirurgia Plástica/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Resultado do Tratamento , Procedimentos Cirúrgicos Urológicos Masculinos/efeitos adversos , Procedimentos Cirúrgicos Urológicos Masculinos/métodos
7.
J Urol ; 209(5): 994-1003, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36787376

RESUMO

PURPOSE: Urologists rely heavily on videourodynamics to identify patients with neurogenic bladders who are at risk of upper tract injury, but their interpretation has high interobserver variability. Our objective was to develop deep learning models of videourodynamics studies to categorize severity of bladder dysfunction. MATERIALS AND METHODS: We performed a cross-sectional study of patients aged 2 months to 28 years with spina bifida who underwent videourodynamics at a single institution between 2019 and 2021. The outcome was degree of bladder dysfunction, defined as none/mild, moderate, and severe, defined by a panel of 5 expert reviewers. Reviewers considered factors that increase the risk of upper tract injury, such as poor compliance, elevated detrusor leak point pressure, and detrusor sphincter dyssynergia, in determining bladder dysfunction severity. We built 4 models to predict severity of bladder dysfunction: (1) a random forest clinical model using prospectively collected clinical data from videourodynamics studies, (2) a deep learning convolutional neural network of raw data from the volume-pressure recordings, (3) a deep learning imaging model of fluoroscopic images, (4) an ensemble model averaging the risk probabilities of the volume-pressure and fluoroscopic models. RESULTS: Among 306 videourodynamics studies, the accuracy and weighted kappa of the ensemble model classification of bladder dysfunction when at least 75% expected bladder capacity was reached were 70% (95% CI 66%,76%) and 0.54 (moderate agreement), respectively. The performance of the clinical model built from data extracted by pediatric urologists was the poorest with an accuracy of 61% (55%, 66%) and a weighted kappa of 0.37. CONCLUSIONS: Our models built from urodynamic pressure-volume tracings and fluoroscopic images were able to automatically classify bladder dysfunction with moderately high accuracy.


Assuntos
Aprendizado Profundo , Disrafismo Espinal , Bexiga Urinaria Neurogênica , Criança , Humanos , Bexiga Urinária/diagnóstico por imagem , Estudos Transversais , Bexiga Urinaria Neurogênica/diagnóstico , Bexiga Urinaria Neurogênica/etiologia , Disrafismo Espinal/complicações , Urodinâmica
8.
Ophthalmology ; 130(6): 598-607, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36739981

RESUMO

PURPOSE: To validate the prognostic usefulness of gene expression profile (GEP) testing in patients with uveal melanoma. To determine whether combining tumor size with the GEP classification provides additional prognostic value. DESIGN: Retrospective analysis. PARTICIPANTS: Patients with a diagnosis of choroidal melanoma examined at Yale New Haven Hospital; University of California, San Diego; and Memorial Sloan Kettering Cancer Center. METHODS: Patients' demographic and clinical data and tumor characteristics were collected. Univariate and multivariate Cox hazard regression analysis were used to assess the association between tumor characteristics and GEP classification with metastasis as an outcome. MAIN OUTCOME MEASURES: Metastasis-free survival (MFS). RESULTS: Of the 337 individuals included in the study, 87 demonstrated metastases. The mean follow-up time was 37.2 (standard deviation [SD], 40.2) months for patients with metastases and 55.0 (SD, 49.3) months for those without metastases. Tumors of larger thickness and GEP class 2 (vs. class 1) were associated significantly with increased risk of metastasis. Tumor thickness showed better prognostic usefulness than GEP classification (Wald statistic, 40.7 and 24.2, respectively). Class 2 tumors with a thickness of 7.0 mm or more were associated with increased risk of metastasis than tumors with a thickness of < 7.0 mm (hazard ratio [HR], 3.23; 95% confidence interval [CI], 1.61-6.51), whereas class 1 tumors with a thickness of 9.0 mm or more were associated with increased risk of metastasis than tumors with a thickness of < 9.0 mm (HR, 2.07; 95% CI, 0.86-4.99). No difference in MFS was found between patients with class 1A tumors compared with those with class 1B tumors (P = 0.8). Patients with class 2 tumors showed an observed 5-year MFS of 47.5% (95% CI, 36.0%-62.8%). CONCLUSIONS: Tumor size was the most significant predictor of metastasis and provided additional prognostic value independent of GEP classification. In addition, rates of metastasis for class 2 tumors were lower than estimates reported by Castle Bioscience, and no difference in rates of metastasis were found between class 1A and 1B tumors. This indicates that tumor size should be accounted for when relying on GEP for prognostication and that patients with GEP class 1A or 1B tumors may benefit from the same metastatic surveillance protocols. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.


Assuntos
Melanoma , Neoplasias Uveais , Humanos , Prognóstico , Estudos Retrospectivos , Melanoma/diagnóstico , Melanoma/genética , Melanoma/metabolismo , Neoplasias Uveais/diagnóstico , Neoplasias Uveais/genética , Neoplasias Uveais/patologia , Perfilação da Expressão Gênica/métodos
9.
Pediatr Nephrol ; 38(3): 839-846, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-35867160

RESUMO

BACKGROUND: We sought to use deep learning to extract anatomic features from postnatal kidney ultrasounds and evaluate their performance in predicting the risk and timing of chronic kidney disease (CKD) progression for boys with posterior urethral valves (PUV). We hypothesized that these features would predict CKD progression better than clinical characteristics such as nadir creatinine alone. METHODS: We performed a retrospective cohort study of boys with PUV treated at two pediatric health systems from 1990 to 2021. Features of kidneys were extracted from initial postnatal kidney ultrasound images using a deep learning model. Three time-to-event prediction models were built using random survival forests. The Imaging Model included deep learning imaging features, the Clinical Model included clinical data, and the Ensemble Model combined imaging features and clinical data. Separate models were built to include time-dependent clinical data that were available at 6 months, 1 year, 3 years, and 5 years. RESULTS: Two-hundred and twenty-five patients were included in the analysis. All models performed well with C-indices of 0.7 or greater. The Clinical Model outperformed the Imaging Model at all time points with nadir creatinine driving the performance of the Clinical Model. Combining the 6-month Imaging Model (C-index 0.7; 95% confidence interval [CI] 0.6, 0.79) with the 6-month Clinical Model (C-index 0.79; 95% CI 0.71, 0.86) resulted in a 6-month Ensemble Model that performed better (C-index 0.82; 95% CI 0.77, 0.88) than either model alone. CONCLUSIONS: Deep learning imaging features extracted from initial postnatal kidney ultrasounds may improve early prediction of CKD progression among children with PUV. A higher resolution version of the Graphical abstract is available as Supplementary information.


Assuntos
Aprendizado Profundo , Insuficiência Renal Crônica , Obstrução Uretral , Masculino , Humanos , Criança , Lactente , Uretra/diagnóstico por imagem , Estudos Retrospectivos , Creatinina , Progressão da Doença , Insuficiência Renal Crônica/diagnóstico por imagem , Rim/diagnóstico por imagem
10.
Public Health Nutr ; 26(7): 1338-1344, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37069046

RESUMO

OBJECTIVE: This study estimates the prevalence of, and associations between, family food insecurity and overweight/obesity among Native Hawaiian and Pacific Islander (NHPI) adolescents and explores socio-demographic factors which might have a moderation effect on the association. DESIGN: Cross-sectional study using 2014 NHPI-National Health Interview Survey data reported by a parent or guardian. Family-level food security was assessed by the US Department of Agriculture 10-item questionnaire. BMI for age and sex ≥ 85th and 95th percentiles defined overweight and obesity, respectively, according to US Centers for Disease Control and Prevention criteria. SETTING: The USA, including all 50 states and the District of Columbia. PARTICIPANTS: 383 NHPI adolescents aged 12-17 in the USA. RESULTS: A third (33·5 %) of NHPI adolescents aged 12-17 were overweight (19·1 %) or obese (14·4 %); 8·1 % had low food security; and 8·5 % had very low food security. Mean family food security score was 1·06, which corresponds to marginal food security. We found no association between family food insecurity and adolescent overweight/obesity or between any other covariates and overweight/obesity, except for family Supplemental Nutrition Assistance Program (SNAP) participation. Odds of being overweight/obese were 77 % lower for adolescents in families participating in SNAP (OR: 0·23, 95 % CI: 0·08, 0·64, P = 0·007). The association between SNAP participation and lower odds of overweight/obesity was particularly pronounced for adolescent girls in food-insecure families. CONCLUSIONS: The association between SNAP participation and lower odds of overweight/obesity suggests potential benefit of research to determine whether interventions to increase SNAP enrollment would improve NHPI adolescents' health outcomes.


Assuntos
Assistência Alimentar , Insegurança Alimentar , Sobrepeso , Obesidade Infantil , Adolescente , Feminino , Humanos , Índice de Massa Corporal , Estudos Transversais , Abastecimento de Alimentos , Havaiano Nativo ou Outro Ilhéu do Pacífico , Sobrepeso/epidemiologia , Obesidade Infantil/epidemiologia , Obesidade Infantil/etiologia , Pobreza , Prevalência , Criança , Masculino
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA