Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 404
Filtrar
Mais filtros

Base de dados
Tipo de documento
Intervalo de ano de publicação
1.
Cell ; 165(2): 289-302, 2016 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-27040497

RESUMO

Chromosomal translocations encode oncogenic fusion proteins that have been proven to be causally involved in tumorigenesis. Our understanding of whether such genomic alterations also affect non-coding RNAs is limited, and their impact on circular RNAs (circRNAs) has not been explored. Here, we show that well-established cancer-associated chromosomal translocations give rise to fusion circRNAs (f-circRNA) that are produced from transcribed exons of distinct genes affected by the translocations. F-circRNAs contribute to cellular transformation, promote cell viability and resistance upon therapy, and have tumor-promoting properties in in vivo models. Our work expands the current knowledge regarding molecular mechanisms involved in cancer onset and progression, with potential diagnostic and therapeutic implications.


Assuntos
Neoplasias/genética , RNA/metabolismo , Translocação Genética , Animais , Sequência de Bases , Proliferação de Células , Transformação Celular Neoplásica , Humanos , Leucemia/genética , Camundongos , Dados de Sequência Molecular , Proteína de Leucina Linfoide-Mieloide/genética , Neoplasias/patologia , Proteínas de Fusão Oncogênica/genética , RNA Circular
2.
Cell ; 163(2): 506-19, 2015 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-26451490

RESUMO

Invasive lobular carcinoma (ILC) is the second most prevalent histologic subtype of invasive breast cancer. Here, we comprehensively profiled 817 breast tumors, including 127 ILC, 490 ductal (IDC), and 88 mixed IDC/ILC. Besides E-cadherin loss, the best known ILC genetic hallmark, we identified mutations targeting PTEN, TBX3, and FOXA1 as ILC enriched features. PTEN loss associated with increased AKT phosphorylation, which was highest in ILC among all breast cancer subtypes. Spatially clustered FOXA1 mutations correlated with increased FOXA1 expression and activity. Conversely, GATA3 mutations and high expression characterized luminal A IDC, suggesting differential modulation of ER activity in ILC and IDC. Proliferation and immune-related signatures determined three ILC transcriptional subtypes associated with survival differences. Mixed IDC/ILC cases were molecularly classified as ILC-like and IDC-like revealing no true hybrid features. This multidimensional molecular atlas sheds new light on the genetic bases of ILC and provides potential clinical options.


Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Carcinoma Lobular/genética , Carcinoma Lobular/patologia , Antígenos CD , Neoplasias da Mama/metabolismo , Caderinas/química , Caderinas/genética , Caderinas/metabolismo , Carcinoma Ductal de Mama/genética , Carcinoma Ductal de Mama/patologia , Carcinoma Lobular/metabolismo , Feminino , Fator 3-alfa Nuclear de Hepatócito/química , Fator 3-alfa Nuclear de Hepatócito/genética , Fator 3-alfa Nuclear de Hepatócito/metabolismo , Humanos , Modelos Moleculares , Mutação , Análise de Sequência com Séries de Oligonucleotídeos , Proteína Oncogênica v-akt/metabolismo , Transcriptoma
3.
Cell ; 158(3): 564-78, 2014 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-25083868

RESUMO

Stromal cells within the tumor microenvironment are essential for tumor progression and metastasis. Surprisingly little is known about the factors that drive the transcriptional reprogramming of stromal cells within tumors. We report that the transcriptional regulator heat shock factor 1 (HSF1) is frequently activated in cancer-associated fibroblasts (CAFs), where it is a potent enabler of malignancy. HSF1 drives a transcriptional program in CAFs that complements, yet is completely different from, the program it drives in adjacent cancer cells. This CAF program is uniquely structured to support malignancy in a non-cell-autonomous way. Two central stromal signaling molecules-TGF-ß and SDF1-play a critical role. In early-stage breast and lung cancer, high stromal HSF1 activation is strongly associated with poor patient outcome. Thus, tumors co-opt the ancient survival functions of HSF1 to orchestrate malignancy in both cell-autonomous and non-cell-autonomous ways, with far-reaching therapeutic implications.


Assuntos
Neoplasias da Mama/metabolismo , Proteínas de Ligação a DNA/metabolismo , Neoplasias Pulmonares/metabolismo , Fatores de Transcrição/metabolismo , Animais , Quimiocina CXCL12/metabolismo , Fibroblastos/metabolismo , Fatores de Transcrição de Choque Térmico , Xenoenxertos , Humanos , Células MCF-7 , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Transplante de Neoplasias , Fator de Crescimento Transformador beta/metabolismo
5.
Am J Transplant ; 24(3): 448-457, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37898318

RESUMO

Children exposed to disproportionately higher levels of air pollution experience worse health outcomes. In this population-based, observational registry study, we examine the association between air pollution and graft failure/death in children following liver transplantation (LT) in the US. We modeled the associations between air pollution (PM2.5) levels localized to the patient's ZIP code at the time of transplant and graft failure or death using Cox proportional-hazards models in pediatric LT recipients aged <19 years in the US from 2005-2015. In univariable analysis, high neighborhood PM2.5 was associated with a 56% increased hazard of graft failure/death (HR: 1.56; 95% CI: 1.32, 1.83; P < .001). In multivariable analysis, high neighborhood PM2.5 was associated with a 54% increased risk of graft failure/death (HR: 1.54; 95% CI: 1.29, 1.83; P < .001) after adjusting for race as a proxy for racism, insurance status, rurality, and neighborhood socioeconomic deprivation. Children living in high air pollution neighborhoods have an increased risk of graft failure and death posttransplant, even after controlling for sociodemographic variables. Our findings add further evidence that air pollution contributes to adverse health outcomes for children posttransplant and lay the groundwork for future studies to evaluate underlying mechanisms linking PM2.5 to adverse LT outcomes.


Assuntos
Poluição do Ar , Transplante de Fígado , Humanos , Criança , Transplante de Fígado/efeitos adversos , Poluição do Ar/efeitos adversos , Cobertura do Seguro , Sistema de Registros , Material Particulado/efeitos adversos , Exposição Ambiental
6.
Am J Transplant ; 24(2): 239-249, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37776976

RESUMO

Children from minoritized/socioeconomically deprived backgrounds suffer disproportionately high rates of uninsurance and graft failure/death after liver transplant. Medicaid expansion was developed to expand access to public insurance. Our objective was to characterize the impact of Medicaid expansion policies on long-term graft/patient survival after pediatric liver transplantation. All pediatric patients (<19 years) who received a liver transplant between January 1, 2005, and December 31, 2020 in the US were identified in the Scientific Registry of Transplant Recipients (N = 8489). Medicaid expansion was modeled as a time-varying exposure based on transplant and expansion dates. We used Cox proportional hazards models to evaluate the impact of Medicaid expansion on a composite outcome of graft failure/death over 10 years. As a sensitivity analysis, we conducted an intention-to-treat analysis from time of waitlisting to death (N = 1 1901). In multivariable analysis, Medicaid expansion was associated with a 30% decreased hazard of graft failure/death (hazard ratio, 0.70; 95% confidence interval, 0.62, 0.79; P < .001) after adjusting for Black race, public insurance, neighborhood deprivation, and living in a primary care shortage area. In intention-to-treat analyses, Medicaid expansion was associated with a 72% decreased hazard of patient death (hazard ratio, 0.28; 95% confidence interval, 0.23-0.35; P < .001). Policies that enable broader health insurance access may help improve outcomes and reduce disparities for children undergoing liver transplantation.


Assuntos
Transplante de Fígado , Medicaid , Estados Unidos , Humanos , Criança , Cobertura do Seguro , Seguro Saúde , Pessoas sem Cobertura de Seguro de Saúde
7.
J Pediatr ; 268: 113930, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38309525

RESUMO

OBJECTIVE: To evaluate whether racial and socioeconomic inequities in pediatric palliative care utilization extend to children with high-intensity neurologic impairment (HI-NI), which is a chronic neurological diagnosis resulting in substantial functional morbidity and mortality. STUDY DESIGN: We conducted a retrospective study of patients with HI-NI who received primary care services at a tertiary care center from 2014 through 2019. HI-NI diagnoses that warranted a palliative care referral were identified by consensus of a multidisciplinary team. The outcome was referral to palliative care. The primary exposure was race, categorized as Black or non-Black to represent the impact of anti-Black racism. Additional exposures included ethnicity (Hispanic/non-Hispanic) and insurance status (Medicaid/non-Medicaid). Descriptive statistics, bivariate analyses, and multivariable logistic regression models were performed to assess associations between exposures and palliative care referral. RESULTS: A total of 801 patients with HI-NI were included; 7.5% received a palliative referral. There were no differences in gestational age, sex, or ethnicity between patients who received a referral and those who did not. In multivariable analysis, adjusting for ethnicity, sex, gestational age, and presence of complex chronic conditions, Black children (aOR 0.47, 95% CI 0.26, 0.84) and children with Medicaid insurance (aOR 0.40, 95% CI 0.23, 0.70) each had significantly lower odds of palliative referral compared with their non-Black and non-Medicaid-insured peers, respectively. CONCLUSIONS: We identified inequities in pediatric palliative care referral among children with HI-NI by race and insurance status. Future work is needed to develop interventions, with families, aimed at promoting more equitable, antiracist systems of palliative care.


Assuntos
Disparidades em Assistência à Saúde , Doenças do Sistema Nervoso , Cuidados Paliativos , Encaminhamento e Consulta , Humanos , Cuidados Paliativos/estatística & dados numéricos , Masculino , Feminino , Estudos Retrospectivos , Encaminhamento e Consulta/estatística & dados numéricos , Criança , Disparidades em Assistência à Saúde/etnologia , Disparidades em Assistência à Saúde/estatística & dados numéricos , Pré-Escolar , Doenças do Sistema Nervoso/terapia , Doenças do Sistema Nervoso/etnologia , Lactente , Estados Unidos , Adolescente , Negro ou Afro-Americano/estatística & dados numéricos , Fatores Socioeconômicos , Medicaid/estatística & dados numéricos , Racismo
8.
J Pediatr ; 265: 113818, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37931698

RESUMO

OBJECTIVE: To determine the association between food insecurity and pediatric nonalcoholic fatty liver disease (NAFLD). METHODS: Cross-sectional study of patients < 21 years of age with histologically confirmed NAFLD. The Household Food Security Survey Module was administered to determine food insecurity status. Skin lipidomics were performed to explore pathophysiologic mechanisms. RESULTS: Seventy-three patients with histologically confirmed NAFLD completed the Household Food Security Survey Module. Of these, the majority were male (81%) and non-Hispanic (53%), with a mean age at biopsy of 13 ± 3 years. Food insecurity was seen in 42% (n = 31). Comparison of features between food insecure and food secure subgroups revealed no differences in sex, ethnicity, BMI z-score, aminotransferases, or histologic severity. However, children experiencing food insecurity presented on average 2 years before their food secure counterparts (12.3 ± 3.0 vs 14.4 ± 3.6 years, P = .015). A subset of 31 patients provided skin samples. Skin lipidomics revealed that food insecurity was associated with down-regulated features from the lipoamino acid class of lipids, previously linked to inflammation and adipocyte differentiation. CONCLUSIONS: Food insecurity is highly prevalent in children with NAFLD and is associated with earlier presentation. Lipidomic analyses suggest a possible pathophysiologic link that warrants further exploration.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Humanos , Criança , Masculino , Feminino , Adolescente , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Estudos Transversais , Abastecimento de Alimentos , Etnicidade , Insegurança Alimentar
9.
Ann Allergy Asthma Immunol ; 132(5): 602-609.e4, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38141810

RESUMO

BACKGROUND: In the United States, a few studies have evaluated geographic variation of severe asthma at the subnational level. OBJECTIVE: To assess state-level geographic variation in the prevalence and characteristics of severe persistent asthma in the United States. METHODS: Patients aged above or equal to 12 years with severe persistent asthma were identified using nationally representative data from IQVIA open-source Medical/Pharmacy Claims and PharMetrics Plus databases (January 2019-December 2020). The index date was defined as the patient's earliest qualifying date for a severe asthma diagnosis. Baseline characteristics were measured during the 12-month pre-index period. Outcomes including exacerbation occurrence, asthma control, and medication use were measured during the 12-month post-index period and compared across states using census-level projections. RESULTS: A total of 2,092,799 patients with asthma were identified; 496,750 (23.7%) met criteria for severe persistent asthma and all inclusion criteria. Mean age was 50.5 years; 68.4% were females. The prevalence of severe persistent asthma varied across states, ranging from 19.6% (New Mexico) to 31.9% (Alaska). Among patients with severe persistent asthma, 40.9% had more than or equal to 1 exacerbation, ranging from 34.2% (Vermont) to 45.6% (Louisiana); 21.1% had uncontrolled disease, ranging from 16.5% (Vermont) to 24.0% (Arizona). Among patients with exacerbations, 13.7% had exacerbation-related emergency department visits or hospitalizations, ranging from 7.0% (North Carolina) to 17.7% (Nevada). Among patients with severe uncontrolled asthma, 15.6% used biologics post-index, ranging from 2.2% (Hawaii) to 27.9% (Mississippi). CONCLUSION: There is significant variability in severe persistent asthma prevalence and disease burden across US states. Reasons for geographic variation may include differences in socioeconomic/environmental factors or asthma management.


Assuntos
Asma , Índice de Gravidade de Doença , Humanos , Asma/epidemiologia , Estados Unidos/epidemiologia , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Prevalência , Adolescente , Criança , Efeitos Psicossociais da Doença , Idoso , Adulto Jovem
10.
Mol Cell ; 63(6): 1006-20, 2016 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-27635760

RESUMO

While much research has examined the use of glucose and glutamine by tumor cells, many cancers instead prefer to metabolize fats. Despite the pervasiveness of this phenotype, knowledge of pathways that drive fatty acid oxidation (FAO) in cancer is limited. Prolyl hydroxylase domain proteins hydroxylate substrate proline residues and have been linked to fuel switching. Here, we reveal that PHD3 rapidly triggers repression of FAO in response to nutrient abundance via hydroxylation of acetyl-coA carboxylase 2 (ACC2). We find that PHD3 expression is strongly decreased in subsets of cancer including acute myeloid leukemia (AML) and is linked to a reliance on fat catabolism regardless of external nutrient cues. Overexpressing PHD3 limits FAO via regulation of ACC2 and consequently impedes leukemia cell proliferation. Thus, loss of PHD3 enables greater utilization of fatty acids but may also serve as a metabolic and therapeutic liability by indicating cancer cell susceptibility to FAO inhibition.


Assuntos
Acetil-CoA Carboxilase/metabolismo , Ácidos Graxos/metabolismo , Regulação Neoplásica da Expressão Gênica , Prolina Dioxigenases do Fator Induzível por Hipóxia/metabolismo , Leucemia Mieloide Aguda/metabolismo , Prolina/metabolismo , Acetil-CoA Carboxilase/antagonistas & inibidores , Acetil-CoA Carboxilase/química , Acetil-CoA Carboxilase/genética , Sequência de Aminoácidos , Animais , Linhagem Celular Tumoral , Células HEK293 , Humanos , Hidroxilação , Prolina Dioxigenases do Fator Induzível por Hipóxia/química , Prolina Dioxigenases do Fator Induzível por Hipóxia/genética , Células K562 , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/patologia , Masculino , Redes e Vias Metabólicas/genética , Camundongos , Camundongos Endogâmicos NOD , Modelos Moleculares , Transplante de Neoplasias , Oxirredução , Prolina/química , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Transdução de Sinais , Homologia Estrutural de Proteína , Análise de Sobrevida
11.
Eur J Public Health ; 34(1): 196-201, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-37995320

RESUMO

BACKGROUND: While the modes of transmission of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are well studied, the risk of transmission in various group settings or activities is less clear. This living scoping review aims to summarize the risk factors of coronavirus disease 2019 (COVID-19) spread in common group activities (e.g. social gatherings) or settings (e.g. schools, hospitals, shared workplaces) to understand the drivers of transmission and to inform a risk assessment profile tool for use of rapid antigen detection tests. METHODS: We systematically searched electronic databases, MEDLINE and Embase, from January 2019 until February 2022. We included studies that evaluated the risk of SARS-CoV-2 transmission in activities and settings, deemed strategically important to government departments in Ireland, provided by the Department of Health (Ireland) Expert Advisory Group on Rapid Testing. RESULTS: After screening 14 052 records, data from 139 studies were narratively synthesized. The risk was consistently reported as 'high' for large social events (e.g. weddings) and indoor sports, working in healthcare settings and shared workplaces, working/living in residential settings and travelling via public transportation. Most studies were from healthcare settings, with common risk factors including close contact with COVID-19 cases, working in high-risk departments and inappropriate use of personal protective equipment. For other settings and activities, lack of infection prevention and control practices reportedly contributed to infection transmission. CONCLUSION: The heterogeneity across studies and lack of direct information on dominant variants, preventive measures, vaccination coverage necessitates further research on transmission risk within group activities to inform infection prevention and control measures.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Viagem , Medição de Risco , Fatores de Risco
12.
J Paediatr Child Health ; 60(6): 193-199, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38695512

RESUMO

AIM: Delays in care may be a driver of inequities in perforated appendicitis rates. The goal of this study was to explore potential causes of delay in care for children with perforated appendicitis. METHODS: We conducted an interview study of caregivers of children admitted with perforated appendicitis to a children's hospital between December 2022 and March 2023. Semi-structured interviews based on an iteratively revised interview guide were conducted in-person during the child's admission. All interviews were transcribed, coded and underwent a process of thematic analysis. RESULTS: We reached thematic saturation after 12 interviews. The median age for children was 13.5 years, 50% were male, 83% of caregivers self-identified as White, and one interview required an interpreter. Through thematic analysis, four major themes for potential causes of delay emerged. The first theme of symptom recognition includes delays related to recognising the symptoms, their severity and the need for medical evaluation. The second theme - accessing care - describes delays that occur after a decision was made to seek care until the child was evaluated. The third theme includes delays that occur in making the diagnosis after evaluation. The last theme captures potential delays in definitive treatment after a diagnosis of appendicitis is made. CONCLUSION: We identify four major themes from the patient and family perspective, each with multiple sub-themes, for potential delays in definitive care for children with perforated appendicitis. Additional research is needed to further characterise these potential delays and quantify their role in contributing to inequities in perforation rates.


Assuntos
Apendicite , Entrevistas como Assunto , Humanos , Masculino , Feminino , Adolescente , Criança , Estudos Prospectivos , Diagnóstico Tardio , Tempo para o Tratamento , Pesquisa Qualitativa , Hospitais Pediátricos , Pré-Escolar
13.
Pediatr Cardiol ; 45(5): 1072-1078, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38472658

RESUMO

Associations between social determinants of health (SDOH) and adverse outcomes for children with congenital heart disease (CHD) are starting to be recognized; however, such links remain understudied. We examined the relationship between community-level material deprivation on mortality, readmission, and length of stay (LOS) for children undergoing surgery for CHD. We performed a retrospective cohort study of patients who underwent cardiac surgery at our institution from 2015 to 2018. A community-level deprivation index (DI), a marker of community material deprivation, was generated to contextualize the lived experience of children with CHD. Generalized mixed-effects models were used to assess links between the DI and outcomes of mortality, readmission, and LOS following cardiac surgery. The DI and components were scaled to provide mean differences for a one standard deviation (SD) increase in deprivation. We identified 1,187 unique patients with surgical admissions. The median LOS was 11 days, with an overall mortality rate of 4.6% and readmission rate of 7.6%. The DI ranged from 0.08 to 0.85 with a mean of 0.37 (SD 0.12). The DI was associated with increased LOS for patients with more complex heart disease (STAT 3, 4, and 5), which persisted after adjusting for factors that could prolong LOS (all p < 0.05). The DI approached but did not meet a significant association with mortality (p = 0.0528); it was not associated with readmission (p = 0.36). Community-level deprivation is associated with increased LOS for patients undergoing cardiac surgery. Future work to identify the specific health-related social needs contributing to LOS and identify targets for intervention is needed.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Cardiopatias Congênitas , Tempo de Internação , Readmissão do Paciente , Humanos , Cardiopatias Congênitas/cirurgia , Cardiopatias Congênitas/mortalidade , Feminino , Masculino , Estudos Retrospectivos , Readmissão do Paciente/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Lactente , Pré-Escolar , Determinantes Sociais da Saúde , Criança , Fatores Socioeconômicos , Recém-Nascido
14.
Euro Surveill ; 29(28)2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38994600

RESUMO

We investigated a variant of measles virus that encodes three mismatches to the reverse priming site for a widely used diagnostic real-time RT-PCR assay; reduction of sensitivity was hypothesised. We examined performance of the assay in context of the variant using in silico data, synthetic RNA templates and clinical specimens. Sensitivity was reduced observed at low copy numbers for templates encoding the variant sequence. We designed and tested an alternate priming strategy, rescuing the sensitivity of the assay.


Assuntos
Vírus do Sarampo , Sarampo , RNA Viral , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sensibilidade e Especificidade , Humanos , Sarampo/diagnóstico , Sarampo/virologia , Vírus do Sarampo/genética , Vírus do Sarampo/isolamento & purificação , Reação em Cadeia da Polimerase em Tempo Real/métodos , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , RNA Viral/genética
15.
Artigo em Inglês | MEDLINE | ID: mdl-39321404

RESUMO

As the COVID-19 pandemic progressed, reliable, accessible, and equitable community-based testing strategies were sought that did not flood already overburdened hospitals and emergency departments. In Hamilton County, Ohio, home to ~800 000 people across urban, suburban, and rural areas, we sought to develop and optimize an accessible, equitable county-wide COVID-19 testing program. Using Coronavirus Aid, Relief, and Economic Security Act funding, multidisciplinary, multiorganization partners created the test and protect program to deliver safe, reliable testing in neighborhoods and organizations needing it most. Our approach involved: (1) use of geospatial analytics to identify testing locations positioned to optimize access; (2) community engagement to ensure sites were in trusted places; and (3) tracking of data over time to facilitate ongoing improvement. Between August 2020 and December 2021, more than 65 000 tests were completed for nearly 46 000 individuals at community-based testing sites. These methods could have application beyond COVID-19 and our region.

16.
Mod Pathol ; 36(6): 100124, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36841434

RESUMO

Ulcerative colitis is a chronic inflammatory bowel disease that is characterized by a relapsing and remitting course. Assessment of disease activity critically informs treatment decisions. In addition to endoscopic remission, histologic remission is emerging as a treatment target and a key factor in the evaluation of disease activity and therapeutic efficacy. However, manual pathologist evaluation is semiquantitative and limited in granularity. Machine learning approaches are increasingly being developed to aid pathologists in accurate and reproducible scoring of histology, enabling precise quantitation of clinically relevant features. Here, we report the development and validation of convolutional neural network models that quantify histologic features pertinent to ulcerative colitis disease activity, directly from hematoxylin and eosin-stained whole slide images. Tissue and cell model predictions were used to generate quantitative human-interpretable features to fully characterize the histology samples. Tissue and cell predictions showed comparable agreement to pathologist annotations, and the extracted slide-level human-interpretable features demonstrated strong correlations with disease severity and pathologist-assigned Nancy histological index scores. Moreover, using a random forest classifier based on 13 human-interpretable features derived from the tissue and cell models, we were able to accurately predict Nancy histological index scores, with a weighted kappa (κ = 0.91) and Spearman correlation (⍴ = 0.89, P < .001) when compared with pathologist consensus Nancy histological index scores. We were also able to predict histologic remission, based on the absence of neutrophil extravasation, with a high accuracy of 0.97. This work demonstrates the potential of computer vision to enable a standardized and robust assessment of ulcerative colitis histopathology for translational research and improved evaluation of disease activity and prognosis.


Assuntos
Colite Ulcerativa , Doenças Inflamatórias Intestinais , Humanos , Colite Ulcerativa/tratamento farmacológico , Inteligência Artificial , Índice de Gravidade de Doença , Doenças Inflamatórias Intestinais/patologia , Mucosa Intestinal/patologia , Colonoscopia
17.
J Pediatr ; 260: 113522, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37244575

RESUMO

OBJECTIVE: To describe racial inequities in pediatric inflammatory bowel disease care and explore potential drivers. METHODS: We undertook a single-center, comparative cohort study of newly diagnosed Black and non-Hispanic White patients with inflammatory bowel disease, aged <21 years, from January 2013 through 2020. Primary outcome was corticosteroid-free remission (CSFR) at 1 year. Other longitudinal outcomes included sustained CSFR, time to anti-tumor necrosis factor therapy, and evaluation of health service utilization. RESULTS: Among 519 children (89% White, 11% Black), 73% presented with Crohn's disease and 27% with ulcerative colitis. Disease phenotype did not differ by race. More patients from Black families had public insurance (58% vs 30%, P < .001). Black patients were less likely to achieve CSFR 1-year post diagnosis (OR: 0.52, 95% CI:0.3-0.9) and less likely to achieve sustained CSFR (OR: 0.48, 95% CI: 0.25-0.92). When adjusted by insurance type, differences by race to 1-year CSFR were no longer significant (aOR: 0.58; 95% CI: 0.33, 1.04; P = .07). Black patients were more likely to transition from remission to a worsened state, and less likely to transition to remission. We found no differences in biologic therapy utilization or surgical outcomes by race. Black patients had fewer gastroenterology clinic visits and 2-fold increased odds for emergency department visits. CONCLUSIONS: We observed no differences by race in phenotypic presentation and medication usage. Black patients had half the odds of achieving clinical remission, but a degree of this was mediated by insurance status. Understanding the cause of such differences will require further exploration of social determinants of health.


Assuntos
Disparidades em Assistência à Saúde , Doenças Inflamatórias Intestinais , Humanos , Estudos de Coortes , Serviços de Saúde , Doenças Inflamatórias Intestinais/terapia , Negro ou Afro-Americano , Brancos , Criança
18.
Hepatology ; 75(1): 115-124, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34387881

RESUMO

BACKGROUND AND AIMS: Racial/ethnic minority children have worse liver transplant (LT) outcomes. We evaluated whether neighborhood socioeconomic deprivation affected associations between race/ethnicity and wait-list mortality. APPROACH AND RESULTS: We included children (age <18) listed 2005-2015 in the Scientific Registry of Transplant Recipients. We categorized patients as non-Hispanic White, Black, Hispanic, and other. We matched patient ZIP codes to a neighborhood socioeconomic deprivation index (range, 0-1; higher values indicate worse deprivation). Primary outcomes were wait-list mortality, defined as death/delisting for too sick, and receipt of living donor liver transplant (LDLT). Competing risk analyses modeled the association between race/ethnicity and wait-list mortality, with deceased donor liver transplant (DDLT) and LDLT as competing risks, and race/ethnicity and LDLT, with wait-list mortality and DDLT as competing risks. Of 7716 children, 17% and 24% identified as Black and Hispanic, respectively. Compared to White children, Black and Hispanic children had increased unadjusted hazard of wait-list mortality (subhazard ratio [sHR], 1.44; 95% CI, 1.18, 1.75 and sHR, 1.48; 95% CI, 1.25, 1.76, respectively). After adjusting for neighborhood deprivation, insurance, and listing laboratory Model for End-Stage Liver Disease/Pediatric End-Stage Liver Disease, Black and Hispanic children did not have increased hazard of wait-list mortality (sHR, 1.12; 95% CI, 0.91, 1.39 and sHR, 1.21; 95% CI, 1.00, 1.47, respectively). Similarly, Black and Hispanic children had a decreased likelihood of LDLT (sHR, 0.58; 95% CI, 0.45, 0.75 and sHR, 0.61; 95% CI, 0.49, 0.75, respectively). Adjustment attenuated the effect of Black and Hispanic race/ethnicity on likelihood of LDLT (sHR, 0.79; 95% CI, 0.60, 1.02 and sHR, 0.89; 95% CI, 0.70, 1.11, respectively). CONCLUSIONS: Household and neighborhood socioeconomic factors and disease severity at wait-list entry help explain racial/ethnic disparities for children awaiting transplant. A nuanced understanding of how social adversity contributes to wait-list outcomes may inform strategies to improve outcomes.


Assuntos
Doença Hepática Terminal/mortalidade , Minorias Étnicas e Raciais/estatística & dados numéricos , Disparidades nos Níveis de Saúde , Transplante de Fígado/estatística & dados numéricos , Fatores Socioeconômicos , Adolescente , Criança , Estudos de Coortes , Doença Hepática Terminal/diagnóstico , Doença Hepática Terminal/cirurgia , Humanos , Masculino , Características de Residência/estatística & dados numéricos , Índice de Gravidade de Doença , Listas de Espera/mortalidade
19.
Eur J Clin Invest ; 53(11): e14058, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37424144

RESUMO

BACKGROUND: Rapid antigen detection tests (RADTs) for SARS-CoV-2 testing offer several advantages over molecular tests, but there is little evidence supporting an ideal testing algorithm. We aimed to examine the diagnostic test accuracy (DTA) and the effectiveness of different RADT SARS-CoV-2 testing strategies. METHODS: Following PRISMA DTA guidance, we carried out a living rapid review and meta-analysis. Searches were conducted in Ovid MEDLINE® ALL, Embase and Cochrane CENTRAL electronic databases until February 2022. Results were visualized using forest plots and included in random-effects univariate meta-analyses, where eligible. RESULTS: After screening 8010 records, 18 studies were included. Only one study provided data on incidence outcomes. Seventeen studies were DTA reports with direct comparisons of RADT strategies, using RT-PCR as the reference standard. Testing settings varied, corresponding to original SARS-CoV-2 or early variants. Strategies included differences in serial testing, the individual collecting swabs and swab sample locations. Overall, specificity remained high (>98%) across strategies. Although results were heterogeneous, the sensitivity for healthcare worker-collected samples was greater than for self-collected samples. Nasal samples had comparable sensitivity when compared to paired RADTs with nasopharyngeal samples, but sensitivity was much lower for saliva samples. The limited evidence for serial testing suggested higher sensitivity if RADTs were administered every 3 days compared to less frequent testing. CONCLUSIONS: Additional high-quality research is needed to confirm our findings; all studies were judged to be at risk of bias, with significant heterogeneity in sensitivity estimates. Evaluations of testing algorithms in real-world settings are recommended, especially for transmission and incidence outcomes.

20.
J Asthma ; 60(12): 2189-2197, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37345884

RESUMO

Objective: The Child Asthma Risk Assessment Tool (CARAT) identifies risk factors for asthma morbidity. We hypothesized that CARAT-identified risk factors (using a CARAT adapted for inpatient use) would be associated with future healthcare utilization and would identify areas for intervention.Methods: We reviewed CARAT data collected during pediatric asthma admissions from 2010-2015, assessing for risk factors in environmental, medical, and social domains and providing prompts for inpatient (specialist consultation or social services engagement) and post-discharge interventions (home care visit or home environmental assessment). Confirmatory factor analysis identified groups of CARAT-identified risk factors with similar effects on healthcare utilization (latent factors). Structural equation models then evaluated relationships between latent factors and future utilization.Results: There were 2731 unique patients admitted for asthma exacerbations; 1015 (37%) had complete CARAT assessments and were included in analyses. Those with incomplete CARAT assessments were more often younger and privately-insured. CARAT-identified risk factors across domains were common in children hospitalized for exacerbations. Risks in the environmental domain were most common. Inpatient asthma consults by pulmonologists or allergists and home care referrals were the most frequent interventions indicated (62%, 628/1015, and 50%, 510/1015, respectively). Two latent factors were positively associated with healthcare utilization in the year after index stay - social stressors and known/suspected allergies (both p < 0.05). Stratified analyses analyzing data just from those children with prior healthcare utilization also indicated known/suspected allergies to be positively associated with future utilization.Conclusions: Inpatient interventions to address social stressors and allergic profiles may be warranted to reduce subsequent asthma morbidity.


Assuntos
Asma , Hipersensibilidade , Humanos , Criança , Asma/diagnóstico , Asma/epidemiologia , Asma/terapia , Assistência ao Convalescente , Alta do Paciente , Hospitalização , Medição de Risco , Hipersensibilidade/complicações
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA