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1.
Int J Mol Sci ; 24(14)2023 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-37511178

RESUMO

Endocrine-resistant, hormone receptor-positive, and HER2-negative (HR+/HER2-) metastatic breast cancer (mBC) is largely governed by acquired mutations in the estrogen receptor, which promote ligand-independent activation, and by truncal alterations in the PI3K signaling pathway, with a broader range of gene alterations occurring with less prevalence. Circulating tumor DNA (ctDNA)-based technologies are progressively permeating the clinical setting. However, their utility for serial monitoring has been hindered by their significant costs, inter-technique variability, and real-world patient heterogeneity. We interrogated a longitudinal collection of 180 plasma samples from 75 HR+/HER2- mBC patients who progressed or relapsed after exposure to aromatase inhibitors and were subsequently treated with endocrine therapy (ET) by means of highly sensitive and affordable digital PCR and SafeSEQ sequencing. Baseline PIK3CA and TP53 mutations were prognostic of a shorter progression-free survival in our population. Mutant PIK3CA was prognostic in the subset of patients receiving fulvestrant monotherapy after progression to a CDK4/6 inhibitor (CDK4/6i)-containing regimen, and its suppression was predictive in a case of long-term benefit with alpelisib. Mutant ESR1 was prognostic in patients who did not receive concurrent CDK4/6i, an impact influenced by the variant allele frequency, and its early suppression was strongly predictive of efficacy and associated with long-term benefit in the whole cohort. Mutations in ESR1, TP53, and KRAS emerged as putative drivers of acquired resistance. These findings collectively contribute to the characterization of longitudinal ctDNA in real-world cases of HR+/HER2- mBC previously exposed to aromatase inhibitors and support ongoing studies either targeting actionable alterations or leveraging the ultra-sensitive tracking of ctDNA.


Assuntos
Inibidores da Aromatase , Neoplasias da Mama , Feminino , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/sangue , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Classe I de Fosfatidilinositol 3-Quinases/genética , Biópsia Líquida , Fosfatidilinositol 3-Quinases , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Mutação
2.
Int J Cancer ; 148(10): 2389-2397, 2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-33270902

RESUMO

Coronavirus disease 2019 (COVID-19) pandemic is affecting a high percentage of the population at an unprecedented rate. Cancer patients comprise a subgroup especially vulnerable to this infection. Herein, we present a prospective analysis of epidemiological, clinical, radiological and laboratory data of consecutive adult cancer patients seen in the Clínico San Carlos University Hospital (Madrid, Spain), and admitted to hospital and tested for COVID-19 between 21 February 2020 and 8 May 2020 due to clinical suspicion of infection. Data from 73 patients with confirmed COVID-19 and active solid tumors or diagnosed within the previous 5 years were analyzed. The most frequent malignancy was lung cancer (19%) and 54 patients (74%) were on active cancer treatment. Most common findings on presentation included cough (55%), fever (52%) and dyspnea (45%), and 32 (44%) patients showed oxygen saturation levels below 95%. Radiologically, 54 (73%) patients presented an abnormal pattern, the most frequent being infiltrates (64%). 18 (24.7%) patients died in hospital and 55 (75.3%) were discharged with clinical resolution of the event. Multivariable logistic regression adjusted for age and tumor stage showed higher odds of in-hospital death associated with a history of cardiovascular disease, hospitalization in the previous 30 days, and several features on admission including dyspnea, higher qSOFA score, higher C-reactive protein levels and an abnormal neutrophil count. We present prospective, real-world evidence that can help articulate cancer care protocols for patients infected with SARS-CoV-2, with special focus on features on admission that can stratify patients with a higher risk of death from COVID-19.

3.
South Med J ; 113(4): 183-190, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32239231

RESUMO

OBJECTIVE: Although substantial research has explored the Hispanic health paradox (HHP) and suggests that Latinx immigrants experience positive health outcomes relative to those born in the United States, less research has assessed the role of immigration status. Our aim was to examine this role in Latinx health. METHODS: Using survey data collected at two free/reduced-cost clinics in southernmost Texas, we examined differences in the mental and self-rated health, substance, alcohol, and tobacco use of low-income patients by undocumented/documented immigrant and US-born/naturalized citizen status (N = 588). RESULTS: Based on ordinary least squares regression results, undocumented Latinx immigrants report lower negative self-rated health (coefficient -0.27, 95% confidence interval -0.50 to -0.01) and lower depressive symptoms (coefficient -0.34, 95% confidence interval -0.67 to -0.02]) compared with their US citizen peers (P < 0.05). Logistic regression results suggest that undocumented and documented Latinx immigrants do not differ in alcohol, tobacco, or substance use relative to their citizen peers. CONCLUSIONS: Despite facing potentially adverse social environments, undocumented Latinx immigrants experience positive health outcomes relative to US-born/naturalized citizen peers.


Assuntos
Emigrantes e Imigrantes/psicologia , Hispânico ou Latino/estatística & dados numéricos , Transtornos Relacionados ao Uso de Substâncias/psicologia , Adulto , Emigrantes e Imigrantes/estatística & dados numéricos , Feminino , Custos de Cuidados de Saúde/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Inquéritos e Questionários , Texas/epidemiologia , Uso de Tabaco/epidemiologia , Uso de Tabaco/psicologia
4.
J Community Health ; 44(1): 127-136, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30094723

RESUMO

U.S.-Mexico border communities are uniquely vulnerable to sexually transmitted infection (STI) transmission given the economic and social challenges these communities face. This study examines how marginalized statuses of U.S. border residents are associated with STI awareness and sexual behaviors. We surveyed low-income residents receiving STI testing and/or HIV/AIDS care in the lower Rio Grande Valley of southernmost Texas. Respondents aged 18+ took a self-administered survey available in English or Spanish in a clinic waiting room (N = 282). Approximately 52% of respondents reported being HIV+, and 32% of respondents reported having a prior STI other than HIV. Although most respondents had heard of HPV (72%), awareness of the HPV vaccine was low across all subgroups (28%), including women (< 35%), reflecting previous findings that border residents are less knowledgeable about the HPV vaccine. Almost half of respondents reported always using a condom (45%), which is higher than elsewhere in the U.S. Male and non-Hispanic respondents had higher estimated prevalence ratios (PR) of lifetime partners [PR 1.39 (95% confidence interval 1.43-3.68), PR 1.88 (1.04-3.41), respectively] and sexual partners met online [PR 3.73 (1.00-14.06), PR 19.98 (5.70-70.10), respectively]. Sexual minority, non-Hispanic, and male respondents had higher adjusted odds ratios (AOR) of utilizing the internet to find sexual partners than their peers [AOR 2.45 (1.60-3.87), AOR 1.52 (1.11-2.07), AOR 1.97 (1.20-3.24), respectively], placing them at greater STI-transmission risk. We found diversity in dimensions of STI awareness and sexual behaviors in our sample. Results can help tailor public health interventions to the unique STI risks of marginalized groups in border communities.


Assuntos
Hispânico ou Latino/estatística & dados numéricos , Pobreza/estatística & dados numéricos , Infecções Sexualmente Transmissíveis/epidemiologia , Determinantes Sociais da Saúde/estatística & dados numéricos , Adolescente , Adulto , Feminino , Infecções por HIV/prevenção & controle , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , México , Comportamento Sexual/estatística & dados numéricos , Parceiros Sexuais , Texas , Adulto Jovem
5.
Interv Neuroradiol ; 24(3): 277-283, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29383976

RESUMO

We describe two contrasting patients with multiple cerebral aneurysms and a previous history of resected cardiac myxomas with no cardiac recurrence on follow-up echocardiography. Both patients presented with stroke- like symptoms; one with a left visual defect and the other with right hemiplegia. Magnetic resonance imaging of the brain of both patients showed the presence of multiple cerebral aneurysms that was later confirmed on conventional angiography. Both patients' aneurysms were managed conservatively. Serial angiograms were performed during their follow-up, which spanned several years. One patient's aneurysms remained static while the evolution of the other patient's aneurysms displayed a dynamic quality with some increasing in size while others diminished. This is the first description in which some aneurysms progressed while others regressed simultaneously in the same patient. Aneurysms in patients with a history of cardiac myxoma can be active years after primary tumor resection and it is difficult to predict how they will develop. We reviewed the literature of all patients with multiple myxomatous aneurysms who were treated conservatively to better understand the natural history of this rare disease. Long-term follow-up of these patients may be necessary.


Assuntos
Embolização Terapêutica/métodos , Neoplasias Cardíacas/complicações , Aneurisma Intracraniano/etiologia , Aneurisma Intracraniano/terapia , Mixoma/complicações , Angiografia Cerebral , Diagnóstico Diferencial , Ecocardiografia , Feminino , Neoplasias Cardíacas/diagnóstico por imagem , Humanos , Aneurisma Intracraniano/diagnóstico por imagem , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Mixoma/diagnóstico por imagem , Adulto Jovem
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