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1.
AJR Am J Roentgenol ; 222(5): e2330720, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38353447

RESUMO

BACKGROUND. The 2022 Society of Radiologists in Ultrasound (SRU) consensus conference recommendations for small gallbladder polyps support management that is less aggressive than earlier approaches and may help standardize evaluation of polyps by radiologists. OBJECTIVE. The purpose of the present study was to assess the interreader agreement of radiologists in applying SRU recommendations for management of incidental gallbladder polyps on ultrasound. METHODS. This retrospective study included 105 patients (75 women and 30 men; median age, 51 years) with a gallbladder polyp on ultrasound (without features highly suspicious for invasive or malignant tumor) who underwent cholecystectomy between January 1, 2003, and January 1, 2021. Ten abdominal radiologists independently reviewed ultrasound examinations and, using the SRU recommendations, assessed one polyp per patient to assign risk category (extremely low risk, low risk, or indeterminate risk) and make a possible recommendation for surgical consultation. Five radiologists were considered less experienced (< 5 years of experience), and five were considered more experienced (≥ 5 years of experience). Interreader agreement was evaluated. Polyps were classified pathologically as nonneoplastic or neoplastic. RESULTS. For risk category assignments, interreader agreement was substantial among all readers (k = 0.710), less-experienced readers (k = 0.705), and more-experienced readers (k = 0.692). For surgical consultation recommendations, inter-reader agreement was substantial among all readers (k = 0.795) and more-experienced readers (k = 0.740) and was almost perfect among less-experienced readers (k = 0.811). Of 10 readers, a median of 5.0 (IQR, 2.0-8.0), 4.0 (IQR, 2.0-7.0), and 0.0 (IQR, 0.0-0.0) readers classified polyps as extremely low risk, low risk, and indeterminate risk, respectively. Across readers, the percentage of polyps classified as extremely low risk ranged from 32% to 72%; as low risk, from 24% to 65%; and as indeterminate risk, from 0% to 8%. Of 10 readers, a median of zero change to 0 (IQR, 0.0-1.0) readers recommended surgical consultation; the percentage of polyps receiving a recommendation for surgical consultation ranged from 4% to 22%. Of a total of 105 polyps, 102 were nonneo-plastic and three were neoplastic (all benign). Based on readers' most common assessments for nonneoplastic polyps, the risk category was extremely low risk for 53 polyps, low risk for 48 polyps, and indeterminate risk for one polyp; surgical consultation was recommended for 16 polyps. CONCLUSION. Ten abdominal radiologists showed substantial agreement for polyp risk categorizations and surgical consultation recommendations, although areas of reader variability were identified. CLINICAL IMPACT. The findings support the overall reproducibility of the SRU recommendations, while indicating opportunity for improvement.


Assuntos
Achados Incidentais , Pólipos , Ultrassonografia , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Pólipos/diagnóstico por imagem , Pólipos/cirurgia , Estudos Retrospectivos , Ultrassonografia/métodos , Adulto , Doenças da Vesícula Biliar/diagnóstico por imagem , Doenças da Vesícula Biliar/cirurgia , Idoso , Variações Dependentes do Observador , Radiologistas , Sociedades Médicas , Consenso , Guias de Prática Clínica como Assunto
2.
Artigo em Inglês | MEDLINE | ID: mdl-38438338

RESUMO

ABSTRACT: Recent advances in molecular pathology and an improved understanding of the etiology of neuroendocrine neoplasms (NENs) have given rise to an updated World Health Organization classification. Since gastroenteropancreatic NENs (GEP-NENs) are the most common forms of NENs and their incidence has been increasing constantly, they will be the focus of our attention. Here, we review the findings at the foundation of the new classification system, discuss how it impacts imaging research and radiological practice, and illustrate typical and atypical imaging and pathological findings. Gastroenteropancreatic NENs have a highly variable clinical course, which existing classification schemes based on proliferation rate were unable to fully capture. While well- and poorly differentiated NENs both express neuroendocrine markers, they are fundamentally different diseases, which may show similar proliferation rates. Genetic alterations specific to well-differentiated neuroendocrine tumors graded 1 to 3 and poorly differentiated neuroendocrine cancers of small cell and large-cell subtype have been identified. The new tumor classification places new demands and creates opportunities for radiologists to continue providing the clinically most relevant report and on researchers to design projects, which continue to be clinically applicable.

5.
J Vasc Interv Radiol ; 29(2): 219-224, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29128157

RESUMO

PURPOSE: To evaluate efficacy and safety of prophylactic internal iliac occlusion balloon placement before cesarean hysterectomy for invasive placenta. MATERIAL AND METHODS: A retrospective analysis was performed of patients with invasive placenta treated with and without occlusion balloon placement. Preoperative occlusion balloons were placed in 90 patients; 61 patients were treated without balloon placement (control group). Baseline demographics, including patient age, gestational age at delivery, gravidity, parity, and number of previous cesarean sections, were not significantly different (P > .05). Of the balloon placement group, 56% had placenta percreta compared with 25% in the control group (P < .001), and 83% had placenta previa compared with 66% in the control group (P = .012). RESULTS: Median blood loss was 2 L (range, 1.5-2.5 L) in the balloon placement group versus 2.5 L (range, 2-4 L) in the control group (P = .002). Patients with occlusion balloons were transfused a median of 2 U (range, 0-5 U) of packed red blood cells versus 5 U (range, 2-8 U) in patients in the control group (P = .002). In the balloon placement group, 34% had large volume blood loss > 2,500 mL versus 61% in the control group (P = .001), and 21% required blood transfusion > 6 U versus 44% in the control group (P = .002). Eight complications (9%) were attributed to occlusion balloon placement. CONCLUSIONS: Prophylactic internal iliac artery occlusion balloon placement reduces operative blood loss and transfusion requirements in patients undergoing hysterectomy for invasive placenta.


Assuntos
Oclusão com Balão , Perda Sanguínea Cirúrgica/prevenção & controle , Artéria Ilíaca , Placenta Acreta/cirurgia , Adulto , Transfusão de Sangue/estatística & dados numéricos , Cesárea , Feminino , Número de Gestações , Humanos , Histerectomia , Paridade , Gravidez , Radiografia Intervencionista , Estudos Retrospectivos , Resultado do Tratamento
6.
Proc Natl Acad Sci U S A ; 112(37): 11583-8, 2015 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-26324937

RESUMO

The tumor protein 53 (TP53) tumor suppressor gene is the most frequently somatically altered gene in human cancers. Here we show expression of N-Myc down-regulated gene 1 (NDRG1) is induced by p53 during physiologic low proliferative states, and mediates centrosome homeostasis, thus maintaining genome stability. When placed in physiologic low-proliferating conditions, human TP53 null cells fail to increase expression of NDRG1 compared with isogenic wild-type controls and TP53 R248W knockin cells. Overexpression and RNA interference studies demonstrate that NDRG1 regulates centrosome number and amplification. Mechanistically, NDRG1 physically associates with γ-tubulin, a key component of the centrosome, with reduced association in p53 null cells. Strikingly, TP53 homozygous loss was mutually exclusive of NDRG1 overexpression in over 96% of human cancers, supporting the broad applicability of these results. Our study elucidates a mechanism of how TP53 loss leads to abnormal centrosome numbers and genomic instability mediated by NDRG1.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Centrossomo/ultraestrutura , Regulação Neoplásica da Expressão Gênica , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Aneuploidia , Animais , Mama/metabolismo , Linhagem Celular , Proliferação de Células , Centrossomo/metabolismo , Feminino , Genoma , Heterozigoto , Homeostase , Homozigoto , Humanos , Hibridização in Situ Fluorescente , Camundongos , Camundongos Knockout , Neoplasias/patologia , Fenótipo , Interferência de RNA , Tubulina (Proteína)/metabolismo
7.
Proc Natl Acad Sci U S A ; 112(45): E6205-14, 2015 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-26508629

RESUMO

Recurrent human epidermal growth factor receptor 2 (HER2) missense mutations have been reported in human cancers. These mutations occur primarily in the absence of HER2 gene amplification such that most HER2-mutant tumors are classified as "negative" by FISH or immunohistochemistry assays. It remains unclear whether nonamplified HER2 missense mutations are oncogenic and whether they are targets for HER2-directed therapies that are currently approved for the treatment of HER2 gene-amplified breast cancers. Here we functionally characterize HER2 kinase and extracellular domain mutations through gene editing of the endogenous loci in HER2 nonamplified human breast epithelial cells. In in vitro and in vivo assays, the majority of HER2 missense mutations do not impart detectable oncogenic changes. However, the HER2 V777L mutation increased biochemical pathway activation and, in the context of a PIK3CA mutation, enhanced migratory features in vitro. However, the V777L mutation did not alter in vivo tumorigenicity or sensitivity to HER2-directed therapies in proliferation assays. Our results suggest the oncogenicity and potential targeting of HER2 missense mutations should be considered in the context of cooperating genetic alterations and provide previously unidentified insights into functional analysis of HER2 mutations and strategies to target them.


Assuntos
Movimento Celular/genética , Mutação de Sentido Incorreto/genética , Neoplasias/genética , Receptor ErbB-2/genética , Transdução de Sinais/genética , Western Blotting , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Ensaio de Unidades Formadoras de Colônias , Citometria de Fluxo , Marcação de Genes , Células HEK293 , Humanos , Immunoblotting , Lapatinib , Quinazolinas , Quinolinas , Tiazóis
8.
Breast Cancer Res Treat ; 162(3): 451-464, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28190247

RESUMO

BACKGROUND/PURPOSE: The combined contributions of oncogenes and tumor suppressor genes toward carcinogenesis remain poorly understood. Elucidation of cancer gene cooperativity can provide new insights leading to more effective use of therapies. EXPERIMENTAL DESIGN/METHODS: We used somatic cell genome editing to introduce singly and in combination PIK3CA mutations (E545K or H1047R) with TP53 alterations (R248W or knockout), to assess any enhanced cancerous phenotypes. The non-tumorigenic human breast epithelial cell line, MCF10A, was used as the parental cell line, and resultant cells were assessed via various in vitro assays, growth as xenografts, and drug sensitivity assays using targeted agents and chemotherapies. RESULTS: Compared to single-gene-targeted cells and parental controls, cells with both a PIK3CA mutation and TP53 alteration had increased cancerous phenotypes including cell proliferation, soft agar colony formation, aberrant morphology in acinar formation assays, and genomic heterogeneity. Cells also displayed varying sensitivities to anti-neoplastic drugs, although all cells with PIK3CA mutations showed a relative increased sensitivity to paclitaxel. All cell lines remained non-tumorigenic. CONCLUSIONS: This cell line panel provides a resource for further elucidating cooperative genetic mediators of carcinogenesis and response to therapies.


Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Classe I de Fosfatidilinositol 3-Quinases/genética , Mutação , Fenótipo , Proteína Supressora de Tumor p53/genética , Animais , Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Centrômero/genética , Variações do Número de Cópias de DNA , Modelos Animais de Doenças , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Amplificação de Genes , Edição de Genes , Técnicas de Inativação de Genes , Instabilidade Genômica , Genótipo , Humanos , Camundongos , Paclitaxel/farmacologia
9.
Proc Natl Acad Sci U S A ; 111(34): 12486-91, 2014 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-25114222

RESUMO

Although aerobic glycolysis provides an advantage in the hypoxic tumor microenvironment, some cancer cells can also respire via oxidative phosphorylation. These respiring ("non-Warburg") cells were previously thought not to play a key role in tumorigenesis and thus fell from favor in the literature. We sought to determine whether subpopulations of hypoxic cancer cells have different metabolic phenotypes and gene-expression profiles that could influence tumorigenicity and therapeutic response, and we therefore developed a dual fluorescent protein reporter, HypoxCR, that detects hypoxic [hypoxia-inducible factor (HIF) active] and/or cycling cells. Using HEK293T cells as a model, we identified four distinct hypoxic cell populations by flow cytometry. The non-HIF/noncycling cell population expressed a unique set of genes involved in mitochondrial function. Relative to the other subpopulations, these hypoxic "non-Warburg" cells had highest oxygen consumption rates and mitochondrial capacity consistent with increased mitochondrial respiration. We found that these respiring cells were unexpectedly tumorigenic, suggesting that continued respiration under limiting oxygen conditions may be required for tumorigenicity.


Assuntos
Ciclo Celular/fisiologia , Hipóxia Celular/fisiologia , Neoplasias/metabolismo , Neoplasias/patologia , Animais , Ciclo Celular/genética , Hipóxia Celular/genética , Respiração Celular , Expressão Gênica , Genes Mitocondriais , Genes Reporter , Células HEK293 , Xenoenxertos , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Masculino , Camundongos , Camundongos Nus , Modelos Biológicos , Transplante de Neoplasias , Neoplasias/genética , Oncogenes , Consumo de Oxigênio
10.
Proc Natl Acad Sci U S A ; 111(49): 17606-11, 2014 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-25422431

RESUMO

Tamoxifen is effective for treating estrogen receptor-alpha (ER) positive breast cancers. However, few molecular mediators of tamoxifen resistance have been elucidated. Here we describe a previously unidentified gene, MACROD2 that confers tamoxifen resistance and estrogen independent growth. We found MACROD2 is amplified and overexpressed in metastatic tamoxifen-resistant tumors. Transgene overexpression of MACROD2 in breast cancer cell lines results in tamoxifen resistance, whereas RNAi-mediated gene knock down reverses this phenotype. MACROD2 overexpression also leads to estrogen independent growth in xenograft assays. Mechanistically, MACROD2 increases p300 binding to estrogen response elements in a subset of ER regulated genes. Primary breast cancers and matched metastases demonstrate MACROD2 expression can change with disease evolution, and increased expression and amplification of MACROD2 in primary tumors is associated with worse overall survival. These studies establish MACROD2 as a key mediator of estrogen independent growth and tamoxifen resistance, as well as a potential novel target for diagnostics and therapy.


Assuntos
Neoplasias da Mama/metabolismo , Enzimas Reparadoras do DNA/metabolismo , Resistencia a Medicamentos Antineoplásicos , Estrogênios/metabolismo , Hidrolases/metabolismo , Tamoxifeno/farmacologia , Sequência de Bases , Linhagem Celular Tumoral , Proliferação de Células , Epigênese Genética , Feminino , Deleção de Genes , Dosagem de Genes , Humanos , Dados de Sequência Molecular , Transplante de Neoplasias , Fenótipo , Prognóstico , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Receptores de Estrogênio/metabolismo , Transgenes , Resultado do Tratamento
12.
Proteomics ; 15(2-3): 318-26, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25367220

RESUMO

The PIK3CA gene encodes for the p110 alpha isoform of PI3 kinase and is one of the most frequently mutated oncogenes in human cancers. However, the mechanisms by which PIK3CA mutations activate cell signaling are not fully understood. Here we used a phosphoproteomic approach to compare differential phosphorylation patterns between human breast epithelial cells and two isogenic somatic cell knock in derivatives, each harboring a distinct PIK3CA mutation. We demonstrated differential phosphorylation patterns between isogenic cell lines containing a PIK3CA helical domain mutation (E545K) compared to cells with a PIK3CA kinase domain mutation (H1047R). In particular, the receptor tyrosine kinase, HER3, showed increased phosphorylation at tyrosine 1328 in H1047R cells versus E545K cells. Genetic studies using shRNA demonstrated that H1047R cells have a profound decrease in growth factor independent proliferation upon HER3 knock down, but this effect was attenuated in E545K cells. In addition, HER3 knock down led to reductions in both PI3 kinase and MAP kinase pathway activation in H1047R cells, but in E545K cells only PI3 kinase pathway diminution was observed. These studies demonstrate the power of using paired isogenic cell lines for proteomic analysis to gain new insights into oncogenic signal transduction pathways.


Assuntos
Neoplasias da Mama/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteômica , Receptor ErbB-3/metabolismo , Transdução de Sinais , Neoplasias da Mama/genética , Linhagem Celular , Linhagem Celular Tumoral , Proliferação de Células , Classe I de Fosfatidilinositol 3-Quinases , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Mutação , Fosfatidilinositol 3-Quinases/química , Fosfatidilinositol 3-Quinases/genética , Fosforilação , Estrutura Terciária de Proteína , Interferência de RNA , Receptor ErbB-3/genética
13.
Proc Natl Acad Sci U S A ; 108(43): 17773-8, 2011 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-21987798

RESUMO

Biallelic inactivation of cancer susceptibility gene BRCA1 leads to breast and ovarian carcinogenesis. Paradoxically, BRCA1 deficiency in mice results in early embryonic lethality, and similarly, lack of BRCA1 in human cells is thought to result in cellular lethality in view of BRCA1's essential function. To survive homozygous BRCA1 inactivation during tumorigenesis, precancerous cells must accumulate additional genetic alterations, such as p53 mutations, but this requirement for an extra genetic "hit" contradicts the two-hit theory for the accelerated carcinogenesis associated with familial cancer syndromes. Here, we show that heterozygous BRCA1 inactivation results in genomic instability in nontumorigenic human breast epithelial cells in vitro and in vivo. Using somatic cell gene targeting, we demonstrated that a heterozygous BRCA1 185delAG mutation confers impaired homology-mediated DNA repair and hypersensitivity to genotoxic stress. Heterozygous mutant BRCA1 cell clones also showed a higher degree of gene copy number loss and loss of heterozygosity in SNP array analyses. In BRCA1 heterozygous clones and nontumorigenic breast epithelial tissues from BRCA mutation carriers, FISH revealed elevated genomic instability when compared with their respective controls. Thus, BRCA1 haploinsufficiency may accelerate hereditary breast carcinogenesis by facilitating additional genetic alterations.


Assuntos
Mama/citologia , Células Epiteliais/fisiologia , Genes BRCA1 , Instabilidade Genômica/genética , Haploinsuficiência/genética , Feminino , Inativação Gênica , Instabilidade Genômica/fisiologia , Heterozigoto , Humanos , Hibridização in Situ Fluorescente , Polimorfismo de Nucleotídeo Único , Deleção de Sequência/genética
14.
Magn Reson Imaging Clin N Am ; 31(3): 413-431, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37414469

RESUMO

Magnetic resonance venography (MRV) represents a distinct imaging approach that may be used to evaluate a wide spectrum of venous pathology. Despite duplex ultrasound and computed tomography venography representing the dominant imaging modalities in investigating suspected venous disease, MRV is increasingly used due to its lack of ionizing radiation, unique ability to be performed without administration of intravenous contrast, and recent technical improvements resulting in improved sensitivity, image quality, and faster acquisition times. In this review, the authors discuss commonly used body and extremity MRV techniques, different clinical applications, and future directions.


Assuntos
Angiografia por Ressonância Magnética , Imageamento por Ressonância Magnética , Humanos , Imageamento por Ressonância Magnética/métodos , Flebografia/métodos , Angiografia por Ressonância Magnética/métodos , Extremidades , Tomografia Computadorizada por Raios X
15.
Radiol Case Rep ; 18(1): 353-357, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36411848

RESUMO

Hemorrhagic cholecystitis is a rare disorder associated with considerable morbidity and mortality. The clinical presentation of hemorrhagic cholecystitis is non-specific and imaging findings can be difficult to accurately interpret without a high level of suspicion. Most recent reports of hemorrhagic cholecystitis have been associated with concurrent therapeutic anticoagulation. Here, we report imaging findings of a case of acute, spontaneous hemorrhagic cholecystitis in a 67-year-old male patient admitted for hypoxic respiratory failure secondary to COVID-19 pneumonia.

16.
J Biol Chem ; 286(34): 29718-24, 2011 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-21730071

RESUMO

The cholinesterases, acetylcholinesterase (AChE) and butyrylcholinesterase, are primary targets of organophosphates (OPs). Exposure to OPs can lead to serious cardiovascular complications, respiratory compromise, and death. Current therapy to combat OP poisoning involves an oxime reactivator (2-PAM, obidoxime, TMB4, or HI-6) combined with atropine and on occasion an anticonvulsant. Butyrylcholinesterase, administered in the plasma compartment as a bio-scavenger, has also shown efficacy but is limited by its strict stoichiometric scavenging, slow reactivation, and a propensity for aging. Here, we characterize 10 human (h) AChE mutants that, when coupled with an oxime, give rise to catalytic reactivation and aging resistance of the soman conjugate. With the most efficient human AChE mutant Y337A/F338A, we show enhanced reactivation rates for several OP-hAChE conjugates compared with wild-type hAChE when reactivated with HI-6 (1-(2'-hydroxyiminomethyl-1'-pyridinium)-3-(4'-carbamoyl-1-pyridinium)). In addition, we interrogated an 840-member novel oxime library for reactivation of Y337A/F338A hAChE-OP conjugates to delineate the most efficient oxime-mutant enzyme pairs for catalytic bio-scavenging. Combining the increased accessibility of the Y337A mutation to oximes within the space-impacted active center gorge with the aging resistance of the F338A mutation provides increased substrate diversity in scavenging potential for aging-prone alkyl phosphate inhibitors.


Assuntos
Acetilcolinesterase/química , Envelhecimento , Organofosfatos/química , Oximas/química , Compostos de Piridínio/química , Acetilcolinesterase/genética , Acetilcolinesterase/metabolismo , Domínio Catalítico/fisiologia , Humanos , Mutação de Sentido Incorreto , Oximas/metabolismo , Compostos de Piridínio/metabolismo
17.
Radiol Case Rep ; 17(12): 4924-4927, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36299866

RESUMO

IgG4-related disease (IgG4-RD) is an immune-mediated multiorgan fibroinflammatory disorder with variable clinical presentations. IgG4-RD cardiovascular involvement is considered rare, with pulmonary arterial involvement reported in a small subset of cases. Known pulmonary artery manifestations include pulmonary arteritis, pulmonary artery stenoses and central pulmonary artery aneurysms. Here we report 2 different patients with multifocal dilatation of the segmental and subsegmental pulmonary arteries with differing degrees of severity. Both patients also had coronary arterial abnormalities.

18.
Oncotarget ; 13: 373-386, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35186194

RESUMO

Activating variants in the PEST region of NOTCH1 have been associated with aggressive phenotypes in human cancers, including triple-negative breast cancer (TNBC). Previous studies suggested that PEST domain variants in TNBC patients resulted in increased cell proliferation, invasiveness, and decreased overall survival. In this study, we assess the phenotypic transformation of activating NOTCH1 variants and their response to standard of care therapies. AAV-mediated gene targeting was used to isogenically incorporate 3 NOTCH1 variants, including a novel TNBC frameshift variant, in two non-tumorigenic breast epithelial cell lines, MCF10A and hTERT-IMEC. Two different variants at the NOTCH1 A2241 site (A2441fs and A2441T) both demonstrated increased transformative properties when compared to a non-transformative PEST domain variant (S2523L). These phenotypic changes include proliferation, migration, anchorage-independent growth, and MAPK pathway activation. In contrast to previous studies, activating NOTCH1 variants did not display sensitivity to a gamma secretase inhibitor (GSI) or resistance to chemotherapies. This study demonstrates distinct transformative phenotypes are specific to a given variant within NOTCH1 and these phenotypes do not correlate with sensitivities or resistance to chemotherapies or GSIs. Although previous studies have suggested NOTCH1 variants may be prognostic for TNBC, our study does not demonstrate prognostic ability of these variants and suggests further characterization would be required for clinical applications.


Assuntos
Neoplasias de Mama Triplo Negativas , Linhagem Celular Tumoral , Proliferação de Células/genética , Inibidores e Moduladores de Secretases gama , Humanos , Receptor Notch1/genética , Receptor Notch1/metabolismo , Transdução de Sinais , Padrão de Cuidado , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/terapia
19.
Cardiovasc Intervent Radiol ; 44(8): 1165-1173, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33855582

RESUMO

PURPOSE: Diabetic patients are at increased risk of developing lower extremity peripheral arterial disease (PAD) requiring revascularization. This study assessed the effect of insulin dependence in diabetics on post-procedural outcomes following infra-inguinal endovascular intervention. MATERIALS AND METHODS: The American College of Surgeon's National Surgical Quality Improvement Program database was used to identify 8022 patients undergoing infra-inguinal endovascular interventions between 2014 and 2017. Thirty-day post-procedural outcomes for patients without diabetes, with non-insulin-dependent diabetes mellitus (NIDDM), and with insulin-dependent diabetes mellitus (IDDM) were compared. RESULTS: At presentation, IDDM patients were more likely to present with critical limb ischemia compared to NIDDM and non-diabetic patients. In propensity score-weighted logistic regression analysis, IDDM status was an independent predictor for increased renal complication (odds ratio [OR] = 3.08, confidence interval [CI] = 1.44-6.65), sepsis (OR = 1.68, CI = 1.13-2.48), wound complication (OR = 1.57, CI = 1.09-2.25, p = 0.006), UTI (OR = 2.07, CI = 1.09-3.94, p = 0.03), and readmission (OR = 1.21, CI = 1.03-1.42). NIDDM status was an independent predictor for increased risk of renal complications (OR = 2.80, CI = 1.18-6.63). CONCLUSIONS: IDDM status is an independent predictor for increased risk of 30-day post-procedural complications and readmission compared to both NIDDM and non-diabetic status in patients undergoing lower extremity endovascular interventions for PAD.


Assuntos
Diabetes Mellitus/sangue , Procedimentos Endovasculares/métodos , Insulina/sangue , Isquemia/etiologia , Doença Arterial Periférica/complicações , Doença Arterial Periférica/cirurgia , Complicações Pós-Operatórias/etiologia , Idoso , Idoso de 80 Anos ou mais , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/complicações , Procedimentos Endovasculares/efeitos adversos , Feminino , Humanos , Isquemia/sangue , Extremidade Inferior/irrigação sanguínea , Extremidade Inferior/cirurgia , Masculino , Pessoa de Meia-Idade , Razão de Chances , Doença Arterial Periférica/sangue , Complicações Pós-Operatórias/sangue , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Estados Unidos
20.
Curr Probl Diagn Radiol ; 50(3): 284-287, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33483191

RESUMO

The COVID-19 pandemic has challenged the capacity of interventional radiology departments worldwide to effectively treat COVID-19 and non-COVID-19 patients while preventing disease transmission among patients and healthcare workers. In this review, we describe the various data driven infection control measures implemented by the interventional radiology department of a large tertiary care center in the United States including the use and novel re-use of personal protective equipment, COVID-19 testing strategies, modifications in procedural workflows and the leveraging of telehealth visits. Herein, we provide effective triage, procedural, and management algorithms that may guide other interventional radiology departments during the ongoing COVID-19 pandemic and in future infectious disease outbreaks.


Assuntos
COVID-19/prevenção & controle , Controle de Infecções/métodos , Serviço Hospitalar de Radiologia , Radiologia Intervencionista/métodos , Humanos , Pandemias , Equipamento de Proteção Individual , SARS-CoV-2 , Centros de Atenção Terciária , Estados Unidos
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